MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amicar® may be confused with amikacin, Amikin®, Omacor®
U.S. BRAND NAMES — Amicar®
PHARMACOLOGIC CATEGORY
Antifibrinolytic Agent
Antihemophilic Agent
Hemostatic Agent
Lysine Analog
DOSING: ADULTS
Acute bleeding syndrome: Oral, I.V.: Loading dose: 4-5 g during the first hour, followed by 1 g/hour for 8 hours (or 1.25 g/hour using oral solution) or until bleeding controlled (maximum daily dose: 30 g)
Control of bleeding in thrombocytopenia (unlabeled use):
Initial: I.V.: 100 mg/kg over 30-60 minutes
Maintenance: Oral: 1-3 g every 6 hours
Control of oral bleeding in congenital and acquired coagulation disorder (unlabeled use): Oral: 50-60 mg/kg every 4 hours
Prevention of dental procedure bleeding in patients on oral anticoagulant therapy (unlabeled use): Oral rinse: Hold 4 g/10 mL in mouth for 2 minutes then spit out. Repeat every 6 hours for 2 days after procedure (Souto, 1996). Concentration and frequency may vary by institution and product availability.
Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): I.V.: 10 g over 20-30 minutes prior to skin incision, followed by 1-2.5 g/hour (usual dose 2 g/hour) until the end of operation (may continue infusion for 4 hours after protamine reversal of heparin). May add 10 g to cardiopulmonary bypass circuit priming solution.
or
10 g over 20-30 minutes prior to skin incision, followed by 10 g after heparin administration then 10 g at discontinuation of cardiopulmonary bypass prior to protamine reversal of heparin
Traumatic hyphema (unlabeled use): Oral: 100 mg/kg/dose every 4 hours (maximum daily dose: 30 g)
DOSING: PEDIATRIC
(For additional information see "Aminocaproic acid: Pediatric drug information")
Acute bleeding syndrome (unlabeled use): Oral, I.V.: Loading dose: 100-200 mg/kg during the first hour, followed by continuous infusion at 33.3 mg/kg/hour (I.V.) or 100 mg/kg (oral or I.V.) every 6 hours
Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): I.V.: 100 mg/kg given over 20-30 minutes after induction and prior to incision, 100 mg/kg during cardiopulmonary bypass, and 100 mg/kg after protamine reversal of heparin
Traumatic hyphema (unlabeled use): Oral: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — May accumulate in patients with decreased renal function.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 250 mg/mL (20 mL)
Solution, oral: 1.25 g/5 mL (240 mL, 480 mL)
Syrup:
Amicar®: 1.25 g/5 mL (480 mL) [raspberry flavor]
Tablet [scored]: 500 mg
Amicar®: 500 mg, 1000 mg
DOSAGE FORMS: CONCISE
Injection, solution: 250 mg/mL (20 mL)
Solution, oral: 1.25 g/5 mL (480 mL)
Syrup:
Amicar®: 1.25 g/5 mL
Tablet [scored]: 500 mg
Amicar®: 500 mg, 1000 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Rapid I.V. injection (IVP) of undiluted solution is not recommended due to possible hypotension, bradycardia, and arrhythmia.
I.V.: Acute bleeding syndrome: Administer loading dose over 1 hour, followed by a continuous infusion
I.V.: Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): Administer loading dose over 20-30 minutes prior to skin incision, followed by a continuous infusion until the end of operation or as 2 additional bolus doses (over 20-30 minutes) given after heparin administration and at discontinuation of cardiopulmonary bypass prior to protamine reversal of heparin.
COMPATIBILITY — Stable in D5W, NS, Ringer's injection
USE — To enhance hemostasis when fibrinolysis contributes to bleeding (causes may include cardiac surgery, hematologic disorders, neoplastic disorders, abruption placentae, hepatic cirrhosis, and urinary fibrinolysis)
USE - UNLABELED / INVESTIGATIONAL — Treatment of traumatic hyphema; control bleeding in thrombocytopenia; control oral bleeding in congenital and acquired coagulation disorders; topical treatment (mouth rinse) of bleeding associated with dental procedures in patients on oral anticoagulant therapy; prevention of perioperative bleeding associated with cardiac surgery
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmia, bradycardia, edema, hypotension, intracranial hypertension, peripheral ischemia, syncope, thrombosis
Central nervous system: Confusion, delirium, dizziness, fatigue, hallucinations, headache, malaise, seizure, stroke
Dermatologic: Rash, pruritus
Gastrointestinal: Abdominal pain, anorexia, cramps, diarrhea, GI irritation, nausea, vomiting
Genitourinary: Dry ejaculation
Hematologic: Agranulocytosis, bleeding time increased, leukopenia, thrombocytopenia
Local: Injection site necrosis, injection site pain, injectionsite reactions
Neuromuscular & skeletal: CPK increased, myalgia, myositis, myopathy, rhabdomyolysis (rare), weakness
Ophthalmic: Vision decreased, watery eyes
Otic: Tinnitus
Renal: BUN increased, intrarenal obstruction (glomerular capillary thrombosis), myoglobinuria (rare), renal failure (rare)
Respiratory: Dyspnea, nasal congestion, pulmonary embolism
Miscellaneous: Allergic reaction, anaphylactoid reaction, anaphylaxis
Postmarketing and/or case reports: Hepatic lesion, myocardial lesion
CONTRAINDICATIONS — Disseminated intravascular coagulation (without heparin); evidence of an active intravascular clotting process
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Intrarenal obstruction: May occur secondary to glomerular capillary thrombosis or clots in the renal pelvis and ureters; do not use in hematuria of upper urinary tract origin unless possible benefits outweigh risks. Skeletal muscle weakness: Ranging from mild myalgias and fatigue to severe myopathy with rhabdomyolysis and acute renal failure has been reported with prolonged use. Monitor CPK; discontinue treatment with a rise in CPK.
Disease-related concerns: Renal impairment: Use with caution in patients with renal impairment; may accumulate.
Concurrent drug therapy issues: Blood products: Do not administer with factor IX complex concentrates or anti-inhibitor coagulant complexes; may increase risk for thrombosis.
Dosage form specific issues: Benzyl alcohol: Injection contains benzyl alcohol which has been associated with "gasping syndrome" in neonates.
Other warnings/precautions: Appropriate use: Do not administer without a definite diagnosis of laboratory findings indicative of hyperfibrinolysis. Inhibition of fibrinolysis may promote clotting or thrombosis; more likely due to the presence of DIC. I.V. administration: Avoid rapid I.V. administration; may induce hypotension, bradycardia, or arrhythmia; rapid injection of undiluted solution is not recommended.
DRUG INTERACTIONS
Anti-inhibitor Coagulant Complex: Antifibrinolytic Agents may enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex. Risk X: Avoid combination
Factor IX: Aminocaproic Acid may enhance the adverse/toxic effect of Factor IX. Specifically, use of this combination may increase the risk of thrombosis. Risk X: Avoid combination
Factor IX Complex (Human): Aminocaproic Acid may enhance the adverse/toxic effect of Factor IX Complex (Human). Specifically, use of this combination may increase the risk of thrombosis. Risk X: Avoid combination
Fibrinogen Concentrate (Human): Antifibrinolytic Agents may enhance the adverse/toxic effect of Fibrinogen Concentrate (Human). Specifically, the risk for thrombosis may be increased. Fibrinogen Concentrate (Human) may enhance the adverse/toxic effect of Antifibrinolytic Agents. Specifically, the risk for thrombosis may be increased. Risk C: Monitor therapy
Tretinoin (Oral): May enhance the thrombogenic effect of Antifibrinolytic Agents. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal reproductive studies have not been conducted.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Tablets (Amicar)
500 mg (30): $103.40
Tablets (Aminocaproic Acid)
500 mg (100): $177.59
MONITORING PARAMETERS — Fibrinogen, fibrin split products, creatine phosphokinase (with long-term therapy), BUN, creatinine
INTERNATIONAL BRAND NAMES — Acepramin (HU); Acidum e-aminocapronicum (PL); Amicar (AE, AU, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE, ZA); Caproamin (ES, VE); Caproamin Fides (ES); Caprolest (NL); Caprolisin (IT); EAC (DE); Epsamon (CH); Epsicaprom (PT); Epsilon (FI); Hamostat (IN); Hemocaprol (ES); Hexalense (FR); Ipron (TW); Ipsilon (AR, BR, JP, PY, UY); Resplamin (JP); Syrop acidi e-aminocapronici (PL)
MECHANISM OF ACTION — Binds competitively to plasminogen; blocking the binding of plasminogen to fibrin and the subsequent conversion to plasmin, resulting in inhibition of fibrin degradation (fibrinolysis).
PHARMACODYNAMICS / KINETICS
Onset of action: ~1-72 hours
Distribution: Widely through intravascular and extravascular compartments
Vd: Oral: 23 L, I.V.: 30 L
Metabolism: Minimally hepatic
Half-life elimination: ~2 hours
Time to peak: Oral: Within 2 hours
Excretion: Urine (65% as unchanged drug, 11% as metabolite)
PATIENT INFORMATION — Report any signs of bleeding; change positions slowly to minimize dizziness
Aminocaproic acid
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amicar® may be confused with amikacin, Amikin®, Omacor®
U.S. BRAND NAMES — Amicar®
PHARMACOLOGIC CATEGORY
Antifibrinolytic Agent
Antihemophilic Agent
Hemostatic Agent
Lysine Analog
DOSING: ADULTS
Acute bleeding syndrome: Oral, I.V.: Loading dose: 4-5 g during the first hour, followed by 1 g/hour for 8 hours (or 1.25 g/hour using oral solution) or until bleeding controlled (maximum daily dose: 30 g)
Control of bleeding in thrombocytopenia (unlabeled use):
Initial: I.V.: 100 mg/kg over 30-60 minutes
Maintenance: Oral: 1-3 g every 6 hours
Control of oral bleeding in congenital and acquired coagulation disorder (unlabeled use): Oral: 50-60 mg/kg every 4 hours
Prevention of dental procedure bleeding in patients on oral anticoagulant therapy (unlabeled use): Oral rinse: Hold 4 g/10 mL in mouth for 2 minutes then spit out. Repeat every 6 hours for 2 days after procedure (Souto, 1996). Concentration and frequency may vary by institution and product availability.
Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): I.V.: 10 g over 20-30 minutes prior to skin incision, followed by 1-2.5 g/hour (usual dose 2 g/hour) until the end of operation (may continue infusion for 4 hours after protamine reversal of heparin). May add 10 g to cardiopulmonary bypass circuit priming solution.
or
10 g over 20-30 minutes prior to skin incision, followed by 10 g after heparin administration then 10 g at discontinuation of cardiopulmonary bypass prior to protamine reversal of heparin
Traumatic hyphema (unlabeled use): Oral: 100 mg/kg/dose every 4 hours (maximum daily dose: 30 g)
DOSING: PEDIATRIC
(For additional information see "Aminocaproic acid: Pediatric drug information")
Acute bleeding syndrome (unlabeled use): Oral, I.V.: Loading dose: 100-200 mg/kg during the first hour, followed by continuous infusion at 33.3 mg/kg/hour (I.V.) or 100 mg/kg (oral or I.V.) every 6 hours
Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): I.V.: 100 mg/kg given over 20-30 minutes after induction and prior to incision, 100 mg/kg during cardiopulmonary bypass, and 100 mg/kg after protamine reversal of heparin
Traumatic hyphema (unlabeled use): Oral: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — May accumulate in patients with decreased renal function.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 250 mg/mL (20 mL)
Solution, oral: 1.25 g/5 mL (240 mL, 480 mL)
Syrup:
Amicar®: 1.25 g/5 mL (480 mL) [raspberry flavor]
Tablet [scored]: 500 mg
Amicar®: 500 mg, 1000 mg
DOSAGE FORMS: CONCISE
Injection, solution: 250 mg/mL (20 mL)
Solution, oral: 1.25 g/5 mL (480 mL)
Syrup:
Amicar®: 1.25 g/5 mL
Tablet [scored]: 500 mg
Amicar®: 500 mg, 1000 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Rapid I.V. injection (IVP) of undiluted solution is not recommended due to possible hypotension, bradycardia, and arrhythmia.
I.V.: Acute bleeding syndrome: Administer loading dose over 1 hour, followed by a continuous infusion
I.V.: Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): Administer loading dose over 20-30 minutes prior to skin incision, followed by a continuous infusion until the end of operation or as 2 additional bolus doses (over 20-30 minutes) given after heparin administration and at discontinuation of cardiopulmonary bypass prior to protamine reversal of heparin.
COMPATIBILITY — Stable in D5W, NS, Ringer's injection
USE — To enhance hemostasis when fibrinolysis contributes to bleeding (causes may include cardiac surgery, hematologic disorders, neoplastic disorders, abruption placentae, hepatic cirrhosis, and urinary fibrinolysis)
USE - UNLABELED / INVESTIGATIONAL — Treatment of traumatic hyphema; control bleeding in thrombocytopenia; control oral bleeding in congenital and acquired coagulation disorders; topical treatment (mouth rinse) of bleeding associated with dental procedures in patients on oral anticoagulant therapy; prevention of perioperative bleeding associated with cardiac surgery
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmia, bradycardia, edema, hypotension, intracranial hypertension, peripheral ischemia, syncope, thrombosis
Central nervous system: Confusion, delirium, dizziness, fatigue, hallucinations, headache, malaise, seizure, stroke
Dermatologic: Rash, pruritus
Gastrointestinal: Abdominal pain, anorexia, cramps, diarrhea, GI irritation, nausea, vomiting
Genitourinary: Dry ejaculation
Hematologic: Agranulocytosis, bleeding time increased, leukopenia, thrombocytopenia
Local: Injection site necrosis, injection site pain, injectionsite reactions
Neuromuscular & skeletal: CPK increased, myalgia, myositis, myopathy, rhabdomyolysis (rare), weakness
Ophthalmic: Vision decreased, watery eyes
Otic: Tinnitus
Renal: BUN increased, intrarenal obstruction (glomerular capillary thrombosis), myoglobinuria (rare), renal failure (rare)
Respiratory: Dyspnea, nasal congestion, pulmonary embolism
Miscellaneous: Allergic reaction, anaphylactoid reaction, anaphylaxis
Postmarketing and/or case reports: Hepatic lesion, myocardial lesion
CONTRAINDICATIONS — Disseminated intravascular coagulation (without heparin); evidence of an active intravascular clotting process
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Intrarenal obstruction: May occur secondary to glomerular capillary thrombosis or clots in the renal pelvis and ureters; do not use in hematuria of upper urinary tract origin unless possible benefits outweigh risks. Skeletal muscle weakness: Ranging from mild myalgias and fatigue to severe myopathy with rhabdomyolysis and acute renal failure has been reported with prolonged use. Monitor CPK; discontinue treatment with a rise in CPK.
Disease-related concerns: Renal impairment: Use with caution in patients with renal impairment; may accumulate.
Concurrent drug therapy issues: Blood products: Do not administer with factor IX complex concentrates or anti-inhibitor coagulant complexes; may increase risk for thrombosis.
Dosage form specific issues: Benzyl alcohol: Injection contains benzyl alcohol which has been associated with "gasping syndrome" in neonates.
Other warnings/precautions: Appropriate use: Do not administer without a definite diagnosis of laboratory findings indicative of hyperfibrinolysis. Inhibition of fibrinolysis may promote clotting or thrombosis; more likely due to the presence of DIC. I.V. administration: Avoid rapid I.V. administration; may induce hypotension, bradycardia, or arrhythmia; rapid injection of undiluted solution is not recommended.
DRUG INTERACTIONS
Anti-inhibitor Coagulant Complex: Antifibrinolytic Agents may enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex. Risk X: Avoid combination
Factor IX: Aminocaproic Acid may enhance the adverse/toxic effect of Factor IX. Specifically, use of this combination may increase the risk of thrombosis. Risk X: Avoid combination
Factor IX Complex (Human): Aminocaproic Acid may enhance the adverse/toxic effect of Factor IX Complex (Human). Specifically, use of this combination may increase the risk of thrombosis. Risk X: Avoid combination
Fibrinogen Concentrate (Human): Antifibrinolytic Agents may enhance the adverse/toxic effect of Fibrinogen Concentrate (Human). Specifically, the risk for thrombosis may be increased. Fibrinogen Concentrate (Human) may enhance the adverse/toxic effect of Antifibrinolytic Agents. Specifically, the risk for thrombosis may be increased. Risk C: Monitor therapy
Tretinoin (Oral): May enhance the thrombogenic effect of Antifibrinolytic Agents. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal reproductive studies have not been conducted.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Tablets (Amicar)
500 mg (30): $103.40
Tablets (Aminocaproic Acid)
500 mg (100): $177.59
MONITORING PARAMETERS — Fibrinogen, fibrin split products, creatine phosphokinase (with long-term therapy), BUN, creatinine
INTERNATIONAL BRAND NAMES — Acepramin (HU); Acidum e-aminocapronicum (PL); Amicar (AE, AU, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE, ZA); Caproamin (ES, VE); Caproamin Fides (ES); Caprolest (NL); Caprolisin (IT); EAC (DE); Epsamon (CH); Epsicaprom (PT); Epsilon (FI); Hamostat (IN); Hemocaprol (ES); Hexalense (FR); Ipron (TW); Ipsilon (AR, BR, JP, PY, UY); Resplamin (JP); Syrop acidi e-aminocapronici (PL)
MECHANISM OF ACTION — Binds competitively to plasminogen; blocking the binding of plasminogen to fibrin and the subsequent conversion to plasmin, resulting in inhibition of fibrin degradation (fibrinolysis).
PHARMACODYNAMICS / KINETICS
Onset of action: ~1-72 hours
Distribution: Widely through intravascular and extravascular compartments
Vd: Oral: 23 L, I.V.: 30 L
Metabolism: Minimally hepatic
Half-life elimination: ~2 hours
Time to peak: Oral: Within 2 hours
Excretion: Urine (65% as unchanged drug, 11% as metabolite)
PATIENT INFORMATION — Report any signs of bleeding; change positions slowly to minimize dizziness
Sound-alike/look-alike issues:
Amicar® may be confused with amikacin, Amikin®, Omacor®
U.S. BRAND NAMES — Amicar®
PHARMACOLOGIC CATEGORY
Antifibrinolytic Agent
Antihemophilic Agent
Hemostatic Agent
Lysine Analog
DOSING: ADULTS
Acute bleeding syndrome: Oral, I.V.: Loading dose: 4-5 g during the first hour, followed by 1 g/hour for 8 hours (or 1.25 g/hour using oral solution) or until bleeding controlled (maximum daily dose: 30 g)
Control of bleeding in thrombocytopenia (unlabeled use):
Initial: I.V.: 100 mg/kg over 30-60 minutes
Maintenance: Oral: 1-3 g every 6 hours
Control of oral bleeding in congenital and acquired coagulation disorder (unlabeled use): Oral: 50-60 mg/kg every 4 hours
Prevention of dental procedure bleeding in patients on oral anticoagulant therapy (unlabeled use): Oral rinse: Hold 4 g/10 mL in mouth for 2 minutes then spit out. Repeat every 6 hours for 2 days after procedure (Souto, 1996). Concentration and frequency may vary by institution and product availability.
Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): I.V.: 10 g over 20-30 minutes prior to skin incision, followed by 1-2.5 g/hour (usual dose 2 g/hour) until the end of operation (may continue infusion for 4 hours after protamine reversal of heparin). May add 10 g to cardiopulmonary bypass circuit priming solution.
or
10 g over 20-30 minutes prior to skin incision, followed by 10 g after heparin administration then 10 g at discontinuation of cardiopulmonary bypass prior to protamine reversal of heparin
Traumatic hyphema (unlabeled use): Oral: 100 mg/kg/dose every 4 hours (maximum daily dose: 30 g)
DOSING: PEDIATRIC
(For additional information see "Aminocaproic acid: Pediatric drug information")
Acute bleeding syndrome (unlabeled use): Oral, I.V.: Loading dose: 100-200 mg/kg during the first hour, followed by continuous infusion at 33.3 mg/kg/hour (I.V.) or 100 mg/kg (oral or I.V.) every 6 hours
Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): I.V.: 100 mg/kg given over 20-30 minutes after induction and prior to incision, 100 mg/kg during cardiopulmonary bypass, and 100 mg/kg after protamine reversal of heparin
Traumatic hyphema (unlabeled use): Oral: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — May accumulate in patients with decreased renal function.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 250 mg/mL (20 mL)
Solution, oral: 1.25 g/5 mL (240 mL, 480 mL)
Syrup:
Amicar®: 1.25 g/5 mL (480 mL) [raspberry flavor]
Tablet [scored]: 500 mg
Amicar®: 500 mg, 1000 mg
DOSAGE FORMS: CONCISE
Injection, solution: 250 mg/mL (20 mL)
Solution, oral: 1.25 g/5 mL (480 mL)
Syrup:
Amicar®: 1.25 g/5 mL
Tablet [scored]: 500 mg
Amicar®: 500 mg, 1000 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Rapid I.V. injection (IVP) of undiluted solution is not recommended due to possible hypotension, bradycardia, and arrhythmia.
I.V.: Acute bleeding syndrome: Administer loading dose over 1 hour, followed by a continuous infusion
I.V.: Prevention of perioperative bleeding associated with cardiac surgery (unlabeled use): Administer loading dose over 20-30 minutes prior to skin incision, followed by a continuous infusion until the end of operation or as 2 additional bolus doses (over 20-30 minutes) given after heparin administration and at discontinuation of cardiopulmonary bypass prior to protamine reversal of heparin.
COMPATIBILITY — Stable in D5W, NS, Ringer's injection
USE — To enhance hemostasis when fibrinolysis contributes to bleeding (causes may include cardiac surgery, hematologic disorders, neoplastic disorders, abruption placentae, hepatic cirrhosis, and urinary fibrinolysis)
USE - UNLABELED / INVESTIGATIONAL — Treatment of traumatic hyphema; control bleeding in thrombocytopenia; control oral bleeding in congenital and acquired coagulation disorders; topical treatment (mouth rinse) of bleeding associated with dental procedures in patients on oral anticoagulant therapy; prevention of perioperative bleeding associated with cardiac surgery
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Arrhythmia, bradycardia, edema, hypotension, intracranial hypertension, peripheral ischemia, syncope, thrombosis
Central nervous system: Confusion, delirium, dizziness, fatigue, hallucinations, headache, malaise, seizure, stroke
Dermatologic: Rash, pruritus
Gastrointestinal: Abdominal pain, anorexia, cramps, diarrhea, GI irritation, nausea, vomiting
Genitourinary: Dry ejaculation
Hematologic: Agranulocytosis, bleeding time increased, leukopenia, thrombocytopenia
Local: Injection site necrosis, injection site pain, injectionsite reactions
Neuromuscular & skeletal: CPK increased, myalgia, myositis, myopathy, rhabdomyolysis (rare), weakness
Ophthalmic: Vision decreased, watery eyes
Otic: Tinnitus
Renal: BUN increased, intrarenal obstruction (glomerular capillary thrombosis), myoglobinuria (rare), renal failure (rare)
Respiratory: Dyspnea, nasal congestion, pulmonary embolism
Miscellaneous: Allergic reaction, anaphylactoid reaction, anaphylaxis
Postmarketing and/or case reports: Hepatic lesion, myocardial lesion
CONTRAINDICATIONS — Disseminated intravascular coagulation (without heparin); evidence of an active intravascular clotting process
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Intrarenal obstruction: May occur secondary to glomerular capillary thrombosis or clots in the renal pelvis and ureters; do not use in hematuria of upper urinary tract origin unless possible benefits outweigh risks. Skeletal muscle weakness: Ranging from mild myalgias and fatigue to severe myopathy with rhabdomyolysis and acute renal failure has been reported with prolonged use. Monitor CPK; discontinue treatment with a rise in CPK.
Disease-related concerns: Renal impairment: Use with caution in patients with renal impairment; may accumulate.
Concurrent drug therapy issues: Blood products: Do not administer with factor IX complex concentrates or anti-inhibitor coagulant complexes; may increase risk for thrombosis.
Dosage form specific issues: Benzyl alcohol: Injection contains benzyl alcohol which has been associated with "gasping syndrome" in neonates.
Other warnings/precautions: Appropriate use: Do not administer without a definite diagnosis of laboratory findings indicative of hyperfibrinolysis. Inhibition of fibrinolysis may promote clotting or thrombosis; more likely due to the presence of DIC. I.V. administration: Avoid rapid I.V. administration; may induce hypotension, bradycardia, or arrhythmia; rapid injection of undiluted solution is not recommended.
DRUG INTERACTIONS
Anti-inhibitor Coagulant Complex: Antifibrinolytic Agents may enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex. Risk X: Avoid combination
Factor IX: Aminocaproic Acid may enhance the adverse/toxic effect of Factor IX. Specifically, use of this combination may increase the risk of thrombosis. Risk X: Avoid combination
Factor IX Complex (Human): Aminocaproic Acid may enhance the adverse/toxic effect of Factor IX Complex (Human). Specifically, use of this combination may increase the risk of thrombosis. Risk X: Avoid combination
Fibrinogen Concentrate (Human): Antifibrinolytic Agents may enhance the adverse/toxic effect of Fibrinogen Concentrate (Human). Specifically, the risk for thrombosis may be increased. Fibrinogen Concentrate (Human) may enhance the adverse/toxic effect of Antifibrinolytic Agents. Specifically, the risk for thrombosis may be increased. Risk C: Monitor therapy
Tretinoin (Oral): May enhance the thrombogenic effect of Antifibrinolytic Agents. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal reproductive studies have not been conducted.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)
Tablets (Amicar)
500 mg (30): $103.40
Tablets (Aminocaproic Acid)
500 mg (100): $177.59
MONITORING PARAMETERS — Fibrinogen, fibrin split products, creatine phosphokinase (with long-term therapy), BUN, creatinine
INTERNATIONAL BRAND NAMES — Acepramin (HU); Acidum e-aminocapronicum (PL); Amicar (AE, AU, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE, ZA); Caproamin (ES, VE); Caproamin Fides (ES); Caprolest (NL); Caprolisin (IT); EAC (DE); Epsamon (CH); Epsicaprom (PT); Epsilon (FI); Hamostat (IN); Hemocaprol (ES); Hexalense (FR); Ipron (TW); Ipsilon (AR, BR, JP, PY, UY); Resplamin (JP); Syrop acidi e-aminocapronici (PL)
MECHANISM OF ACTION — Binds competitively to plasminogen; blocking the binding of plasminogen to fibrin and the subsequent conversion to plasmin, resulting in inhibition of fibrin degradation (fibrinolysis).
PHARMACODYNAMICS / KINETICS
Onset of action: ~1-72 hours
Distribution: Widely through intravascular and extravascular compartments
Vd: Oral: 23 L, I.V.: 30 L
Metabolism: Minimally hepatic
Half-life elimination: ~2 hours
Time to peak: Oral: Within 2 hours
Excretion: Urine (65% as unchanged drug, 11% as metabolite)
PATIENT INFORMATION — Report any signs of bleeding; change positions slowly to minimize dizziness
Amino acid injection
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
TrophAmine® may be confused with tromethamine
U.S. BRAND NAMES — Aminosyn®; Aminosyn® II; Aminosyn®-HBC; Aminosyn®-PF; Aminosyn®-RF; BranchAmin®; Clinisol®; FreAmine®; FreAmine® HBC®; FreAmine® III; HepatAmine®; Hepatasol®; NephrAmine®; PremaSol™ ; Prosol; Renamin®; Travasol®; TrophAmine®
PHARMACOLOGIC CATEGORY
Intravenous Nutritional Therapy
DOSING: ADULTS — Protein as amino acids: I.V. (as a component of parenteral nutrition):
Maintenance: 0.8-1 g/kg/day
Normal/mild stress level: 1-1.2 g/kg/day
Moderate stress level: 1.2-1.5 g/kg/day
Severe stress level: 1.5-2 g/kg/day
Burn patients (severe): Increase protein until significant wound healing achieved
Solid organ transplant: Perioperative: 1.5-2 g/kg/day
Renal failure:
Acute (severely malnourished or hypercatabolic): 1.5-1.8 g/kg/day
Chronic, with dialysis: 1.2-1.3 g/kg/day
Chronic, without dialysis: 0.6-0.8 g/kg/day
Continuous hemofiltration: ≥ 1 g/kg/day
Hepatic failure:
Acute management when other treatments have failed:
With encephalopathy: 0.6-1 g/kg/day
Without encephalopathy: 1-1.5 g/kg/day
Chronic encephalopathy: Use branch chain amino acid enriched diets only if unresponsive to pharmacotherapy
Pregnant women in second or third trimester: Add an additional 10-14 g/day
DOSING: PEDIATRIC — Protein as amino acids: I.V. (as a component of parenteral nutrition):
Term: Initial: 2.5 g/kg/day; Goal: 3 g/kg/day
Extremely (<1000 g) and very (<1500 g) low-birth-weight (stable): Initial: 1-1.5 g/kg/day; Goal: 3.5-3.85 g/kg/day to promote utero growth rates
Sepsis, hypoxia: Initial: 1 g/kg/day; goal: 3-3.85 g/kg/day
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Peripheral parenteral nutrition and total parenteral nutrition are usually compounded from optimal combinations of macronutrients (water, protein, dextrose, and lipids) and micronutrients (electrolytes, trace elements, and vitamins) to meet the specific nutritional requirements of a patient. Individual hospitals may have designated standard TPN formulas. There are a few commercially-available amino acids with electrolytes solutions; however, these products may not meet an individual's specific nutritional requirements. Consult with nutrition support service to determine adequate formula based upon patient specifics.
Injection, solution [branched chain]:
Aminosyn®-HBC: 7% (500 mL, 1000 mL) [contains aluminum]
BranchAmin®: 4% (500 mL) [contains alumnium]
FreAmine® HBC: 6.9% (750 mL) [contains aluminum, sodium bisulfate]
Injection, solution [crystalline]:
Aminosyn®: 3.5% (1000 mL) [contains aluminum]; 5% (500 mL, 1000 mL) [contains aluminum]; 7% (500 mL, 1000 mL) [contains aluminum]; 8.5% (500 mL, 1000 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
Aminosyn® ll: 7% (500 mL) [contains aluminum]; 8.5% (500 mL, 1000 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
Aminosyn® ll: 10% (2000 mL) [contains aluminum, sodium hydrosulfite]; 15% (2000 mL) [contains aluminum, sodium hydrosulfite]
Clinisol®: 15% (500 mL, 2000 mL) [contains aluminum]
FreAmine® III: 8.5% (500 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
PremaSol™ : 6% (500 mL); 10% (500 mL, 1000 mL, 2000 mL)
Prosol: 20% (2000 mL) [contains aluminum]
Travasol®: 10% (500 mL, 1000 mL, 2000 mL)
Injection, solution [hepatic]:
Aminosyn®-HF: 8% (500 mL) [contains aluminum, sodium hydrosulfite]
HepatAmine®: 8% (500 mL) [contains aluminum, sodium hydrosulfite]
Hepatasol®: 8% (500 mL) [contains aluminum]
Injection, solution [pediatric]:
Aminosyn®-PF: 7% (500 mL) [contains aluminum]; 10% (1000 mL) [contains aluminum]
TrophAmine®: 6% (500 mL); 10% (500 mL) [contains aluminum, sodium metabisulfate]
Injection, solution [renal]:
Aminosyn®-RF: 5.2% (500 mL) [contains aluminum]
NephrAmine®: 5.4% (250 mL) [contains aluminum, sodium hydrosulfite]
Renamin®: 6.5% (500 mL) [contains aluminum, sodium hydrosulfite]
DOSAGE FORMS: CONCISE — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Peripheral parenteral nutrition and total parenteral nutrition are usually compounded from optimal combinations of macronutrients (water, protein, dextrose, and lipids) and micronutrients (electrolytes, trace elements, and vitamins) to meet the specific nutritional requirements of a patient. Individual hospitals may have designated standard TPN formulas. There are a few commercially-available amino acids with electrolytes solutions; however, these products may not meet an individual's specific nutritional requirements. Consult with nutrition support service to determine adequate formula based upon patient specifics.
Injection, solution [branched chain]:
Aminosyn®-HBC: 7%
BranchAmin®: 4%
FreAmine® HBC: 6.9%
Injection, solution [crystalline]:
Aminosyn®: 3.5%, 5%, 7%, 8.5%, 10%
Aminosyn® ll: 7%, 8.5%, 10%, 15%
Clinisol®: 15%
FreAmine® III: 8.5%, 10%
PremaSol™ : 6%, 10%
Prosol: 20%
Travasol®: 10%
Injection, solution [hepatic]:
Aminosyn®-HF, HepatAmine®, Hepatasol®: 8%
Injection, solution [pediatric]:
Aminosyn®-PF: 7%, 10%
TrophAmine®: 6%, 10%
Injection, solution [renal]:
Aminosyn®-RF: 5.2%
NephrAmine®: 5.4%
Renamin®: 6.5%
ADMINISTRATION — Administered as a component of peripheral parenteral or total parenteral nutrition. Peripheral administration of nutrition is dependent upon osmolality of solution. Total parenteral nutrition must be administered via central venous access.
USE — As part of parenteral nutrition to prevent nitrogen loss or treat negative nitrogen balance when alimentary tract cannot be used (eg, GI absorption is impaired, bowel rest is needed). Specialty amino acid formulas may be considered only in certain instances.
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Endocrine & metabolic: Fluid, electrolyte imbalance
Local: Erythema, phlebitis, thrombosis
Renal: Azotemia
CONTRAINDICATIONS — Inborn errors of amino acid metabolism
WARNINGS / PRECAUTIONS
Disease-related concerns: Heart failure: Use with caution in patients sensitive to volume overload (eg, heart failure, hepatic failure); consider concentrated total parenteral nutrition formula. Hepatic impairment: Use caution in protein delivery especially in patients with hepatic encephalopathy; dosage adjustments may be necessary. Consider volume status in patients with hepatic failure, may require concentrated total parenteral nutrition formula. Renal impairment: Use with caution in patients with severe renal impairment; dosage adjustments may be necessary depending upon renal replacement therapy options. It is essential to provide adequate calories in a minimal amount of fluid. Monitor fluid balance closely.
Dosage form specific issues: Aluminum: Solutions may contain aluminum; toxic levels may occur following prolonged administration in premature neonates or patients with renal impairment. Sulfites: Some products contain sulfites as preservatives.
Other warning/precautions: Monitoring: Monitor fluid and electrolyte status.
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — General patient monitoring during I.V. nutritional therapy
Bone densitometry: Perform upon initiation of long-term therapy.
Efficacy: Nutrition and outcome parameters should be measured serially.
Electrolytes: Sodium, potassium, chloride, and bicarbonate should be monitored frequently upon initiation and until stable; phosphate should be monitored closely in patients with pulmonary disease.
Glucose: In patients with diabetes or patients with glucose intolerance risk factors, monitor closely. Monitor frequently upon initiation of therapy and with any changes in insulin dose or renal function.
Line site: Monitor for signs and symptoms of infection.
Liver function tests: Monitor periodically.
Neonates: Sodium, calcium, and phosphate should be monitored closely. Frequent (some advise
Refeeding syndrome: Patients at risk should have phosphorus, magnesium, potassium, and glucose levels monitored closely at initiation.
Triglycerides: Before initiation of lipid therapy and at least weekly during therapy.
Vitamin A status: Should be carefully monitored in patients with chronic renal failure.
CANADIAN BRAND NAMES — Aminosyn; Aminosyn-PF; Aminosyn-RF; Primene®
Sound-alike/look-alike issues:
TrophAmine® may be confused with tromethamine
U.S. BRAND NAMES — Aminosyn®; Aminosyn® II; Aminosyn®-HBC; Aminosyn®-PF; Aminosyn®-RF; BranchAmin®; Clinisol®; FreAmine®; FreAmine® HBC®; FreAmine® III; HepatAmine®; Hepatasol®; NephrAmine®; PremaSol™ ; Prosol; Renamin®; Travasol®; TrophAmine®
PHARMACOLOGIC CATEGORY
Intravenous Nutritional Therapy
DOSING: ADULTS — Protein as amino acids: I.V. (as a component of parenteral nutrition):
Maintenance: 0.8-1 g/kg/day
Normal/mild stress level: 1-1.2 g/kg/day
Moderate stress level: 1.2-1.5 g/kg/day
Severe stress level: 1.5-2 g/kg/day
Burn patients (severe): Increase protein until significant wound healing achieved
Solid organ transplant: Perioperative: 1.5-2 g/kg/day
Renal failure:
Acute (severely malnourished or hypercatabolic): 1.5-1.8 g/kg/day
Chronic, with dialysis: 1.2-1.3 g/kg/day
Chronic, without dialysis: 0.6-0.8 g/kg/day
Continuous hemofiltration: ≥ 1 g/kg/day
Hepatic failure:
Acute management when other treatments have failed:
With encephalopathy: 0.6-1 g/kg/day
Without encephalopathy: 1-1.5 g/kg/day
Chronic encephalopathy: Use branch chain amino acid enriched diets only if unresponsive to pharmacotherapy
Pregnant women in second or third trimester: Add an additional 10-14 g/day
DOSING: PEDIATRIC — Protein as amino acids: I.V. (as a component of parenteral nutrition):
Term: Initial: 2.5 g/kg/day; Goal: 3 g/kg/day
Extremely (<1000 g) and very (<1500 g) low-birth-weight (stable): Initial: 1-1.5 g/kg/day; Goal: 3.5-3.85 g/kg/day to promote utero growth rates
Sepsis, hypoxia: Initial: 1 g/kg/day; goal: 3-3.85 g/kg/day
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Peripheral parenteral nutrition and total parenteral nutrition are usually compounded from optimal combinations of macronutrients (water, protein, dextrose, and lipids) and micronutrients (electrolytes, trace elements, and vitamins) to meet the specific nutritional requirements of a patient. Individual hospitals may have designated standard TPN formulas. There are a few commercially-available amino acids with electrolytes solutions; however, these products may not meet an individual's specific nutritional requirements. Consult with nutrition support service to determine adequate formula based upon patient specifics.
Injection, solution [branched chain]:
Aminosyn®-HBC: 7% (500 mL, 1000 mL) [contains aluminum]
BranchAmin®: 4% (500 mL) [contains alumnium]
FreAmine® HBC: 6.9% (750 mL) [contains aluminum, sodium bisulfate]
Injection, solution [crystalline]:
Aminosyn®: 3.5% (1000 mL) [contains aluminum]; 5% (500 mL, 1000 mL) [contains aluminum]; 7% (500 mL, 1000 mL) [contains aluminum]; 8.5% (500 mL, 1000 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
Aminosyn® ll: 7% (500 mL) [contains aluminum]; 8.5% (500 mL, 1000 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
Aminosyn® ll: 10% (2000 mL) [contains aluminum, sodium hydrosulfite]; 15% (2000 mL) [contains aluminum, sodium hydrosulfite]
Clinisol®: 15% (500 mL, 2000 mL) [contains aluminum]
FreAmine® III: 8.5% (500 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
PremaSol™ : 6% (500 mL); 10% (500 mL, 1000 mL, 2000 mL)
Prosol: 20% (2000 mL) [contains aluminum]
Travasol®: 10% (500 mL, 1000 mL, 2000 mL)
Injection, solution [hepatic]:
Aminosyn®-HF: 8% (500 mL) [contains aluminum, sodium hydrosulfite]
HepatAmine®: 8% (500 mL) [contains aluminum, sodium hydrosulfite]
Hepatasol®: 8% (500 mL) [contains aluminum]
Injection, solution [pediatric]:
Aminosyn®-PF: 7% (500 mL) [contains aluminum]; 10% (1000 mL) [contains aluminum]
TrophAmine®: 6% (500 mL); 10% (500 mL) [contains aluminum, sodium metabisulfate]
Injection, solution [renal]:
Aminosyn®-RF: 5.2% (500 mL) [contains aluminum]
NephrAmine®: 5.4% (250 mL) [contains aluminum, sodium hydrosulfite]
Renamin®: 6.5% (500 mL) [contains aluminum, sodium hydrosulfite]
DOSAGE FORMS: CONCISE — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Peripheral parenteral nutrition and total parenteral nutrition are usually compounded from optimal combinations of macronutrients (water, protein, dextrose, and lipids) and micronutrients (electrolytes, trace elements, and vitamins) to meet the specific nutritional requirements of a patient. Individual hospitals may have designated standard TPN formulas. There are a few commercially-available amino acids with electrolytes solutions; however, these products may not meet an individual's specific nutritional requirements. Consult with nutrition support service to determine adequate formula based upon patient specifics.
Injection, solution [branched chain]:
Aminosyn®-HBC: 7%
BranchAmin®: 4%
FreAmine® HBC: 6.9%
Injection, solution [crystalline]:
Aminosyn®: 3.5%, 5%, 7%, 8.5%, 10%
Aminosyn® ll: 7%, 8.5%, 10%, 15%
Clinisol®: 15%
FreAmine® III: 8.5%, 10%
PremaSol™ : 6%, 10%
Prosol: 20%
Travasol®: 10%
Injection, solution [hepatic]:
Aminosyn®-HF, HepatAmine®, Hepatasol®: 8%
Injection, solution [pediatric]:
Aminosyn®-PF: 7%, 10%
TrophAmine®: 6%, 10%
Injection, solution [renal]:
Aminosyn®-RF: 5.2%
NephrAmine®: 5.4%
Renamin®: 6.5%
ADMINISTRATION — Administered as a component of peripheral parenteral or total parenteral nutrition. Peripheral administration of nutrition is dependent upon osmolality of solution. Total parenteral nutrition must be administered via central venous access.
USE — As part of parenteral nutrition to prevent nitrogen loss or treat negative nitrogen balance when alimentary tract cannot be used (eg, GI absorption is impaired, bowel rest is needed). Specialty amino acid formulas may be considered only in certain instances.
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Endocrine & metabolic: Fluid, electrolyte imbalance
Local: Erythema, phlebitis, thrombosis
Renal: Azotemia
CONTRAINDICATIONS — Inborn errors of amino acid metabolism
WARNINGS / PRECAUTIONS
Disease-related concerns: Heart failure: Use with caution in patients sensitive to volume overload (eg, heart failure, hepatic failure); consider concentrated total parenteral nutrition formula. Hepatic impairment: Use caution in protein delivery especially in patients with hepatic encephalopathy; dosage adjustments may be necessary. Consider volume status in patients with hepatic failure, may require concentrated total parenteral nutrition formula. Renal impairment: Use with caution in patients with severe renal impairment; dosage adjustments may be necessary depending upon renal replacement therapy options. It is essential to provide adequate calories in a minimal amount of fluid. Monitor fluid balance closely.
Dosage form specific issues: Aluminum: Solutions may contain aluminum; toxic levels may occur following prolonged administration in premature neonates or patients with renal impairment. Sulfites: Some products contain sulfites as preservatives.
Other warning/precautions: Monitoring: Monitor fluid and electrolyte status.
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — General patient monitoring during I.V. nutritional therapy
Bone densitometry: Perform upon initiation of long-term therapy.
Efficacy: Nutrition and outcome parameters should be measured serially.
Electrolytes: Sodium, potassium, chloride, and bicarbonate should be monitored frequently upon initiation and until stable; phosphate should be monitored closely in patients with pulmonary disease.
Glucose: In patients with diabetes or patients with glucose intolerance risk factors, monitor closely. Monitor frequently upon initiation of therapy and with any changes in insulin dose or renal function.
Line site: Monitor for signs and symptoms of infection.
Liver function tests: Monitor periodically.
Neonates: Sodium, calcium, and phosphate should be monitored closely. Frequent (some advise
Refeeding syndrome: Patients at risk should have phosphorus, magnesium, potassium, and glucose levels monitored closely at initiation.
Triglycerides: Before initiation of lipid therapy and at least weekly during therapy.
Vitamin A status: Should be carefully monitored in patients with chronic renal failure.
CANADIAN BRAND NAMES — Aminosyn; Aminosyn-PF; Aminosyn-RF; Primene®
Amiloride and hydrochlorothiazide
PHARMACOLOGIC CATEGORY
Diuretic, Combination
DOSING: ADULTS — Hypertension, edema: Oral: Initial: 1 tablet/day; may be increased to 2 tablets/day if needed; usually given in a single dose
DOSING: ELDERLY — Oral: Initial: 1/2 to 1 tablet/day
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 5/50: Amiloride hydrochloride 5 mg and hydrochlorothiazide 50 mg
DOSAGE FORMS: CONCISE
Tablet: 5/50: Amiloride 5 mg and hydrochlorothiazide 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Potassium-sparing diuretic; antihypertensive
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Electrolyte disturbances: Hypochloremic alkalosis and hyponatremia can occur. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction. Photosensitivity: Photosensitization may occur with hydrochlorothiazide. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Diabetes: Use with extreme caution in patients with diabetes mellitus; may see a change in glucose control. Monitor closely; discontinue amiloride 3 days prior to glucose tolerance testing. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated with hydrochlorothiazide. Hepatic impairment: Use hydrochlorothiazide with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use hydrochlorothiazide with caution in patients with moderate or high cholesterol concentrations. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes). Renal impairment: Avoid use of hydrochlorothiazide in severe renal disease (ineffective). Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Refer to Hydrochlorothiazide.
LACTATION — Excretion in breast milk unknown/contraindicated
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)
Tablets (Amiloride-Hydrochlorothiazide)
5-50 mg (100): $27.99
CANADIAN BRAND NAMES — Apo-Amilzide®; Gen-Amilazide; Moduret; Novamilor; Nu-Amilzide
INTERNATIONAL BRAND NAMES — Adco-Retic (ZA); Add-Acten (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Ameride (ES); Amil-Co (GB); Amilco (DK); Amilco Mite (DK); Amilocomp beta (DE); Amiloretic (ZA); Amizide (AU, TW); Amuretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Apo-Amilzide (MY); Biduret (IN); Bildiuretic (TH); Co-Amilozide (AU, GB); Hydrozide (NZ); Hyperetic (TH); Kaluril (IL); Lorinid Mite (ID); Mengdaqing (CL); Moduretic (AU, BE, BF, BJ, BR, CH, CI, CO, CZ, DE, EE, ET, FI, GB, GH, GM, GN, GR, HK, IE, IT, KE, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, NL, PE, PK, PT, PY, SC, SD, SE, SL, SN, TH, TN, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Moure-M (TH); Mourinate (TH); Sefaretic (HK); Sparkal (DK); Tiaden (TW); Uniretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Yostiretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
PHARMACODYNAMICS / KINETICS — See individual agents.
Diuretic, Combination
DOSING: ADULTS — Hypertension, edema: Oral: Initial: 1 tablet/day; may be increased to 2 tablets/day if needed; usually given in a single dose
DOSING: ELDERLY — Oral: Initial: 1/2 to 1 tablet/day
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 5/50: Amiloride hydrochloride 5 mg and hydrochlorothiazide 50 mg
DOSAGE FORMS: CONCISE
Tablet: 5/50: Amiloride 5 mg and hydrochlorothiazide 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Potassium-sparing diuretic; antihypertensive
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Electrolyte disturbances: Hypochloremic alkalosis and hyponatremia can occur. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction. Photosensitivity: Photosensitization may occur with hydrochlorothiazide. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Diabetes: Use with extreme caution in patients with diabetes mellitus; may see a change in glucose control. Monitor closely; discontinue amiloride 3 days prior to glucose tolerance testing. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated with hydrochlorothiazide. Hepatic impairment: Use hydrochlorothiazide with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use hydrochlorothiazide with caution in patients with moderate or high cholesterol concentrations. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes). Renal impairment: Avoid use of hydrochlorothiazide in severe renal disease (ineffective). Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Refer to Hydrochlorothiazide.
LACTATION — Excretion in breast milk unknown/contraindicated
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)
Tablets (Amiloride-Hydrochlorothiazide)
5-50 mg (100): $27.99
CANADIAN BRAND NAMES — Apo-Amilzide®; Gen-Amilazide; Moduret; Novamilor; Nu-Amilzide
INTERNATIONAL BRAND NAMES — Adco-Retic (ZA); Add-Acten (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Ameride (ES); Amil-Co (GB); Amilco (DK); Amilco Mite (DK); Amilocomp beta (DE); Amiloretic (ZA); Amizide (AU, TW); Amuretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Apo-Amilzide (MY); Biduret (IN); Bildiuretic (TH); Co-Amilozide (AU, GB); Hydrozide (NZ); Hyperetic (TH); Kaluril (IL); Lorinid Mite (ID); Mengdaqing (CL); Moduretic (AU, BE, BF, BJ, BR, CH, CI, CO, CZ, DE, EE, ET, FI, GB, GH, GM, GN, GR, HK, IE, IT, KE, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, NL, PE, PK, PT, PY, SC, SD, SE, SL, SN, TH, TN, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Moure-M (TH); Mourinate (TH); Sefaretic (HK); Sparkal (DK); Tiaden (TW); Uniretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Yostiretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
PHARMACODYNAMICS / KINETICS — See individual agents.
Amiloride and hydrochlorothiazide
PHARMACOLOGIC CATEGORY
Diuretic, Combination
DOSING: ADULTS — Hypertension, edema: Oral: Initial: 1 tablet/day; may be increased to 2 tablets/day if needed; usually given in a single dose
DOSING: ELDERLY — Oral: Initial: 1/2 to 1 tablet/day
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 5/50: Amiloride hydrochloride 5 mg and hydrochlorothiazide 50 mg
DOSAGE FORMS: CONCISE
Tablet: 5/50: Amiloride 5 mg and hydrochlorothiazide 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Potassium-sparing diuretic; antihypertensive
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Electrolyte disturbances: Hypochloremic alkalosis and hyponatremia can occur. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction. Photosensitivity: Photosensitization may occur with hydrochlorothiazide. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Diabetes: Use with extreme caution in patients with diabetes mellitus; may see a change in glucose control. Monitor closely; discontinue amiloride 3 days prior to glucose tolerance testing. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated with hydrochlorothiazide. Hepatic impairment: Use hydrochlorothiazide with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use hydrochlorothiazide with caution in patients with moderate or high cholesterol concentrations. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes). Renal impairment: Avoid use of hydrochlorothiazide in severe renal disease (ineffective). Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Refer to Hydrochlorothiazide.
LACTATION — Excretion in breast milk unknown/contraindicated
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)
Tablets (Amiloride-Hydrochlorothiazide)
5-50 mg (100): $27.99
CANADIAN BRAND NAMES — Apo-Amilzide®; Gen-Amilazide; Moduret; Novamilor; Nu-Amilzide
INTERNATIONAL BRAND NAMES — Adco-Retic (ZA); Add-Acten (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Ameride (ES); Amil-Co (GB); Amilco (DK); Amilco Mite (DK); Amilocomp beta (DE); Amiloretic (ZA); Amizide (AU, TW); Amuretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Apo-Amilzide (MY); Biduret (IN); Bildiuretic (TH); Co-Amilozide (AU, GB); Hydrozide (NZ); Hyperetic (TH); Kaluril (IL); Lorinid Mite (ID); Mengdaqing (CL); Moduretic (AU, BE, BF, BJ, BR, CH, CI, CO, CZ, DE, EE, ET, FI, GB, GH, GM, GN, GR, HK, IE, IT, KE, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, NL, PE, PK, PT, PY, SC, SD, SE, SL, SN, TH, TN, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Moure-M (TH); Mourinate (TH); Sefaretic (HK); Sparkal (DK); Tiaden (TW); Uniretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Yostiretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
PHARMACODYNAMICS / KINETICS — See individual agents.
Diuretic, Combination
DOSING: ADULTS — Hypertension, edema: Oral: Initial: 1 tablet/day; may be increased to 2 tablets/day if needed; usually given in a single dose
DOSING: ELDERLY — Oral: Initial: 1/2 to 1 tablet/day
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 5/50: Amiloride hydrochloride 5 mg and hydrochlorothiazide 50 mg
DOSAGE FORMS: CONCISE
Tablet: 5/50: Amiloride 5 mg and hydrochlorothiazide 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Potassium-sparing diuretic; antihypertensive
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Electrolyte disturbances: Hypochloremic alkalosis and hyponatremia can occur. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction. Photosensitivity: Photosensitization may occur with hydrochlorothiazide. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Diabetes: Use with extreme caution in patients with diabetes mellitus; may see a change in glucose control. Monitor closely; discontinue amiloride 3 days prior to glucose tolerance testing. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated with hydrochlorothiazide. Hepatic impairment: Use hydrochlorothiazide with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use hydrochlorothiazide with caution in patients with moderate or high cholesterol concentrations. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes). Renal impairment: Avoid use of hydrochlorothiazide in severe renal disease (ineffective). Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Refer to Hydrochlorothiazide.
LACTATION — Excretion in breast milk unknown/contraindicated
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)
Tablets (Amiloride-Hydrochlorothiazide)
5-50 mg (100): $27.99
CANADIAN BRAND NAMES — Apo-Amilzide®; Gen-Amilazide; Moduret; Novamilor; Nu-Amilzide
INTERNATIONAL BRAND NAMES — Adco-Retic (ZA); Add-Acten (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Ameride (ES); Amil-Co (GB); Amilco (DK); Amilco Mite (DK); Amilocomp beta (DE); Amiloretic (ZA); Amizide (AU, TW); Amuretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Apo-Amilzide (MY); Biduret (IN); Bildiuretic (TH); Co-Amilozide (AU, GB); Hydrozide (NZ); Hyperetic (TH); Kaluril (IL); Lorinid Mite (ID); Mengdaqing (CL); Moduretic (AU, BE, BF, BJ, BR, CH, CI, CO, CZ, DE, EE, ET, FI, GB, GH, GM, GN, GR, HK, IE, IT, KE, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, NL, PE, PK, PT, PY, SC, SD, SE, SL, SN, TH, TN, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Moure-M (TH); Mourinate (TH); Sefaretic (HK); Sparkal (DK); Tiaden (TW); Uniretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Yostiretic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
PHARMACODYNAMICS / KINETICS — See individual agents.
Amino acid injection
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
TrophAmine® may be confused with tromethamine
U.S. BRAND NAMES — Aminosyn®; Aminosyn® II; Aminosyn®-HBC; Aminosyn®-PF; Aminosyn®-RF; BranchAmin®; Clinisol®; FreAmine®; FreAmine® HBC®; FreAmine® III; HepatAmine®; Hepatasol®; NephrAmine®; PremaSol™ ; Prosol; Renamin®; Travasol®; TrophAmine®
PHARMACOLOGIC CATEGORY
Intravenous Nutritional Therapy
DOSING: ADULTS — Protein as amino acids: I.V. (as a component of parenteral nutrition):
Maintenance: 0.8-1 g/kg/day
Normal/mild stress level: 1-1.2 g/kg/day
Moderate stress level: 1.2-1.5 g/kg/day
Severe stress level: 1.5-2 g/kg/day
Burn patients (severe): Increase protein until significant wound healing achieved
Solid organ transplant: Perioperative: 1.5-2 g/kg/day
Renal failure:
Acute (severely malnourished or hypercatabolic): 1.5-1.8 g/kg/day
Chronic, with dialysis: 1.2-1.3 g/kg/day
Chronic, without dialysis: 0.6-0.8 g/kg/day
Continuous hemofiltration: ≥ 1 g/kg/day
Hepatic failure:
Acute management when other treatments have failed:
With encephalopathy: 0.6-1 g/kg/day
Without encephalopathy: 1-1.5 g/kg/day
Chronic encephalopathy: Use branch chain amino acid enriched diets only if unresponsive to pharmacotherapy
Pregnant women in second or third trimester: Add an additional 10-14 g/day
DOSING: PEDIATRIC — Protein as amino acids: I.V. (as a component of parenteral nutrition):
Term: Initial: 2.5 g/kg/day; Goal: 3 g/kg/day
Extremely (<1000 g) and very (<1500 g) low-birth-weight (stable): Initial: 1-1.5 g/kg/day; Goal: 3.5-3.85 g/kg/day to promote utero growth rates
Sepsis, hypoxia: Initial: 1 g/kg/day; goal: 3-3.85 g/kg/day
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Peripheral parenteral nutrition and total parenteral nutrition are usually compounded from optimal combinations of macronutrients (water, protein, dextrose, and lipids) and micronutrients (electrolytes, trace elements, and vitamins) to meet the specific nutritional requirements of a patient. Individual hospitals may have designated standard TPN formulas. There are a few commercially-available amino acids with electrolytes solutions; however, these products may not meet an individual's specific nutritional requirements. Consult with nutrition support service to determine adequate formula based upon patient specifics.
Injection, solution [branched chain]:
Aminosyn®-HBC: 7% (500 mL, 1000 mL) [contains aluminum]
BranchAmin®: 4% (500 mL) [contains alumnium]
FreAmine® HBC: 6.9% (750 mL) [contains aluminum, sodium bisulfate]
Injection, solution [crystalline]:
Aminosyn®: 3.5% (1000 mL) [contains aluminum]; 5% (500 mL, 1000 mL) [contains aluminum]; 7% (500 mL, 1000 mL) [contains aluminum]; 8.5% (500 mL, 1000 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
Aminosyn® ll: 7% (500 mL) [contains aluminum]; 8.5% (500 mL, 1000 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
Aminosyn® ll: 10% (2000 mL) [contains aluminum, sodium hydrosulfite]; 15% (2000 mL) [contains aluminum, sodium hydrosulfite]
Clinisol®: 15% (500 mL, 2000 mL) [contains aluminum]
FreAmine® III: 8.5% (500 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
PremaSol™ : 6% (500 mL); 10% (500 mL, 1000 mL, 2000 mL)
Prosol: 20% (2000 mL) [contains aluminum]
Travasol®: 10% (500 mL, 1000 mL, 2000 mL)
Injection, solution [hepatic]:
Aminosyn®-HF: 8% (500 mL) [contains aluminum, sodium hydrosulfite]
HepatAmine®: 8% (500 mL) [contains aluminum, sodium hydrosulfite]
Hepatasol®: 8% (500 mL) [contains aluminum]
Injection, solution [pediatric]:
Aminosyn®-PF: 7% (500 mL) [contains aluminum]; 10% (1000 mL) [contains aluminum]
TrophAmine®: 6% (500 mL); 10% (500 mL) [contains aluminum, sodium metabisulfate]
Injection, solution [renal]:
Aminosyn®-RF: 5.2% (500 mL) [contains aluminum]
NephrAmine®: 5.4% (250 mL) [contains aluminum, sodium hydrosulfite]
Renamin®: 6.5% (500 mL) [contains aluminum, sodium hydrosulfite]
DOSAGE FORMS: CONCISE — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Peripheral parenteral nutrition and total parenteral nutrition are usually compounded from optimal combinations of macronutrients (water, protein, dextrose, and lipids) and micronutrients (electrolytes, trace elements, and vitamins) to meet the specific nutritional requirements of a patient. Individual hospitals may have designated standard TPN formulas. There are a few commercially-available amino acids with electrolytes solutions; however, these products may not meet an individual's specific nutritional requirements. Consult with nutrition support service to determine adequate formula based upon patient specifics.
Injection, solution [branched chain]:
Aminosyn®-HBC: 7%
BranchAmin®: 4%
FreAmine® HBC: 6.9%
Injection, solution [crystalline]:
Aminosyn®: 3.5%, 5%, 7%, 8.5%, 10%
Aminosyn® ll: 7%, 8.5%, 10%, 15%
Clinisol®: 15%
FreAmine® III: 8.5%, 10%
PremaSol™ : 6%, 10%
Prosol: 20%
Travasol®: 10%
Injection, solution [hepatic]:
Aminosyn®-HF, HepatAmine®, Hepatasol®: 8%
Injection, solution [pediatric]:
Aminosyn®-PF: 7%, 10%
TrophAmine®: 6%, 10%
Injection, solution [renal]:
Aminosyn®-RF: 5.2%
NephrAmine®: 5.4%
Renamin®: 6.5%
ADMINISTRATION — Administered as a component of peripheral parenteral or total parenteral nutrition. Peripheral administration of nutrition is dependent upon osmolality of solution. Total parenteral nutrition must be administered via central venous access.
USE — As part of parenteral nutrition to prevent nitrogen loss or treat negative nitrogen balance when alimentary tract cannot be used (eg, GI absorption is impaired, bowel rest is needed). Specialty amino acid formulas may be considered only in certain instances.
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Endocrine & metabolic: Fluid, electrolyte imbalance
Local: Erythema, phlebitis, thrombosis
Renal: Azotemia
CONTRAINDICATIONS — Inborn errors of amino acid metabolism
WARNINGS / PRECAUTIONS
Disease-related concerns: Heart failure: Use with caution in patients sensitive to volume overload (eg, heart failure, hepatic failure); consider concentrated total parenteral nutrition formula. Hepatic impairment: Use caution in protein delivery especially in patients with hepatic encephalopathy; dosage adjustments may be necessary. Consider volume status in patients with hepatic failure, may require concentrated total parenteral nutrition formula. Renal impairment: Use with caution in patients with severe renal impairment; dosage adjustments may be necessary depending upon renal replacement therapy options. It is essential to provide adequate calories in a minimal amount of fluid. Monitor fluid balance closely.
Dosage form specific issues: Aluminum: Solutions may contain aluminum; toxic levels may occur following prolonged administration in premature neonates or patients with renal impairment. Sulfites: Some products contain sulfites as preservatives.
Other warning/precautions: Monitoring: Monitor fluid and electrolyte status.
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — General patient monitoring during I.V. nutritional therapy
Bone densitometry: Perform upon initiation of long-term therapy.
Efficacy: Nutrition and outcome parameters should be measured serially.
Electrolytes: Sodium, potassium, chloride, and bicarbonate should be monitored frequently upon initiation and until stable; phosphate should be monitored closely in patients with pulmonary disease.
Glucose: In patients with diabetes or patients with glucose intolerance risk factors, monitor closely. Monitor frequently upon initiation of therapy and with any changes in insulin dose or renal function.
Line site: Monitor for signs and symptoms of infection.
Liver function tests: Monitor periodically.
Neonates: Sodium, calcium, and phosphate should be monitored closely. Frequent (some advise
Refeeding syndrome: Patients at risk should have phosphorus, magnesium, potassium, and glucose levels monitored closely at initiation.
Triglycerides: Before initiation of lipid therapy and at least weekly during therapy.
Vitamin A status: Should be carefully monitored in patients with chronic renal failure.
CANADIAN BRAND NAMES — Aminosyn; Aminosyn-PF; Aminosyn-RF; Primene®
Sound-alike/look-alike issues:
TrophAmine® may be confused with tromethamine
U.S. BRAND NAMES — Aminosyn®; Aminosyn® II; Aminosyn®-HBC; Aminosyn®-PF; Aminosyn®-RF; BranchAmin®; Clinisol®; FreAmine®; FreAmine® HBC®; FreAmine® III; HepatAmine®; Hepatasol®; NephrAmine®; PremaSol™ ; Prosol; Renamin®; Travasol®; TrophAmine®
PHARMACOLOGIC CATEGORY
Intravenous Nutritional Therapy
DOSING: ADULTS — Protein as amino acids: I.V. (as a component of parenteral nutrition):
Maintenance: 0.8-1 g/kg/day
Normal/mild stress level: 1-1.2 g/kg/day
Moderate stress level: 1.2-1.5 g/kg/day
Severe stress level: 1.5-2 g/kg/day
Burn patients (severe): Increase protein until significant wound healing achieved
Solid organ transplant: Perioperative: 1.5-2 g/kg/day
Renal failure:
Acute (severely malnourished or hypercatabolic): 1.5-1.8 g/kg/day
Chronic, with dialysis: 1.2-1.3 g/kg/day
Chronic, without dialysis: 0.6-0.8 g/kg/day
Continuous hemofiltration: ≥ 1 g/kg/day
Hepatic failure:
Acute management when other treatments have failed:
With encephalopathy: 0.6-1 g/kg/day
Without encephalopathy: 1-1.5 g/kg/day
Chronic encephalopathy: Use branch chain amino acid enriched diets only if unresponsive to pharmacotherapy
Pregnant women in second or third trimester: Add an additional 10-14 g/day
DOSING: PEDIATRIC — Protein as amino acids: I.V. (as a component of parenteral nutrition):
Term: Initial: 2.5 g/kg/day; Goal: 3 g/kg/day
Extremely (<1000 g) and very (<1500 g) low-birth-weight (stable): Initial: 1-1.5 g/kg/day; Goal: 3.5-3.85 g/kg/day to promote utero growth rates
Sepsis, hypoxia: Initial: 1 g/kg/day; goal: 3-3.85 g/kg/day
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Peripheral parenteral nutrition and total parenteral nutrition are usually compounded from optimal combinations of macronutrients (water, protein, dextrose, and lipids) and micronutrients (electrolytes, trace elements, and vitamins) to meet the specific nutritional requirements of a patient. Individual hospitals may have designated standard TPN formulas. There are a few commercially-available amino acids with electrolytes solutions; however, these products may not meet an individual's specific nutritional requirements. Consult with nutrition support service to determine adequate formula based upon patient specifics.
Injection, solution [branched chain]:
Aminosyn®-HBC: 7% (500 mL, 1000 mL) [contains aluminum]
BranchAmin®: 4% (500 mL) [contains alumnium]
FreAmine® HBC: 6.9% (750 mL) [contains aluminum, sodium bisulfate]
Injection, solution [crystalline]:
Aminosyn®: 3.5% (1000 mL) [contains aluminum]; 5% (500 mL, 1000 mL) [contains aluminum]; 7% (500 mL, 1000 mL) [contains aluminum]; 8.5% (500 mL, 1000 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
Aminosyn® ll: 7% (500 mL) [contains aluminum]; 8.5% (500 mL, 1000 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
Aminosyn® ll: 10% (2000 mL) [contains aluminum, sodium hydrosulfite]; 15% (2000 mL) [contains aluminum, sodium hydrosulfite]
Clinisol®: 15% (500 mL, 2000 mL) [contains aluminum]
FreAmine® III: 8.5% (500 mL) [contains aluminum]; 10% (500 mL, 1000 mL) [contains aluminum]
PremaSol™ : 6% (500 mL); 10% (500 mL, 1000 mL, 2000 mL)
Prosol: 20% (2000 mL) [contains aluminum]
Travasol®: 10% (500 mL, 1000 mL, 2000 mL)
Injection, solution [hepatic]:
Aminosyn®-HF: 8% (500 mL) [contains aluminum, sodium hydrosulfite]
HepatAmine®: 8% (500 mL) [contains aluminum, sodium hydrosulfite]
Hepatasol®: 8% (500 mL) [contains aluminum]
Injection, solution [pediatric]:
Aminosyn®-PF: 7% (500 mL) [contains aluminum]; 10% (1000 mL) [contains aluminum]
TrophAmine®: 6% (500 mL); 10% (500 mL) [contains aluminum, sodium metabisulfate]
Injection, solution [renal]:
Aminosyn®-RF: 5.2% (500 mL) [contains aluminum]
NephrAmine®: 5.4% (250 mL) [contains aluminum, sodium hydrosulfite]
Renamin®: 6.5% (500 mL) [contains aluminum, sodium hydrosulfite]
DOSAGE FORMS: CONCISE — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Peripheral parenteral nutrition and total parenteral nutrition are usually compounded from optimal combinations of macronutrients (water, protein, dextrose, and lipids) and micronutrients (electrolytes, trace elements, and vitamins) to meet the specific nutritional requirements of a patient. Individual hospitals may have designated standard TPN formulas. There are a few commercially-available amino acids with electrolytes solutions; however, these products may not meet an individual's specific nutritional requirements. Consult with nutrition support service to determine adequate formula based upon patient specifics.
Injection, solution [branched chain]:
Aminosyn®-HBC: 7%
BranchAmin®: 4%
FreAmine® HBC: 6.9%
Injection, solution [crystalline]:
Aminosyn®: 3.5%, 5%, 7%, 8.5%, 10%
Aminosyn® ll: 7%, 8.5%, 10%, 15%
Clinisol®: 15%
FreAmine® III: 8.5%, 10%
PremaSol™ : 6%, 10%
Prosol: 20%
Travasol®: 10%
Injection, solution [hepatic]:
Aminosyn®-HF, HepatAmine®, Hepatasol®: 8%
Injection, solution [pediatric]:
Aminosyn®-PF: 7%, 10%
TrophAmine®: 6%, 10%
Injection, solution [renal]:
Aminosyn®-RF: 5.2%
NephrAmine®: 5.4%
Renamin®: 6.5%
ADMINISTRATION — Administered as a component of peripheral parenteral or total parenteral nutrition. Peripheral administration of nutrition is dependent upon osmolality of solution. Total parenteral nutrition must be administered via central venous access.
USE — As part of parenteral nutrition to prevent nitrogen loss or treat negative nitrogen balance when alimentary tract cannot be used (eg, GI absorption is impaired, bowel rest is needed). Specialty amino acid formulas may be considered only in certain instances.
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Endocrine & metabolic: Fluid, electrolyte imbalance
Local: Erythema, phlebitis, thrombosis
Renal: Azotemia
CONTRAINDICATIONS — Inborn errors of amino acid metabolism
WARNINGS / PRECAUTIONS
Disease-related concerns: Heart failure: Use with caution in patients sensitive to volume overload (eg, heart failure, hepatic failure); consider concentrated total parenteral nutrition formula. Hepatic impairment: Use caution in protein delivery especially in patients with hepatic encephalopathy; dosage adjustments may be necessary. Consider volume status in patients with hepatic failure, may require concentrated total parenteral nutrition formula. Renal impairment: Use with caution in patients with severe renal impairment; dosage adjustments may be necessary depending upon renal replacement therapy options. It is essential to provide adequate calories in a minimal amount of fluid. Monitor fluid balance closely.
Dosage form specific issues: Aluminum: Solutions may contain aluminum; toxic levels may occur following prolonged administration in premature neonates or patients with renal impairment. Sulfites: Some products contain sulfites as preservatives.
Other warning/precautions: Monitoring: Monitor fluid and electrolyte status.
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — General patient monitoring during I.V. nutritional therapy
Bone densitometry: Perform upon initiation of long-term therapy.
Efficacy: Nutrition and outcome parameters should be measured serially.
Electrolytes: Sodium, potassium, chloride, and bicarbonate should be monitored frequently upon initiation and until stable; phosphate should be monitored closely in patients with pulmonary disease.
Glucose: In patients with diabetes or patients with glucose intolerance risk factors, monitor closely. Monitor frequently upon initiation of therapy and with any changes in insulin dose or renal function.
Line site: Monitor for signs and symptoms of infection.
Liver function tests: Monitor periodically.
Neonates: Sodium, calcium, and phosphate should be monitored closely. Frequent (some advise
Refeeding syndrome: Patients at risk should have phosphorus, magnesium, potassium, and glucose levels monitored closely at initiation.
Triglycerides: Before initiation of lipid therapy and at least weekly during therapy.
Vitamin A status: Should be carefully monitored in patients with chronic renal failure.
CANADIAN BRAND NAMES — Aminosyn; Aminosyn-PF; Aminosyn-RF; Primene®
Amiloride
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
AMILoride may be confused with amiodarone, amLODIPine, amrinone
PHARMACOLOGIC CATEGORY
Diuretic, Potassium Sparing
DOSING: ADULTS — Hypertension, edema (to limit potassium loss): Oral: Initial: 5-10 mg/day (up to 20 mg)
Hypertension (JNC 7): 5-10 mg/day in 1-2 divided doses
DOSING: PEDIATRIC — Hypertension (unlabeled use): Children 1-17 years: Oral: 0.4-0.625 mg/kg/day (maximum: 20 mg/day)
(For additional information see "Amiloride: Pediatric drug information")
DOSING: ELDERLY — Oral: Initial: 5 mg once daily or every other day
DOSING: RENAL IMPAIRMENT — Oral:
Clcr 10-50 mL/minute: Administer 50% of normal dose.
Clcr <10 mL/minute: Avoid use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 5 mg
DOSAGE FORMS: CONCISE
Tablet: 5 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer with food or meals to avoid GI upset.
USE — Counteracts potassium loss induced by other diuretics in the treatment of hypertension or edematous conditions including CHF, hepatic cirrhosis, and hypoaldosteronism; usually used in conjunction with more potent diuretics such as thiazides or loop diuretics
USE - UNLABELED / INVESTIGATIONAL — Investigational: Cystic fibrosis; reduction of lithium-induced polyuria; pediatric hypertension
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Headache, fatigue, dizziness
Endocrine & metabolic: Hyperkalemia (up to 10%; risk reduced in patients receiving kaliuretic diuretics), hyperchloremic metabolic acidosis, dehydration, hyponatremia, gynecomastia
Gastrointestinal: Nausea, diarrhea, vomiting, abdominal pain, gas pain, appetite changes, constipation
Genitourinary: Impotence
Neuromuscular & skeletal: Muscle cramps, weakness
Respiratory: Cough, dyspnea
<1% (Limited to important or life-threatening): Alopecia, arrhythmia, bladder spasms, chest pain, dyspnea, dysuria, GI bleeding, intraocular pressure increased, jaundice, orthostatic hypotension, palpitation, polyuria
CONTRAINDICATIONS — Hypersensitivity to amiloride or any component of the formulation; presence of elevated serum potassium levels (>5.5 mEq/L); if patient is receiving other potassium-conserving agents (eg, spironolactone, triamterene) or potassium supplementation (medicine, potassium-containing salt substitutes, potassium-rich diet); anuria; acute or chronic renal insufficiency; evidence of diabetic nephropathy. Patients with evidence of renal impairment or diabetes mellitus should not receive this medicine without close, frequent monitoring of serum electrolytes and renal function.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction.
Disease-related concerns: Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Diabetes: Use with extreme caution in patients with diabetes mellitus; monitor closely. Discontinue amiloride 3 days prior to glucose tolerance testing. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Hyperkalemia may result if amiloride is taken with potassium-containing foods.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Take with food or meals to avoid GI upset. Do not use salt substitutes or low salt milk without checking with your healthcare provider; too much potassium can be as harmful as too little.
PRICING — (data from drugstore.com)
Tablets (Amiloride HCl)
5 mg (30): $50.45
Tablets (Midamor)
5 mg (30): $25.99
MONITORING PARAMETERS — I & O, daily weights, blood pressure, serum electrolytes, renal function
CANADIAN BRAND NAMES — Apo-Amiloride®
INTERNATIONAL BRAND NAMES — Alverix (CY); Amiclaran (CZ); Amiduret Trom (DE); Amikal (DK); Amilamont (GB); Amilo (KP); Amilo 5 (KP); Amiloberag (DE); Amilorid NM Pharma (SE); Amilozid (HN); Amiride (IL); Berkamil (IE); Edepin (TW); Kaluril (AU, TW); Midamor (AT, CH, FI, GB, IE, NL, NO, NZ, SE); Modamide (FR); Moduretic (Combinado con hidroclorotiazida) (MX); Nirulid (DK); Pandiuren (AR); Puritrid (FI)
MECHANISM OF ACTION — Inhibits sodium reabsorption in the distal tubule, cortical collecting tubule, and collecting duct subsequently reducing both potassium and hydrogen excretion resulting in weak natriuretic, diuretic, and antihypertensive activity; increases sodium loss; increases potassium retention; decreases calcium excretion; decreases magnesium loss
PHARMACODYNAMICS / KINETICS
Onset of action: 2 hours
Duration: 24 hours
Absorption: ~15% to 25%
Distribution: Vd: 350-380 L
Protein binding: 23%
Metabolism: No active metabolites
Half-life elimination: Normal renal function: 6-9 hours; End-stage renal disease: 8-144 hours
Time to peak, serum: 6-10 hours
Excretion: Urine and feces (equal amounts as unchanged drug)
PATIENT INFORMATION — Report any muscle cramps, weakness, nausea, or dizziness. Use caution operating machinery or performing other tasks requiring alertness.
Sound-alike/look-alike issues:
AMILoride may be confused with amiodarone, amLODIPine, amrinone
PHARMACOLOGIC CATEGORY
Diuretic, Potassium Sparing
DOSING: ADULTS — Hypertension, edema (to limit potassium loss): Oral: Initial: 5-10 mg/day (up to 20 mg)
Hypertension (JNC 7): 5-10 mg/day in 1-2 divided doses
DOSING: PEDIATRIC — Hypertension (unlabeled use): Children 1-17 years: Oral: 0.4-0.625 mg/kg/day (maximum: 20 mg/day)
(For additional information see "Amiloride: Pediatric drug information")
DOSING: ELDERLY — Oral: Initial: 5 mg once daily or every other day
DOSING: RENAL IMPAIRMENT — Oral:
Clcr 10-50 mL/minute: Administer 50% of normal dose.
Clcr <10 mL/minute: Avoid use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 5 mg
DOSAGE FORMS: CONCISE
Tablet: 5 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer with food or meals to avoid GI upset.
USE — Counteracts potassium loss induced by other diuretics in the treatment of hypertension or edematous conditions including CHF, hepatic cirrhosis, and hypoaldosteronism; usually used in conjunction with more potent diuretics such as thiazides or loop diuretics
USE - UNLABELED / INVESTIGATIONAL — Investigational: Cystic fibrosis; reduction of lithium-induced polyuria; pediatric hypertension
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Headache, fatigue, dizziness
Endocrine & metabolic: Hyperkalemia (up to 10%; risk reduced in patients receiving kaliuretic diuretics), hyperchloremic metabolic acidosis, dehydration, hyponatremia, gynecomastia
Gastrointestinal: Nausea, diarrhea, vomiting, abdominal pain, gas pain, appetite changes, constipation
Genitourinary: Impotence
Neuromuscular & skeletal: Muscle cramps, weakness
Respiratory: Cough, dyspnea
<1% (Limited to important or life-threatening): Alopecia, arrhythmia, bladder spasms, chest pain, dyspnea, dysuria, GI bleeding, intraocular pressure increased, jaundice, orthostatic hypotension, palpitation, polyuria
CONTRAINDICATIONS — Hypersensitivity to amiloride or any component of the formulation; presence of elevated serum potassium levels (>5.5 mEq/L); if patient is receiving other potassium-conserving agents (eg, spironolactone, triamterene) or potassium supplementation (medicine, potassium-containing salt substitutes, potassium-rich diet); anuria; acute or chronic renal insufficiency; evidence of diabetic nephropathy. Patients with evidence of renal impairment or diabetes mellitus should not receive this medicine without close, frequent monitoring of serum electrolytes and renal function.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction.
Disease-related concerns: Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Diabetes: Use with extreme caution in patients with diabetes mellitus; monitor closely. Discontinue amiloride 3 days prior to glucose tolerance testing. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Hyperkalemia may result if amiloride is taken with potassium-containing foods.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Take with food or meals to avoid GI upset. Do not use salt substitutes or low salt milk without checking with your healthcare provider; too much potassium can be as harmful as too little.
PRICING — (data from drugstore.com)
Tablets (Amiloride HCl)
5 mg (30): $50.45
Tablets (Midamor)
5 mg (30): $25.99
MONITORING PARAMETERS — I & O, daily weights, blood pressure, serum electrolytes, renal function
CANADIAN BRAND NAMES — Apo-Amiloride®
INTERNATIONAL BRAND NAMES — Alverix (CY); Amiclaran (CZ); Amiduret Trom (DE); Amikal (DK); Amilamont (GB); Amilo (KP); Amilo 5 (KP); Amiloberag (DE); Amilorid NM Pharma (SE); Amilozid (HN); Amiride (IL); Berkamil (IE); Edepin (TW); Kaluril (AU, TW); Midamor (AT, CH, FI, GB, IE, NL, NO, NZ, SE); Modamide (FR); Moduretic (Combinado con hidroclorotiazida) (MX); Nirulid (DK); Pandiuren (AR); Puritrid (FI)
MECHANISM OF ACTION — Inhibits sodium reabsorption in the distal tubule, cortical collecting tubule, and collecting duct subsequently reducing both potassium and hydrogen excretion resulting in weak natriuretic, diuretic, and antihypertensive activity; increases sodium loss; increases potassium retention; decreases calcium excretion; decreases magnesium loss
PHARMACODYNAMICS / KINETICS
Onset of action: 2 hours
Duration: 24 hours
Absorption: ~15% to 25%
Distribution: Vd: 350-380 L
Protein binding: 23%
Metabolism: No active metabolites
Half-life elimination: Normal renal function: 6-9 hours; End-stage renal disease: 8-144 hours
Time to peak, serum: 6-10 hours
Excretion: Urine and feces (equal amounts as unchanged drug)
PATIENT INFORMATION — Report any muscle cramps, weakness, nausea, or dizziness. Use caution operating machinery or performing other tasks requiring alertness.
Amiloride
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
AMILoride may be confused with amiodarone, amLODIPine, amrinone
PHARMACOLOGIC CATEGORY
Diuretic, Potassium Sparing
DOSING: ADULTS — Hypertension, edema (to limit potassium loss): Oral: Initial: 5-10 mg/day (up to 20 mg)
Hypertension (JNC 7): 5-10 mg/day in 1-2 divided doses
DOSING: PEDIATRIC — Hypertension (unlabeled use): Children 1-17 years: Oral: 0.4-0.625 mg/kg/day (maximum: 20 mg/day)
(For additional information see "Amiloride: Pediatric drug information")
DOSING: ELDERLY — Oral: Initial: 5 mg once daily or every other day
DOSING: RENAL IMPAIRMENT — Oral:
Clcr 10-50 mL/minute: Administer 50% of normal dose.
Clcr <10 mL/minute: Avoid use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 5 mg
DOSAGE FORMS: CONCISE
Tablet: 5 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer with food or meals to avoid GI upset.
USE — Counteracts potassium loss induced by other diuretics in the treatment of hypertension or edematous conditions including CHF, hepatic cirrhosis, and hypoaldosteronism; usually used in conjunction with more potent diuretics such as thiazides or loop diuretics
USE - UNLABELED / INVESTIGATIONAL — Investigational: Cystic fibrosis; reduction of lithium-induced polyuria; pediatric hypertension
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Headache, fatigue, dizziness
Endocrine & metabolic: Hyperkalemia (up to 10%; risk reduced in patients receiving kaliuretic diuretics), hyperchloremic metabolic acidosis, dehydration, hyponatremia, gynecomastia
Gastrointestinal: Nausea, diarrhea, vomiting, abdominal pain, gas pain, appetite changes, constipation
Genitourinary: Impotence
Neuromuscular & skeletal: Muscle cramps, weakness
Respiratory: Cough, dyspnea
<1% (Limited to important or life-threatening): Alopecia, arrhythmia, bladder spasms, chest pain, dyspnea, dysuria, GI bleeding, intraocular pressure increased, jaundice, orthostatic hypotension, palpitation, polyuria
CONTRAINDICATIONS — Hypersensitivity to amiloride or any component of the formulation; presence of elevated serum potassium levels (>5.5 mEq/L); if patient is receiving other potassium-conserving agents (eg, spironolactone, triamterene) or potassium supplementation (medicine, potassium-containing salt substitutes, potassium-rich diet); anuria; acute or chronic renal insufficiency; evidence of diabetic nephropathy. Patients with evidence of renal impairment or diabetes mellitus should not receive this medicine without close, frequent monitoring of serum electrolytes and renal function.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction.
Disease-related concerns: Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Diabetes: Use with extreme caution in patients with diabetes mellitus; monitor closely. Discontinue amiloride 3 days prior to glucose tolerance testing. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Hyperkalemia may result if amiloride is taken with potassium-containing foods.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Take with food or meals to avoid GI upset. Do not use salt substitutes or low salt milk without checking with your healthcare provider; too much potassium can be as harmful as too little.
PRICING — (data from drugstore.com)
Tablets (Amiloride HCl)
5 mg (30): $50.45
Tablets (Midamor)
5 mg (30): $25.99
MONITORING PARAMETERS — I & O, daily weights, blood pressure, serum electrolytes, renal function
CANADIAN BRAND NAMES — Apo-Amiloride®
INTERNATIONAL BRAND NAMES — Alverix (CY); Amiclaran (CZ); Amiduret Trom (DE); Amikal (DK); Amilamont (GB); Amilo (KP); Amilo 5 (KP); Amiloberag (DE); Amilorid NM Pharma (SE); Amilozid (HN); Amiride (IL); Berkamil (IE); Edepin (TW); Kaluril (AU, TW); Midamor (AT, CH, FI, GB, IE, NL, NO, NZ, SE); Modamide (FR); Moduretic (Combinado con hidroclorotiazida) (MX); Nirulid (DK); Pandiuren (AR); Puritrid (FI)
MECHANISM OF ACTION — Inhibits sodium reabsorption in the distal tubule, cortical collecting tubule, and collecting duct subsequently reducing both potassium and hydrogen excretion resulting in weak natriuretic, diuretic, and antihypertensive activity; increases sodium loss; increases potassium retention; decreases calcium excretion; decreases magnesium loss
PHARMACODYNAMICS / KINETICS
Onset of action: 2 hours
Duration: 24 hours
Absorption: ~15% to 25%
Distribution: Vd: 350-380 L
Protein binding: 23%
Metabolism: No active metabolites
Half-life elimination: Normal renal function: 6-9 hours; End-stage renal disease: 8-144 hours
Time to peak, serum: 6-10 hours
Excretion: Urine and feces (equal amounts as unchanged drug)
PATIENT INFORMATION — Report any muscle cramps, weakness, nausea, or dizziness. Use caution operating machinery or performing other tasks requiring alertness.
Sound-alike/look-alike issues:
AMILoride may be confused with amiodarone, amLODIPine, amrinone
PHARMACOLOGIC CATEGORY
Diuretic, Potassium Sparing
DOSING: ADULTS — Hypertension, edema (to limit potassium loss): Oral: Initial: 5-10 mg/day (up to 20 mg)
Hypertension (JNC 7): 5-10 mg/day in 1-2 divided doses
DOSING: PEDIATRIC — Hypertension (unlabeled use): Children 1-17 years: Oral: 0.4-0.625 mg/kg/day (maximum: 20 mg/day)
(For additional information see "Amiloride: Pediatric drug information")
DOSING: ELDERLY — Oral: Initial: 5 mg once daily or every other day
DOSING: RENAL IMPAIRMENT — Oral:
Clcr 10-50 mL/minute: Administer 50% of normal dose.
Clcr <10 mL/minute: Avoid use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 5 mg
DOSAGE FORMS: CONCISE
Tablet: 5 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer with food or meals to avoid GI upset.
USE — Counteracts potassium loss induced by other diuretics in the treatment of hypertension or edematous conditions including CHF, hepatic cirrhosis, and hypoaldosteronism; usually used in conjunction with more potent diuretics such as thiazides or loop diuretics
USE - UNLABELED / INVESTIGATIONAL — Investigational: Cystic fibrosis; reduction of lithium-induced polyuria; pediatric hypertension
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Headache, fatigue, dizziness
Endocrine & metabolic: Hyperkalemia (up to 10%; risk reduced in patients receiving kaliuretic diuretics), hyperchloremic metabolic acidosis, dehydration, hyponatremia, gynecomastia
Gastrointestinal: Nausea, diarrhea, vomiting, abdominal pain, gas pain, appetite changes, constipation
Genitourinary: Impotence
Neuromuscular & skeletal: Muscle cramps, weakness
Respiratory: Cough, dyspnea
<1% (Limited to important or life-threatening): Alopecia, arrhythmia, bladder spasms, chest pain, dyspnea, dysuria, GI bleeding, intraocular pressure increased, jaundice, orthostatic hypotension, palpitation, polyuria
CONTRAINDICATIONS — Hypersensitivity to amiloride or any component of the formulation; presence of elevated serum potassium levels (>5.5 mEq/L); if patient is receiving other potassium-conserving agents (eg, spironolactone, triamterene) or potassium supplementation (medicine, potassium-containing salt substitutes, potassium-rich diet); anuria; acute or chronic renal insufficiency; evidence of diabetic nephropathy. Patients with evidence of renal impairment or diabetes mellitus should not receive this medicine without close, frequent monitoring of serum electrolytes and renal function.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction.
Disease-related concerns: Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Diabetes: Use with extreme caution in patients with diabetes mellitus; monitor closely. Discontinue amiloride 3 days prior to glucose tolerance testing. Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, uncontrolled diabetes).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Hyperkalemia may result if amiloride is taken with potassium-containing foods.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Take with food or meals to avoid GI upset. Do not use salt substitutes or low salt milk without checking with your healthcare provider; too much potassium can be as harmful as too little.
PRICING — (data from drugstore.com)
Tablets (Amiloride HCl)
5 mg (30): $50.45
Tablets (Midamor)
5 mg (30): $25.99
MONITORING PARAMETERS — I & O, daily weights, blood pressure, serum electrolytes, renal function
CANADIAN BRAND NAMES — Apo-Amiloride®
INTERNATIONAL BRAND NAMES — Alverix (CY); Amiclaran (CZ); Amiduret Trom (DE); Amikal (DK); Amilamont (GB); Amilo (KP); Amilo 5 (KP); Amiloberag (DE); Amilorid NM Pharma (SE); Amilozid (HN); Amiride (IL); Berkamil (IE); Edepin (TW); Kaluril (AU, TW); Midamor (AT, CH, FI, GB, IE, NL, NO, NZ, SE); Modamide (FR); Moduretic (Combinado con hidroclorotiazida) (MX); Nirulid (DK); Pandiuren (AR); Puritrid (FI)
MECHANISM OF ACTION — Inhibits sodium reabsorption in the distal tubule, cortical collecting tubule, and collecting duct subsequently reducing both potassium and hydrogen excretion resulting in weak natriuretic, diuretic, and antihypertensive activity; increases sodium loss; increases potassium retention; decreases calcium excretion; decreases magnesium loss
PHARMACODYNAMICS / KINETICS
Onset of action: 2 hours
Duration: 24 hours
Absorption: ~15% to 25%
Distribution: Vd: 350-380 L
Protein binding: 23%
Metabolism: No active metabolites
Half-life elimination: Normal renal function: 6-9 hours; End-stage renal disease: 8-144 hours
Time to peak, serum: 6-10 hours
Excretion: Urine and feces (equal amounts as unchanged drug)
PATIENT INFORMATION — Report any muscle cramps, weakness, nausea, or dizziness. Use caution operating machinery or performing other tasks requiring alertness.
Amikacin
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amikacin may be confused with Amicar®, anakinra
Amikin® may be confused with Amicar®, Kineret®
PHARMACOLOGIC CATEGORY
Antibiotic, Aminoglycoside
DOSING: ADULTS — Individualization is critical because of the low therapeutic index
Note: Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
Usual dosage range: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
Note: Some clinicians suggest a daily dose of 15-20 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.
Indication-specific dosing:
Endophthalmitis, bacterial (unlabeled use): Intravitreal: 0.4 mg/0.1 mL NS in combination with vancomycin
Hospital-acquired pneumonia (HAP): I.V.: 20 mg/kg/day with antipseudomonal beta-lactam or carbapenem (American Thoracic Society/ATS guidelines)
Meningitis(Pseudomonas aeruginosa): I.V.: 5 mg/kg every 8 hours (administered with another bacteriocidal drug)
Mycobacterium fortuitum, M. chelonae, or M. abscessus: I.V.: 10-15 mg/kg daily for at least 2 weeks with high dose cefoxitin
DOSING: PEDIATRIC — Usual dosage range: Infants and Children: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
(For additional information see "Amikacin: Pediatric drug information")
Note: Individualization is critical because of the low therapeutic index
Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients).
Clcr ≥ 60 mL/minute: Administer every 8 hours
Clcr 40-60 mL/minute: Administer every 12 hours
Clcr 20-40 mL/minute: Administer every 24 hours
Clcr <20 mL/minute: Loading dose, then monitor levels
Dialyzable (50% to 100%)
Administer dose postdialysis or administer 2/3 normal dose as a supplemental dose postdialysis and follow levels.
Peritoneal dialysis effects: Dose as for Clcr <20 mL/minute: Follow levels.
Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 10-40 mL/minute: Follow levels.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sulfate: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
DOSAGE FORMS: CONCISE
Injection, solution: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Do not mix with other drugs, administer separately.
I.M.: Administer I.M. injection in large muscle mass.
I.V.: Infuse over 30-60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in dextran 75 6% in NS, D5LR, D51/4NS, D51/3NS, D51/2NS, D5NS, D10NS, D5W, D10W, D20W, mannitol 20%, 1/4NS, 1/2NS, NS; variable stability (consult detailed reference) in peritoneal dialysis solutions.
Y-site administration: Compatible: Acyclovir, alatrofloxacin, amifostine, amiodarone, amsacrine, aztreonam, cefpirome, cisatracurium, cyclophosphamide, dexamethasone sodium phosphate, diltiazem, docetaxel, enalaprilat, esmolol, etoposide, filgrastim, fluconazole, fludarabine, foscarnet, furosemide, gatifloxacin, gemcitabine, granisetron, idarubicin, IL-2, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, melphalan, midazolam, morphine, ondansetron, paclitaxel, perphenazine, remifentanil, sargramostim, teniposide, thiotepa, vinorelbine, warfarin, zidovudine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, hetastarch, propofol.
Compatibility in syringe: Compatible: Clindamycin, doxapram. Incompatible: Heparin.
Compatibility when admixed: Compatible: Amobarbital, ascorbic acid injection, bleomycin, calcium chloride, calcium gluconate, cefepime, cefoxitin, chloramphenicol, chlorpheniramine, cimetidine, ciprofloxacin, clindamycin, colistimethate, dimenhydrinate, diphenhydramine, epinephrine, ergonovine, fluconazole, furosemide, hyaluronidase, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, lincomycin, metaraminol, metronidazole, metronidazole with sodium bicarbonate, norepinephrine, pentobarbital, phenobarbital, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine, ranitidine, sodium bicarbonate, succinylcholine, vancomycin, verapamil. Incompatible: Amphotericin B, ampicillin, cefazolin, chlorothiazide, heparin, phenytoin, thiopental, vitamin B complex with C. Variable (consult detailed reference): Aminophylline, dexamethasone sodium phosphate, oxacillin, penicillin G potassium, potassium chloride.
USE — Treatment of serious infections (bone infections, respiratory tract infections, endocarditis, and septicemia) due to organisms resistant to gentamicin and tobramycin, including Pseudomonas, Proteus, Serratia, and other gram-negative bacilli; documented infection of mycobacterial organisms susceptible to amikacin
USE - UNLABELED / INVESTIGATIONAL — Bacterial endophthalmitis
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Neurotoxicity
Otic: Ototoxicity (auditory), ototoxicity (vestibular)
Renal: Nephrotoxicity
<1% (Limited to important or life-threatening): Allergic reaction, dyspnea, eosinophilia
CONTRAINDICATIONS — Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides
WARNINGS / PRECAUTIONS
Boxed Warnings: Nephrotoxicity: . Neuromuscular blockade and respiratory paralysis: . Neurotoxicity: .
Concerns related to adverse effects: Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; usual risk factors include pre-existing renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible. Neuromuscular blockade and respiratory paralysis: [U.S. Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants. Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss. Hypocalcemia: Use with caution in patients with hypocalcemia. Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis. Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.
Dosage form specific issues: Sulfite: Solution contains sodium metabisulfate; use caution in patients with sulfite allergy.
DRUG INTERACTIONS
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Risk D: Consider therapy modification
CycloSPORINE: Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Gallium Nitrate: Aminoglycosides may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Methicillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Risk D: Consider therapy modification
RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Amikacin crosses the placenta, produces detectable serum levels in the fetus, and concentrates in the fetal kidneys. Because of several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy, the manufacturer classifies amikacin as pregnancy risk factor D. Renal toxicity has been observed in animals, but fetal toxicity in humans has not been reported. No adequate and well-controlled studies have been conducted in pregnant women and it is not known whether amikacin can cause fetal harm. Although the manufacturer considers amikacin pregnancy risk factor D, amikacin-specific clinical data would suggest pregnancy risk factor C.
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of amikacin may be altered. Pregnant women have an average-to-larger volume of distribution which may result in lower peak serum levels than for the same dose in nonpregnant women. Serum half-life is also shorter.
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Amikacin is excreted into breast milk in trace amounts; however, it is not absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora.
DIETARY CONSIDERATIONS — Sodium content of 1 g: 29.9 mg (1.3 mEq)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
REFERENCE RANGE
Sample size: 0.5-2 mL blood (red top tube) or 0.1-1 mL serum (separated)
Therapeutic levels:
Peak:
Life-threatening infections: 25-40 mcg/mL
Serious infections: 20-25 mcg/mL
Urinary tract infections: 15-20 mcg/mL
Trough: <8 mcg/mL
The American Thoracic Society (ATS) recommends trough levels of <4-5 mcg/mL for patients with hospital-acquired pneumonia.
Toxic concentration: Peak: >40 mcg/mL; Trough: >10 mcg/mL
Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose
CANADIAN BRAND NAMES — Amikacin Sulfate Injection, USP; Amikin®
INTERNATIONAL BRAND NAMES — Acemycin (TW); Agnicin (MX); Akacin (MX, TH); Akicin (TH); Alostil (ID); Amicasil (IT); Amicin (IN); Amikabiot (PE); Amikacin Fresenius (DE); Amikacina (CN); Amikacina Medical (ES); Amikacina Normon (ES, PT); Amikacine Aguettant (FR); Amikacine Dakota Pharm (FR); Amikacine Panpharma (FR); Amikafur (MX); Amikan (IT); Amikaxing (CL); Amikayect (MX); Amikin (AU, BF, BG, BJ, BR, CH, CI, CO, CZ, EE, ET, GB, GH, GM, GN, HK, HN, HU, ID, IE, KE, KP, LR, MA, ML, MR, MU, MW, MY, NE, NG, PE, PH, PK, PL, SC, SD, SG, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Amikin. (MX); Amiklin (FR); Amikozit (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amukin (BE, LU, NL); Biclin (ES, MX, PT); Biklin (AR, AT, DE, FI, PH, SE, VE); Biodacyna (PL); Biokacin (MX, PY); Briclin (UY); Briklin (GR); Chemacin (IT); Cidacid (PH); Cinmik (PH); Eukacin (TW); Gamikal (MX); Glukamin (EC); Kacinth-A (ZA); Kamin (PH); Kamina (PT); Kanbine (ES); Karmikin (MX); Kormakin (PH); Lanomycin (GR); Likacin (AE, BH, CY, EG, HU, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Lisobac (MX); Lukadin (IT); Miacin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Mikasul (PH); Nica (PH); Novamin (BR); Oprad (MX); Orlobin (GR); Panmikin (PH); Riklinak (AR); Savox (TW); Selaxa (GR); Selemycin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sikacin (TW); Tybikin (TH); Vijomikin (GT, HN, PA, SV); Yectamid (MX)
MECHANISM OF ACTION — Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
PHARMACODYNAMICS / KINETICS
Absorption:
I.M.: Rapid
Oral: Poorly absorbed
Distribution: Primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)
CSF:blood level ratio: Normal meninges: 10% to 20%; Inflamed meninges: 15% to 24%
Protein-binding: 0% to 11%
Half-life elimination (renal function and age dependent):
Infants: Low birth weight (1-3 days): 7-9 hours; Full-term >7 days: 4-5 hours
Children: 1.6-2.5 hours
Adults: Normal renal function: 1.4-2.3 hours; Anuria/end-stage renal disease: 28-86 hours
Time to peak, serum: I.M.: 45-120 minutes
Excretion: Urine (94% to 98%)
PATIENT INFORMATION — Report loss of hearing, ringing or roaring in the ears, or feeling of fullness in head
Sound-alike/look-alike issues:
Amikacin may be confused with Amicar®, anakinra
Amikin® may be confused with Amicar®, Kineret®
PHARMACOLOGIC CATEGORY
Antibiotic, Aminoglycoside
DOSING: ADULTS — Individualization is critical because of the low therapeutic index
Note: Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
Usual dosage range: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
Note: Some clinicians suggest a daily dose of 15-20 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.
Indication-specific dosing:
Endophthalmitis, bacterial (unlabeled use): Intravitreal: 0.4 mg/0.1 mL NS in combination with vancomycin
Hospital-acquired pneumonia (HAP): I.V.: 20 mg/kg/day with antipseudomonal beta-lactam or carbapenem (American Thoracic Society/ATS guidelines)
Meningitis(Pseudomonas aeruginosa): I.V.: 5 mg/kg every 8 hours (administered with another bacteriocidal drug)
Mycobacterium fortuitum, M. chelonae, or M. abscessus: I.V.: 10-15 mg/kg daily for at least 2 weeks with high dose cefoxitin
DOSING: PEDIATRIC — Usual dosage range: Infants and Children: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
(For additional information see "Amikacin: Pediatric drug information")
Note: Individualization is critical because of the low therapeutic index
Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients).
Clcr ≥ 60 mL/minute: Administer every 8 hours
Clcr 40-60 mL/minute: Administer every 12 hours
Clcr 20-40 mL/minute: Administer every 24 hours
Clcr <20 mL/minute: Loading dose, then monitor levels
Dialyzable (50% to 100%)
Administer dose postdialysis or administer 2/3 normal dose as a supplemental dose postdialysis and follow levels.
Peritoneal dialysis effects: Dose as for Clcr <20 mL/minute: Follow levels.
Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 10-40 mL/minute: Follow levels.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sulfate: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
DOSAGE FORMS: CONCISE
Injection, solution: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Do not mix with other drugs, administer separately.
I.M.: Administer I.M. injection in large muscle mass.
I.V.: Infuse over 30-60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in dextran 75 6% in NS, D5LR, D51/4NS, D51/3NS, D51/2NS, D5NS, D10NS, D5W, D10W, D20W, mannitol 20%, 1/4NS, 1/2NS, NS; variable stability (consult detailed reference) in peritoneal dialysis solutions.
Y-site administration: Compatible: Acyclovir, alatrofloxacin, amifostine, amiodarone, amsacrine, aztreonam, cefpirome, cisatracurium, cyclophosphamide, dexamethasone sodium phosphate, diltiazem, docetaxel, enalaprilat, esmolol, etoposide, filgrastim, fluconazole, fludarabine, foscarnet, furosemide, gatifloxacin, gemcitabine, granisetron, idarubicin, IL-2, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, melphalan, midazolam, morphine, ondansetron, paclitaxel, perphenazine, remifentanil, sargramostim, teniposide, thiotepa, vinorelbine, warfarin, zidovudine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, hetastarch, propofol.
Compatibility in syringe: Compatible: Clindamycin, doxapram. Incompatible: Heparin.
Compatibility when admixed: Compatible: Amobarbital, ascorbic acid injection, bleomycin, calcium chloride, calcium gluconate, cefepime, cefoxitin, chloramphenicol, chlorpheniramine, cimetidine, ciprofloxacin, clindamycin, colistimethate, dimenhydrinate, diphenhydramine, epinephrine, ergonovine, fluconazole, furosemide, hyaluronidase, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, lincomycin, metaraminol, metronidazole, metronidazole with sodium bicarbonate, norepinephrine, pentobarbital, phenobarbital, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine, ranitidine, sodium bicarbonate, succinylcholine, vancomycin, verapamil. Incompatible: Amphotericin B, ampicillin, cefazolin, chlorothiazide, heparin, phenytoin, thiopental, vitamin B complex with C. Variable (consult detailed reference): Aminophylline, dexamethasone sodium phosphate, oxacillin, penicillin G potassium, potassium chloride.
USE — Treatment of serious infections (bone infections, respiratory tract infections, endocarditis, and septicemia) due to organisms resistant to gentamicin and tobramycin, including Pseudomonas, Proteus, Serratia, and other gram-negative bacilli; documented infection of mycobacterial organisms susceptible to amikacin
USE - UNLABELED / INVESTIGATIONAL — Bacterial endophthalmitis
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Neurotoxicity
Otic: Ototoxicity (auditory), ototoxicity (vestibular)
Renal: Nephrotoxicity
<1% (Limited to important or life-threatening): Allergic reaction, dyspnea, eosinophilia
CONTRAINDICATIONS — Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides
WARNINGS / PRECAUTIONS
Boxed Warnings: Nephrotoxicity: . Neuromuscular blockade and respiratory paralysis: . Neurotoxicity: .
Concerns related to adverse effects: Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; usual risk factors include pre-existing renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible. Neuromuscular blockade and respiratory paralysis: [U.S. Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants. Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss. Hypocalcemia: Use with caution in patients with hypocalcemia. Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis. Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.
Dosage form specific issues: Sulfite: Solution contains sodium metabisulfate; use caution in patients with sulfite allergy.
DRUG INTERACTIONS
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Risk D: Consider therapy modification
CycloSPORINE: Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Gallium Nitrate: Aminoglycosides may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Methicillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Risk D: Consider therapy modification
RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Amikacin crosses the placenta, produces detectable serum levels in the fetus, and concentrates in the fetal kidneys. Because of several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy, the manufacturer classifies amikacin as pregnancy risk factor D. Renal toxicity has been observed in animals, but fetal toxicity in humans has not been reported. No adequate and well-controlled studies have been conducted in pregnant women and it is not known whether amikacin can cause fetal harm. Although the manufacturer considers amikacin pregnancy risk factor D, amikacin-specific clinical data would suggest pregnancy risk factor C.
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of amikacin may be altered. Pregnant women have an average-to-larger volume of distribution which may result in lower peak serum levels than for the same dose in nonpregnant women. Serum half-life is also shorter.
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Amikacin is excreted into breast milk in trace amounts; however, it is not absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora.
DIETARY CONSIDERATIONS — Sodium content of 1 g: 29.9 mg (1.3 mEq)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
REFERENCE RANGE
Sample size: 0.5-2 mL blood (red top tube) or 0.1-1 mL serum (separated)
Therapeutic levels:
Peak:
Life-threatening infections: 25-40 mcg/mL
Serious infections: 20-25 mcg/mL
Urinary tract infections: 15-20 mcg/mL
Trough: <8 mcg/mL
The American Thoracic Society (ATS) recommends trough levels of <4-5 mcg/mL for patients with hospital-acquired pneumonia.
Toxic concentration: Peak: >40 mcg/mL; Trough: >10 mcg/mL
Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose
CANADIAN BRAND NAMES — Amikacin Sulfate Injection, USP; Amikin®
INTERNATIONAL BRAND NAMES — Acemycin (TW); Agnicin (MX); Akacin (MX, TH); Akicin (TH); Alostil (ID); Amicasil (IT); Amicin (IN); Amikabiot (PE); Amikacin Fresenius (DE); Amikacina (CN); Amikacina Medical (ES); Amikacina Normon (ES, PT); Amikacine Aguettant (FR); Amikacine Dakota Pharm (FR); Amikacine Panpharma (FR); Amikafur (MX); Amikan (IT); Amikaxing (CL); Amikayect (MX); Amikin (AU, BF, BG, BJ, BR, CH, CI, CO, CZ, EE, ET, GB, GH, GM, GN, HK, HN, HU, ID, IE, KE, KP, LR, MA, ML, MR, MU, MW, MY, NE, NG, PE, PH, PK, PL, SC, SD, SG, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Amikin. (MX); Amiklin (FR); Amikozit (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amukin (BE, LU, NL); Biclin (ES, MX, PT); Biklin (AR, AT, DE, FI, PH, SE, VE); Biodacyna (PL); Biokacin (MX, PY); Briclin (UY); Briklin (GR); Chemacin (IT); Cidacid (PH); Cinmik (PH); Eukacin (TW); Gamikal (MX); Glukamin (EC); Kacinth-A (ZA); Kamin (PH); Kamina (PT); Kanbine (ES); Karmikin (MX); Kormakin (PH); Lanomycin (GR); Likacin (AE, BH, CY, EG, HU, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Lisobac (MX); Lukadin (IT); Miacin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Mikasul (PH); Nica (PH); Novamin (BR); Oprad (MX); Orlobin (GR); Panmikin (PH); Riklinak (AR); Savox (TW); Selaxa (GR); Selemycin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sikacin (TW); Tybikin (TH); Vijomikin (GT, HN, PA, SV); Yectamid (MX)
MECHANISM OF ACTION — Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
PHARMACODYNAMICS / KINETICS
Absorption:
I.M.: Rapid
Oral: Poorly absorbed
Distribution: Primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)
CSF:blood level ratio: Normal meninges: 10% to 20%; Inflamed meninges: 15% to 24%
Protein-binding: 0% to 11%
Half-life elimination (renal function and age dependent):
Infants: Low birth weight (1-3 days): 7-9 hours; Full-term >7 days: 4-5 hours
Children: 1.6-2.5 hours
Adults: Normal renal function: 1.4-2.3 hours; Anuria/end-stage renal disease: 28-86 hours
Time to peak, serum: I.M.: 45-120 minutes
Excretion: Urine (94% to 98%)
PATIENT INFORMATION — Report loss of hearing, ringing or roaring in the ears, or feeling of fullness in head
Amikacin
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Amikacin may be confused with Amicar®, anakinra
Amikin® may be confused with Amicar®, Kineret®
PHARMACOLOGIC CATEGORY
Antibiotic, Aminoglycoside
DOSING: ADULTS — Individualization is critical because of the low therapeutic index
Note: Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
Usual dosage range: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
Note: Some clinicians suggest a daily dose of 15-20 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.
Indication-specific dosing:
Endophthalmitis, bacterial (unlabeled use): Intravitreal: 0.4 mg/0.1 mL NS in combination with vancomycin
Hospital-acquired pneumonia (HAP): I.V.: 20 mg/kg/day with antipseudomonal beta-lactam or carbapenem (American Thoracic Society/ATS guidelines)
Meningitis(Pseudomonas aeruginosa): I.V.: 5 mg/kg every 8 hours (administered with another bacteriocidal drug)
Mycobacterium fortuitum, M. chelonae, or M. abscessus: I.V.: 10-15 mg/kg daily for at least 2 weeks with high dose cefoxitin
DOSING: PEDIATRIC — Usual dosage range: Infants and Children: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
(For additional information see "Amikacin: Pediatric drug information")
Note: Individualization is critical because of the low therapeutic index
Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients).
Clcr ≥ 60 mL/minute: Administer every 8 hours
Clcr 40-60 mL/minute: Administer every 12 hours
Clcr 20-40 mL/minute: Administer every 24 hours
Clcr <20 mL/minute: Loading dose, then monitor levels
Dialyzable (50% to 100%)
Administer dose postdialysis or administer 2/3 normal dose as a supplemental dose postdialysis and follow levels.
Peritoneal dialysis effects: Dose as for Clcr <20 mL/minute: Follow levels.
Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 10-40 mL/minute: Follow levels.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sulfate: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
DOSAGE FORMS: CONCISE
Injection, solution: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Do not mix with other drugs, administer separately.
I.M.: Administer I.M. injection in large muscle mass.
I.V.: Infuse over 30-60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in dextran 75 6% in NS, D5LR, D51/4NS, D51/3NS, D51/2NS, D5NS, D10NS, D5W, D10W, D20W, mannitol 20%, 1/4NS, 1/2NS, NS; variable stability (consult detailed reference) in peritoneal dialysis solutions.
Y-site administration: Compatible: Acyclovir, alatrofloxacin, amifostine, amiodarone, amsacrine, aztreonam, cefpirome, cisatracurium, cyclophosphamide, dexamethasone sodium phosphate, diltiazem, docetaxel, enalaprilat, esmolol, etoposide, filgrastim, fluconazole, fludarabine, foscarnet, furosemide, gatifloxacin, gemcitabine, granisetron, idarubicin, IL-2, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, melphalan, midazolam, morphine, ondansetron, paclitaxel, perphenazine, remifentanil, sargramostim, teniposide, thiotepa, vinorelbine, warfarin, zidovudine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, hetastarch, propofol.
Compatibility in syringe: Compatible: Clindamycin, doxapram. Incompatible: Heparin.
Compatibility when admixed: Compatible: Amobarbital, ascorbic acid injection, bleomycin, calcium chloride, calcium gluconate, cefepime, cefoxitin, chloramphenicol, chlorpheniramine, cimetidine, ciprofloxacin, clindamycin, colistimethate, dimenhydrinate, diphenhydramine, epinephrine, ergonovine, fluconazole, furosemide, hyaluronidase, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, lincomycin, metaraminol, metronidazole, metronidazole with sodium bicarbonate, norepinephrine, pentobarbital, phenobarbital, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine, ranitidine, sodium bicarbonate, succinylcholine, vancomycin, verapamil. Incompatible: Amphotericin B, ampicillin, cefazolin, chlorothiazide, heparin, phenytoin, thiopental, vitamin B complex with C. Variable (consult detailed reference): Aminophylline, dexamethasone sodium phosphate, oxacillin, penicillin G potassium, potassium chloride.
USE — Treatment of serious infections (bone infections, respiratory tract infections, endocarditis, and septicemia) due to organisms resistant to gentamicin and tobramycin, including Pseudomonas, Proteus, Serratia, and other gram-negative bacilli; documented infection of mycobacterial organisms susceptible to amikacin
USE - UNLABELED / INVESTIGATIONAL — Bacterial endophthalmitis
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Neurotoxicity
Otic: Ototoxicity (auditory), ototoxicity (vestibular)
Renal: Nephrotoxicity
<1% (Limited to important or life-threatening): Allergic reaction, dyspnea, eosinophilia
CONTRAINDICATIONS — Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides
WARNINGS / PRECAUTIONS
Boxed Warnings: Nephrotoxicity: . Neuromuscular blockade and respiratory paralysis: . Neurotoxicity: .
Concerns related to adverse effects: Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; usual risk factors include pre-existing renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible. Neuromuscular blockade and respiratory paralysis: [U.S. Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants. Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss. Hypocalcemia: Use with caution in patients with hypocalcemia. Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis. Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.
Dosage form specific issues: Sulfite: Solution contains sodium metabisulfate; use caution in patients with sulfite allergy.
DRUG INTERACTIONS
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Risk D: Consider therapy modification
CycloSPORINE: Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Gallium Nitrate: Aminoglycosides may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Methicillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Risk D: Consider therapy modification
RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Amikacin crosses the placenta, produces detectable serum levels in the fetus, and concentrates in the fetal kidneys. Because of several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy, the manufacturer classifies amikacin as pregnancy risk factor D. Renal toxicity has been observed in animals, but fetal toxicity in humans has not been reported. No adequate and well-controlled studies have been conducted in pregnant women and it is not known whether amikacin can cause fetal harm. Although the manufacturer considers amikacin pregnancy risk factor D, amikacin-specific clinical data would suggest pregnancy risk factor C.
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of amikacin may be altered. Pregnant women have an average-to-larger volume of distribution which may result in lower peak serum levels than for the same dose in nonpregnant women. Serum half-life is also shorter.
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Amikacin is excreted into breast milk in trace amounts; however, it is not absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora.
DIETARY CONSIDERATIONS — Sodium content of 1 g: 29.9 mg (1.3 mEq)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
REFERENCE RANGE
Sample size: 0.5-2 mL blood (red top tube) or 0.1-1 mL serum (separated)
Therapeutic levels:
Peak:
Life-threatening infections: 25-40 mcg/mL
Serious infections: 20-25 mcg/mL
Urinary tract infections: 15-20 mcg/mL
Trough: <8 mcg/mL
The American Thoracic Society (ATS) recommends trough levels of <4-5 mcg/mL for patients with hospital-acquired pneumonia.
Toxic concentration: Peak: >40 mcg/mL; Trough: >10 mcg/mL
Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose
CANADIAN BRAND NAMES — Amikacin Sulfate Injection, USP; Amikin®
INTERNATIONAL BRAND NAMES — Acemycin (TW); Agnicin (MX); Akacin (MX, TH); Akicin (TH); Alostil (ID); Amicasil (IT); Amicin (IN); Amikabiot (PE); Amikacin Fresenius (DE); Amikacina (CN); Amikacina Medical (ES); Amikacina Normon (ES, PT); Amikacine Aguettant (FR); Amikacine Dakota Pharm (FR); Amikacine Panpharma (FR); Amikafur (MX); Amikan (IT); Amikaxing (CL); Amikayect (MX); Amikin (AU, BF, BG, BJ, BR, CH, CI, CO, CZ, EE, ET, GB, GH, GM, GN, HK, HN, HU, ID, IE, KE, KP, LR, MA, ML, MR, MU, MW, MY, NE, NG, PE, PH, PK, PL, SC, SD, SG, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Amikin. (MX); Amiklin (FR); Amikozit (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amukin (BE, LU, NL); Biclin (ES, MX, PT); Biklin (AR, AT, DE, FI, PH, SE, VE); Biodacyna (PL); Biokacin (MX, PY); Briclin (UY); Briklin (GR); Chemacin (IT); Cidacid (PH); Cinmik (PH); Eukacin (TW); Gamikal (MX); Glukamin (EC); Kacinth-A (ZA); Kamin (PH); Kamina (PT); Kanbine (ES); Karmikin (MX); Kormakin (PH); Lanomycin (GR); Likacin (AE, BH, CY, EG, HU, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Lisobac (MX); Lukadin (IT); Miacin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Mikasul (PH); Nica (PH); Novamin (BR); Oprad (MX); Orlobin (GR); Panmikin (PH); Riklinak (AR); Savox (TW); Selaxa (GR); Selemycin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sikacin (TW); Tybikin (TH); Vijomikin (GT, HN, PA, SV); Yectamid (MX)
MECHANISM OF ACTION — Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
PHARMACODYNAMICS / KINETICS
Absorption:
I.M.: Rapid
Oral: Poorly absorbed
Distribution: Primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)
CSF:blood level ratio: Normal meninges: 10% to 20%; Inflamed meninges: 15% to 24%
Protein-binding: 0% to 11%
Half-life elimination (renal function and age dependent):
Infants: Low birth weight (1-3 days): 7-9 hours; Full-term >7 days: 4-5 hours
Children: 1.6-2.5 hours
Adults: Normal renal function: 1.4-2.3 hours; Anuria/end-stage renal disease: 28-86 hours
Time to peak, serum: I.M.: 45-120 minutes
Excretion: Urine (94% to 98%)
PATIENT INFORMATION — Report loss of hearing, ringing or roaring in the ears, or feeling of fullness in head
Sound-alike/look-alike issues:
Amikacin may be confused with Amicar®, anakinra
Amikin® may be confused with Amicar®, Kineret®
PHARMACOLOGIC CATEGORY
Antibiotic, Aminoglycoside
DOSING: ADULTS — Individualization is critical because of the low therapeutic index
Note: Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
Usual dosage range: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
Note: Some clinicians suggest a daily dose of 15-20 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.
Indication-specific dosing:
Endophthalmitis, bacterial (unlabeled use): Intravitreal: 0.4 mg/0.1 mL NS in combination with vancomycin
Hospital-acquired pneumonia (HAP): I.V.: 20 mg/kg/day with antipseudomonal beta-lactam or carbapenem (American Thoracic Society/ATS guidelines)
Meningitis(Pseudomonas aeruginosa): I.V.: 5 mg/kg every 8 hours (administered with another bacteriocidal drug)
Mycobacterium fortuitum, M. chelonae, or M. abscessus: I.V.: 10-15 mg/kg daily for at least 2 weeks with high dose cefoxitin
DOSING: PEDIATRIC — Usual dosage range: Infants and Children: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
(For additional information see "Amikacin: Pediatric drug information")
Note: Individualization is critical because of the low therapeutic index
Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients).
Clcr ≥ 60 mL/minute: Administer every 8 hours
Clcr 40-60 mL/minute: Administer every 12 hours
Clcr 20-40 mL/minute: Administer every 24 hours
Clcr <20 mL/minute: Loading dose, then monitor levels
Dialyzable (50% to 100%)
Administer dose postdialysis or administer 2/3 normal dose as a supplemental dose postdialysis and follow levels.
Peritoneal dialysis effects: Dose as for Clcr <20 mL/minute: Follow levels.
Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 10-40 mL/minute: Follow levels.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sulfate: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
DOSAGE FORMS: CONCISE
Injection, solution: 50 mg/mL (2 mL); 250 mg/mL (2 mL, 4 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer around-the-clock to promote less variation in peak and trough serum levels. Do not mix with other drugs, administer separately.
I.M.: Administer I.M. injection in large muscle mass.
I.V.: Infuse over 30-60 minutes.
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.
COMPATIBILITY — Stable in dextran 75 6% in NS, D5LR, D51/4NS, D51/3NS, D51/2NS, D5NS, D10NS, D5W, D10W, D20W, mannitol 20%, 1/4NS, 1/2NS, NS; variable stability (consult detailed reference) in peritoneal dialysis solutions.
Y-site administration: Compatible: Acyclovir, alatrofloxacin, amifostine, amiodarone, amsacrine, aztreonam, cefpirome, cisatracurium, cyclophosphamide, dexamethasone sodium phosphate, diltiazem, docetaxel, enalaprilat, esmolol, etoposide, filgrastim, fluconazole, fludarabine, foscarnet, furosemide, gatifloxacin, gemcitabine, granisetron, idarubicin, IL-2, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, melphalan, midazolam, morphine, ondansetron, paclitaxel, perphenazine, remifentanil, sargramostim, teniposide, thiotepa, vinorelbine, warfarin, zidovudine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, hetastarch, propofol.
Compatibility in syringe: Compatible: Clindamycin, doxapram. Incompatible: Heparin.
Compatibility when admixed: Compatible: Amobarbital, ascorbic acid injection, bleomycin, calcium chloride, calcium gluconate, cefepime, cefoxitin, chloramphenicol, chlorpheniramine, cimetidine, ciprofloxacin, clindamycin, colistimethate, dimenhydrinate, diphenhydramine, epinephrine, ergonovine, fluconazole, furosemide, hyaluronidase, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, lincomycin, metaraminol, metronidazole, metronidazole with sodium bicarbonate, norepinephrine, pentobarbital, phenobarbital, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine, ranitidine, sodium bicarbonate, succinylcholine, vancomycin, verapamil. Incompatible: Amphotericin B, ampicillin, cefazolin, chlorothiazide, heparin, phenytoin, thiopental, vitamin B complex with C. Variable (consult detailed reference): Aminophylline, dexamethasone sodium phosphate, oxacillin, penicillin G potassium, potassium chloride.
USE — Treatment of serious infections (bone infections, respiratory tract infections, endocarditis, and septicemia) due to organisms resistant to gentamicin and tobramycin, including Pseudomonas, Proteus, Serratia, and other gram-negative bacilli; documented infection of mycobacterial organisms susceptible to amikacin
USE - UNLABELED / INVESTIGATIONAL — Bacterial endophthalmitis
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Neurotoxicity
Otic: Ototoxicity (auditory), ototoxicity (vestibular)
Renal: Nephrotoxicity
<1% (Limited to important or life-threatening): Allergic reaction, dyspnea, eosinophilia
CONTRAINDICATIONS — Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides
WARNINGS / PRECAUTIONS
Boxed Warnings: Nephrotoxicity: . Neuromuscular blockade and respiratory paralysis: . Neurotoxicity: .
Concerns related to adverse effects: Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; usual risk factors include pre-existing renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible. Neuromuscular blockade and respiratory paralysis: [U.S. Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants. Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss. Hypocalcemia: Use with caution in patients with hypocalcemia. Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis. Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.
Dosage form specific issues: Sulfite: Solution contains sodium metabisulfate; use caution in patients with sulfite allergy.
DRUG INTERACTIONS
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Risk D: Consider therapy modification
CycloSPORINE: Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
Gallium Nitrate: Aminoglycosides may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Methicillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Risk D: Consider therapy modification
RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Amikacin crosses the placenta, produces detectable serum levels in the fetus, and concentrates in the fetal kidneys. Because of several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy, the manufacturer classifies amikacin as pregnancy risk factor D. Renal toxicity has been observed in animals, but fetal toxicity in humans has not been reported. No adequate and well-controlled studies have been conducted in pregnant women and it is not known whether amikacin can cause fetal harm. Although the manufacturer considers amikacin pregnancy risk factor D, amikacin-specific clinical data would suggest pregnancy risk factor C.
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of amikacin may be altered. Pregnant women have an average-to-larger volume of distribution which may result in lower peak serum levels than for the same dose in nonpregnant women. Serum half-life is also shorter.
LACTATION — Enters breast milk/compatible
BREAST-FEEDING CONSIDERATIONS — Amikacin is excreted into breast milk in trace amounts; however, it is not absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora.
DIETARY CONSIDERATIONS — Sodium content of 1 g: 29.9 mg (1.3 mEq)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
REFERENCE RANGE
Sample size: 0.5-2 mL blood (red top tube) or 0.1-1 mL serum (separated)
Therapeutic levels:
Peak:
Life-threatening infections: 25-40 mcg/mL
Serious infections: 20-25 mcg/mL
Urinary tract infections: 15-20 mcg/mL
Trough: <8 mcg/mL
The American Thoracic Society (ATS) recommends trough levels of <4-5 mcg/mL for patients with hospital-acquired pneumonia.
Toxic concentration: Peak: >40 mcg/mL; Trough: >10 mcg/mL
Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose
CANADIAN BRAND NAMES — Amikacin Sulfate Injection, USP; Amikin®
INTERNATIONAL BRAND NAMES — Acemycin (TW); Agnicin (MX); Akacin (MX, TH); Akicin (TH); Alostil (ID); Amicasil (IT); Amicin (IN); Amikabiot (PE); Amikacin Fresenius (DE); Amikacina (CN); Amikacina Medical (ES); Amikacina Normon (ES, PT); Amikacine Aguettant (FR); Amikacine Dakota Pharm (FR); Amikacine Panpharma (FR); Amikafur (MX); Amikan (IT); Amikaxing (CL); Amikayect (MX); Amikin (AU, BF, BG, BJ, BR, CH, CI, CO, CZ, EE, ET, GB, GH, GM, GN, HK, HN, HU, ID, IE, KE, KP, LR, MA, ML, MR, MU, MW, MY, NE, NG, PE, PH, PK, PL, SC, SD, SG, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Amikin. (MX); Amiklin (FR); Amikozit (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amukin (BE, LU, NL); Biclin (ES, MX, PT); Biklin (AR, AT, DE, FI, PH, SE, VE); Biodacyna (PL); Biokacin (MX, PY); Briclin (UY); Briklin (GR); Chemacin (IT); Cidacid (PH); Cinmik (PH); Eukacin (TW); Gamikal (MX); Glukamin (EC); Kacinth-A (ZA); Kamin (PH); Kamina (PT); Kanbine (ES); Karmikin (MX); Kormakin (PH); Lanomycin (GR); Likacin (AE, BH, CY, EG, HU, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Lisobac (MX); Lukadin (IT); Miacin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Mikasul (PH); Nica (PH); Novamin (BR); Oprad (MX); Orlobin (GR); Panmikin (PH); Riklinak (AR); Savox (TW); Selaxa (GR); Selemycin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Sikacin (TW); Tybikin (TH); Vijomikin (GT, HN, PA, SV); Yectamid (MX)
MECHANISM OF ACTION — Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
PHARMACODYNAMICS / KINETICS
Absorption:
I.M.: Rapid
Oral: Poorly absorbed
Distribution: Primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)
CSF:blood level ratio: Normal meninges: 10% to 20%; Inflamed meninges: 15% to 24%
Protein-binding: 0% to 11%
Half-life elimination (renal function and age dependent):
Infants: Low birth weight (1-3 days): 7-9 hours; Full-term >7 days: 4-5 hours
Children: 1.6-2.5 hours
Adults: Normal renal function: 1.4-2.3 hours; Anuria/end-stage renal disease: 28-86 hours
Time to peak, serum: I.M.: 45-120 minutes
Excretion: Urine (94% to 98%)
PATIENT INFORMATION — Report loss of hearing, ringing or roaring in the ears, or feeling of fullness in head
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