U.S. BRAND NAMES — Fabrazyme®
CANADIAN BRAND NAMES — Fabrazyme®
SYNONYMS — Fabrase; Recombinant Human Alpha-Galactosidase A
THERAPEUTIC CATEGORY Enzyme, alpha-galactosidase AFabry's Disease, Treatment Agent
DOSING — I.V.: Children and Adults: 1 mg/kg/dose every two weeks
(For additional information see "Agalsidase beta: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 5 mg [contains mannitol 33 mg; derived from Chinese hamster cells]; 35 mg [contains mannitol 222 mg/vial; derived from Chinese hamster cells]
GENERIC AVAILABLE — No
ADMINISTRATION — I.V.: Reconstitute vial with 7.2 mL SWI to result in 5 mg/mL concentration; swirl to dissolve; do not shake; further dilute dosage in 500 mL NS*. Initial infusion not to exceed 15 mg/hour (0.25 mg/minute); after patient tolerance to initial infusion rate is established, the infusion rate may be increased in increments of 3-5 mg/hour (0.05-0.08 mg/minute) with subsequent infusions. In clinical studies, patients have tolerated infusion rates 33 mg/hour. Pretreatment with acetaminophen and an antihistamine is recommended to reduce infusion related side effects (See Warnings)
*Agalsidase beta stability when diluted in NS at a concentration of 2.55 mg/mL has been demonstrated by the manufacturer. Infusion volumes as low as 100 mL were used in phase I/II clinical trials. (Personal communication, Genzyme Corporation, 2003)
USE — Treatment of Fabry's disease
ADVERSE REACTIONS Cardiovascular: Tachycardia, hypertension, hypotension, chest pain, chest tightness, bradycardia, arrhythmias, cardiac arrest, edema, pallor
Central nervous system: Headache, dizziness, fever, anxiety, depression, chills, rigors, vertigo
Dermatologic: Pruritus, urticaria
Gastrointestinal: Dyspepsia, nausea, abdominal pain, vomiting
Genitourinary: Testicular pain
Neuromuscular & skeletal: Arthrosis, skeletal pain, myalgia
Otic: Hypoacousia
Respiratory: Bronchitis, bronchospasm, laryngitis, pharyngitis, sinusitis, rhinitis, dyspnea
Miscellaneous: Hypersensitivity reactions
CONTRAINDICATIONS — Hypersensitivity to agalsidase beta or any component
PRECAUTIONS — Use with caution in patients with compromised cardiac function (seen in advanced Fabry's disease) due to an increased potential for severe infusion related reactions; monitor these patients closely; patients may develop IgG antibodies to agalsidase beta
WARNINGS — Infusion-related reactions (ranging from mild to severe) including fever, rigors, chest tightness, hypertension, hypotension, pruritus, myalgia, dyspnea, urticaria, abdominal pain, and headache have been reported; these reactions may be minimized by pretreatment with acetaminophen and an antihistamine; if an infusion related reaction occurs, regardless of pretreatment, decreasing the infusion rate, temporarily stopping the infusion, and/or additional administration of analgesics, antihistamines, or corticosteroids may ameliorate the reaction.
DRUG INTERACTIONS — None as yet have been identified
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — Vital signs during infusion; globotriaosylceramide (GL3) plasma levels; improvement in symptomatology
REFERENCE RANGE — Normal endogenous activity of alpha-galactosidase A in plasma is approximately 170 nmol/hour/mL; in patients with Fabry's disease this activity is <1.5 nmol/hour/mL
Normal (goal) globotriaosylceramide (GL3) <1.2 ng/microliter
STABILITY — Store in refrigerator 2ºC to 8ºC (36ºF to 46ºF); reconstituted solution is stable for 24 hours refrigerated
MECHANISM OF ACTION — Agalsidase beta is a recombinant human alpha-galactosidase A enzyme with the same amino acid sequence as the naturally-occurring enzyme. Fabry's disease is an X-linked genetic disorder occurring in 1 in 50,000 male births, which results in a deficiency of alpha-galactosidase A. Lack of this enzyme leads to a progressive accumulation of glycosphingolipids, predominantly GL-3, in the vascular endothelium, leading to ischemia and infarction, especially in the kidney, heart, and brain. Clinical manifestations of Fabry's disease in childhood include intermittent severe pain in the extremities, characteristic vascular skin lesions (angiokeratomas), corneal and lenticular opacities that do not affect vision, decreased ability to sweat, intolerance to heat, cold, and exercise, mild proteinuria, and GI problems. By adulthood, this progresses to renal failure, cardiomyopathy, and cerebrovascular accidents.
PHARMACOKINETICS Distribution: Vd: Adults: 80-330 mL/kg
Half-life: Adults: 45-102 minutes (dose dependent)
ADDITIONAL INFORMATION — Agalsidase beta is an orphan drug; a Fabry Patient Support Group (800-745-4447) is available to assist patients in obtaining reimbursement from private insurers, Medicare, and Medicaid, and a Charitable Access Program sponsored by Genzyme provides the drug gratis to those patients in need. Detailed information regarding organizations and websites is also available in the Expert Panel Recommendations (Desnick, 2003)
Agalsidase bet
U.S. BRAND NAMES — Fabrazyme®
CANADIAN BRAND NAMES — Fabrazyme®
SYNONYMS — Fabrase; Recombinant Human Alpha-Galactosidase A
THERAPEUTIC CATEGORY Enzyme, alpha-galactosidase AFabry's Disease, Treatment Agent
DOSING — I.V.: Children and Adults: 1 mg/kg/dose every two weeks
(For additional information see "Agalsidase beta: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 5 mg [contains mannitol 33 mg; derived from Chinese hamster cells]; 35 mg [contains mannitol 222 mg/vial; derived from Chinese hamster cells]
GENERIC AVAILABLE — No
ADMINISTRATION — I.V.: Reconstitute vial with 7.2 mL SWI to result in 5 mg/mL concentration; swirl to dissolve; do not shake; further dilute dosage in 500 mL NS*. Initial infusion not to exceed 15 mg/hour (0.25 mg/minute); after patient tolerance to initial infusion rate is established, the infusion rate may be increased in increments of 3-5 mg/hour (0.05-0.08 mg/minute) with subsequent infusions. In clinical studies, patients have tolerated infusion rates 33 mg/hour. Pretreatment with acetaminophen and an antihistamine is recommended to reduce infusion related side effects (See Warnings)
*Agalsidase beta stability when diluted in NS at a concentration of 2.55 mg/mL has been demonstrated by the manufacturer. Infusion volumes as low as 100 mL were used in phase I/II clinical trials. (Personal communication, Genzyme Corporation, 2003)
USE — Treatment of Fabry's disease
ADVERSE REACTIONS Cardiovascular: Tachycardia, hypertension, hypotension, chest pain, chest tightness, bradycardia, arrhythmias, cardiac arrest, edema, pallor
Central nervous system: Headache, dizziness, fever, anxiety, depression, chills, rigors, vertigo
Dermatologic: Pruritus, urticaria
Gastrointestinal: Dyspepsia, nausea, abdominal pain, vomiting
Genitourinary: Testicular pain
Neuromuscular & skeletal: Arthrosis, skeletal pain, myalgia
Otic: Hypoacousia
Respiratory: Bronchitis, bronchospasm, laryngitis, pharyngitis, sinusitis, rhinitis, dyspnea
Miscellaneous: Hypersensitivity reactions
CONTRAINDICATIONS — Hypersensitivity to agalsidase beta or any component
PRECAUTIONS — Use with caution in patients with compromised cardiac function (seen in advanced Fabry's disease) due to an increased potential for severe infusion related reactions; monitor these patients closely; patients may develop IgG antibodies to agalsidase beta
WARNINGS — Infusion-related reactions (ranging from mild to severe) including fever, rigors, chest tightness, hypertension, hypotension, pruritus, myalgia, dyspnea, urticaria, abdominal pain, and headache have been reported; these reactions may be minimized by pretreatment with acetaminophen and an antihistamine; if an infusion related reaction occurs, regardless of pretreatment, decreasing the infusion rate, temporarily stopping the infusion, and/or additional administration of analgesics, antihistamines, or corticosteroids may ameliorate the reaction.
DRUG INTERACTIONS — None as yet have been identified
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — Vital signs during infusion; globotriaosylceramide (GL3) plasma levels; improvement in symptomatology
REFERENCE RANGE — Normal endogenous activity of alpha-galactosidase A in plasma is approximately 170 nmol/hour/mL; in patients with Fabry's disease this activity is <1.5 nmol/hour/mL
Normal (goal) globotriaosylceramide (GL3) <1.2 ng/microliter
STABILITY — Store in refrigerator 2ºC to 8ºC (36ºF to 46ºF); reconstituted solution is stable for 24 hours refrigerated
MECHANISM OF ACTION — Agalsidase beta is a recombinant human alpha-galactosidase A enzyme with the same amino acid sequence as the naturally-occurring enzyme. Fabry's disease is an X-linked genetic disorder occurring in 1 in 50,000 male births, which results in a deficiency of alpha-galactosidase A. Lack of this enzyme leads to a progressive accumulation of glycosphingolipids, predominantly GL-3, in the vascular endothelium, leading to ischemia and infarction, especially in the kidney, heart, and brain. Clinical manifestations of Fabry's disease in childhood include intermittent severe pain in the extremities, characteristic vascular skin lesions (angiokeratomas), corneal and lenticular opacities that do not affect vision, decreased ability to sweat, intolerance to heat, cold, and exercise, mild proteinuria, and GI problems. By adulthood, this progresses to renal failure, cardiomyopathy, and cerebrovascular accidents.
PHARMACOKINETICS Distribution: Vd: Adults: 80-330 mL/kg
Half-life: Adults: 45-102 minutes (dose dependent)
ADDITIONAL INFORMATION — Agalsidase beta is an orphan drug; a Fabry Patient Support Group (800-745-4447) is available to assist patients in obtaining reimbursement from private insurers, Medicare, and Medicaid, and a Charitable Access Program sponsored by Genzyme provides the drug gratis to those patients in need. Detailed information regarding organizations and websites is also available in the Expert Panel Recommendations (Desnick, 2003)
CANADIAN BRAND NAMES — Fabrazyme®
SYNONYMS — Fabrase; Recombinant Human Alpha-Galactosidase A
THERAPEUTIC CATEGORY Enzyme, alpha-galactosidase AFabry's Disease, Treatment Agent
DOSING — I.V.: Children and Adults: 1 mg/kg/dose every two weeks
(For additional information see "Agalsidase beta: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 5 mg [contains mannitol 33 mg; derived from Chinese hamster cells]; 35 mg [contains mannitol 222 mg/vial; derived from Chinese hamster cells]
GENERIC AVAILABLE — No
ADMINISTRATION — I.V.: Reconstitute vial with 7.2 mL SWI to result in 5 mg/mL concentration; swirl to dissolve; do not shake; further dilute dosage in 500 mL NS*. Initial infusion not to exceed 15 mg/hour (0.25 mg/minute); after patient tolerance to initial infusion rate is established, the infusion rate may be increased in increments of 3-5 mg/hour (0.05-0.08 mg/minute) with subsequent infusions. In clinical studies, patients have tolerated infusion rates 33 mg/hour. Pretreatment with acetaminophen and an antihistamine is recommended to reduce infusion related side effects (See Warnings)
*Agalsidase beta stability when diluted in NS at a concentration of 2.55 mg/mL has been demonstrated by the manufacturer. Infusion volumes as low as 100 mL were used in phase I/II clinical trials. (Personal communication, Genzyme Corporation, 2003)
USE — Treatment of Fabry's disease
ADVERSE REACTIONS Cardiovascular: Tachycardia, hypertension, hypotension, chest pain, chest tightness, bradycardia, arrhythmias, cardiac arrest, edema, pallor
Central nervous system: Headache, dizziness, fever, anxiety, depression, chills, rigors, vertigo
Dermatologic: Pruritus, urticaria
Gastrointestinal: Dyspepsia, nausea, abdominal pain, vomiting
Genitourinary: Testicular pain
Neuromuscular & skeletal: Arthrosis, skeletal pain, myalgia
Otic: Hypoacousia
Respiratory: Bronchitis, bronchospasm, laryngitis, pharyngitis, sinusitis, rhinitis, dyspnea
Miscellaneous: Hypersensitivity reactions
CONTRAINDICATIONS — Hypersensitivity to agalsidase beta or any component
PRECAUTIONS — Use with caution in patients with compromised cardiac function (seen in advanced Fabry's disease) due to an increased potential for severe infusion related reactions; monitor these patients closely; patients may develop IgG antibodies to agalsidase beta
WARNINGS — Infusion-related reactions (ranging from mild to severe) including fever, rigors, chest tightness, hypertension, hypotension, pruritus, myalgia, dyspnea, urticaria, abdominal pain, and headache have been reported; these reactions may be minimized by pretreatment with acetaminophen and an antihistamine; if an infusion related reaction occurs, regardless of pretreatment, decreasing the infusion rate, temporarily stopping the infusion, and/or additional administration of analgesics, antihistamines, or corticosteroids may ameliorate the reaction.
DRUG INTERACTIONS — None as yet have been identified
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — Vital signs during infusion; globotriaosylceramide (GL3) plasma levels; improvement in symptomatology
REFERENCE RANGE — Normal endogenous activity of alpha-galactosidase A in plasma is approximately 170 nmol/hour/mL; in patients with Fabry's disease this activity is <1.5 nmol/hour/mL
Normal (goal) globotriaosylceramide (GL3) <1.2 ng/microliter
STABILITY — Store in refrigerator 2ºC to 8ºC (36ºF to 46ºF); reconstituted solution is stable for 24 hours refrigerated
MECHANISM OF ACTION — Agalsidase beta is a recombinant human alpha-galactosidase A enzyme with the same amino acid sequence as the naturally-occurring enzyme. Fabry's disease is an X-linked genetic disorder occurring in 1 in 50,000 male births, which results in a deficiency of alpha-galactosidase A. Lack of this enzyme leads to a progressive accumulation of glycosphingolipids, predominantly GL-3, in the vascular endothelium, leading to ischemia and infarction, especially in the kidney, heart, and brain. Clinical manifestations of Fabry's disease in childhood include intermittent severe pain in the extremities, characteristic vascular skin lesions (angiokeratomas), corneal and lenticular opacities that do not affect vision, decreased ability to sweat, intolerance to heat, cold, and exercise, mild proteinuria, and GI problems. By adulthood, this progresses to renal failure, cardiomyopathy, and cerebrovascular accidents.
PHARMACOKINETICS Distribution: Vd: Adults: 80-330 mL/kg
Half-life: Adults: 45-102 minutes (dose dependent)
ADDITIONAL INFORMATION — Agalsidase beta is an orphan drug; a Fabry Patient Support Group (800-745-4447) is available to assist patients in obtaining reimbursement from private insurers, Medicare, and Medicaid, and a Charitable Access Program sponsored by Genzyme provides the drug gratis to those patients in need. Detailed information regarding organizations and websites is also available in the Expert Panel Recommendations (Desnick, 2003)
Adenosine
U.S. BRAND NAMES — Adenocard®; Adenoscan®
CANADIAN BRAND NAMES — Adenocard®; Adenoscan®; Adenosine Injection, USP
SYNONYMS — 9-Beta-D-ribofuranosyladenine
THERAPEUTIC CATEGORY Antiarrhythmic Agent, Miscellaneous
DOSING — Note: Adequate controlled studies in pediatric patients have not been conducted.
(For additional information see "Adenosine: Drug information")
Manufacturer's recommendations: Rapid I.V.: Neonates, Infants, Children, and Adolescents weighing <50 kg: Initial dose: 0.05-0.1 mg/kg; if not effective within 1-2 minutes, increase dose by 0.05-0.1 mg/kg increments every 1-2 minutes to a maximum single dose of 0.3 mg/kg or until termination of PSVT Children and Adolescents weighing 50 kg and Adults: 6 mg, if not effective within 1-2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed
Alternative pediatric dosing: Neonates: Rapid I.V.: Initial dose: 0.05 mg/kg; if not effective within 2 minutes, increase dose by 0.05 mg/kg increments every 2 minutes to a maximum dose of 0.25 mg/kg or until termination of PSVT Infants and Children: PALS dose for treatment of SVT: Rapid I.V.; I.O.: Initial: 0.1 mg/kg (maximum: 6 mg); if not effective, give 0.2 mg/kg (maximum: 12 mg)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL) Adenocard®: 3 mg/mL (2 mL, 4 mL) Adenoscan®: 3 mg/mL (20 mL, 30 mL)
GENERIC AVAILABLE — Yes
ADMINISTRATION — Parenteral: For rapid bolus I.V. use, administer over 1-2 seconds at peripheral I.V. site closest to patient's heart (I.V. administration into lower extremities may result in therapeutic failure or requirement of higher doses); follow each bolus with NS flush (infants and children: 5-10 mL; adults: 20 mL); if given peripherally in adults, elevate the extremity for 10-20 seconds after the NS flush. To administer doses <600 mcg (0.2 mL of commercial product), a dilution with NS (final concentration: 300 mcg/mL) may be made. Note: Preliminary results in adults suggest adenosine may be administered via a central line at lower doses (eg, Adults: Initial dose: 3 mg); FDA approved labeling for pediatric patients weighing <50 kg states that doses listed may be administered either peripherally or centrally (further studies are needed)
USE — Treatment of paroxysmal supraventricular tachycardia (PSVT); used in adult ACLS algorithms for narrow-complex tachycardias, stable narrow-complex supraventricular tachycardias, and wide-complex tachycardias that are supraventricular in origin; used in PALS algorithms for probable supraventricular tachycardia; investigationally used as a continuous infusion for the treatment of primary pulmonary hypertension in adults and persistent pulmonary hypertension of the newborn (PPHN) (see Additional Information)
ADVERSE REACTIONS Cardiovascular: Flushing, arrhythmias, palpitations, chest pain, bradycardia, heart block, minimal hemodynamic disturbances, hypotension (<1%)
Central nervous system: Irritability, headaches, lightheadedness, dizziness
Gastrointestinal: Nausea, metallic taste
Respiratory: Dyspnea, hyperventilation, bronchoconstriction in asthmatics
CONTRAINDICATIONS — Hypersensitivity to adenosine or any component; second and third degree A-V block or sick sinus syndrome unless pacemaker placed
PRECAUTIONS — Bronchoconstriction may occur in asthmatics (avoid use in patients with bronchospasm or bronchoconstriction); use with caution in patients with underlying dysfunction of sinus or A-V node, obstructive lung disease, and those taking digoxin or verapamil; initial adenosine dose should be significantly decreased in patients receiving dipyridamole
WARNINGS — Heart block, including transient or prolonged asystole may occur as well as other arrhythmias; episodes of asystole or other arrhythmias may be fatal; if arrhythmia is not due to re-entry pathway through A-V node or sinus node (ie, atrial fibrillation, flutter, or tachycardia or ventricular tachycardia), adenosine will not terminate the arrhythmia but can produce transient ventriculoatrial or A-V block; possible mutagenic effects
DRUG INTERACTIONS — Dipyridamole potentiates effects of adenosine (dose of adenosine should be significantly reduced); methylxanthines (aminophylline, theophylline, caffeine) antagonize adenosine's effects so that larger doses of adenosine or an alternative agent may be required; carbamazepine may increase heart block; digoxin and verapamil may cause ventricular fibrillation (rare cases reported)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Continuous EKG, heart rate, blood pressure, respirations
STABILITY — Do not refrigerate, precipitation may occur; contains no preservatives, discard unused portion
MECHANISM OF ACTION — Slows conduction time through the A-V node, interrupting the re-entry pathways through the A-V node, restoring normal sinus rhythm
PHARMACODYNAMICS Onset of action: Rapid
Duration: Very brief
PHARMACOKINETICS Metabolism: Removed from systemic circulation primarily by vascular endothelial cells and erythrocytes (by cellular uptake); rapidly metabolized intracellularly; phosphorylated by adenosine kinase to adenosine monophosphate (AMP) which is then incorporated into high-energy pool; intracellular adenosine is also deaminated by adenosine deaminase to inosine; inosine can be metabolized to hypoxanthine, then xanthine and finally to uric acid.
Half-life: <10 seconds
NURSING IMPLICATIONS — Be alert for dyspnea, shortness of breath, and possible exacerbation of asthma
ADDITIONAL INFORMATION — Not effective in atrial flutter, atrial fibrillation, or ventricular tachycardia; short duration of action is an advantage as adverse effects are usually rapidly self-limiting; effects may be prolonged in patients with denervated transplanted hearts. Individualize treatment of prolonged adverse effects: Give I.V. fluids for hypotension, aminophylline/theophylline may antagonize effects.
Limited information is available regarding the use of adenosine for the treatment of persistent pulmonary hypertension of the newborn (PPHN); efficacy, optimal dose, and duration of therapy is not established; a randomized, masked, placebo-controlled pilot study of 18 term infants with PPHN used initial doses of 25 mcg/kg/minute (n=9); after 30 minutes, doses were increased to 50 mcg/kg/minute if no improvement in PaO2 was observed; all patients received study drug via central line into the right atrium (inserted via the umbilical vein); significant improvement in oxygenation was observed in 4 of 9 newborns receiving 50 mcg/kg/minute; hypotension or tachycardia were not observed; further studies are needed (Kondur, 1996).
Adenosine is also available as Adenoscan®, which is used in adults as an adjunct to thallium-201 myocardial perfusion scintigraphy; see package insert for further information on this use.
CANADIAN BRAND NAMES — Adenocard®; Adenoscan®; Adenosine Injection, USP
SYNONYMS — 9-Beta-D-ribofuranosyladenine
THERAPEUTIC CATEGORY Antiarrhythmic Agent, Miscellaneous
DOSING — Note: Adequate controlled studies in pediatric patients have not been conducted.
(For additional information see "Adenosine: Drug information")
Manufacturer's recommendations: Rapid I.V.: Neonates, Infants, Children, and Adolescents weighing <50 kg: Initial dose: 0.05-0.1 mg/kg; if not effective within 1-2 minutes, increase dose by 0.05-0.1 mg/kg increments every 1-2 minutes to a maximum single dose of 0.3 mg/kg or until termination of PSVT Children and Adolescents weighing 50 kg and Adults: 6 mg, if not effective within 1-2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed
Alternative pediatric dosing: Neonates: Rapid I.V.: Initial dose: 0.05 mg/kg; if not effective within 2 minutes, increase dose by 0.05 mg/kg increments every 2 minutes to a maximum dose of 0.25 mg/kg or until termination of PSVT Infants and Children: PALS dose for treatment of SVT: Rapid I.V.; I.O.: Initial: 0.1 mg/kg (maximum: 6 mg); if not effective, give 0.2 mg/kg (maximum: 12 mg)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL) Adenocard®: 3 mg/mL (2 mL, 4 mL) Adenoscan®: 3 mg/mL (20 mL, 30 mL)
GENERIC AVAILABLE — Yes
ADMINISTRATION — Parenteral: For rapid bolus I.V. use, administer over 1-2 seconds at peripheral I.V. site closest to patient's heart (I.V. administration into lower extremities may result in therapeutic failure or requirement of higher doses); follow each bolus with NS flush (infants and children: 5-10 mL; adults: 20 mL); if given peripherally in adults, elevate the extremity for 10-20 seconds after the NS flush. To administer doses <600 mcg (0.2 mL of commercial product), a dilution with NS (final concentration: 300 mcg/mL) may be made. Note: Preliminary results in adults suggest adenosine may be administered via a central line at lower doses (eg, Adults: Initial dose: 3 mg); FDA approved labeling for pediatric patients weighing <50 kg states that doses listed may be administered either peripherally or centrally (further studies are needed)
USE — Treatment of paroxysmal supraventricular tachycardia (PSVT); used in adult ACLS algorithms for narrow-complex tachycardias, stable narrow-complex supraventricular tachycardias, and wide-complex tachycardias that are supraventricular in origin; used in PALS algorithms for probable supraventricular tachycardia; investigationally used as a continuous infusion for the treatment of primary pulmonary hypertension in adults and persistent pulmonary hypertension of the newborn (PPHN) (see Additional Information)
ADVERSE REACTIONS Cardiovascular: Flushing, arrhythmias, palpitations, chest pain, bradycardia, heart block, minimal hemodynamic disturbances, hypotension (<1%)
Central nervous system: Irritability, headaches, lightheadedness, dizziness
Gastrointestinal: Nausea, metallic taste
Respiratory: Dyspnea, hyperventilation, bronchoconstriction in asthmatics
CONTRAINDICATIONS — Hypersensitivity to adenosine or any component; second and third degree A-V block or sick sinus syndrome unless pacemaker placed
PRECAUTIONS — Bronchoconstriction may occur in asthmatics (avoid use in patients with bronchospasm or bronchoconstriction); use with caution in patients with underlying dysfunction of sinus or A-V node, obstructive lung disease, and those taking digoxin or verapamil; initial adenosine dose should be significantly decreased in patients receiving dipyridamole
WARNINGS — Heart block, including transient or prolonged asystole may occur as well as other arrhythmias; episodes of asystole or other arrhythmias may be fatal; if arrhythmia is not due to re-entry pathway through A-V node or sinus node (ie, atrial fibrillation, flutter, or tachycardia or ventricular tachycardia), adenosine will not terminate the arrhythmia but can produce transient ventriculoatrial or A-V block; possible mutagenic effects
DRUG INTERACTIONS — Dipyridamole potentiates effects of adenosine (dose of adenosine should be significantly reduced); methylxanthines (aminophylline, theophylline, caffeine) antagonize adenosine's effects so that larger doses of adenosine or an alternative agent may be required; carbamazepine may increase heart block; digoxin and verapamil may cause ventricular fibrillation (rare cases reported)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Continuous EKG, heart rate, blood pressure, respirations
STABILITY — Do not refrigerate, precipitation may occur; contains no preservatives, discard unused portion
MECHANISM OF ACTION — Slows conduction time through the A-V node, interrupting the re-entry pathways through the A-V node, restoring normal sinus rhythm
PHARMACODYNAMICS Onset of action: Rapid
Duration: Very brief
PHARMACOKINETICS Metabolism: Removed from systemic circulation primarily by vascular endothelial cells and erythrocytes (by cellular uptake); rapidly metabolized intracellularly; phosphorylated by adenosine kinase to adenosine monophosphate (AMP) which is then incorporated into high-energy pool; intracellular adenosine is also deaminated by adenosine deaminase to inosine; inosine can be metabolized to hypoxanthine, then xanthine and finally to uric acid.
Half-life: <10 seconds
NURSING IMPLICATIONS — Be alert for dyspnea, shortness of breath, and possible exacerbation of asthma
ADDITIONAL INFORMATION — Not effective in atrial flutter, atrial fibrillation, or ventricular tachycardia; short duration of action is an advantage as adverse effects are usually rapidly self-limiting; effects may be prolonged in patients with denervated transplanted hearts. Individualize treatment of prolonged adverse effects: Give I.V. fluids for hypotension, aminophylline/theophylline may antagonize effects.
Limited information is available regarding the use of adenosine for the treatment of persistent pulmonary hypertension of the newborn (PPHN); efficacy, optimal dose, and duration of therapy is not established; a randomized, masked, placebo-controlled pilot study of 18 term infants with PPHN used initial doses of 25 mcg/kg/minute (n=9); after 30 minutes, doses were increased to 50 mcg/kg/minute if no improvement in PaO2 was observed; all patients received study drug via central line into the right atrium (inserted via the umbilical vein); significant improvement in oxygenation was observed in 4 of 9 newborns receiving 50 mcg/kg/minute; hypotension or tachycardia were not observed; further studies are needed (Kondur, 1996).
Adenosine is also available as Adenoscan®, which is used in adults as an adjunct to thallium-201 myocardial perfusion scintigraphy; see package insert for further information on this use.
Adenosine
U.S. BRAND NAMES — Adenocard®; Adenoscan®
CANADIAN BRAND NAMES — Adenocard®; Adenoscan®; Adenosine Injection, USP
SYNONYMS — 9-Beta-D-ribofuranosyladenine
THERAPEUTIC CATEGORY Antiarrhythmic Agent, Miscellaneous
DOSING — Note: Adequate controlled studies in pediatric patients have not been conducted.
(For additional information see "Adenosine: Drug information")
Manufacturer's recommendations: Rapid I.V.: Neonates, Infants, Children, and Adolescents weighing <50 kg: Initial dose: 0.05-0.1 mg/kg; if not effective within 1-2 minutes, increase dose by 0.05-0.1 mg/kg increments every 1-2 minutes to a maximum single dose of 0.3 mg/kg or until termination of PSVT Children and Adolescents weighing 50 kg and Adults: 6 mg, if not effective within 1-2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed
Alternative pediatric dosing: Neonates: Rapid I.V.: Initial dose: 0.05 mg/kg; if not effective within 2 minutes, increase dose by 0.05 mg/kg increments every 2 minutes to a maximum dose of 0.25 mg/kg or until termination of PSVT Infants and Children: PALS dose for treatment of SVT: Rapid I.V.; I.O.: Initial: 0.1 mg/kg (maximum: 6 mg); if not effective, give 0.2 mg/kg (maximum: 12 mg)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL) Adenocard®: 3 mg/mL (2 mL, 4 mL) Adenoscan®: 3 mg/mL (20 mL, 30 mL)
GENERIC AVAILABLE — Yes
ADMINISTRATION — Parenteral: For rapid bolus I.V. use, administer over 1-2 seconds at peripheral I.V. site closest to patient's heart (I.V. administration into lower extremities may result in therapeutic failure or requirement of higher doses); follow each bolus with NS flush (infants and children: 5-10 mL; adults: 20 mL); if given peripherally in adults, elevate the extremity for 10-20 seconds after the NS flush. To administer doses <600 mcg (0.2 mL of commercial product), a dilution with NS (final concentration: 300 mcg/mL) may be made. Note: Preliminary results in adults suggest adenosine may be administered via a central line at lower doses (eg, Adults: Initial dose: 3 mg); FDA approved labeling for pediatric patients weighing <50 kg states that doses listed may be administered either peripherally or centrally (further studies are needed)
USE — Treatment of paroxysmal supraventricular tachycardia (PSVT); used in adult ACLS algorithms for narrow-complex tachycardias, stable narrow-complex supraventricular tachycardias, and wide-complex tachycardias that are supraventricular in origin; used in PALS algorithms for probable supraventricular tachycardia; investigationally used as a continuous infusion for the treatment of primary pulmonary hypertension in adults and persistent pulmonary hypertension of the newborn (PPHN) (see Additional Information)
ADVERSE REACTIONS Cardiovascular: Flushing, arrhythmias, palpitations, chest pain, bradycardia, heart block, minimal hemodynamic disturbances, hypotension (<1%)
Central nervous system: Irritability, headaches, lightheadedness, dizziness
Gastrointestinal: Nausea, metallic taste
Respiratory: Dyspnea, hyperventilation, bronchoconstriction in asthmatics
CONTRAINDICATIONS — Hypersensitivity to adenosine or any component; second and third degree A-V block or sick sinus syndrome unless pacemaker placed
PRECAUTIONS — Bronchoconstriction may occur in asthmatics (avoid use in patients with bronchospasm or bronchoconstriction); use with caution in patients with underlying dysfunction of sinus or A-V node, obstructive lung disease, and those taking digoxin or verapamil; initial adenosine dose should be significantly decreased in patients receiving dipyridamole
WARNINGS — Heart block, including transient or prolonged asystole may occur as well as other arrhythmias; episodes of asystole or other arrhythmias may be fatal; if arrhythmia is not due to re-entry pathway through A-V node or sinus node (ie, atrial fibrillation, flutter, or tachycardia or ventricular tachycardia), adenosine will not terminate the arrhythmia but can produce transient ventriculoatrial or A-V block; possible mutagenic effects
DRUG INTERACTIONS — Dipyridamole potentiates effects of adenosine (dose of adenosine should be significantly reduced); methylxanthines (aminophylline, theophylline, caffeine) antagonize adenosine's effects so that larger doses of adenosine or an alternative agent may be required; carbamazepine may increase heart block; digoxin and verapamil may cause ventricular fibrillation (rare cases reported)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Continuous EKG, heart rate, blood pressure, respirations
STABILITY — Do not refrigerate, precipitation may occur; contains no preservatives, discard unused portion
MECHANISM OF ACTION — Slows conduction time through the A-V node, interrupting the re-entry pathways through the A-V node, restoring normal sinus rhythm
PHARMACODYNAMICS Onset of action: Rapid
Duration: Very brief
PHARMACOKINETICS Metabolism: Removed from systemic circulation primarily by vascular endothelial cells and erythrocytes (by cellular uptake); rapidly metabolized intracellularly; phosphorylated by adenosine kinase to adenosine monophosphate (AMP) which is then incorporated into high-energy pool; intracellular adenosine is also deaminated by adenosine deaminase to inosine; inosine can be metabolized to hypoxanthine, then xanthine and finally to uric acid.
Half-life: <10 seconds
NURSING IMPLICATIONS — Be alert for dyspnea, shortness of breath, and possible exacerbation of asthma
ADDITIONAL INFORMATION — Not effective in atrial flutter, atrial fibrillation, or ventricular tachycardia; short duration of action is an advantage as adverse effects are usually rapidly self-limiting; effects may be prolonged in patients with denervated transplanted hearts. Individualize treatment of prolonged adverse effects: Give I.V. fluids for hypotension, aminophylline/theophylline may antagonize effects.
Limited information is available regarding the use of adenosine for the treatment of persistent pulmonary hypertension of the newborn (PPHN); efficacy, optimal dose, and duration of therapy is not established; a randomized, masked, placebo-controlled pilot study of 18 term infants with PPHN used initial doses of 25 mcg/kg/minute (n=9); after 30 minutes, doses were increased to 50 mcg/kg/minute if no improvement in PaO2 was observed; all patients received study drug via central line into the right atrium (inserted via the umbilical vein); significant improvement in oxygenation was observed in 4 of 9 newborns receiving 50 mcg/kg/minute; hypotension or tachycardia were not observed; further studies are needed (Kondur, 1996).
Adenosine is also available as Adenoscan®, which is used in adults as an adjunct to thallium-201 myocardial perfusion scintigraphy; see package insert for further information on this use.
CANADIAN BRAND NAMES — Adenocard®; Adenoscan®; Adenosine Injection, USP
SYNONYMS — 9-Beta-D-ribofuranosyladenine
THERAPEUTIC CATEGORY Antiarrhythmic Agent, Miscellaneous
DOSING — Note: Adequate controlled studies in pediatric patients have not been conducted.
(For additional information see "Adenosine: Drug information")
Manufacturer's recommendations: Rapid I.V.: Neonates, Infants, Children, and Adolescents weighing <50 kg: Initial dose: 0.05-0.1 mg/kg; if not effective within 1-2 minutes, increase dose by 0.05-0.1 mg/kg increments every 1-2 minutes to a maximum single dose of 0.3 mg/kg or until termination of PSVT Children and Adolescents weighing 50 kg and Adults: 6 mg, if not effective within 1-2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed
Alternative pediatric dosing: Neonates: Rapid I.V.: Initial dose: 0.05 mg/kg; if not effective within 2 minutes, increase dose by 0.05 mg/kg increments every 2 minutes to a maximum dose of 0.25 mg/kg or until termination of PSVT Infants and Children: PALS dose for treatment of SVT: Rapid I.V.; I.O.: Initial: 0.1 mg/kg (maximum: 6 mg); if not effective, give 0.2 mg/kg (maximum: 12 mg)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL) Adenocard®: 3 mg/mL (2 mL, 4 mL) Adenoscan®: 3 mg/mL (20 mL, 30 mL)
GENERIC AVAILABLE — Yes
ADMINISTRATION — Parenteral: For rapid bolus I.V. use, administer over 1-2 seconds at peripheral I.V. site closest to patient's heart (I.V. administration into lower extremities may result in therapeutic failure or requirement of higher doses); follow each bolus with NS flush (infants and children: 5-10 mL; adults: 20 mL); if given peripherally in adults, elevate the extremity for 10-20 seconds after the NS flush. To administer doses <600 mcg (0.2 mL of commercial product), a dilution with NS (final concentration: 300 mcg/mL) may be made. Note: Preliminary results in adults suggest adenosine may be administered via a central line at lower doses (eg, Adults: Initial dose: 3 mg); FDA approved labeling for pediatric patients weighing <50 kg states that doses listed may be administered either peripherally or centrally (further studies are needed)
USE — Treatment of paroxysmal supraventricular tachycardia (PSVT); used in adult ACLS algorithms for narrow-complex tachycardias, stable narrow-complex supraventricular tachycardias, and wide-complex tachycardias that are supraventricular in origin; used in PALS algorithms for probable supraventricular tachycardia; investigationally used as a continuous infusion for the treatment of primary pulmonary hypertension in adults and persistent pulmonary hypertension of the newborn (PPHN) (see Additional Information)
ADVERSE REACTIONS Cardiovascular: Flushing, arrhythmias, palpitations, chest pain, bradycardia, heart block, minimal hemodynamic disturbances, hypotension (<1%)
Central nervous system: Irritability, headaches, lightheadedness, dizziness
Gastrointestinal: Nausea, metallic taste
Respiratory: Dyspnea, hyperventilation, bronchoconstriction in asthmatics
CONTRAINDICATIONS — Hypersensitivity to adenosine or any component; second and third degree A-V block or sick sinus syndrome unless pacemaker placed
PRECAUTIONS — Bronchoconstriction may occur in asthmatics (avoid use in patients with bronchospasm or bronchoconstriction); use with caution in patients with underlying dysfunction of sinus or A-V node, obstructive lung disease, and those taking digoxin or verapamil; initial adenosine dose should be significantly decreased in patients receiving dipyridamole
WARNINGS — Heart block, including transient or prolonged asystole may occur as well as other arrhythmias; episodes of asystole or other arrhythmias may be fatal; if arrhythmia is not due to re-entry pathway through A-V node or sinus node (ie, atrial fibrillation, flutter, or tachycardia or ventricular tachycardia), adenosine will not terminate the arrhythmia but can produce transient ventriculoatrial or A-V block; possible mutagenic effects
DRUG INTERACTIONS — Dipyridamole potentiates effects of adenosine (dose of adenosine should be significantly reduced); methylxanthines (aminophylline, theophylline, caffeine) antagonize adenosine's effects so that larger doses of adenosine or an alternative agent may be required; carbamazepine may increase heart block; digoxin and verapamil may cause ventricular fibrillation (rare cases reported)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Continuous EKG, heart rate, blood pressure, respirations
STABILITY — Do not refrigerate, precipitation may occur; contains no preservatives, discard unused portion
MECHANISM OF ACTION — Slows conduction time through the A-V node, interrupting the re-entry pathways through the A-V node, restoring normal sinus rhythm
PHARMACODYNAMICS Onset of action: Rapid
Duration: Very brief
PHARMACOKINETICS Metabolism: Removed from systemic circulation primarily by vascular endothelial cells and erythrocytes (by cellular uptake); rapidly metabolized intracellularly; phosphorylated by adenosine kinase to adenosine monophosphate (AMP) which is then incorporated into high-energy pool; intracellular adenosine is also deaminated by adenosine deaminase to inosine; inosine can be metabolized to hypoxanthine, then xanthine and finally to uric acid.
Half-life: <10 seconds
NURSING IMPLICATIONS — Be alert for dyspnea, shortness of breath, and possible exacerbation of asthma
ADDITIONAL INFORMATION — Not effective in atrial flutter, atrial fibrillation, or ventricular tachycardia; short duration of action is an advantage as adverse effects are usually rapidly self-limiting; effects may be prolonged in patients with denervated transplanted hearts. Individualize treatment of prolonged adverse effects: Give I.V. fluids for hypotension, aminophylline/theophylline may antagonize effects.
Limited information is available regarding the use of adenosine for the treatment of persistent pulmonary hypertension of the newborn (PPHN); efficacy, optimal dose, and duration of therapy is not established; a randomized, masked, placebo-controlled pilot study of 18 term infants with PPHN used initial doses of 25 mcg/kg/minute (n=9); after 30 minutes, doses were increased to 50 mcg/kg/minute if no improvement in PaO2 was observed; all patients received study drug via central line into the right atrium (inserted via the umbilical vein); significant improvement in oxygenation was observed in 4 of 9 newborns receiving 50 mcg/kg/minute; hypotension or tachycardia were not observed; further studies are needed (Kondur, 1996).
Adenosine is also available as Adenoscan®, which is used in adults as an adjunct to thallium-201 myocardial perfusion scintigraphy; see package insert for further information on this use.
Adapalene
U.S. BRAND NAMES — Differin®
CANADIAN BRAND NAMES — Differin® XP; Differin®
SYNONYMS — CD271
THERAPEUTIC CATEGORY Acne Products
DOSING — Topical: Children >12 years and Adults: Apply topically once daily in the evening
(For additional information see "Adapalene: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Cream, topical: 0.1% (15 g, 45 g)
Gel, topical: 0.1% (15 g, 45 g) [alcohol free]
Pledget, topical: 0.1% (60s) [DSC]
Solution, topical: 0.1% (30 mL) [DSC]
GENERIC AVAILABLE — No
ADMINISTRATION — Topical: After cleansing the affected area with mild or soapless cleanser, using gloves, apply a thin film of medication (cream or gel) before retiring in the evening. Avoid contact with eyes, angles of the nose, lips and mucous membranes.
USE — Topical treatment of acne vulgaris
ADVERSE REACTIONS Dermatologic: Erythema, scaling, dry skin, skin irritation, pruritus, acne flares, photosensitivity, sunburn, skin discoloration
Local: Pruritus or burning immediately after application
Ophthalmic: Eyelid edema, conjunctivitis
CONTRAINDICATIONS — Hypersensitivity to adapalene or any component; sunburn
PRECAUTIONS — Use with caution in patients with eczema
WARNINGS — Avoid excessive exposure to sunlight and sunlamps; avoid contact with abraded skin, mucous membranes, eyes, mouth, or angles of the nose
DRUG INTERACTIONS — Topical sulfur, benzoyl peroxide, salicylic acid, and resorcinol potentiate adverse reactions seen with adapalene; other topical products containing alcohol, astringents, or lime may increase drying effects
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Reduction in lesion size and/or inflammation; reduction in the number of lesions
STABILITY — Store at controlled room temperature
MECHANISM OF ACTION — Retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris
PHARMACODYNAMICS — Onset of action: 8-12 weeks
PHARMACOKINETICS Absorption: Absorption through the skin is very low; only trace amounts have been measured in serum after chronic application
Elimination: Primarily in bile
PATIENT INFORMATION — For external use only; apply using gloves; avoid contact with eyes, mouth, mucous membranes, or open wounds. Do not apply occlusive dressing. Moisturizers may be used if necessary; however, products containing alpha hydroxy or glycolic acids should be avoided. Wax epilation should not be performed on treated skin due to the potential for skin erosions. Transient burning or stinging immediately after applying may occur. Mild to moderate redness, dryness, scaling, burning or itching are likely to occur during the first 2-4 weeks and will usually lessen with continued use; report worsening of condition or skin redness, dryness, peeling, or burning that persists between applications to the healthcare provider. May cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid exposure to sunlight and artificial light sources (sunlamps, tanning booth/bed); wear protective clothing, wide-brimmed hats, sunglasses, and lip sunscreen (SPF 15); use a sunscreen [broad-spectrum sunscreen or physical sunscreen(preferred) or sunblock with SPF 15]; contact physician if reaction occurs.
CANADIAN BRAND NAMES — Differin® XP; Differin®
SYNONYMS — CD271
THERAPEUTIC CATEGORY Acne Products
DOSING — Topical: Children >12 years and Adults: Apply topically once daily in the evening
(For additional information see "Adapalene: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Cream, topical: 0.1% (15 g, 45 g)
Gel, topical: 0.1% (15 g, 45 g) [alcohol free]
Pledget, topical: 0.1% (60s) [DSC]
Solution, topical: 0.1% (30 mL) [DSC]
GENERIC AVAILABLE — No
ADMINISTRATION — Topical: After cleansing the affected area with mild or soapless cleanser, using gloves, apply a thin film of medication (cream or gel) before retiring in the evening. Avoid contact with eyes, angles of the nose, lips and mucous membranes.
USE — Topical treatment of acne vulgaris
ADVERSE REACTIONS Dermatologic: Erythema, scaling, dry skin, skin irritation, pruritus, acne flares, photosensitivity, sunburn, skin discoloration
Local: Pruritus or burning immediately after application
Ophthalmic: Eyelid edema, conjunctivitis
CONTRAINDICATIONS — Hypersensitivity to adapalene or any component; sunburn
PRECAUTIONS — Use with caution in patients with eczema
WARNINGS — Avoid excessive exposure to sunlight and sunlamps; avoid contact with abraded skin, mucous membranes, eyes, mouth, or angles of the nose
DRUG INTERACTIONS — Topical sulfur, benzoyl peroxide, salicylic acid, and resorcinol potentiate adverse reactions seen with adapalene; other topical products containing alcohol, astringents, or lime may increase drying effects
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Reduction in lesion size and/or inflammation; reduction in the number of lesions
STABILITY — Store at controlled room temperature
MECHANISM OF ACTION — Retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris
PHARMACODYNAMICS — Onset of action: 8-12 weeks
PHARMACOKINETICS Absorption: Absorption through the skin is very low; only trace amounts have been measured in serum after chronic application
Elimination: Primarily in bile
PATIENT INFORMATION — For external use only; apply using gloves; avoid contact with eyes, mouth, mucous membranes, or open wounds. Do not apply occlusive dressing. Moisturizers may be used if necessary; however, products containing alpha hydroxy or glycolic acids should be avoided. Wax epilation should not be performed on treated skin due to the potential for skin erosions. Transient burning or stinging immediately after applying may occur. Mild to moderate redness, dryness, scaling, burning or itching are likely to occur during the first 2-4 weeks and will usually lessen with continued use; report worsening of condition or skin redness, dryness, peeling, or burning that persists between applications to the healthcare provider. May cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid exposure to sunlight and artificial light sources (sunlamps, tanning booth/bed); wear protective clothing, wide-brimmed hats, sunglasses, and lip sunscreen (SPF 15); use a sunscreen [broad-spectrum sunscreen or physical sunscreen(preferred) or sunblock with SPF 15]; contact physician if reaction occurs.
Adapalene
U.S. BRAND NAMES — Differin®
CANADIAN BRAND NAMES — Differin® XP; Differin®
SYNONYMS — CD271
THERAPEUTIC CATEGORY Acne Products
DOSING — Topical: Children >12 years and Adults: Apply topically once daily in the evening
(For additional information see "Adapalene: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Cream, topical: 0.1% (15 g, 45 g)
Gel, topical: 0.1% (15 g, 45 g) [alcohol free]
Pledget, topical: 0.1% (60s) [DSC]
Solution, topical: 0.1% (30 mL) [DSC]
GENERIC AVAILABLE — No
ADMINISTRATION — Topical: After cleansing the affected area with mild or soapless cleanser, using gloves, apply a thin film of medication (cream or gel) before retiring in the evening. Avoid contact with eyes, angles of the nose, lips and mucous membranes.
USE — Topical treatment of acne vulgaris
ADVERSE REACTIONS Dermatologic: Erythema, scaling, dry skin, skin irritation, pruritus, acne flares, photosensitivity, sunburn, skin discoloration
Local: Pruritus or burning immediately after application
Ophthalmic: Eyelid edema, conjunctivitis
CONTRAINDICATIONS — Hypersensitivity to adapalene or any component; sunburn
PRECAUTIONS — Use with caution in patients with eczema
WARNINGS — Avoid excessive exposure to sunlight and sunlamps; avoid contact with abraded skin, mucous membranes, eyes, mouth, or angles of the nose
DRUG INTERACTIONS — Topical sulfur, benzoyl peroxide, salicylic acid, and resorcinol potentiate adverse reactions seen with adapalene; other topical products containing alcohol, astringents, or lime may increase drying effects
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Reduction in lesion size and/or inflammation; reduction in the number of lesions
STABILITY — Store at controlled room temperature
MECHANISM OF ACTION — Retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris
PHARMACODYNAMICS — Onset of action: 8-12 weeks
PHARMACOKINETICS Absorption: Absorption through the skin is very low; only trace amounts have been measured in serum after chronic application
Elimination: Primarily in bile
PATIENT INFORMATION — For external use only; apply using gloves; avoid contact with eyes, mouth, mucous membranes, or open wounds. Do not apply occlusive dressing. Moisturizers may be used if necessary; however, products containing alpha hydroxy or glycolic acids should be avoided. Wax epilation should not be performed on treated skin due to the potential for skin erosions. Transient burning or stinging immediately after applying may occur. Mild to moderate redness, dryness, scaling, burning or itching are likely to occur during the first 2-4 weeks and will usually lessen with continued use; report worsening of condition or skin redness, dryness, peeling, or burning that persists between applications to the healthcare provider. May cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid exposure to sunlight and artificial light sources (sunlamps, tanning booth/bed); wear protective clothing, wide-brimmed hats, sunglasses, and lip sunscreen (SPF 15); use a sunscreen [broad-spectrum sunscreen or physical sunscreen(preferred) or sunblock with SPF 15]; contact physician if reaction occurs.
CANADIAN BRAND NAMES — Differin® XP; Differin®
SYNONYMS — CD271
THERAPEUTIC CATEGORY Acne Products
DOSING — Topical: Children >12 years and Adults: Apply topically once daily in the evening
(For additional information see "Adapalene: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Cream, topical: 0.1% (15 g, 45 g)
Gel, topical: 0.1% (15 g, 45 g) [alcohol free]
Pledget, topical: 0.1% (60s) [DSC]
Solution, topical: 0.1% (30 mL) [DSC]
GENERIC AVAILABLE — No
ADMINISTRATION — Topical: After cleansing the affected area with mild or soapless cleanser, using gloves, apply a thin film of medication (cream or gel) before retiring in the evening. Avoid contact with eyes, angles of the nose, lips and mucous membranes.
USE — Topical treatment of acne vulgaris
ADVERSE REACTIONS Dermatologic: Erythema, scaling, dry skin, skin irritation, pruritus, acne flares, photosensitivity, sunburn, skin discoloration
Local: Pruritus or burning immediately after application
Ophthalmic: Eyelid edema, conjunctivitis
CONTRAINDICATIONS — Hypersensitivity to adapalene or any component; sunburn
PRECAUTIONS — Use with caution in patients with eczema
WARNINGS — Avoid excessive exposure to sunlight and sunlamps; avoid contact with abraded skin, mucous membranes, eyes, mouth, or angles of the nose
DRUG INTERACTIONS — Topical sulfur, benzoyl peroxide, salicylic acid, and resorcinol potentiate adverse reactions seen with adapalene; other topical products containing alcohol, astringents, or lime may increase drying effects
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Reduction in lesion size and/or inflammation; reduction in the number of lesions
STABILITY — Store at controlled room temperature
MECHANISM OF ACTION — Retinoid-like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris
PHARMACODYNAMICS — Onset of action: 8-12 weeks
PHARMACOKINETICS Absorption: Absorption through the skin is very low; only trace amounts have been measured in serum after chronic application
Elimination: Primarily in bile
PATIENT INFORMATION — For external use only; apply using gloves; avoid contact with eyes, mouth, mucous membranes, or open wounds. Do not apply occlusive dressing. Moisturizers may be used if necessary; however, products containing alpha hydroxy or glycolic acids should be avoided. Wax epilation should not be performed on treated skin due to the potential for skin erosions. Transient burning or stinging immediately after applying may occur. Mild to moderate redness, dryness, scaling, burning or itching are likely to occur during the first 2-4 weeks and will usually lessen with continued use; report worsening of condition or skin redness, dryness, peeling, or burning that persists between applications to the healthcare provider. May cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid exposure to sunlight and artificial light sources (sunlamps, tanning booth/bed); wear protective clothing, wide-brimmed hats, sunglasses, and lip sunscreen (SPF 15); use a sunscreen [broad-spectrum sunscreen or physical sunscreen(preferred) or sunblock with SPF 15]; contact physician if reaction occurs.
Acyclovir
U.S. BRAND NAMES — Zovirax®
CANADIAN BRAND NAMES — Apo-Acyclovir®; Gen-Acyclovir; Nu-Acyclovir; ratio-Acyclovir; Zovirax®
SYNONYMS — Aciclovir; ACV; Acycloguanosine
THERAPEUTIC CATEGORY Antiviral Agent, OralAntiviral Agent, ParenteralAntiviral Agent, Topical
DOSING
(For additional information see "Acyclovir: Drug information")Genital herpes simplex virus (HSV): First infection: Oral: Children: 40-80 mg/kg/day in 3-4 divided doses for 5-10 days; maximum dose: 1 g/day Adolescents and Adults: 200 mg 5 times/day or 400 mg 3 times/day for 5-10 days I.V.: Children and Adults: 5 mg/kg/dose every 8 hours for 5-7 days
Genital HSV infection: Recurrence: Oral: Adolescents and Adults: 200 mg 5 times/day or 400 mg 3 times/day for 5 days
Recurrent genital and cutaneous (ocular) HSV episodes in a patient with frequent recurrences, chronic suppressive therapy: Oral: Children: 40-80 mg/kg/day in 3 divided doses for up to 12 months; maximum dose: 1 g/day; re-evaluate after 12 months of treatment Adolescents and Adults: 400 mg twice daily or 400 mg 3 times/day or 200 mg 3 times/day for as long as 12 continuous months; re-evaluate after 12 months of treatment
HSV in immunocompromised host: Oral: Children:1000 mg/day in 3-5 divided doses for 7-14 days; maximum dose: 80 mg/kg/day not to exceed 1 g/day Adults: 400 mg 5 times/day for 7-14 days I.V.: Children <12 years: 10 mg/kg/dose every 8 hours for 7-14 days Children 12 years and Adults: 5 mg/kg/dose every 8 hours for 7-14 days
Prophylaxis of HSV in immunocompromised host: Oral: Children and Adults: 600-1000 mg/day in 3-5 divided doses during period of risk; maximum dose in children: 80 mg/kg/day not to exceed 1 g/day
HSV encephalitis: I.V.: Children 3 months to 12 years: 20 mg/kg/dose every 8 hours; some clinicians recommend 500 mg/m2/dose every 8 hours for 14-21 days Children >12 years and Adults: 10-15 mg/kg/dose every 8 hours for 14-21 days
Neonatal HSV: I.V.: 20 mg/kg/dose every 8 hours for 14-21 days
Varicella-zoster in immunocompromised host: I.V.: Infants <1 year: 10 mg/kg/dose every 8 hours for 7-10 days Children 1 year: 500 mg/m2/dose every 8 hours for 7-10 days or 10 mg/kg/dose every 8 hours for 7-10 days
Varicella in immunocompetent host: Oral (initiate treatment within the first 24 hours of rash onset): Children 2 years and 40 kg: 20 mg/kg/dose 4 times/day for 5 days; maximum dose: 3200 mg/day Children >40 kg and Adults: 800 mg 4 times/day for 5 days
Zoster in immunocompetent host: Oral (initiate treatment within 48 hours of rash onset): Children 12 years and Adults: 800 mg 5 times/day for 7-10 days
Prophylaxis in bone marrow transplant recipients: I.V.: Autologous patients who are HSV-seropositive: 250 mg/m2/dose every 8 hours Autologous patients who are CMV seropositive: 500 mg/m2/dose every 8 hours; for clinically symptomatic CMV infection, consider replacing acyclovir with ganciclovir
Children and Adults: Topical: Apply 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Dosing interval in renal impairment: Neonates: I.V.: Scr 0.8-1.1 mg/dL: Administer 20 mg/kg/dose every 12 hours Scr 1.2-1.5 mg/dL: Administer 20 mg/kg/dose every 24 hours Scr >1.5 mg/dL: Administer 10 mg/kg/dose every 24 hours Children 6 months and Adults: Oral:
Usual dose: 200 mg 5 times/day: Adjusted dose for Clcr <10 mL/minute: 200 mg every 12 hours Usual dose: 800 mg 5 times/day: Adjusted dose for Clcr 10-25 mL/minute: 800 mg every 8 hours Adjusted dose for Clcr <10 mL/minute: 800 mg every 12 hours I.V.: Clcr 25-50 mL/minute: Administer normal dose every 12 hours Clcr 10-25 mL/minute: Administer normal dose every 24 hours Clcr <10 mL/minute: 50% decrease in dose, administer every 24 hours Hemodialysis: Administer dose after dialysis CVVHD/CVVH: Adjust dose based upon Clcr 30 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution, as sodium: 500 mg, 1000 mg Zovirax®: 500 mg [DSC]
Injection, solution, as sodium [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL (480 mL) Zovirax®: 200 mg/5 mL (480 mL) [banana flavor]
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
GENERIC AVAILABLE — Yes: Excludes cream, ointment
ADMINISTRATION Oral: May administer with food; shake suspension well before use
Parenteral: Reconstitute vial for injection with paraben-free SWI; administer by slow I.V. infusion over at least 1 hour at a final concentration not to exceed 7 mg/mL since rapid infusions can cause nephrotoxicity with crystalluria and renal tubular damage; in patients who require fluid restriction, a concentration of up to 10 mg/mL has been infused; concentration >10 mg/mL increases the risk of phlebitis
USE — Treatment of initial and prophylaxis of recurrent mucosal and cutaneous herpes simplex (HSV 1 and HSV 2) infections; herpes simplex encephalitis; herpes zoster infections; varicella-zoster infections in healthy, nonpregnant persons >13 years of age, children >12 months of age who have a chronic skin or lung disorder or are receiving long-term aspirin therapy, and immunocompromised patients
ADVERSE REACTIONS Central nervous system: Headache, lethargy, delirium, coma, dizziness, seizures, pain, insomnia, fever, hallucinations, aggressive behavior, ataxia
Dermatologic: Skin rash, pruritus, alopecia, erythema multiforme, urticaria, photosensitivity, Stevens-Johnson syndrome, angioedema
Gastrointestinal: Nausea, vomiting, diarrhea
Hematologic: Bone marrow suppression, neutropenia, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
Hepatic: Elevated liver enzymes, hepatitis, jaundice, hyperbilirubinemia
Local: Phlebitis at injection site, tissue necrosis upon extravasation, local pain and stinging with topical use
Neuromuscular & skeletal: Tremulousness, myalgia, paresthesia
Renal: Nephrotoxicity, hematuria, elevated BUN and serum creatinine
Respiratory: Sore throat
Miscellaneous: Diaphoresis, anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acyclovir, valacyclovir, or any component
PRECAUTIONS — Use with caution in patients with renal disease, dehydration, underlying neurologic disease, and in patients with hypoxia, hepatic, or electrolyte abnormalities; dosage should be reduced in patients with renal impairment
WARNINGS — HSV and VZV with reduced susceptibility to acyclovir have been isolated from immunocompromised patients, especially with advanced HIV infection; renal failure, in some cases resulting in death, has occurred with acyclovir
DRUG INTERACTIONS — Zidovudine (neurotoxicity); probenecid decreases renal clearance of acyclovir
FOOD INTERACTIONS — Food does not appear to affect absorption
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, I & O; liver enzymes, CBC; neutrophil count at least twice weekly in neonates receiving acyclovir 60 mg/kg/day I.V.
STABILITY — Incompatible with blood products and protein-containing solutions; reconstituted 50 mg/mL solution should be used within 12 hours; do not refrigerate reconstituted solutions as they may precipitate
MECHANISM OF ACTION — Inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and by incorporation into viral DNA
PHARMACOKINETICS Absorption: Oral: 15% to 30%
Distribution: Widely distributed throughout the body including brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, and the CSF; CSF acyclovir concentration is 50% of serum concentration; crosses the placenta; excreted into breast milk; Vd: Neonates to 3 months of age: 28.8 L/1.73 m2 Children 1-2 years: 31.6 L/1.73 m2 Children 2-7 years: 42 L/1.73 m2
Protein binding: <30%
Half-life, terminal phase: Neonates: 4 hours Children 1-12 years: 2-3 hours Adults: 2-3.5 hours (with normal renal function)
Time to peak serum concentration: Oral: Within 1.5-2 hours
Elimination: Primary route is the kidney with 30% to 90% of a dose excreted unchanged in the urine; requires dosage adjustment with renal impairment; hemodialysis removes ~60% of a dose while removal by peritoneal dialysis is to a much lesser extent; supplemental dose recommended after hemodialysis
NURSING IMPLICATIONS — Maintain adequate hydration and urine output the first 2 hours after I.V. infusion to decrease the risk of nephrotoxicity; check infusion site for phlebitis; avoid extravasation
ADDITIONAL INFORMATION — Sodium content of 1 g: 4.2 mEq
CANADIAN BRAND NAMES — Apo-Acyclovir®; Gen-Acyclovir; Nu-Acyclovir; ratio-Acyclovir; Zovirax®
SYNONYMS — Aciclovir; ACV; Acycloguanosine
THERAPEUTIC CATEGORY Antiviral Agent, OralAntiviral Agent, ParenteralAntiviral Agent, Topical
DOSING
(For additional information see "Acyclovir: Drug information")Genital herpes simplex virus (HSV): First infection: Oral: Children: 40-80 mg/kg/day in 3-4 divided doses for 5-10 days; maximum dose: 1 g/day Adolescents and Adults: 200 mg 5 times/day or 400 mg 3 times/day for 5-10 days I.V.: Children and Adults: 5 mg/kg/dose every 8 hours for 5-7 days
Genital HSV infection: Recurrence: Oral: Adolescents and Adults: 200 mg 5 times/day or 400 mg 3 times/day for 5 days
Recurrent genital and cutaneous (ocular) HSV episodes in a patient with frequent recurrences, chronic suppressive therapy: Oral: Children: 40-80 mg/kg/day in 3 divided doses for up to 12 months; maximum dose: 1 g/day; re-evaluate after 12 months of treatment Adolescents and Adults: 400 mg twice daily or 400 mg 3 times/day or 200 mg 3 times/day for as long as 12 continuous months; re-evaluate after 12 months of treatment
HSV in immunocompromised host: Oral: Children:1000 mg/day in 3-5 divided doses for 7-14 days; maximum dose: 80 mg/kg/day not to exceed 1 g/day Adults: 400 mg 5 times/day for 7-14 days I.V.: Children <12 years: 10 mg/kg/dose every 8 hours for 7-14 days Children 12 years and Adults: 5 mg/kg/dose every 8 hours for 7-14 days
Prophylaxis of HSV in immunocompromised host: Oral: Children and Adults: 600-1000 mg/day in 3-5 divided doses during period of risk; maximum dose in children: 80 mg/kg/day not to exceed 1 g/day
HSV encephalitis: I.V.: Children 3 months to 12 years: 20 mg/kg/dose every 8 hours; some clinicians recommend 500 mg/m2/dose every 8 hours for 14-21 days Children >12 years and Adults: 10-15 mg/kg/dose every 8 hours for 14-21 days
Neonatal HSV: I.V.: 20 mg/kg/dose every 8 hours for 14-21 days
Varicella-zoster in immunocompromised host: I.V.: Infants <1 year: 10 mg/kg/dose every 8 hours for 7-10 days Children 1 year: 500 mg/m2/dose every 8 hours for 7-10 days or 10 mg/kg/dose every 8 hours for 7-10 days
Varicella in immunocompetent host: Oral (initiate treatment within the first 24 hours of rash onset): Children 2 years and 40 kg: 20 mg/kg/dose 4 times/day for 5 days; maximum dose: 3200 mg/day Children >40 kg and Adults: 800 mg 4 times/day for 5 days
Zoster in immunocompetent host: Oral (initiate treatment within 48 hours of rash onset): Children 12 years and Adults: 800 mg 5 times/day for 7-10 days
Prophylaxis in bone marrow transplant recipients: I.V.: Autologous patients who are HSV-seropositive: 250 mg/m2/dose every 8 hours Autologous patients who are CMV seropositive: 500 mg/m2/dose every 8 hours; for clinically symptomatic CMV infection, consider replacing acyclovir with ganciclovir
Children and Adults: Topical: Apply 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Dosing interval in renal impairment: Neonates: I.V.: Scr 0.8-1.1 mg/dL: Administer 20 mg/kg/dose every 12 hours Scr 1.2-1.5 mg/dL: Administer 20 mg/kg/dose every 24 hours Scr >1.5 mg/dL: Administer 10 mg/kg/dose every 24 hours Children 6 months and Adults: Oral:
Usual dose: 200 mg 5 times/day: Adjusted dose for Clcr <10 mL/minute: 200 mg every 12 hours Usual dose: 800 mg 5 times/day: Adjusted dose for Clcr 10-25 mL/minute: 800 mg every 8 hours Adjusted dose for Clcr <10 mL/minute: 800 mg every 12 hours I.V.: Clcr 25-50 mL/minute: Administer normal dose every 12 hours Clcr 10-25 mL/minute: Administer normal dose every 24 hours Clcr <10 mL/minute: 50% decrease in dose, administer every 24 hours Hemodialysis: Administer dose after dialysis CVVHD/CVVH: Adjust dose based upon Clcr 30 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution, as sodium: 500 mg, 1000 mg Zovirax®: 500 mg [DSC]
Injection, solution, as sodium [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL (480 mL) Zovirax®: 200 mg/5 mL (480 mL) [banana flavor]
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
GENERIC AVAILABLE — Yes: Excludes cream, ointment
ADMINISTRATION Oral: May administer with food; shake suspension well before use
Parenteral: Reconstitute vial for injection with paraben-free SWI; administer by slow I.V. infusion over at least 1 hour at a final concentration not to exceed 7 mg/mL since rapid infusions can cause nephrotoxicity with crystalluria and renal tubular damage; in patients who require fluid restriction, a concentration of up to 10 mg/mL has been infused; concentration >10 mg/mL increases the risk of phlebitis
USE — Treatment of initial and prophylaxis of recurrent mucosal and cutaneous herpes simplex (HSV 1 and HSV 2) infections; herpes simplex encephalitis; herpes zoster infections; varicella-zoster infections in healthy, nonpregnant persons >13 years of age, children >12 months of age who have a chronic skin or lung disorder or are receiving long-term aspirin therapy, and immunocompromised patients
ADVERSE REACTIONS Central nervous system: Headache, lethargy, delirium, coma, dizziness, seizures, pain, insomnia, fever, hallucinations, aggressive behavior, ataxia
Dermatologic: Skin rash, pruritus, alopecia, erythema multiforme, urticaria, photosensitivity, Stevens-Johnson syndrome, angioedema
Gastrointestinal: Nausea, vomiting, diarrhea
Hematologic: Bone marrow suppression, neutropenia, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
Hepatic: Elevated liver enzymes, hepatitis, jaundice, hyperbilirubinemia
Local: Phlebitis at injection site, tissue necrosis upon extravasation, local pain and stinging with topical use
Neuromuscular & skeletal: Tremulousness, myalgia, paresthesia
Renal: Nephrotoxicity, hematuria, elevated BUN and serum creatinine
Respiratory: Sore throat
Miscellaneous: Diaphoresis, anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acyclovir, valacyclovir, or any component
PRECAUTIONS — Use with caution in patients with renal disease, dehydration, underlying neurologic disease, and in patients with hypoxia, hepatic, or electrolyte abnormalities; dosage should be reduced in patients with renal impairment
WARNINGS — HSV and VZV with reduced susceptibility to acyclovir have been isolated from immunocompromised patients, especially with advanced HIV infection; renal failure, in some cases resulting in death, has occurred with acyclovir
DRUG INTERACTIONS — Zidovudine (neurotoxicity); probenecid decreases renal clearance of acyclovir
FOOD INTERACTIONS — Food does not appear to affect absorption
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, I & O; liver enzymes, CBC; neutrophil count at least twice weekly in neonates receiving acyclovir 60 mg/kg/day I.V.
STABILITY — Incompatible with blood products and protein-containing solutions; reconstituted 50 mg/mL solution should be used within 12 hours; do not refrigerate reconstituted solutions as they may precipitate
MECHANISM OF ACTION — Inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and by incorporation into viral DNA
PHARMACOKINETICS Absorption: Oral: 15% to 30%
Distribution: Widely distributed throughout the body including brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, and the CSF; CSF acyclovir concentration is 50% of serum concentration; crosses the placenta; excreted into breast milk; Vd: Neonates to 3 months of age: 28.8 L/1.73 m2 Children 1-2 years: 31.6 L/1.73 m2 Children 2-7 years: 42 L/1.73 m2
Protein binding: <30%
Half-life, terminal phase: Neonates: 4 hours Children 1-12 years: 2-3 hours Adults: 2-3.5 hours (with normal renal function)
Time to peak serum concentration: Oral: Within 1.5-2 hours
Elimination: Primary route is the kidney with 30% to 90% of a dose excreted unchanged in the urine; requires dosage adjustment with renal impairment; hemodialysis removes ~60% of a dose while removal by peritoneal dialysis is to a much lesser extent; supplemental dose recommended after hemodialysis
NURSING IMPLICATIONS — Maintain adequate hydration and urine output the first 2 hours after I.V. infusion to decrease the risk of nephrotoxicity; check infusion site for phlebitis; avoid extravasation
ADDITIONAL INFORMATION — Sodium content of 1 g: 4.2 mEq
Acyclovir
U.S. BRAND NAMES — Zovirax®
CANADIAN BRAND NAMES — Apo-Acyclovir®; Gen-Acyclovir; Nu-Acyclovir; ratio-Acyclovir; Zovirax®
SYNONYMS — Aciclovir; ACV; Acycloguanosine
THERAPEUTIC CATEGORY Antiviral Agent, OralAntiviral Agent, ParenteralAntiviral Agent, Topical
DOSING
(For additional information see "Acyclovir: Drug information")Genital herpes simplex virus (HSV): First infection: Oral: Children: 40-80 mg/kg/day in 3-4 divided doses for 5-10 days; maximum dose: 1 g/day Adolescents and Adults: 200 mg 5 times/day or 400 mg 3 times/day for 5-10 days I.V.: Children and Adults: 5 mg/kg/dose every 8 hours for 5-7 days
Genital HSV infection: Recurrence: Oral: Adolescents and Adults: 200 mg 5 times/day or 400 mg 3 times/day for 5 days
Recurrent genital and cutaneous (ocular) HSV episodes in a patient with frequent recurrences, chronic suppressive therapy: Oral: Children: 40-80 mg/kg/day in 3 divided doses for up to 12 months; maximum dose: 1 g/day; re-evaluate after 12 months of treatment Adolescents and Adults: 400 mg twice daily or 400 mg 3 times/day or 200 mg 3 times/day for as long as 12 continuous months; re-evaluate after 12 months of treatment
HSV in immunocompromised host: Oral: Children:1000 mg/day in 3-5 divided doses for 7-14 days; maximum dose: 80 mg/kg/day not to exceed 1 g/day Adults: 400 mg 5 times/day for 7-14 days I.V.: Children <12 years: 10 mg/kg/dose every 8 hours for 7-14 days Children 12 years and Adults: 5 mg/kg/dose every 8 hours for 7-14 days
Prophylaxis of HSV in immunocompromised host: Oral: Children and Adults: 600-1000 mg/day in 3-5 divided doses during period of risk; maximum dose in children: 80 mg/kg/day not to exceed 1 g/day
HSV encephalitis: I.V.: Children 3 months to 12 years: 20 mg/kg/dose every 8 hours; some clinicians recommend 500 mg/m2/dose every 8 hours for 14-21 days Children >12 years and Adults: 10-15 mg/kg/dose every 8 hours for 14-21 days
Neonatal HSV: I.V.: 20 mg/kg/dose every 8 hours for 14-21 days
Varicella-zoster in immunocompromised host: I.V.: Infants <1 year: 10 mg/kg/dose every 8 hours for 7-10 days Children 1 year: 500 mg/m2/dose every 8 hours for 7-10 days or 10 mg/kg/dose every 8 hours for 7-10 days
Varicella in immunocompetent host: Oral (initiate treatment within the first 24 hours of rash onset): Children 2 years and 40 kg: 20 mg/kg/dose 4 times/day for 5 days; maximum dose: 3200 mg/day Children >40 kg and Adults: 800 mg 4 times/day for 5 days
Zoster in immunocompetent host: Oral (initiate treatment within 48 hours of rash onset): Children 12 years and Adults: 800 mg 5 times/day for 7-10 days
Prophylaxis in bone marrow transplant recipients: I.V.: Autologous patients who are HSV-seropositive: 250 mg/m2/dose every 8 hours Autologous patients who are CMV seropositive: 500 mg/m2/dose every 8 hours; for clinically symptomatic CMV infection, consider replacing acyclovir with ganciclovir
Children and Adults: Topical: Apply 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Dosing interval in renal impairment: Neonates: I.V.: Scr 0.8-1.1 mg/dL: Administer 20 mg/kg/dose every 12 hours Scr 1.2-1.5 mg/dL: Administer 20 mg/kg/dose every 24 hours Scr >1.5 mg/dL: Administer 10 mg/kg/dose every 24 hours Children 6 months and Adults: Oral:
Usual dose: 200 mg 5 times/day: Adjusted dose for Clcr <10 mL/minute: 200 mg every 12 hours Usual dose: 800 mg 5 times/day: Adjusted dose for Clcr 10-25 mL/minute: 800 mg every 8 hours Adjusted dose for Clcr <10 mL/minute: 800 mg every 12 hours I.V.: Clcr 25-50 mL/minute: Administer normal dose every 12 hours Clcr 10-25 mL/minute: Administer normal dose every 24 hours Clcr <10 mL/minute: 50% decrease in dose, administer every 24 hours Hemodialysis: Administer dose after dialysis CVVHD/CVVH: Adjust dose based upon Clcr 30 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution, as sodium: 500 mg, 1000 mg Zovirax®: 500 mg [DSC]
Injection, solution, as sodium [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL (480 mL) Zovirax®: 200 mg/5 mL (480 mL) [banana flavor]
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
GENERIC AVAILABLE — Yes: Excludes cream, ointment
ADMINISTRATION Oral: May administer with food; shake suspension well before use
Parenteral: Reconstitute vial for injection with paraben-free SWI; administer by slow I.V. infusion over at least 1 hour at a final concentration not to exceed 7 mg/mL since rapid infusions can cause nephrotoxicity with crystalluria and renal tubular damage; in patients who require fluid restriction, a concentration of up to 10 mg/mL has been infused; concentration >10 mg/mL increases the risk of phlebitis
USE — Treatment of initial and prophylaxis of recurrent mucosal and cutaneous herpes simplex (HSV 1 and HSV 2) infections; herpes simplex encephalitis; herpes zoster infections; varicella-zoster infections in healthy, nonpregnant persons >13 years of age, children >12 months of age who have a chronic skin or lung disorder or are receiving long-term aspirin therapy, and immunocompromised patients
ADVERSE REACTIONS Central nervous system: Headache, lethargy, delirium, coma, dizziness, seizures, pain, insomnia, fever, hallucinations, aggressive behavior, ataxia
Dermatologic: Skin rash, pruritus, alopecia, erythema multiforme, urticaria, photosensitivity, Stevens-Johnson syndrome, angioedema
Gastrointestinal: Nausea, vomiting, diarrhea
Hematologic: Bone marrow suppression, neutropenia, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
Hepatic: Elevated liver enzymes, hepatitis, jaundice, hyperbilirubinemia
Local: Phlebitis at injection site, tissue necrosis upon extravasation, local pain and stinging with topical use
Neuromuscular & skeletal: Tremulousness, myalgia, paresthesia
Renal: Nephrotoxicity, hematuria, elevated BUN and serum creatinine
Respiratory: Sore throat
Miscellaneous: Diaphoresis, anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acyclovir, valacyclovir, or any component
PRECAUTIONS — Use with caution in patients with renal disease, dehydration, underlying neurologic disease, and in patients with hypoxia, hepatic, or electrolyte abnormalities; dosage should be reduced in patients with renal impairment
WARNINGS — HSV and VZV with reduced susceptibility to acyclovir have been isolated from immunocompromised patients, especially with advanced HIV infection; renal failure, in some cases resulting in death, has occurred with acyclovir
DRUG INTERACTIONS — Zidovudine (neurotoxicity); probenecid decreases renal clearance of acyclovir
FOOD INTERACTIONS — Food does not appear to affect absorption
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, I & O; liver enzymes, CBC; neutrophil count at least twice weekly in neonates receiving acyclovir 60 mg/kg/day I.V.
STABILITY — Incompatible with blood products and protein-containing solutions; reconstituted 50 mg/mL solution should be used within 12 hours; do not refrigerate reconstituted solutions as they may precipitate
MECHANISM OF ACTION — Inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and by incorporation into viral DNA
PHARMACOKINETICS Absorption: Oral: 15% to 30%
Distribution: Widely distributed throughout the body including brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, and the CSF; CSF acyclovir concentration is 50% of serum concentration; crosses the placenta; excreted into breast milk; Vd: Neonates to 3 months of age: 28.8 L/1.73 m2 Children 1-2 years: 31.6 L/1.73 m2 Children 2-7 years: 42 L/1.73 m2
Protein binding: <30%
Half-life, terminal phase: Neonates: 4 hours Children 1-12 years: 2-3 hours Adults: 2-3.5 hours (with normal renal function)
Time to peak serum concentration: Oral: Within 1.5-2 hours
Elimination: Primary route is the kidney with 30% to 90% of a dose excreted unchanged in the urine; requires dosage adjustment with renal impairment; hemodialysis removes ~60% of a dose while removal by peritoneal dialysis is to a much lesser extent; supplemental dose recommended after hemodialysis
NURSING IMPLICATIONS — Maintain adequate hydration and urine output the first 2 hours after I.V. infusion to decrease the risk of nephrotoxicity; check infusion site for phlebitis; avoid extravasation
ADDITIONAL INFORMATION — Sodium content of 1 g: 4.2 mEq
CANADIAN BRAND NAMES — Apo-Acyclovir®; Gen-Acyclovir; Nu-Acyclovir; ratio-Acyclovir; Zovirax®
SYNONYMS — Aciclovir; ACV; Acycloguanosine
THERAPEUTIC CATEGORY Antiviral Agent, OralAntiviral Agent, ParenteralAntiviral Agent, Topical
DOSING
(For additional information see "Acyclovir: Drug information")Genital herpes simplex virus (HSV): First infection: Oral: Children: 40-80 mg/kg/day in 3-4 divided doses for 5-10 days; maximum dose: 1 g/day Adolescents and Adults: 200 mg 5 times/day or 400 mg 3 times/day for 5-10 days I.V.: Children and Adults: 5 mg/kg/dose every 8 hours for 5-7 days
Genital HSV infection: Recurrence: Oral: Adolescents and Adults: 200 mg 5 times/day or 400 mg 3 times/day for 5 days
Recurrent genital and cutaneous (ocular) HSV episodes in a patient with frequent recurrences, chronic suppressive therapy: Oral: Children: 40-80 mg/kg/day in 3 divided doses for up to 12 months; maximum dose: 1 g/day; re-evaluate after 12 months of treatment Adolescents and Adults: 400 mg twice daily or 400 mg 3 times/day or 200 mg 3 times/day for as long as 12 continuous months; re-evaluate after 12 months of treatment
HSV in immunocompromised host: Oral: Children:1000 mg/day in 3-5 divided doses for 7-14 days; maximum dose: 80 mg/kg/day not to exceed 1 g/day Adults: 400 mg 5 times/day for 7-14 days I.V.: Children <12 years: 10 mg/kg/dose every 8 hours for 7-14 days Children 12 years and Adults: 5 mg/kg/dose every 8 hours for 7-14 days
Prophylaxis of HSV in immunocompromised host: Oral: Children and Adults: 600-1000 mg/day in 3-5 divided doses during period of risk; maximum dose in children: 80 mg/kg/day not to exceed 1 g/day
HSV encephalitis: I.V.: Children 3 months to 12 years: 20 mg/kg/dose every 8 hours; some clinicians recommend 500 mg/m2/dose every 8 hours for 14-21 days Children >12 years and Adults: 10-15 mg/kg/dose every 8 hours for 14-21 days
Neonatal HSV: I.V.: 20 mg/kg/dose every 8 hours for 14-21 days
Varicella-zoster in immunocompromised host: I.V.: Infants <1 year: 10 mg/kg/dose every 8 hours for 7-10 days Children 1 year: 500 mg/m2/dose every 8 hours for 7-10 days or 10 mg/kg/dose every 8 hours for 7-10 days
Varicella in immunocompetent host: Oral (initiate treatment within the first 24 hours of rash onset): Children 2 years and 40 kg: 20 mg/kg/dose 4 times/day for 5 days; maximum dose: 3200 mg/day Children >40 kg and Adults: 800 mg 4 times/day for 5 days
Zoster in immunocompetent host: Oral (initiate treatment within 48 hours of rash onset): Children 12 years and Adults: 800 mg 5 times/day for 7-10 days
Prophylaxis in bone marrow transplant recipients: I.V.: Autologous patients who are HSV-seropositive: 250 mg/m2/dose every 8 hours Autologous patients who are CMV seropositive: 500 mg/m2/dose every 8 hours; for clinically symptomatic CMV infection, consider replacing acyclovir with ganciclovir
Children and Adults: Topical: Apply 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Dosing interval in renal impairment: Neonates: I.V.: Scr 0.8-1.1 mg/dL: Administer 20 mg/kg/dose every 12 hours Scr 1.2-1.5 mg/dL: Administer 20 mg/kg/dose every 24 hours Scr >1.5 mg/dL: Administer 10 mg/kg/dose every 24 hours Children 6 months and Adults: Oral:
Usual dose: 200 mg 5 times/day: Adjusted dose for Clcr <10 mL/minute: 200 mg every 12 hours Usual dose: 800 mg 5 times/day: Adjusted dose for Clcr 10-25 mL/minute: 800 mg every 8 hours Adjusted dose for Clcr <10 mL/minute: 800 mg every 12 hours I.V.: Clcr 25-50 mL/minute: Administer normal dose every 12 hours Clcr 10-25 mL/minute: Administer normal dose every 24 hours Clcr <10 mL/minute: 50% decrease in dose, administer every 24 hours Hemodialysis: Administer dose after dialysis CVVHD/CVVH: Adjust dose based upon Clcr 30 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution, as sodium: 500 mg, 1000 mg Zovirax®: 500 mg [DSC]
Injection, solution, as sodium [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL (480 mL) Zovirax®: 200 mg/5 mL (480 mL) [banana flavor]
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
GENERIC AVAILABLE — Yes: Excludes cream, ointment
ADMINISTRATION Oral: May administer with food; shake suspension well before use
Parenteral: Reconstitute vial for injection with paraben-free SWI; administer by slow I.V. infusion over at least 1 hour at a final concentration not to exceed 7 mg/mL since rapid infusions can cause nephrotoxicity with crystalluria and renal tubular damage; in patients who require fluid restriction, a concentration of up to 10 mg/mL has been infused; concentration >10 mg/mL increases the risk of phlebitis
USE — Treatment of initial and prophylaxis of recurrent mucosal and cutaneous herpes simplex (HSV 1 and HSV 2) infections; herpes simplex encephalitis; herpes zoster infections; varicella-zoster infections in healthy, nonpregnant persons >13 years of age, children >12 months of age who have a chronic skin or lung disorder or are receiving long-term aspirin therapy, and immunocompromised patients
ADVERSE REACTIONS Central nervous system: Headache, lethargy, delirium, coma, dizziness, seizures, pain, insomnia, fever, hallucinations, aggressive behavior, ataxia
Dermatologic: Skin rash, pruritus, alopecia, erythema multiforme, urticaria, photosensitivity, Stevens-Johnson syndrome, angioedema
Gastrointestinal: Nausea, vomiting, diarrhea
Hematologic: Bone marrow suppression, neutropenia, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
Hepatic: Elevated liver enzymes, hepatitis, jaundice, hyperbilirubinemia
Local: Phlebitis at injection site, tissue necrosis upon extravasation, local pain and stinging with topical use
Neuromuscular & skeletal: Tremulousness, myalgia, paresthesia
Renal: Nephrotoxicity, hematuria, elevated BUN and serum creatinine
Respiratory: Sore throat
Miscellaneous: Diaphoresis, anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acyclovir, valacyclovir, or any component
PRECAUTIONS — Use with caution in patients with renal disease, dehydration, underlying neurologic disease, and in patients with hypoxia, hepatic, or electrolyte abnormalities; dosage should be reduced in patients with renal impairment
WARNINGS — HSV and VZV with reduced susceptibility to acyclovir have been isolated from immunocompromised patients, especially with advanced HIV infection; renal failure, in some cases resulting in death, has occurred with acyclovir
DRUG INTERACTIONS — Zidovudine (neurotoxicity); probenecid decreases renal clearance of acyclovir
FOOD INTERACTIONS — Food does not appear to affect absorption
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, I & O; liver enzymes, CBC; neutrophil count at least twice weekly in neonates receiving acyclovir 60 mg/kg/day I.V.
STABILITY — Incompatible with blood products and protein-containing solutions; reconstituted 50 mg/mL solution should be used within 12 hours; do not refrigerate reconstituted solutions as they may precipitate
MECHANISM OF ACTION — Inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and by incorporation into viral DNA
PHARMACOKINETICS Absorption: Oral: 15% to 30%
Distribution: Widely distributed throughout the body including brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, and the CSF; CSF acyclovir concentration is 50% of serum concentration; crosses the placenta; excreted into breast milk; Vd: Neonates to 3 months of age: 28.8 L/1.73 m2 Children 1-2 years: 31.6 L/1.73 m2 Children 2-7 years: 42 L/1.73 m2
Protein binding: <30%
Half-life, terminal phase: Neonates: 4 hours Children 1-12 years: 2-3 hours Adults: 2-3.5 hours (with normal renal function)
Time to peak serum concentration: Oral: Within 1.5-2 hours
Elimination: Primary route is the kidney with 30% to 90% of a dose excreted unchanged in the urine; requires dosage adjustment with renal impairment; hemodialysis removes ~60% of a dose while removal by peritoneal dialysis is to a much lesser extent; supplemental dose recommended after hemodialysis
NURSING IMPLICATIONS — Maintain adequate hydration and urine output the first 2 hours after I.V. infusion to decrease the risk of nephrotoxicity; check infusion site for phlebitis; avoid extravasation
ADDITIONAL INFORMATION — Sodium content of 1 g: 4.2 mEq
Acetylcysteine
U.S. BRAND NAMES — Acetadote®
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
SYNONYMS — N-Acetyl-L-Cysteine; N-Acetylcysteine; Mercapturic Acid; NAC
THERAPEUTIC CATEGORY Antidote, AcetaminophenMucolytic Agent
DOSING
(For additional information see "Acetylcysteine: Drug information")Acetaminophen poisoning: Children and Adults: Begin treatment within 8 hours of ingestion to optimize therapy in patients whose serum acetaminophen levels fall above the "possible" toxicity line on the Rumack-Matthew nomogram Treatment is also indicated in patients with a history of known or suspected acute acetaminophen ingestion of >150 mg/kg (child) or >7.5 g (adolescent or adult) total dose when plasma levels are not available within 8-10 hours of ingestion or in patients presenting >24 hours after acute ingestion who have a measurable acetaminophen level. See Warnings. I.V.: 150 mg/kg infused over 60 minutes; followed by a 4-hour infusion of 50 mg/kg; followed by a 16-hour infusion of 100 mg/kg; equivalent to a total dose of 300 mg/kg infused over 21 hours Oral: 140 mg/kg; followed by 17 doses of 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration; therapy should continue until all doses are administered even though the acetaminophen plasma level has dropped below the toxic range
Nebulized inhalation: Infants: 1-2 mL of 20% solution or 2-4 mL of 10% solution until nebulized, given 3-4 times/day Children: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized, given 3-4 times/day Adolescents: 5-10 mL of 10% to 20% solution until nebulized, given 3-4 times/day Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Intratracheal: Children and Adults: 1-2 mL of 10% to 20% solution every 1-4 hours as needed
Distal intestinal obstruction syndrome (previously known as meconium ileus equivalent): Varying regimens have been reported (polyethylene glycol has become more widely used for this indication): Oral: Children <10 years: 30 mL of 10% solution diluted in 30 mL juice or soda 3 times/day for 24 hours Children 10 years and Adults: 60 mL of 10% solution diluted in 60 mL juice or soda 3 times/day for 24 hours Note: Prior to treatment, administer a phosphosoda enema. A clear liquid diet should be used during the 24-hour acetylcysteine treatment Rectal enema: Children: Varying dosages; 100-300 mL of 4% to 6% solution 2-4 times/day; 50 mL of 20% solution 1-4 times/day and 5-30 mL of 10% to 20% solution 3-4 times/day have been used; rectal enemas appear to have less favorable results than oral administration (Mascarenhas, 2003) Prevention of radiocontrast-induced renal dysfunction (unlabeled use): Adults: Oral: 600 mg twice daily for 2 days (beginning the day before the procedure); hydrate patient concurrently
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL) [contains disodium edetate]
Solution, inhalation/oral: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
GENERIC AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION Parenteral: I.V.: Three infusions (See Usual Dosage) of different lengths: Dilute first dose (150 mg/kg) in 200 mL D5W and infuse over 60 minutes; dilute second dose (50 mg/kg) in 500 mL D5W and infuse over 4 hours; dilute third dose (100 mg/kg) in 1000 mL D5W and infuse over 16 hours; for children <40 kg and patients who are fluid restricted, the manufacturer recommends reducing the diluent to a "proportional" amount. See table for manufacturer's recommended infusion guideline for patients <40 kg. Or as an alternative to proportionally lower the diluent volume, a reasonable approach might be to utilize the concentrations resulting from using the recommended dilution for the dosage in a 50 kg patient. The calculated concentration would range between 5 mg/mL (maintenance infusion) to 37.5 mg/mL (loading dose).
Infusion Guide by Weight for Patients <40 kg Body Weight = 10 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 30 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 500 mg (2.5 mL) 5% dextrose: 70 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL Body Weight = 15 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 2250 mg (11.25 mL) 5% dextrose: 45 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 750 mg (3.75 mL) 5% dextrose: 105 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 210 mL Body Weight = 20 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 60 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2000 mg (10 mL) 5% dextrose: 280 mL Body Weight = 25 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3750 mg (18.75 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1250 mg (6.25 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2500 mg (12.5 mL) 5% dextrose: 500 mL Body Weight = 30 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 4500 mg (22.5 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 500 mL
Oral: For treatment of acetaminophen overdosage, administer as a 5% solution; dilute the 20% solution (inhalation formulation) 1:3 with a cola, orange juice, or other soft drink; use within 1 hour of preparation
Oral inhalation: May be administered by nebulization either undiluted (both 10% and 20%) or diluted in NS
Rectal: Dilute the inhalation solution in NS to the desired final concentration and administer rectally
USE Inhalation: Adjunctive therapy in patients with abnormal or viscid mucous secretions in bronchopulmonary diseases, pulmonary complications of surgery, and cystic fibrosis; diagnostic bronchial studies
Injection, Oral: Antidote for acute acetaminophen toxicity; prevention of radiocontrast-induced renal dysfunction
Oral, rectal: Treatment of distal intestinal obstruction syndrome (previously known as "meconium ileus or its equivalent")
ADVERSE REACTIONS Cardiovascular: Tachycardia, hypotension, syncope, chest tightness, vasodilation, hypertension (after large oral doses)
Central nervous system: Drowsiness, chills, dysphoria
Dermatologic: Generalized urticaria, rash, pruritus, erythema, angioedema
Gastrointestinal: Stomatitis, nausea, vomiting, dyspepsia, hemoptysis
Hepatic: Mild elevations in liver function tests have occurred after oral therapy
Ocular: Eye pain
Respiratory: Bronchospasm, rhinorrhea, cough
Miscellaneous: Anaphylactoid reactions (I.V. use; 17% in an open label study; 1% reported as severe or moderate in 10% of patients within 15 minutes of the first infusion; severe in 1% or mild to moderate in 6% to 7% of patients after the 60 minute infusion); diaphoresis, unpleasant odor during administration
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component
PRECAUTIONS — Use with caution in patients with asthma or previous history of bronchospasm
WARNINGS — Serious anaphylactoid reactions including death in a patient with asthma have been reported after I.V. use; acute flushing and erythema may occur 30-60 minutes into an I.V. infusion, resolving spontaneously; the infusion may be interrupted until treatment of allergic symptoms is initiated; if acute hypersensitivity reactions occur which do not respond to medical management (eg, antihistamines, H2 blockers) or temporarily halting infusion, discontinue use and pursue alternative management. Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow.
Acetaminophen overdose: The modified Rumack-Matthew nomogram allows for stratification of patients into risk categories based on the relationship between the serum acetaminophen level and time after ingestion. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained prior to 4-hour postingestion are not interpretable; patients presenting late may have undetectable serum concentrations, but have received a lethal dose. The nomogram is less predictive in a chronic ingestion or in an overdose with an extended release product. Acetylcysteine should be administered for any signs of hepatotoxicity even if acetaminophen serum level is low or undetectable. The nomogram also does not take into account patients at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients) or individuals ingesting higher than recommended acetaminophen doses for extended periods of time (repeated supratherapeutic ingestion).
DRUG INTERACTIONS — May potentiate the hemodynamic effects of nitroglycerin; acetylcysteine is adsorbed by activated charcoal
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — When used in acetaminophen overdose, determine acetaminophen level as soon as possible, but no sooner than 4 hours after ingestion of immediate release formulations or 2 hours after ingestion of liquid formulations (to ensure peak levels have been obtained); coingestion of acetaminophen with other medications which may delay GI peristalsis eg, antihistamines, opioids, may require repeated serum levels to determine the peak serum level; liver function tests
STABILITY — Store at room temperature; I.V. formulation is preservative free and stable 24 hours after dilution at room temperature; opened inhalation solution vials may be stored in the refrigerator; use within 96 hours; contact with rubber, copper, iron, and cork may inactivate the drug; the light purple color of solution does not affect its activity. I.V. acetylcysteine is hyperosmolar (2600 mOsm/L) and is compatible with 5% dextrose, 0.45% sodium chloride, and SWI.
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering the viscosity. The exact mechanism of action in acetaminophen toxicity is unknown. It may act by maintaining or restoring glutathione levels or by acting as an alternative substrate for conjugation with the acetaminophen's toxic metabolite.
PHARMACODYNAMICS Onset of action: Upon inhalation, mucus liquefaction occurs maximally within 5-10 minutes
Duration of mucus liquefaction: More than 1 hour
PHARMACOKINETICS Distribution: Vd: 0.47 L/kg
Protein binding: 83%
Half-life: Reduced acetylcysteine: 2 hours Total acetylcysteine: Newborns: 11 hours Adults: 5.6 hours
Time to peak serum concentration: Oral: 1-2 hours
Elimination: Clearance: Adults: 0.11 L/hour/kg
PATIENT INFORMATION — Clear airway by coughing deeply before aerosol treatment
(For additional information see "Acetylcysteine: Patient drug information")
NURSING IMPLICATIONS — Anaphylactoid reactions following I.V. administration have been reported; have emergency treatments such as antihistamines and H2 blockers readily available for potential adverse effects; assess patient for nausea, vomiting, and skin rash following oral administration for treatment of acetaminophen poisoning; intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
SYNONYMS — N-Acetyl-L-Cysteine; N-Acetylcysteine; Mercapturic Acid; NAC
THERAPEUTIC CATEGORY Antidote, AcetaminophenMucolytic Agent
DOSING
(For additional information see "Acetylcysteine: Drug information")Acetaminophen poisoning: Children and Adults: Begin treatment within 8 hours of ingestion to optimize therapy in patients whose serum acetaminophen levels fall above the "possible" toxicity line on the Rumack-Matthew nomogram Treatment is also indicated in patients with a history of known or suspected acute acetaminophen ingestion of >150 mg/kg (child) or >7.5 g (adolescent or adult) total dose when plasma levels are not available within 8-10 hours of ingestion or in patients presenting >24 hours after acute ingestion who have a measurable acetaminophen level. See Warnings. I.V.: 150 mg/kg infused over 60 minutes; followed by a 4-hour infusion of 50 mg/kg; followed by a 16-hour infusion of 100 mg/kg; equivalent to a total dose of 300 mg/kg infused over 21 hours Oral: 140 mg/kg; followed by 17 doses of 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration; therapy should continue until all doses are administered even though the acetaminophen plasma level has dropped below the toxic range
Nebulized inhalation: Infants: 1-2 mL of 20% solution or 2-4 mL of 10% solution until nebulized, given 3-4 times/day Children: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized, given 3-4 times/day Adolescents: 5-10 mL of 10% to 20% solution until nebulized, given 3-4 times/day Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Intratracheal: Children and Adults: 1-2 mL of 10% to 20% solution every 1-4 hours as needed
Distal intestinal obstruction syndrome (previously known as meconium ileus equivalent): Varying regimens have been reported (polyethylene glycol has become more widely used for this indication): Oral: Children <10 years: 30 mL of 10% solution diluted in 30 mL juice or soda 3 times/day for 24 hours Children 10 years and Adults: 60 mL of 10% solution diluted in 60 mL juice or soda 3 times/day for 24 hours Note: Prior to treatment, administer a phosphosoda enema. A clear liquid diet should be used during the 24-hour acetylcysteine treatment Rectal enema: Children: Varying dosages; 100-300 mL of 4% to 6% solution 2-4 times/day; 50 mL of 20% solution 1-4 times/day and 5-30 mL of 10% to 20% solution 3-4 times/day have been used; rectal enemas appear to have less favorable results than oral administration (Mascarenhas, 2003) Prevention of radiocontrast-induced renal dysfunction (unlabeled use): Adults: Oral: 600 mg twice daily for 2 days (beginning the day before the procedure); hydrate patient concurrently
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL) [contains disodium edetate]
Solution, inhalation/oral: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
GENERIC AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION Parenteral: I.V.: Three infusions (See Usual Dosage) of different lengths: Dilute first dose (150 mg/kg) in 200 mL D5W and infuse over 60 minutes; dilute second dose (50 mg/kg) in 500 mL D5W and infuse over 4 hours; dilute third dose (100 mg/kg) in 1000 mL D5W and infuse over 16 hours; for children <40 kg and patients who are fluid restricted, the manufacturer recommends reducing the diluent to a "proportional" amount. See table for manufacturer's recommended infusion guideline for patients <40 kg. Or as an alternative to proportionally lower the diluent volume, a reasonable approach might be to utilize the concentrations resulting from using the recommended dilution for the dosage in a 50 kg patient. The calculated concentration would range between 5 mg/mL (maintenance infusion) to 37.5 mg/mL (loading dose).
Infusion Guide by Weight for Patients <40 kg Body Weight = 10 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 30 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 500 mg (2.5 mL) 5% dextrose: 70 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL Body Weight = 15 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 2250 mg (11.25 mL) 5% dextrose: 45 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 750 mg (3.75 mL) 5% dextrose: 105 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 210 mL Body Weight = 20 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 60 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2000 mg (10 mL) 5% dextrose: 280 mL Body Weight = 25 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3750 mg (18.75 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1250 mg (6.25 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2500 mg (12.5 mL) 5% dextrose: 500 mL Body Weight = 30 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 4500 mg (22.5 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 500 mL
Oral: For treatment of acetaminophen overdosage, administer as a 5% solution; dilute the 20% solution (inhalation formulation) 1:3 with a cola, orange juice, or other soft drink; use within 1 hour of preparation
Oral inhalation: May be administered by nebulization either undiluted (both 10% and 20%) or diluted in NS
Rectal: Dilute the inhalation solution in NS to the desired final concentration and administer rectally
USE Inhalation: Adjunctive therapy in patients with abnormal or viscid mucous secretions in bronchopulmonary diseases, pulmonary complications of surgery, and cystic fibrosis; diagnostic bronchial studies
Injection, Oral: Antidote for acute acetaminophen toxicity; prevention of radiocontrast-induced renal dysfunction
Oral, rectal: Treatment of distal intestinal obstruction syndrome (previously known as "meconium ileus or its equivalent")
ADVERSE REACTIONS Cardiovascular: Tachycardia, hypotension, syncope, chest tightness, vasodilation, hypertension (after large oral doses)
Central nervous system: Drowsiness, chills, dysphoria
Dermatologic: Generalized urticaria, rash, pruritus, erythema, angioedema
Gastrointestinal: Stomatitis, nausea, vomiting, dyspepsia, hemoptysis
Hepatic: Mild elevations in liver function tests have occurred after oral therapy
Ocular: Eye pain
Respiratory: Bronchospasm, rhinorrhea, cough
Miscellaneous: Anaphylactoid reactions (I.V. use; 17% in an open label study; 1% reported as severe or moderate in 10% of patients within 15 minutes of the first infusion; severe in 1% or mild to moderate in 6% to 7% of patients after the 60 minute infusion); diaphoresis, unpleasant odor during administration
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component
PRECAUTIONS — Use with caution in patients with asthma or previous history of bronchospasm
WARNINGS — Serious anaphylactoid reactions including death in a patient with asthma have been reported after I.V. use; acute flushing and erythema may occur 30-60 minutes into an I.V. infusion, resolving spontaneously; the infusion may be interrupted until treatment of allergic symptoms is initiated; if acute hypersensitivity reactions occur which do not respond to medical management (eg, antihistamines, H2 blockers) or temporarily halting infusion, discontinue use and pursue alternative management. Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow.
Acetaminophen overdose: The modified Rumack-Matthew nomogram allows for stratification of patients into risk categories based on the relationship between the serum acetaminophen level and time after ingestion. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained prior to 4-hour postingestion are not interpretable; patients presenting late may have undetectable serum concentrations, but have received a lethal dose. The nomogram is less predictive in a chronic ingestion or in an overdose with an extended release product. Acetylcysteine should be administered for any signs of hepatotoxicity even if acetaminophen serum level is low or undetectable. The nomogram also does not take into account patients at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients) or individuals ingesting higher than recommended acetaminophen doses for extended periods of time (repeated supratherapeutic ingestion).
DRUG INTERACTIONS — May potentiate the hemodynamic effects of nitroglycerin; acetylcysteine is adsorbed by activated charcoal
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — When used in acetaminophen overdose, determine acetaminophen level as soon as possible, but no sooner than 4 hours after ingestion of immediate release formulations or 2 hours after ingestion of liquid formulations (to ensure peak levels have been obtained); coingestion of acetaminophen with other medications which may delay GI peristalsis eg, antihistamines, opioids, may require repeated serum levels to determine the peak serum level; liver function tests
STABILITY — Store at room temperature; I.V. formulation is preservative free and stable 24 hours after dilution at room temperature; opened inhalation solution vials may be stored in the refrigerator; use within 96 hours; contact with rubber, copper, iron, and cork may inactivate the drug; the light purple color of solution does not affect its activity. I.V. acetylcysteine is hyperosmolar (2600 mOsm/L) and is compatible with 5% dextrose, 0.45% sodium chloride, and SWI.
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering the viscosity. The exact mechanism of action in acetaminophen toxicity is unknown. It may act by maintaining or restoring glutathione levels or by acting as an alternative substrate for conjugation with the acetaminophen's toxic metabolite.
PHARMACODYNAMICS Onset of action: Upon inhalation, mucus liquefaction occurs maximally within 5-10 minutes
Duration of mucus liquefaction: More than 1 hour
PHARMACOKINETICS Distribution: Vd: 0.47 L/kg
Protein binding: 83%
Half-life: Reduced acetylcysteine: 2 hours Total acetylcysteine: Newborns: 11 hours Adults: 5.6 hours
Time to peak serum concentration: Oral: 1-2 hours
Elimination: Clearance: Adults: 0.11 L/hour/kg
PATIENT INFORMATION — Clear airway by coughing deeply before aerosol treatment
(For additional information see "Acetylcysteine: Patient drug information")
NURSING IMPLICATIONS — Anaphylactoid reactions following I.V. administration have been reported; have emergency treatments such as antihistamines and H2 blockers readily available for potential adverse effects; assess patient for nausea, vomiting, and skin rash following oral administration for treatment of acetaminophen poisoning; intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime
Acetylcysteine
U.S. BRAND NAMES — Acetadote®
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
SYNONYMS — N-Acetyl-L-Cysteine; N-Acetylcysteine; Mercapturic Acid; NAC
THERAPEUTIC CATEGORY Antidote, AcetaminophenMucolytic Agent
DOSING
(For additional information see "Acetylcysteine: Drug information")Acetaminophen poisoning: Children and Adults: Begin treatment within 8 hours of ingestion to optimize therapy in patients whose serum acetaminophen levels fall above the "possible" toxicity line on the Rumack-Matthew nomogram Treatment is also indicated in patients with a history of known or suspected acute acetaminophen ingestion of >150 mg/kg (child) or >7.5 g (adolescent or adult) total dose when plasma levels are not available within 8-10 hours of ingestion or in patients presenting >24 hours after acute ingestion who have a measurable acetaminophen level. See Warnings. I.V.: 150 mg/kg infused over 60 minutes; followed by a 4-hour infusion of 50 mg/kg; followed by a 16-hour infusion of 100 mg/kg; equivalent to a total dose of 300 mg/kg infused over 21 hours Oral: 140 mg/kg; followed by 17 doses of 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration; therapy should continue until all doses are administered even though the acetaminophen plasma level has dropped below the toxic range
Nebulized inhalation: Infants: 1-2 mL of 20% solution or 2-4 mL of 10% solution until nebulized, given 3-4 times/day Children: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized, given 3-4 times/day Adolescents: 5-10 mL of 10% to 20% solution until nebulized, given 3-4 times/day Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Intratracheal: Children and Adults: 1-2 mL of 10% to 20% solution every 1-4 hours as needed
Distal intestinal obstruction syndrome (previously known as meconium ileus equivalent): Varying regimens have been reported (polyethylene glycol has become more widely used for this indication): Oral: Children <10 years: 30 mL of 10% solution diluted in 30 mL juice or soda 3 times/day for 24 hours Children 10 years and Adults: 60 mL of 10% solution diluted in 60 mL juice or soda 3 times/day for 24 hours Note: Prior to treatment, administer a phosphosoda enema. A clear liquid diet should be used during the 24-hour acetylcysteine treatment Rectal enema: Children: Varying dosages; 100-300 mL of 4% to 6% solution 2-4 times/day; 50 mL of 20% solution 1-4 times/day and 5-30 mL of 10% to 20% solution 3-4 times/day have been used; rectal enemas appear to have less favorable results than oral administration (Mascarenhas, 2003) Prevention of radiocontrast-induced renal dysfunction (unlabeled use): Adults: Oral: 600 mg twice daily for 2 days (beginning the day before the procedure); hydrate patient concurrently
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL) [contains disodium edetate]
Solution, inhalation/oral: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
GENERIC AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION Parenteral: I.V.: Three infusions (See Usual Dosage) of different lengths: Dilute first dose (150 mg/kg) in 200 mL D5W and infuse over 60 minutes; dilute second dose (50 mg/kg) in 500 mL D5W and infuse over 4 hours; dilute third dose (100 mg/kg) in 1000 mL D5W and infuse over 16 hours; for children <40 kg and patients who are fluid restricted, the manufacturer recommends reducing the diluent to a "proportional" amount. See table for manufacturer's recommended infusion guideline for patients <40 kg. Or as an alternative to proportionally lower the diluent volume, a reasonable approach might be to utilize the concentrations resulting from using the recommended dilution for the dosage in a 50 kg patient. The calculated concentration would range between 5 mg/mL (maintenance infusion) to 37.5 mg/mL (loading dose).
Infusion Guide by Weight for Patients <40 kg Body Weight = 10 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 30 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 500 mg (2.5 mL) 5% dextrose: 70 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL Body Weight = 15 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 2250 mg (11.25 mL) 5% dextrose: 45 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 750 mg (3.75 mL) 5% dextrose: 105 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 210 mL Body Weight = 20 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 60 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2000 mg (10 mL) 5% dextrose: 280 mL Body Weight = 25 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3750 mg (18.75 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1250 mg (6.25 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2500 mg (12.5 mL) 5% dextrose: 500 mL Body Weight = 30 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 4500 mg (22.5 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 500 mL
Oral: For treatment of acetaminophen overdosage, administer as a 5% solution; dilute the 20% solution (inhalation formulation) 1:3 with a cola, orange juice, or other soft drink; use within 1 hour of preparation
Oral inhalation: May be administered by nebulization either undiluted (both 10% and 20%) or diluted in NS
Rectal: Dilute the inhalation solution in NS to the desired final concentration and administer rectally
USE Inhalation: Adjunctive therapy in patients with abnormal or viscid mucous secretions in bronchopulmonary diseases, pulmonary complications of surgery, and cystic fibrosis; diagnostic bronchial studies
Injection, Oral: Antidote for acute acetaminophen toxicity; prevention of radiocontrast-induced renal dysfunction
Oral, rectal: Treatment of distal intestinal obstruction syndrome (previously known as "meconium ileus or its equivalent")
ADVERSE REACTIONS Cardiovascular: Tachycardia, hypotension, syncope, chest tightness, vasodilation, hypertension (after large oral doses)
Central nervous system: Drowsiness, chills, dysphoria
Dermatologic: Generalized urticaria, rash, pruritus, erythema, angioedema
Gastrointestinal: Stomatitis, nausea, vomiting, dyspepsia, hemoptysis
Hepatic: Mild elevations in liver function tests have occurred after oral therapy
Ocular: Eye pain
Respiratory: Bronchospasm, rhinorrhea, cough
Miscellaneous: Anaphylactoid reactions (I.V. use; 17% in an open label study; 1% reported as severe or moderate in 10% of patients within 15 minutes of the first infusion; severe in 1% or mild to moderate in 6% to 7% of patients after the 60 minute infusion); diaphoresis, unpleasant odor during administration
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component
PRECAUTIONS — Use with caution in patients with asthma or previous history of bronchospasm
WARNINGS — Serious anaphylactoid reactions including death in a patient with asthma have been reported after I.V. use; acute flushing and erythema may occur 30-60 minutes into an I.V. infusion, resolving spontaneously; the infusion may be interrupted until treatment of allergic symptoms is initiated; if acute hypersensitivity reactions occur which do not respond to medical management (eg, antihistamines, H2 blockers) or temporarily halting infusion, discontinue use and pursue alternative management. Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow.
Acetaminophen overdose: The modified Rumack-Matthew nomogram allows for stratification of patients into risk categories based on the relationship between the serum acetaminophen level and time after ingestion. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained prior to 4-hour postingestion are not interpretable; patients presenting late may have undetectable serum concentrations, but have received a lethal dose. The nomogram is less predictive in a chronic ingestion or in an overdose with an extended release product. Acetylcysteine should be administered for any signs of hepatotoxicity even if acetaminophen serum level is low or undetectable. The nomogram also does not take into account patients at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients) or individuals ingesting higher than recommended acetaminophen doses for extended periods of time (repeated supratherapeutic ingestion).
DRUG INTERACTIONS — May potentiate the hemodynamic effects of nitroglycerin; acetylcysteine is adsorbed by activated charcoal
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — When used in acetaminophen overdose, determine acetaminophen level as soon as possible, but no sooner than 4 hours after ingestion of immediate release formulations or 2 hours after ingestion of liquid formulations (to ensure peak levels have been obtained); coingestion of acetaminophen with other medications which may delay GI peristalsis eg, antihistamines, opioids, may require repeated serum levels to determine the peak serum level; liver function tests
STABILITY — Store at room temperature; I.V. formulation is preservative free and stable 24 hours after dilution at room temperature; opened inhalation solution vials may be stored in the refrigerator; use within 96 hours; contact with rubber, copper, iron, and cork may inactivate the drug; the light purple color of solution does not affect its activity. I.V. acetylcysteine is hyperosmolar (2600 mOsm/L) and is compatible with 5% dextrose, 0.45% sodium chloride, and SWI.
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering the viscosity. The exact mechanism of action in acetaminophen toxicity is unknown. It may act by maintaining or restoring glutathione levels or by acting as an alternative substrate for conjugation with the acetaminophen's toxic metabolite.
PHARMACODYNAMICS Onset of action: Upon inhalation, mucus liquefaction occurs maximally within 5-10 minutes
Duration of mucus liquefaction: More than 1 hour
PHARMACOKINETICS Distribution: Vd: 0.47 L/kg
Protein binding: 83%
Half-life: Reduced acetylcysteine: 2 hours Total acetylcysteine: Newborns: 11 hours Adults: 5.6 hours
Time to peak serum concentration: Oral: 1-2 hours
Elimination: Clearance: Adults: 0.11 L/hour/kg
PATIENT INFORMATION — Clear airway by coughing deeply before aerosol treatment
(For additional information see "Acetylcysteine: Patient drug information")
NURSING IMPLICATIONS — Anaphylactoid reactions following I.V. administration have been reported; have emergency treatments such as antihistamines and H2 blockers readily available for potential adverse effects; assess patient for nausea, vomiting, and skin rash following oral administration for treatment of acetaminophen poisoning; intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
SYNONYMS — N-Acetyl-L-Cysteine; N-Acetylcysteine; Mercapturic Acid; NAC
THERAPEUTIC CATEGORY Antidote, AcetaminophenMucolytic Agent
DOSING
(For additional information see "Acetylcysteine: Drug information")Acetaminophen poisoning: Children and Adults: Begin treatment within 8 hours of ingestion to optimize therapy in patients whose serum acetaminophen levels fall above the "possible" toxicity line on the Rumack-Matthew nomogram Treatment is also indicated in patients with a history of known or suspected acute acetaminophen ingestion of >150 mg/kg (child) or >7.5 g (adolescent or adult) total dose when plasma levels are not available within 8-10 hours of ingestion or in patients presenting >24 hours after acute ingestion who have a measurable acetaminophen level. See Warnings. I.V.: 150 mg/kg infused over 60 minutes; followed by a 4-hour infusion of 50 mg/kg; followed by a 16-hour infusion of 100 mg/kg; equivalent to a total dose of 300 mg/kg infused over 21 hours Oral: 140 mg/kg; followed by 17 doses of 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration; therapy should continue until all doses are administered even though the acetaminophen plasma level has dropped below the toxic range
Nebulized inhalation: Infants: 1-2 mL of 20% solution or 2-4 mL of 10% solution until nebulized, given 3-4 times/day Children: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized, given 3-4 times/day Adolescents: 5-10 mL of 10% to 20% solution until nebulized, given 3-4 times/day Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Intratracheal: Children and Adults: 1-2 mL of 10% to 20% solution every 1-4 hours as needed
Distal intestinal obstruction syndrome (previously known as meconium ileus equivalent): Varying regimens have been reported (polyethylene glycol has become more widely used for this indication): Oral: Children <10 years: 30 mL of 10% solution diluted in 30 mL juice or soda 3 times/day for 24 hours Children 10 years and Adults: 60 mL of 10% solution diluted in 60 mL juice or soda 3 times/day for 24 hours Note: Prior to treatment, administer a phosphosoda enema. A clear liquid diet should be used during the 24-hour acetylcysteine treatment Rectal enema: Children: Varying dosages; 100-300 mL of 4% to 6% solution 2-4 times/day; 50 mL of 20% solution 1-4 times/day and 5-30 mL of 10% to 20% solution 3-4 times/day have been used; rectal enemas appear to have less favorable results than oral administration (Mascarenhas, 2003) Prevention of radiocontrast-induced renal dysfunction (unlabeled use): Adults: Oral: 600 mg twice daily for 2 days (beginning the day before the procedure); hydrate patient concurrently
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL) [contains disodium edetate]
Solution, inhalation/oral: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
GENERIC AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION Parenteral: I.V.: Three infusions (See Usual Dosage) of different lengths: Dilute first dose (150 mg/kg) in 200 mL D5W and infuse over 60 minutes; dilute second dose (50 mg/kg) in 500 mL D5W and infuse over 4 hours; dilute third dose (100 mg/kg) in 1000 mL D5W and infuse over 16 hours; for children <40 kg and patients who are fluid restricted, the manufacturer recommends reducing the diluent to a "proportional" amount. See table for manufacturer's recommended infusion guideline for patients <40 kg. Or as an alternative to proportionally lower the diluent volume, a reasonable approach might be to utilize the concentrations resulting from using the recommended dilution for the dosage in a 50 kg patient. The calculated concentration would range between 5 mg/mL (maintenance infusion) to 37.5 mg/mL (loading dose).
Infusion Guide by Weight for Patients <40 kg Body Weight = 10 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 30 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 500 mg (2.5 mL) 5% dextrose: 70 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL Body Weight = 15 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 2250 mg (11.25 mL) 5% dextrose: 45 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 750 mg (3.75 mL) 5% dextrose: 105 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 210 mL Body Weight = 20 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 60 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2000 mg (10 mL) 5% dextrose: 280 mL Body Weight = 25 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3750 mg (18.75 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1250 mg (6.25 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2500 mg (12.5 mL) 5% dextrose: 500 mL Body Weight = 30 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 4500 mg (22.5 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 500 mL
Oral: For treatment of acetaminophen overdosage, administer as a 5% solution; dilute the 20% solution (inhalation formulation) 1:3 with a cola, orange juice, or other soft drink; use within 1 hour of preparation
Oral inhalation: May be administered by nebulization either undiluted (both 10% and 20%) or diluted in NS
Rectal: Dilute the inhalation solution in NS to the desired final concentration and administer rectally
USE Inhalation: Adjunctive therapy in patients with abnormal or viscid mucous secretions in bronchopulmonary diseases, pulmonary complications of surgery, and cystic fibrosis; diagnostic bronchial studies
Injection, Oral: Antidote for acute acetaminophen toxicity; prevention of radiocontrast-induced renal dysfunction
Oral, rectal: Treatment of distal intestinal obstruction syndrome (previously known as "meconium ileus or its equivalent")
ADVERSE REACTIONS Cardiovascular: Tachycardia, hypotension, syncope, chest tightness, vasodilation, hypertension (after large oral doses)
Central nervous system: Drowsiness, chills, dysphoria
Dermatologic: Generalized urticaria, rash, pruritus, erythema, angioedema
Gastrointestinal: Stomatitis, nausea, vomiting, dyspepsia, hemoptysis
Hepatic: Mild elevations in liver function tests have occurred after oral therapy
Ocular: Eye pain
Respiratory: Bronchospasm, rhinorrhea, cough
Miscellaneous: Anaphylactoid reactions (I.V. use; 17% in an open label study; 1% reported as severe or moderate in 10% of patients within 15 minutes of the first infusion; severe in 1% or mild to moderate in 6% to 7% of patients after the 60 minute infusion); diaphoresis, unpleasant odor during administration
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component
PRECAUTIONS — Use with caution in patients with asthma or previous history of bronchospasm
WARNINGS — Serious anaphylactoid reactions including death in a patient with asthma have been reported after I.V. use; acute flushing and erythema may occur 30-60 minutes into an I.V. infusion, resolving spontaneously; the infusion may be interrupted until treatment of allergic symptoms is initiated; if acute hypersensitivity reactions occur which do not respond to medical management (eg, antihistamines, H2 blockers) or temporarily halting infusion, discontinue use and pursue alternative management. Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow.
Acetaminophen overdose: The modified Rumack-Matthew nomogram allows for stratification of patients into risk categories based on the relationship between the serum acetaminophen level and time after ingestion. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained prior to 4-hour postingestion are not interpretable; patients presenting late may have undetectable serum concentrations, but have received a lethal dose. The nomogram is less predictive in a chronic ingestion or in an overdose with an extended release product. Acetylcysteine should be administered for any signs of hepatotoxicity even if acetaminophen serum level is low or undetectable. The nomogram also does not take into account patients at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients) or individuals ingesting higher than recommended acetaminophen doses for extended periods of time (repeated supratherapeutic ingestion).
DRUG INTERACTIONS — May potentiate the hemodynamic effects of nitroglycerin; acetylcysteine is adsorbed by activated charcoal
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — When used in acetaminophen overdose, determine acetaminophen level as soon as possible, but no sooner than 4 hours after ingestion of immediate release formulations or 2 hours after ingestion of liquid formulations (to ensure peak levels have been obtained); coingestion of acetaminophen with other medications which may delay GI peristalsis eg, antihistamines, opioids, may require repeated serum levels to determine the peak serum level; liver function tests
STABILITY — Store at room temperature; I.V. formulation is preservative free and stable 24 hours after dilution at room temperature; opened inhalation solution vials may be stored in the refrigerator; use within 96 hours; contact with rubber, copper, iron, and cork may inactivate the drug; the light purple color of solution does not affect its activity. I.V. acetylcysteine is hyperosmolar (2600 mOsm/L) and is compatible with 5% dextrose, 0.45% sodium chloride, and SWI.
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering the viscosity. The exact mechanism of action in acetaminophen toxicity is unknown. It may act by maintaining or restoring glutathione levels or by acting as an alternative substrate for conjugation with the acetaminophen's toxic metabolite.
PHARMACODYNAMICS Onset of action: Upon inhalation, mucus liquefaction occurs maximally within 5-10 minutes
Duration of mucus liquefaction: More than 1 hour
PHARMACOKINETICS Distribution: Vd: 0.47 L/kg
Protein binding: 83%
Half-life: Reduced acetylcysteine: 2 hours Total acetylcysteine: Newborns: 11 hours Adults: 5.6 hours
Time to peak serum concentration: Oral: 1-2 hours
Elimination: Clearance: Adults: 0.11 L/hour/kg
PATIENT INFORMATION — Clear airway by coughing deeply before aerosol treatment
(For additional information see "Acetylcysteine: Patient drug information")
NURSING IMPLICATIONS — Anaphylactoid reactions following I.V. administration have been reported; have emergency treatments such as antihistamines and H2 blockers readily available for potential adverse effects; assess patient for nausea, vomiting, and skin rash following oral administration for treatment of acetaminophen poisoning; intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime
Acetylcholine
U.S. BRAND NAMES — Miochol®-E
CANADIAN BRAND NAMES — Miochol®-E
THERAPEUTIC CATEGORY Cholinergic Agent, OphthalmicOphthalmic Agent, Miotic
DOSING — Ophthalmic: Adults: Instill 0.5-2 mL of 1% injection (5-20 mg)
(For additional information see "Acetylcholine: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride: Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC AVAILABLE — No
ADMINISTRATION — Ophthalmic: Instill into anterior chamber before or after securing one or more sutures; instillation should be gentle and parallel to the iris face and tangential to the pupil border; in cataract surgery, acetylcholine should be used only after delivery of the lens
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS Cardiovascular: Transient bradycardia and hypotension
Central nervous system: Headache
Ocular: Iris atrophy, temporary lens opacities (attributed to osmotic effect of 5% mannitol present in preparation)
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component; acute iritis and acute inflammatory disease of the anterior chamber
PRECAUTIONS — Systemic effects rarely occur, but can cause problems for patients with acute CHF, bronchial asthma, peptic ulcer, hyperthyroidism, GI spasm, and urinary tract obstruction
WARNINGS — Open under aseptic conditions only
DRUG INTERACTIONS — Flurbiprofen decreases effectiveness; sodium nitrate antagonizes acetylcholine's effects
PREGNANCY RISK FACTOR — C (show table)
STABILITY — Prepare solution immediately before use; do not use solution which is not clear and colorless
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation
PHARMACODYNAMICS Onset of action: Miosis occurs promptly
Duration: ~10-20 minutes
CANADIAN BRAND NAMES — Miochol®-E
THERAPEUTIC CATEGORY Cholinergic Agent, OphthalmicOphthalmic Agent, Miotic
DOSING — Ophthalmic: Adults: Instill 0.5-2 mL of 1% injection (5-20 mg)
(For additional information see "Acetylcholine: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride: Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC AVAILABLE — No
ADMINISTRATION — Ophthalmic: Instill into anterior chamber before or after securing one or more sutures; instillation should be gentle and parallel to the iris face and tangential to the pupil border; in cataract surgery, acetylcholine should be used only after delivery of the lens
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS Cardiovascular: Transient bradycardia and hypotension
Central nervous system: Headache
Ocular: Iris atrophy, temporary lens opacities (attributed to osmotic effect of 5% mannitol present in preparation)
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component; acute iritis and acute inflammatory disease of the anterior chamber
PRECAUTIONS — Systemic effects rarely occur, but can cause problems for patients with acute CHF, bronchial asthma, peptic ulcer, hyperthyroidism, GI spasm, and urinary tract obstruction
WARNINGS — Open under aseptic conditions only
DRUG INTERACTIONS — Flurbiprofen decreases effectiveness; sodium nitrate antagonizes acetylcholine's effects
PREGNANCY RISK FACTOR — C (show table)
STABILITY — Prepare solution immediately before use; do not use solution which is not clear and colorless
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation
PHARMACODYNAMICS Onset of action: Miosis occurs promptly
Duration: ~10-20 minutes
Acetylcholine
U.S. BRAND NAMES — Miochol®-E
CANADIAN BRAND NAMES — Miochol®-E
THERAPEUTIC CATEGORY Cholinergic Agent, OphthalmicOphthalmic Agent, Miotic
DOSING — Ophthalmic: Adults: Instill 0.5-2 mL of 1% injection (5-20 mg)
(For additional information see "Acetylcholine: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride: Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC AVAILABLE — No
ADMINISTRATION — Ophthalmic: Instill into anterior chamber before or after securing one or more sutures; instillation should be gentle and parallel to the iris face and tangential to the pupil border; in cataract surgery, acetylcholine should be used only after delivery of the lens
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS Cardiovascular: Transient bradycardia and hypotension
Central nervous system: Headache
Ocular: Iris atrophy, temporary lens opacities (attributed to osmotic effect of 5% mannitol present in preparation)
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component; acute iritis and acute inflammatory disease of the anterior chamber
PRECAUTIONS — Systemic effects rarely occur, but can cause problems for patients with acute CHF, bronchial asthma, peptic ulcer, hyperthyroidism, GI spasm, and urinary tract obstruction
WARNINGS — Open under aseptic conditions only
DRUG INTERACTIONS — Flurbiprofen decreases effectiveness; sodium nitrate antagonizes acetylcholine's effects
PREGNANCY RISK FACTOR — C (show table)
STABILITY — Prepare solution immediately before use; do not use solution which is not clear and colorless
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation
PHARMACODYNAMICS Onset of action: Miosis occurs promptly
Duration: ~10-20 minutes
CANADIAN BRAND NAMES — Miochol®-E
THERAPEUTIC CATEGORY Cholinergic Agent, OphthalmicOphthalmic Agent, Miotic
DOSING — Ophthalmic: Adults: Instill 0.5-2 mL of 1% injection (5-20 mg)
(For additional information see "Acetylcholine: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride: Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC AVAILABLE — No
ADMINISTRATION — Ophthalmic: Instill into anterior chamber before or after securing one or more sutures; instillation should be gentle and parallel to the iris face and tangential to the pupil border; in cataract surgery, acetylcholine should be used only after delivery of the lens
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS Cardiovascular: Transient bradycardia and hypotension
Central nervous system: Headache
Ocular: Iris atrophy, temporary lens opacities (attributed to osmotic effect of 5% mannitol present in preparation)
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component; acute iritis and acute inflammatory disease of the anterior chamber
PRECAUTIONS — Systemic effects rarely occur, but can cause problems for patients with acute CHF, bronchial asthma, peptic ulcer, hyperthyroidism, GI spasm, and urinary tract obstruction
WARNINGS — Open under aseptic conditions only
DRUG INTERACTIONS — Flurbiprofen decreases effectiveness; sodium nitrate antagonizes acetylcholine's effects
PREGNANCY RISK FACTOR — C (show table)
STABILITY — Prepare solution immediately before use; do not use solution which is not clear and colorless
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation
PHARMACODYNAMICS Onset of action: Miosis occurs promptly
Duration: ~10-20 minutes
Acetazolamide
U.S. BRAND NAMES — Diamox® Sequels®
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (Allen, 1996). When diluted in 120 mL solution of cherry syrup concentrate diluted 1:4 with simple syrup, NF, it is stable 60 days refrigerated (preferred) or at room temperature (Nahata, 2004).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (Allen, 1996). When diluted in 120 mL solution of cherry syrup concentrate diluted 1:4 with simple syrup, NF, it is stable 60 days refrigerated (preferred) or at room temperature (Nahata, 2004).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
Acetazolamide
U.S. BRAND NAMES — Diamox® Sequels®
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (Allen, 1996). When diluted in 120 mL solution of cherry syrup concentrate diluted 1:4 with simple syrup, NF, it is stable 60 days refrigerated (preferred) or at room temperature (Nahata, 2004).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (Allen, 1996). When diluted in 120 mL solution of cherry syrup concentrate diluted 1:4 with simple syrup, NF, it is stable 60 days refrigerated (preferred) or at room temperature (Nahata, 2004).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
Acetaminophen and codeine
U.S. BRAND NAMES — Capital® and Codeine; Tylenol® With Codeine
CANADIAN BRAND NAMES — ratio-Emtec; ratio-Lenoltec; Triatec-30; Triatec-8 Strong; Triatec-8; Tylenol Elixir with Codeine; Tylenol No. 1 Forte; Tylenol No. 1; Tylenol No. 2 with Codeine; Tylenol No. 3 with Codeine; Tylenol No. 4 with Codeine
SYNONYMS — Codeine and Acetaminophen
THERAPEUTIC CATEGORY Analgesic, Narcotic
DOSING — Oral (doses should be titrated to appropriate analgesic effect):
(For additional information see "Acetaminophen and codeine: Drug information")
Children: Analgesic: 0.5-1 mg codeine/kg/dose every 4-6 hours 3-6 years: 5 mL 3-4 times/day as needed 7-12 years: 10 mL 3-4 times/day as needed >12 years: 15 mL every 4 hours as needed
Adults: 1-2 tablets every 4 hours; maximum dose: 12 tablets/24 hours
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (5 mL, 10 mL, 12.5 mL, 15 mL, 120 mL, 480 mL) [contains alcohol 7%] Tylenol® with Codeine [DSC]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [contains alcohol 7%; cherry flavor] Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine phosphate 8 mg per 5 mL (500 mL) [contains alcohol 7%, sucrose 31%; cherry flavor; not available in the U.S.]
Suspension, oral [C-V] (Capital® and Codeine): Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [alcohol free; fruit punch flavor]
Tablet [C-III]: Acetaminophen 300 mg and codeine phosphate 15 mg; acetaminophen 300 mg and codeine phosphate 30 mg; acetaminophen 300 mg and codeine phosphate 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine phosphate 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 2 [CAN], Tylenol No. 2 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 15 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 3 [CAN], Tylenol No. 3 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 30 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 4 [CAN], Tylenol No. 4 with Codeine [CAN]: Acetaminophen 300 mg and codeine phosphate 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine phosphate 30 mg [contains sodium metabisulfite] Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine phosphate 60 mg [contains sodium metabisulfite]
GENERIC AVAILABLE — Yes
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use
USE — Relief of mild to moderate pain
ADVERSE REACTIONS Acetaminophen: Dermatologic: Rash Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia) Hepatic: Hepatic necrosis with overdose Renal: Renal injury with chronic use Miscellaneous: Hypersensitivity reactions (rare)
Codeine: Cardiovascular: Palpitations, hypotension, bradycardia, peripheral vasodilation Central nervous system: CNS depression, dizziness, drowsiness, sedation, elevated intracranial pressure Dermatologic: Pruritus Endocrine & metabolic: Antidiuretic hormone release Gastrointestinal: Nausea, vomiting, constipation, biliary tract spasm Genitourinary: Urinary retention Ocular: Miosis Respiratory: Respiratory depression Miscellaneous: Histamine release, physical and psychological dependence with prolonged use
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine phosphate, or any component (see Warnings)
PRECAUTIONS — Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (morphine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone) or respiratory disease/compromise.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — Some tablets contain metabisulfite which may cause allergic reactions in susceptible individuals. Elixir may contain sodium benzoate; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen and codeine products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
RESTRICTIONS — C-III; C-V
DRUG INTERACTIONS — See Acetaminophen and Codeine
FOOD INTERACTIONS — Rate of absorption of acetaminophen may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — C (show table)
MECHANISM OF ACTION — See individual monographs for Acetaminophen and Codeine
PHARMACOKINETICS — See individual monographs for Acetaminophen and Codeine
PATIENT INFORMATION — Codeine may be habit-forming; avoid abrupt discontinuation after prolonged use; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination; avoid alcohol
(For additional information see "Acetaminophen and codeine: Patient drug information")
NURSING IMPLICATIONS — Observe patient for excessive sedation, respiratory depression
ADDITIONAL INFORMATION — Tylenol® With Codeine elixir contains saccharin
CANADIAN BRAND NAMES — ratio-Emtec; ratio-Lenoltec; Triatec-30; Triatec-8 Strong; Triatec-8; Tylenol Elixir with Codeine; Tylenol No. 1 Forte; Tylenol No. 1; Tylenol No. 2 with Codeine; Tylenol No. 3 with Codeine; Tylenol No. 4 with Codeine
SYNONYMS — Codeine and Acetaminophen
THERAPEUTIC CATEGORY Analgesic, Narcotic
DOSING — Oral (doses should be titrated to appropriate analgesic effect):
(For additional information see "Acetaminophen and codeine: Drug information")
Children: Analgesic: 0.5-1 mg codeine/kg/dose every 4-6 hours 3-6 years: 5 mL 3-4 times/day as needed 7-12 years: 10 mL 3-4 times/day as needed >12 years: 15 mL every 4 hours as needed
Adults: 1-2 tablets every 4 hours; maximum dose: 12 tablets/24 hours
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (5 mL, 10 mL, 12.5 mL, 15 mL, 120 mL, 480 mL) [contains alcohol 7%] Tylenol® with Codeine [DSC]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [contains alcohol 7%; cherry flavor] Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine phosphate 8 mg per 5 mL (500 mL) [contains alcohol 7%, sucrose 31%; cherry flavor; not available in the U.S.]
Suspension, oral [C-V] (Capital® and Codeine): Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [alcohol free; fruit punch flavor]
Tablet [C-III]: Acetaminophen 300 mg and codeine phosphate 15 mg; acetaminophen 300 mg and codeine phosphate 30 mg; acetaminophen 300 mg and codeine phosphate 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine phosphate 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 2 [CAN], Tylenol No. 2 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 15 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 3 [CAN], Tylenol No. 3 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 30 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 4 [CAN], Tylenol No. 4 with Codeine [CAN]: Acetaminophen 300 mg and codeine phosphate 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine phosphate 30 mg [contains sodium metabisulfite] Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine phosphate 60 mg [contains sodium metabisulfite]
GENERIC AVAILABLE — Yes
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use
USE — Relief of mild to moderate pain
ADVERSE REACTIONS Acetaminophen: Dermatologic: Rash Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia) Hepatic: Hepatic necrosis with overdose Renal: Renal injury with chronic use Miscellaneous: Hypersensitivity reactions (rare)
Codeine: Cardiovascular: Palpitations, hypotension, bradycardia, peripheral vasodilation Central nervous system: CNS depression, dizziness, drowsiness, sedation, elevated intracranial pressure Dermatologic: Pruritus Endocrine & metabolic: Antidiuretic hormone release Gastrointestinal: Nausea, vomiting, constipation, biliary tract spasm Genitourinary: Urinary retention Ocular: Miosis Respiratory: Respiratory depression Miscellaneous: Histamine release, physical and psychological dependence with prolonged use
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine phosphate, or any component (see Warnings)
PRECAUTIONS — Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (morphine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone) or respiratory disease/compromise.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — Some tablets contain metabisulfite which may cause allergic reactions in susceptible individuals. Elixir may contain sodium benzoate; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen and codeine products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
RESTRICTIONS — C-III; C-V
DRUG INTERACTIONS — See Acetaminophen and Codeine
FOOD INTERACTIONS — Rate of absorption of acetaminophen may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — C (show table)
MECHANISM OF ACTION — See individual monographs for Acetaminophen and Codeine
PHARMACOKINETICS — See individual monographs for Acetaminophen and Codeine
PATIENT INFORMATION — Codeine may be habit-forming; avoid abrupt discontinuation after prolonged use; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination; avoid alcohol
(For additional information see "Acetaminophen and codeine: Patient drug information")
NURSING IMPLICATIONS — Observe patient for excessive sedation, respiratory depression
ADDITIONAL INFORMATION — Tylenol® With Codeine elixir contains saccharin
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