U.S. BRAND NAMES — Lotronex®
PHARMACOLOGIC CATEGORY Selective 5-HT3 Receptor Antagonist
DOSING: ADULTS — IBS: Female: Oral: Initial: 0.5 mg twice daily for 4 weeks, with or without food; if tolerated, but response is inadequate, may be increased after 4 weeks to 1 mg twice daily. If response is inadequate after 4 weeks of 1 mg twice-daily dosing, discontinue treatment. Note: Discontinue immediately if constipation or signs/symptoms of ischemic colitis occur. Do not reinitiate in patients who develop ischemic colitis.
DOSING: PEDIATRIC — Safety and efficacy have not been established.
DOSING: ELDERLY — Refer to adult dosing. Dosage adjustment is not required; however, postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation.
DOSING: RENAL IMPAIRMENT — The need for dosage adjustment has not been defined (due to limited information on activity of metabolites).
DOSING: HEPATIC IMPAIRMENT — In mild-to-moderate dysfunction (Child-Pugh score 9), use caution. Avoid use in severe hepatic dysfunction (Child-Pugh score >9).
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 0.5 mg, 1 mg
DOSAGE FORMS: CONCISE Tablet: Lotronex®: 0.5 mg, 1 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or with food; however, absorption may be reduced by approximately 25%.
USE — Treatment of women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have failed to respond to conventional therapy
ADVERSE REACTIONS SIGNIFICANT >10%: Gastrointestinal: Constipation (dose related) (29%)
1% to 10%: Gastrointestinal: Abdominal discomfort and pain (7%), nausea (6%), gastrointestinal discomfort and pain (6%), abdominal distention (2%), hemorrhoids (2%), regurgitation and reflux (2%)
<1% (Limited to important or life-threatening): Allergic skin reactions, anxiety, bilirubin level changes, bladder inflammation, bone pain, breathing disorder, cholecystitis, cognitive function disorders, confusion, cramps, colitis, depression, diaphoresis, diverticulitis, dyspepsia symptoms, fatigue, gastroenteritis, GI lesions, GI motility decreased, GI obstructions, GI spasms, headache, hemorrhage, hepatitis, hyperacidity, hyper-/hypoglycemia, hypertension, hypnagogic effects, hypoesthesia, hypothalamus/pituitary dysfunction, ileus, impaction, ischemic colitis, memory effects, muscle pain/stiffness, obstruction, occult stools, pain, perforation, rash, RBC/hemoglobin defects, sedation, sexual dysfunction, skeletal pain, small bowel mesenteric ischemia, tachyarrhythmia, temperature regulation impairment, tremor, ulceration, ulcerative colitis, urinary frequency, urticaria
CONTRAINDICATIONS — Do not start treatment in patients who are constipated. Hypersensitivity to alosetron or any component of the formulation; history of severe or chronic constipation; history of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation and/or adhesions; active diverticulitis, current or history of Crohn's disease, severe hepatic dysfunction, or ulcerative colitis; history of impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; patients unable to understand or comply with "Patient-Physician" agreement; concomitant administration with fluvoxamine
WARNINGS / PRECAUTIONS Box warnings: Constipation: See "Concerns related to adverse effects" below. Ischemic colitis: See "Concerns related to adverse effects" below. Patient-Physician agreement: See "Other warnings/precautions" below.
Concerns related to adverse effects: Constipation: [U.S. Boxed Warning]: Discontinue immediately in patients with constipation. Constipation is a frequent, dose-related side effect; serious complications of constipation have been infrequently reported (obstruction, perforation, impaction, toxic megacolon, secondary ischemia); risk may be increased in elderly, debilitated patients, or with concurrent use of other medications which decrease GI motility. Nonsevere constipation may be managed by temporarily interrupting therapy. Ischemic colitis: [U.S. Boxed Warning]: Acute ischemic colitis has been reported during treatment. Discontinue immediately in patients who experience rectal bleeding or a sudden worsening of abdominal pain, and do not restart therapy if ischemic colitis is diagnosed.
Disease-related concerns: Hepatic impairment: Use caution in mild-to-moderate hepatic impairment (Child-Pugh score 9); do not use in severe impairment (Child-Pugh score 10).
Special populations: Males: Safety and efficacy have not been established in males. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Patient-Physician agreement: [U.S. Boxed Warning]: Patients must read and sign a "Patient-Physician" agreement before receiving the initial prescription.
RESTRICTIONS — Only physicians enrolled in GlaxoSmithKline's Prescribing Program for Lotronex® may prescribe this medication. Program stickers must be affixed to all prescriptions; no phone, fax, or computerized prescriptions are permitted with this program.
An FDA-approved medication guide must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm.
DRUG INTERACTIONS — Substrate of CYP1A2 (major), 2C9 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 2E1 (weak)
CYP1A2 inhibitors: May increase the levels/effects of alosetron. Example inhibitors include ciprofloxacin, fluvoxamine, ketoconazole, norfloxacin, ofloxacin, and rofecoxib.
Fluvoxamine: Concomitant use is contraindicated.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: When administered with food, absorption may be reduced by ~25%.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Alosetron should be used in pregnant women only if clearly needed.
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — Animal studies indicate that alosetron and/or metabolites are excreted in breast milk. It is not known if alosetron in excreted in human milk. Caution should be used in administering alosetron to a nursing woman.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)Tablets (Lotronex) 0.5 mg (30): $252.47
MECHANISM OF ACTION — Alosetron is a potent and selective antagonist of a subtype of the serotonin 5-HT3 receptor. 5-HT3 receptors are ligand-gated ion channels extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels affect the regulation of visceral pain, colonic transit, and gastrointestinal secretions. In patients with irritable bowel syndrome, blockade of these channels may reduce pain, abdominal discomfort, urgency, and diarrhea.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 65-95 L
Protein binding: 82%
Metabolism: Extensive hepatic metabolism. Alosetron is metabolized by CYP2C9, 3A4, and 1A2. Thirteen metabolites have been detected in the urine. Biological activity of these metabolites in unknown.
Bioavailability: Mean: 50% to 60% (range: 30% to >90%); decreased with food (25%)
Half-life elimination: 1.5 hours for alosetron
Time to peak: 1 hour after oral administration
Excretion: Urine (73%) and feces (24%); 7% as unchanged drug (1% feces, 6% urine)
PATIENT INFORMATION — Take with or without food. Do not take if you are frequently constipated; constipation is a side effect associated with this medication and can lead to serious complications. Stop taking this medication and call your prescriber if you become constipated, or if you have sudden worsening of abdominal pain, severe constipation, or blood in your stool. Do not continue taking the medication until you have spoken with your prescriber; if after stopping the medication, constipation does not resolve, call your prescriber again. Notify your prescriber if you are pregnant, plan on becoming pregnant, or if you are breast-feeding.
Almotriptan
U.S. BRAND NAMES — Axert™
PHARMACOLOGIC CATEGORY Antimigraine AgentSerotonin 5-HT1B, 1D Receptor Agonist
DOSING: ADULTS — Migraine: Oral: Initial: 6.25-12.5 mg in a single dose; if the headache returns, repeat the dose after 2 hours; no more than 2 doses in 24-hour period
Note: If the first dose is ineffective, diagnosis needs to be re-evaluated. Safety of treating more than 4 migraines/month has not been established.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSING: HEPATIC IMPAIRMENT — Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as malate: 6.25 mg, 12.5 mg
DOSAGE FORMS: CONCISE Tablet: Axert™: 6.25 mg, 12.5 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Acute treatment of migraine with or without aura
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Headache (>1%), dizziness (>1%), somnolence (>1%) Gastrointestinal: Nausea (1% to 2%), xerostomia (1%) Neuromuscular & skeletal: Paresthesia (1%)
<1% (Limited to important or life-threatening): Colitis, coronary artery vasospasm, hypertension, myocardial ischemia, MI, neuropathy, rash, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo
CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; use as prophylactic therapy for migraine; hemiplegic or basilar migraine; cluster headache; known or suspected ischemic heart disease (angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); peripheral vascular syndromes (including ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivative; concurrent administration or within 2 weeks of discontinuing an MAO inhibitor (specifically MAO type A inhibitors)
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported with 5-HT1 agonist administration. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses. Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT1 agonist administration. Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist. administration.
Disease-related concerns: Coronary artery disease: Should not be given to patients who have risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) without adequate cardiac evaluation. Patients with suspected CAD should have cardiovascular evaluation to rule out CAD before considering use; if cardiovascular evaluation "is satisfactory", first dose should be given in the healthcare provider's office. Periodic evaluation of cardiovascular status should be done in all patients. Hepatic impairment: Use with caution in patients with hepatic impairment. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended. Renal impairment: Use with caution in patients with moderate to severe renal failure.
Concurrent drug therapy issues: Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans) or agents which reduce almotriptan's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children <18 years of age.
Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; if a patient does not respond to the first dose, the diagnosis of migraine should be reconsidered.
DRUG INTERACTIONS — Substrate (minor) of CYP2D6, 3A4
Ergot-containing drugs: Prolong vasospastic reactions; do not use almotriptan or ergot-containing drugs within 24 hours of each other.
Ketoconazole: Increases almotriptan serum concentration. Monitor for increased almotriptan response.
MAO inhibitors (moclobemide [MAO type A inhibitor]): Almotriptan clearance decreased by 27%; Cmax increased by 6%. Avoid concurrent administration of MAO inhibitors or within 2 weeks of discontinuing an MAO inhibitor, specifically MAO type A inhibitors.
Selegiline: Selegiline is a selective MAO type B inhibitor; while not specifically contraindicated, combination has not been studied.
Verapamil: Increased almotriptan serum concentration by 24%. Dose adjustment not necessary.
Serotonin agonists (eg, triptans): Concurrent use of almotriptan with these agents may increase the risk of serotonin syndrome; monitor.
Serotonergic reuptake inhibitors (eg, SSRIs/SNRIs): Concurrent use of almotriptan with these agents may increase the risk of serotonin syndrome; monitor.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use in pregnancy should be limited to situations where benefit outweighs risk to fetus. In some (but not all) animal studies, administration was associated with embryolethality, fetal malformations, and decreased pup weight.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — May be taken without regard to meals
PRICING — (data from drugstore.com)Tablets (Axert) 6.25 mg (6): $120.51
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Hypertension or more serious cardiovascular symptoms may occur. Clinical and electrocardiographic monitoring is needed for at least 20 hours even if patient is asymptomatic. Treatment is symptom-directed and supportive.
CANADIAN BRAND NAMES — Axert™
INTERNATIONAL BRAND NAMES — Almogran (BE, DE, DK, FI, FR, GB, IE, IT, NL); Axert® (CA)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B, 5-HT1D, 5-HT1F receptors) in cranial arteries; causes vasoconstriction and reduce sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine
PHARMACODYNAMICS / KINETICS Absorption: Well absorbed
Distribution: Vd: 180-200 L
Protein binding: ~35%
Metabolism: MAO type A oxidative deamination (~27% of dose); via CYP3A4 and 2D6 (~12% of dose) to inactive metabolites
Bioavailability: 70%
Half-life elimination: 3-4 hours
Time to peak: 1-3 hours
Excretion: Urine (40% as unchanged drug); feces (13% unchanged and metabolized)
PATIENT INFORMATION — This drug is to be used to reduce your migraine not to prevent or reduce the number of attacks. Take exactly as directed. If headache returns or is not fully resolved, the dose may be repeated after 2 hours. Do not use more than two doses in 24 hours. Do not take within 24 hours of other migraine medication without consulting prescriber. You may experience dizziness, fatigue, or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report immediately chest pain, palpitations, feeling of tightness or pressure in chest, jaw, or throat; acute headache or dizziness; muscle cramping, pain, or tremors; skin rash; hallucinations, anxiety, panic; or other adverse reactions.
PHARMACOLOGIC CATEGORY Antimigraine AgentSerotonin 5-HT1B, 1D Receptor Agonist
DOSING: ADULTS — Migraine: Oral: Initial: 6.25-12.5 mg in a single dose; if the headache returns, repeat the dose after 2 hours; no more than 2 doses in 24-hour period
Note: If the first dose is ineffective, diagnosis needs to be re-evaluated. Safety of treating more than 4 migraines/month has not been established.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSING: HEPATIC IMPAIRMENT — Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as malate: 6.25 mg, 12.5 mg
DOSAGE FORMS: CONCISE Tablet: Axert™: 6.25 mg, 12.5 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Acute treatment of migraine with or without aura
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Headache (>1%), dizziness (>1%), somnolence (>1%) Gastrointestinal: Nausea (1% to 2%), xerostomia (1%) Neuromuscular & skeletal: Paresthesia (1%)
<1% (Limited to important or life-threatening): Colitis, coronary artery vasospasm, hypertension, myocardial ischemia, MI, neuropathy, rash, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo
CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; use as prophylactic therapy for migraine; hemiplegic or basilar migraine; cluster headache; known or suspected ischemic heart disease (angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); peripheral vascular syndromes (including ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivative; concurrent administration or within 2 weeks of discontinuing an MAO inhibitor (specifically MAO type A inhibitors)
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported with 5-HT1 agonist administration. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses. Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT1 agonist administration. Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist. administration.
Disease-related concerns: Coronary artery disease: Should not be given to patients who have risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) without adequate cardiac evaluation. Patients with suspected CAD should have cardiovascular evaluation to rule out CAD before considering use; if cardiovascular evaluation "is satisfactory", first dose should be given in the healthcare provider's office. Periodic evaluation of cardiovascular status should be done in all patients. Hepatic impairment: Use with caution in patients with hepatic impairment. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended. Renal impairment: Use with caution in patients with moderate to severe renal failure.
Concurrent drug therapy issues: Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans) or agents which reduce almotriptan's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
Special populations: Pediatrics: Safety and efficacy have not been established in children <18 years of age.
Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; if a patient does not respond to the first dose, the diagnosis of migraine should be reconsidered.
DRUG INTERACTIONS — Substrate (minor) of CYP2D6, 3A4
Ergot-containing drugs: Prolong vasospastic reactions; do not use almotriptan or ergot-containing drugs within 24 hours of each other.
Ketoconazole: Increases almotriptan serum concentration. Monitor for increased almotriptan response.
MAO inhibitors (moclobemide [MAO type A inhibitor]): Almotriptan clearance decreased by 27%; Cmax increased by 6%. Avoid concurrent administration of MAO inhibitors or within 2 weeks of discontinuing an MAO inhibitor, specifically MAO type A inhibitors.
Selegiline: Selegiline is a selective MAO type B inhibitor; while not specifically contraindicated, combination has not been studied.
Verapamil: Increased almotriptan serum concentration by 24%. Dose adjustment not necessary.
Serotonin agonists (eg, triptans): Concurrent use of almotriptan with these agents may increase the risk of serotonin syndrome; monitor.
Serotonergic reuptake inhibitors (eg, SSRIs/SNRIs): Concurrent use of almotriptan with these agents may increase the risk of serotonin syndrome; monitor.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Use in pregnancy should be limited to situations where benefit outweighs risk to fetus. In some (but not all) animal studies, administration was associated with embryolethality, fetal malformations, and decreased pup weight.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — May be taken without regard to meals
PRICING — (data from drugstore.com)Tablets (Axert) 6.25 mg (6): $120.51
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Hypertension or more serious cardiovascular symptoms may occur. Clinical and electrocardiographic monitoring is needed for at least 20 hours even if patient is asymptomatic. Treatment is symptom-directed and supportive.
CANADIAN BRAND NAMES — Axert™
INTERNATIONAL BRAND NAMES — Almogran (BE, DE, DK, FI, FR, GB, IE, IT, NL); Axert® (CA)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B, 5-HT1D, 5-HT1F receptors) in cranial arteries; causes vasoconstriction and reduce sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine
PHARMACODYNAMICS / KINETICS Absorption: Well absorbed
Distribution: Vd: 180-200 L
Protein binding: ~35%
Metabolism: MAO type A oxidative deamination (~27% of dose); via CYP3A4 and 2D6 (~12% of dose) to inactive metabolites
Bioavailability: 70%
Half-life elimination: 3-4 hours
Time to peak: 1-3 hours
Excretion: Urine (40% as unchanged drug); feces (13% unchanged and metabolized)
PATIENT INFORMATION — This drug is to be used to reduce your migraine not to prevent or reduce the number of attacks. Take exactly as directed. If headache returns or is not fully resolved, the dose may be repeated after 2 hours. Do not use more than two doses in 24 hours. Do not take within 24 hours of other migraine medication without consulting prescriber. You may experience dizziness, fatigue, or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report immediately chest pain, palpitations, feeling of tightness or pressure in chest, jaw, or throat; acute headache or dizziness; muscle cramping, pain, or tremors; skin rash; hallucinations, anxiety, panic; or other adverse reactions.
Allopurinol
U.S. BRAND NAMES — Aloprim™; Zyloprim®
PHARMACOLOGIC CATEGORY Xanthine Oxidase Inhibitor
DOSING: ADULTS — Doses >300 mg should be given in divided doses.
Gout: Oral: Mild: 200-300 mg/day; Severe: 400-600 mg/day; to reduce the possibility of acute gouty attacks, initiate dose at 100 mg/day and increase weekly to recommended dosage. Maximum daily dose: 800 mg/day.
Secondary hyperuricemia associated with chemotherapy: Oral: 600-800 mg/day in 2-3 divided doses for prevention of acute uric acid nephropathy for 2-3 days starting 1-2 days before chemotherapy I.V.: 200-400 mg/m2/day (maximum: 600 mg/day) Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. A fluid intake sufficient to yield a daily urinary output of at least 2 L in adults and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Recurrent calcium oxalate stones: 200-300 mg/day in single or divided doses
DOSING: PEDIATRIC
(For additional information see "Allopurinol: Pediatric drug information")Gout: Children >10 years: Refer to adult dosing.
Recurrent calcium oxalate stones: Children >10 years: Refer to adult dosing.
Secondary hyperuricemia associated with chemotherapy: Oral: Children 10 years: 10 mg/kg/day in 2-3 divided doses or 200-300 mg/m2/day in 2-4 divided doses, maximum: 800 mg/24 hours, for prevention of acute uric acid nephropathy (begin 1-2 days before chemotherapy) Alternative (manufacturer labeling): <6>10 years: Refer to adult dosing. I.V.: Children 10 years: Starting dose: 200 mg/m2/day Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. Adequate fluid intake and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable. Children >10 years: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 100 mg/day; increase until desired uric acid level is obtained. Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Oral: Must be adjusted due to accumulation of allopurinol and metabolites;
Adult Maintenance Doses of Allopurinol
Note: Doses are based on a standard maintenance dose of 300 mg of allopurinol per day for a patient with a creatinine clearance of 100 mL/minute. Clcr 140 mL/minute: 400 mg daily Clcr 120 mL/minute: 350 mg daily Clcr 100 mL/minute: 300 mg daily Clcr 80 mL/minute: 250 mg daily Clcr 60 mL/minute: 200 mg daily Clcr 40 mL/minute: 150 mg daily Clcr 20 mL/minute: 100 mg daily Clcr 10 mL/minute: 100 mg every 2 days Clcr 0 mL/minute: 100 mg every 3 days
Hemodialysis: Administer dose after hemodialysis or administer 50% supplemental dose.
I.V.: Clcr 10-20 mL/minute: Administer 200 mg/day. Clcr 3-10 mL/minute: Administer 100 mg/day. Clcr <3 mL/minute: Administer 100 mg/day at extended intervals.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium (Aloprim™): 500 mg
Tablet (Zyloprim®): 100 mg, 300 mg
DOSAGE FORMS: CONCISE Injection, powder for reconstitution: 500 mg Aloprim™: 500 mg
Tablet: 100 mg, 300 mg Zyloprim®: 100 mg, 300 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION Oral: Should administer oral forms after meals with plenty of fluid.
I.V.: Infuse over 15-60 minutes. The rate of infusion depends on the volume of the infusion. Whenever possible, therapy should be initiated at 24-48 hours before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids). I.V. daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour interval.
COMPATIBILITY — Stable in D5W, NS, sterile water for injection.
Y-site administration: Compatible: Acyclovir, aminophylline, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, cefazolin, cefoperazone, cefotetan, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cisplatin, co-trimoxazole, cyclophosphamide, dactinomycin, dexamethasone sodium phosphate, doxorubicin liposome, enalaprilat, etoposide, famotidine, fluconazole, fludarabine, fluorouracil, furosemide, ganciclovir, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, ifosfamide, lorazepam, mannitol, mesna, methotrexate, metronidazole, mitoxantrone, morphine, piperacillin, plicamycin, potassium chloride, ranitidine, thiotepa, ticarcillin, ticarcillin/clavulanate, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Amikacin, amphotericin B, carmustine, cefotaxime, chlorpromazine, cimetidine, clindamycin, cytarabine, dacarbazine, daunorubicin, diphenhydramine, doxorubicin, doxycycline, droperidol, floxuridine, gentamicin, haloperidol, hydroxyzine, idarubicin, imipenem/cilastatin, mechlorethamine, meperidine, methylprednisolone sodium succinate, metoclopramide, minocycline, nalbuphine, netilmicin, ondansetron, prochlorperazine edisylate, promethazine, sodium bicarbonate, streptozocin, tobramycin, vinorelbine.
USE Oral: Prevention of attack of gouty arthritis and nephropathy; treatment of secondary hyperuricemia which may occur during treatment of tumors or leukemia; prevention of recurrent calcium oxalate calculi
I.V.: Treatment of elevated serum and urinary uric acid levels when oral therapy is not tolerated in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer chemotherapy
ADVERSE REACTIONS SIGNIFICANT >1%: Dermatologic: Rash (increased with ampicillin or amoxicillin use, 1.5% per manufacturer, >10% in some reports) Gastrointestinal: Nausea (1.3%), vomiting (1.2%) Renal: Renal failure/impairment (1.2%)
<1% (Limited to important or life-threatening): Acute tubular necrosis, agranulocytosis, angioedema, aplastic anemia, bronchospasm, cataracts, exfoliative dermatitis, granuloma annulare, granulomatous hepatitis, hypersensitivity syndrome, interstitial nephritis, macular retinitis, nephrolithiasis, neuritis, pancreatitis, paresthesia, peripheral neuropathy, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxic pustuloderma, vasculitis
CONTRAINDICATIONS — Hypersensitivity to allopurinol or any component of the formulation
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Rash: Discontinue at first signs of rash.
Disease-related concerns: Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia. Renal impairment: Use with caution in patients with renal impairment; dosage adjustments needed.
Concurrent drug therapy issues: ACE inhibitors: The risk of hypersensitivity may be increased in patients receiving ACE inhibitors. Amoxicillin/ampicillin: Risk of skin rash may be increased in patients receiving amoxicillin or ampicillin. Azathioprine/mercaptopurine: Use with caution in patients taking mercaptopurine or azathioprine. Diuretics: Use with caution in patients taking diuretics concurrently. The risk of hypersensitivity may be increased in patients receiving thiazides.
DRUG INTERACTIONS Ampicillin, amoxicillin: Incidence of rash may be increased.
Anticoagulants: Allopurinol may prolong the half-life of anticoagulants, effect seen with dicumarol; monitor.
ACE inhibitors: Captopril may increase risk of hypersensitivity.
Azathioprine: Metabolism inhibited by allopurinol; reduce azathioprine dose by 1/3 or 1/4.
Chlorpropamide: Half-life of chlorpropamide may be increased.
Cyclosporine: Allopurinol may increase cyclosporine serum levels.
Mercaptopurine: Metabolism inhibited by allopurinol; reduce mercaptopurine dose by 1/3 or 1/4.
Thiazide diuretics: Toxicity and risk of hypersensitivity may be increased.
Theophylline: Half-life of theophylline may be increased.
Vidarabine: Neurotoxicity may be enhanced.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: May decrease effectiveness.
Iron supplements: Hepatic iron uptake may be increased.
Vitamin C: Large amounts of vitamin C may acidify urine and increase kidney stone formation.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are few reports describing the use of allopurinol during pregnancy; no adverse fetal outcomes attributable to allopurinol have been reported in humans; use only if potential benefit outweighs the potential risk to the fetus.
LACTATION — Enters breast milk/use caution (AAP rates "compatible")
DIETARY CONSIDERATIONS — Should administer oral forms after meals with plenty of fluid. Fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).
PRICING — (data from drugstore.com)Tablets (Zyloprim) 100 mg (30): $13.99 300 mg (30): $36.62
MONITORING PARAMETERS — CBC, serum uric acid levels, I & O, hepatic and renal function, especially at start of therapy
REFERENCE RANGE — Uric acid, serum: An increase occurs during childhood
Adults: Male: 3.4-7 mg/dL or slightly more Female: 2.4-6 mg/dL or slightly more
Values >7 mg/dL are sometimes arbitrarily regarded as hyperuricemia, but there is no sharp line between normals on the one hand, and the serum uric acid of those with clinical gout. Normal ranges cannot be adjusted for purine ingestion, but high purine diet increases uric acid. Uric acid may be increased with body size, exercise, and stress.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — At high dosages, it is a theoretical possibility that oxypurinol stones could be formed but no record of such occurrence in overdose exists. Alkalinization of the urine and forced diuresis can help prevent potential xanthine stone formation.
CANADIAN BRAND NAMES — Alloprin®; Apo-Allopurinol®; Novo-Purol; Zyloprim®
INTERNATIONAL BRAND NAMES — Adenock (JP); Alinol (TH); Allo 300 (DE); Allo-Basan (CH); Allo-Puren (DE); Allohexal (AU); Allopin (TH); Alloprin (CA); Allopur (CH, NO); Allopurinol (MY, PL); Alloratio (PL); Alloril (IL); Allorin (NZ); Allosig (AU); Allozym (JP); Allupol (PL); Allurase (PH); Allurit (IT); Alopron (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Alopurinol (HR); Alositol (JP); Alpurase (PH); Alpurin (PH); Alunlan (PH, TW); Alurin (GT); Aluron (VE); Anoprolin (JP); Anzief (JP); Apo-Allopurinol (CA, PL); Aprinol (JP); Apurin (DK, FI, GR); Atisuril (MX); Benoxuric (ID); Bleminal (DE); Caplenal (GB, IE); Capurate (TW); Cellidrin (DE); Clint (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Etindrax (MX); Foligan (CH, DE); Gichtex (AT); Hamarin (GB); Hycemia (ID); Isoric (ID); Ketanrift (JP); Ketobun-A (JP); Licoric (ID); Litinol (VE); Llanol (ID, PH); Lo-Uric (ZA); Lysuron 300 (CH); Masaton (JP); Medoric (TH); Mefanol (EC); Mephanol (AE, BF, BH, BJ, CH, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TZ, UG, YE, ZM, ZW); Milurit (BG, HK, HU, PL); Miniplanor (JP); Neufan (JP); Nipurol (VE); No-Uric (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Novo-Purol (CA); Progout (AU, CN, HK, NZ, SG); Proxuric (ID); Puricos (ZA); Purinol (IE, MY); Puristen (PH); Ranpuric (ZA); Remid (DE); Riball (JP); Rinolic (ID); Salterprim (ZA); Sinoric (ID); Takanarumin (JP); Tonsaric (TW); Trianol (PH); Uric (JP); Uricad (TH); Uricnol (ID); Uriconorm (CH); Urinol (MY); Uripurinol (DE); Urogquad (AR); Uroquad (AN, BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, ID, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, SR, TT, TZ, UG, ZM, ZW); Urosin (AT, DE, EC); Vitralgin (PE); Xanturic (FR); Xanurace (PH); Xylonol (TW); Z300 (NZ); Zylapour (GR); Zylol (IL); Zyloprim (AN, AU, BB, BM, BS, BZ, CA, CR, DO, GT, GY, HN, JM, NI, PA, PH, PY, SR, SV, TT, ZA); Zyloric (AE, AR, BE, BF, BG, BH, BJ, BR, CH, CI, CL, CN, CY, CZ, DE, DK, EG, ES, ET, FI, FR, GB, GH, GM, GN, HK, ID, IE, IN, IQ, IR, IT, JO, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NO, OM, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SY, TH, TW, TZ, UG, UY, VE, YE, ZM, ZW); Zyroric (KR)
MECHANISM OF ACTION — Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase; allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.
PHARMACODYNAMICS / KINETICS Onset of action: Peak effect: 1-2 weeks
Absorption: Oral: ~80%; Rectal: Poor and erratic
Distribution: Vd: ~1.6 L/kg; Vss: 0.84-0.87 L/kg; enters breast milk
Protein binding: <1%
Metabolism: ~75% to active metabolites, chiefly oxypurinol
Bioavailability: 49% to 53%
Half-life elimination: Normal renal function: Parent drug: 1-3 hours; Oxypurinol: 18-30 hours End-stage renal disease: Prolonged
Time to peak, plasma: Oral: 30-120 minutes
Excretion: Urine (76% as oxypurinol, 12% as unchanged drug)
Allopurinol and oxypurinol are dialyzable
PATIENT INFORMATION — Take after meals with plenty of fluid (at least 10-12 glasses of fluids per day); discontinue the drug and contact prescriber at first sign of rash, painful urination, blood in urine, irritation of the eyes, or swelling of the lips or mouth; may cause drowsiness; alcohol decreases effectiveness
PHARMACOLOGIC CATEGORY Xanthine Oxidase Inhibitor
DOSING: ADULTS — Doses >300 mg should be given in divided doses.
Gout: Oral: Mild: 200-300 mg/day; Severe: 400-600 mg/day; to reduce the possibility of acute gouty attacks, initiate dose at 100 mg/day and increase weekly to recommended dosage. Maximum daily dose: 800 mg/day.
Secondary hyperuricemia associated with chemotherapy: Oral: 600-800 mg/day in 2-3 divided doses for prevention of acute uric acid nephropathy for 2-3 days starting 1-2 days before chemotherapy I.V.: 200-400 mg/m2/day (maximum: 600 mg/day) Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. A fluid intake sufficient to yield a daily urinary output of at least 2 L in adults and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Recurrent calcium oxalate stones: 200-300 mg/day in single or divided doses
DOSING: PEDIATRIC
(For additional information see "Allopurinol: Pediatric drug information")Gout: Children >10 years: Refer to adult dosing.
Recurrent calcium oxalate stones: Children >10 years: Refer to adult dosing.
Secondary hyperuricemia associated with chemotherapy: Oral: Children 10 years: 10 mg/kg/day in 2-3 divided doses or 200-300 mg/m2/day in 2-4 divided doses, maximum: 800 mg/24 hours, for prevention of acute uric acid nephropathy (begin 1-2 days before chemotherapy) Alternative (manufacturer labeling): <6>10 years: Refer to adult dosing. I.V.: Children 10 years: Starting dose: 200 mg/m2/day Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. Adequate fluid intake and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable. Children >10 years: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 100 mg/day; increase until desired uric acid level is obtained. Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Oral: Must be adjusted due to accumulation of allopurinol and metabolites;
Adult Maintenance Doses of Allopurinol
Note: Doses are based on a standard maintenance dose of 300 mg of allopurinol per day for a patient with a creatinine clearance of 100 mL/minute. Clcr 140 mL/minute: 400 mg daily Clcr 120 mL/minute: 350 mg daily Clcr 100 mL/minute: 300 mg daily Clcr 80 mL/minute: 250 mg daily Clcr 60 mL/minute: 200 mg daily Clcr 40 mL/minute: 150 mg daily Clcr 20 mL/minute: 100 mg daily Clcr 10 mL/minute: 100 mg every 2 days Clcr 0 mL/minute: 100 mg every 3 days
Hemodialysis: Administer dose after hemodialysis or administer 50% supplemental dose.
I.V.: Clcr 10-20 mL/minute: Administer 200 mg/day. Clcr 3-10 mL/minute: Administer 100 mg/day. Clcr <3 mL/minute: Administer 100 mg/day at extended intervals.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium (Aloprim™): 500 mg
Tablet (Zyloprim®): 100 mg, 300 mg
DOSAGE FORMS: CONCISE Injection, powder for reconstitution: 500 mg Aloprim™: 500 mg
Tablet: 100 mg, 300 mg Zyloprim®: 100 mg, 300 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION Oral: Should administer oral forms after meals with plenty of fluid.
I.V.: Infuse over 15-60 minutes. The rate of infusion depends on the volume of the infusion. Whenever possible, therapy should be initiated at 24-48 hours before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids). I.V. daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour interval.
COMPATIBILITY — Stable in D5W, NS, sterile water for injection.
Y-site administration: Compatible: Acyclovir, aminophylline, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, cefazolin, cefoperazone, cefotetan, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cisplatin, co-trimoxazole, cyclophosphamide, dactinomycin, dexamethasone sodium phosphate, doxorubicin liposome, enalaprilat, etoposide, famotidine, fluconazole, fludarabine, fluorouracil, furosemide, ganciclovir, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, ifosfamide, lorazepam, mannitol, mesna, methotrexate, metronidazole, mitoxantrone, morphine, piperacillin, plicamycin, potassium chloride, ranitidine, thiotepa, ticarcillin, ticarcillin/clavulanate, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Amikacin, amphotericin B, carmustine, cefotaxime, chlorpromazine, cimetidine, clindamycin, cytarabine, dacarbazine, daunorubicin, diphenhydramine, doxorubicin, doxycycline, droperidol, floxuridine, gentamicin, haloperidol, hydroxyzine, idarubicin, imipenem/cilastatin, mechlorethamine, meperidine, methylprednisolone sodium succinate, metoclopramide, minocycline, nalbuphine, netilmicin, ondansetron, prochlorperazine edisylate, promethazine, sodium bicarbonate, streptozocin, tobramycin, vinorelbine.
USE Oral: Prevention of attack of gouty arthritis and nephropathy; treatment of secondary hyperuricemia which may occur during treatment of tumors or leukemia; prevention of recurrent calcium oxalate calculi
I.V.: Treatment of elevated serum and urinary uric acid levels when oral therapy is not tolerated in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer chemotherapy
ADVERSE REACTIONS SIGNIFICANT >1%: Dermatologic: Rash (increased with ampicillin or amoxicillin use, 1.5% per manufacturer, >10% in some reports) Gastrointestinal: Nausea (1.3%), vomiting (1.2%) Renal: Renal failure/impairment (1.2%)
<1% (Limited to important or life-threatening): Acute tubular necrosis, agranulocytosis, angioedema, aplastic anemia, bronchospasm, cataracts, exfoliative dermatitis, granuloma annulare, granulomatous hepatitis, hypersensitivity syndrome, interstitial nephritis, macular retinitis, nephrolithiasis, neuritis, pancreatitis, paresthesia, peripheral neuropathy, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxic pustuloderma, vasculitis
CONTRAINDICATIONS — Hypersensitivity to allopurinol or any component of the formulation
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Rash: Discontinue at first signs of rash.
Disease-related concerns: Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia. Renal impairment: Use with caution in patients with renal impairment; dosage adjustments needed.
Concurrent drug therapy issues: ACE inhibitors: The risk of hypersensitivity may be increased in patients receiving ACE inhibitors. Amoxicillin/ampicillin: Risk of skin rash may be increased in patients receiving amoxicillin or ampicillin. Azathioprine/mercaptopurine: Use with caution in patients taking mercaptopurine or azathioprine. Diuretics: Use with caution in patients taking diuretics concurrently. The risk of hypersensitivity may be increased in patients receiving thiazides.
DRUG INTERACTIONS Ampicillin, amoxicillin: Incidence of rash may be increased.
Anticoagulants: Allopurinol may prolong the half-life of anticoagulants, effect seen with dicumarol; monitor.
ACE inhibitors: Captopril may increase risk of hypersensitivity.
Azathioprine: Metabolism inhibited by allopurinol; reduce azathioprine dose by 1/3 or 1/4.
Chlorpropamide: Half-life of chlorpropamide may be increased.
Cyclosporine: Allopurinol may increase cyclosporine serum levels.
Mercaptopurine: Metabolism inhibited by allopurinol; reduce mercaptopurine dose by 1/3 or 1/4.
Thiazide diuretics: Toxicity and risk of hypersensitivity may be increased.
Theophylline: Half-life of theophylline may be increased.
Vidarabine: Neurotoxicity may be enhanced.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: May decrease effectiveness.
Iron supplements: Hepatic iron uptake may be increased.
Vitamin C: Large amounts of vitamin C may acidify urine and increase kidney stone formation.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — There are few reports describing the use of allopurinol during pregnancy; no adverse fetal outcomes attributable to allopurinol have been reported in humans; use only if potential benefit outweighs the potential risk to the fetus.
LACTATION — Enters breast milk/use caution (AAP rates "compatible")
DIETARY CONSIDERATIONS — Should administer oral forms after meals with plenty of fluid. Fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).
PRICING — (data from drugstore.com)Tablets (Zyloprim) 100 mg (30): $13.99 300 mg (30): $36.62
MONITORING PARAMETERS — CBC, serum uric acid levels, I & O, hepatic and renal function, especially at start of therapy
REFERENCE RANGE — Uric acid, serum: An increase occurs during childhood
Adults: Male: 3.4-7 mg/dL or slightly more Female: 2.4-6 mg/dL or slightly more
Values >7 mg/dL are sometimes arbitrarily regarded as hyperuricemia, but there is no sharp line between normals on the one hand, and the serum uric acid of those with clinical gout. Normal ranges cannot be adjusted for purine ingestion, but high purine diet increases uric acid. Uric acid may be increased with body size, exercise, and stress.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — At high dosages, it is a theoretical possibility that oxypurinol stones could be formed but no record of such occurrence in overdose exists. Alkalinization of the urine and forced diuresis can help prevent potential xanthine stone formation.
CANADIAN BRAND NAMES — Alloprin®; Apo-Allopurinol®; Novo-Purol; Zyloprim®
INTERNATIONAL BRAND NAMES — Adenock (JP); Alinol (TH); Allo 300 (DE); Allo-Basan (CH); Allo-Puren (DE); Allohexal (AU); Allopin (TH); Alloprin (CA); Allopur (CH, NO); Allopurinol (MY, PL); Alloratio (PL); Alloril (IL); Allorin (NZ); Allosig (AU); Allozym (JP); Allupol (PL); Allurase (PH); Allurit (IT); Alopron (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Alopurinol (HR); Alositol (JP); Alpurase (PH); Alpurin (PH); Alunlan (PH, TW); Alurin (GT); Aluron (VE); Anoprolin (JP); Anzief (JP); Apo-Allopurinol (CA, PL); Aprinol (JP); Apurin (DK, FI, GR); Atisuril (MX); Benoxuric (ID); Bleminal (DE); Caplenal (GB, IE); Capurate (TW); Cellidrin (DE); Clint (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Etindrax (MX); Foligan (CH, DE); Gichtex (AT); Hamarin (GB); Hycemia (ID); Isoric (ID); Ketanrift (JP); Ketobun-A (JP); Licoric (ID); Litinol (VE); Llanol (ID, PH); Lo-Uric (ZA); Lysuron 300 (CH); Masaton (JP); Medoric (TH); Mefanol (EC); Mephanol (AE, BF, BH, BJ, CH, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TZ, UG, YE, ZM, ZW); Milurit (BG, HK, HU, PL); Miniplanor (JP); Neufan (JP); Nipurol (VE); No-Uric (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Novo-Purol (CA); Progout (AU, CN, HK, NZ, SG); Proxuric (ID); Puricos (ZA); Purinol (IE, MY); Puristen (PH); Ranpuric (ZA); Remid (DE); Riball (JP); Rinolic (ID); Salterprim (ZA); Sinoric (ID); Takanarumin (JP); Tonsaric (TW); Trianol (PH); Uric (JP); Uricad (TH); Uricnol (ID); Uriconorm (CH); Urinol (MY); Uripurinol (DE); Urogquad (AR); Uroquad (AN, BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, ID, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, SR, TT, TZ, UG, ZM, ZW); Urosin (AT, DE, EC); Vitralgin (PE); Xanturic (FR); Xanurace (PH); Xylonol (TW); Z300 (NZ); Zylapour (GR); Zylol (IL); Zyloprim (AN, AU, BB, BM, BS, BZ, CA, CR, DO, GT, GY, HN, JM, NI, PA, PH, PY, SR, SV, TT, ZA); Zyloric (AE, AR, BE, BF, BG, BH, BJ, BR, CH, CI, CL, CN, CY, CZ, DE, DK, EG, ES, ET, FI, FR, GB, GH, GM, GN, HK, ID, IE, IN, IQ, IR, IT, JO, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NO, OM, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SY, TH, TW, TZ, UG, UY, VE, YE, ZM, ZW); Zyroric (KR)
MECHANISM OF ACTION — Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase; allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.
PHARMACODYNAMICS / KINETICS Onset of action: Peak effect: 1-2 weeks
Absorption: Oral: ~80%; Rectal: Poor and erratic
Distribution: Vd: ~1.6 L/kg; Vss: 0.84-0.87 L/kg; enters breast milk
Protein binding: <1%
Metabolism: ~75% to active metabolites, chiefly oxypurinol
Bioavailability: 49% to 53%
Half-life elimination: Normal renal function: Parent drug: 1-3 hours; Oxypurinol: 18-30 hours End-stage renal disease: Prolonged
Time to peak, plasma: Oral: 30-120 minutes
Excretion: Urine (76% as oxypurinol, 12% as unchanged drug)
Allopurinol and oxypurinol are dialyzable
PATIENT INFORMATION — Take after meals with plenty of fluid (at least 10-12 glasses of fluids per day); discontinue the drug and contact prescriber at first sign of rash, painful urination, blood in urine, irritation of the eyes, or swelling of the lips or mouth; may cause drowsiness; alcohol decreases effectiveness
All-trans retinoic acid
U.S. BRAND NAMES — Vesanoid®
PHARMACOLOGIC CATEGORY Antineoplastic Agent, Miscellaneous
DOSING: ADULTS Acute promyelocytic leukemia (APL): Oral: Remission induction: 45 mg/m2/day in 2-3 divided doses for up to 30 days after complete remission (maximum duration of treatment: 90 days) Remission maintenance: 45-200 mg/m2/day in 2-3 divided doses for up to 12 months.
DOSING: PEDIATRIC — APL induction of remission, remission maintenance: Oral: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 10 mg [contains soybean oil and parabens]
DOSAGE FORMS: CONCISE Capsule: Vesanoid®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer with meals; do not crush capsules
USE — Induction of remission in patients with acute promyelocytic leukemia (APL), French American British (FAB) classification M3 (including the M3 variant)
ADVERSE REACTIONS SIGNIFICANT — Virtually all patients experience some drug-related toxicity, especially headache, fever, weakness and fatigue. These adverse effects are seldom permanent or irreversible nor do they usually require therapy interruption.
>10%: Cardiovascular: Peripheral edema (52%), chest discomfort (32%), edema (29%), arrhythmias (23%), flushing (23%), hypotension (14%), hypertension (11%) Central nervous system: Headache (86%), fever (83%), malaise (66%), pain (37%), dizziness (20%), anxiety (17%), insomnia (14%), depression (14%), confusion (11%) Dermatologic: Skin/mucous membrane dryness (77%), pruritus (20%), rash (54%), alopecia (14%) Endocrine & metabolic: Hypercholesterolemia and/or hypertriglyceridemia (60%) Gastrointestinal: Nausea/vomiting (57%), liver function tests increased (50% to 60%), GI hemorrhage (34%), abdominal pain (31%), mucositis (26%), diarrhea (23%), constipation (17%), dyspepsia (14%), abdominal distention (11%), weight gain (23%), weight loss (17%), xerostomia, anorexia (17%) Hematologic: Hemorrhage (60%), leukocytosis (40%), disseminated intravascular coagulation (DIC) (26%) Local: Phlebitis (11%), injection site reactions (17%) Neuromuscular & skeletal: Bone pain (77%), myalgia (14%), paresthesia (17%) Ocular: Visual disturbances (17%) Otic: Earache/ear fullness (23%) Renal: Renal insufficiency (11%) Respiratory: Upper respiratory tract disorders (63%), dyspnea (60%), respiratory insufficiency (26%), pleural effusion (20%), pneumonia (14%), rales (14%), expiratory wheezing (14%), dry nose Miscellaneous: Infection (58%), shivering (63%), retinoic acid-acute promyelocytic leukemia syndrome (25%), diaphoresis increased (20%)
1% to 10%: Cardiovascular: Cerebral hemorrhage (9%), pallor (6%), cardiac failure (6%), cardiac arrest (3%), enlarged heart (3%), heart murmur (3%), ischemia, stroke (3%), MI (93%), myocarditis (3%), pericarditis (3%), pulmonary hypertension (3%), secondary cardiomyopathy (3%) Central nervous system: Intracranial hypertension (9%), agitation (9%), hallucination (6%), agnosia (3%), aphasia (3%), cerebellar edema (3%), cerebral hemorrhage (9%), seizure (3%), coma (3%), CNS depression (3%), dysarthria (3%), encephalopathy (3%), hypotaxia (3%), light reflex absent (3%), spinal cord disorder (3%), unconsciousness (3%), dementia (3%), forgetfulness (3%), somnolence (3%), slow speech (3%), hypothermia (3%) Dermatologic: Cellulitis (8%), photosensitivity Endocrine & metabolic: Acidosis (3%) Gastrointestinal: Hepatosplenomegaly (9%), hepatitis (3%), ulcer (3%) Genitourinary: Dysuria (9%), acute renal failure (3%), micturition frequency (3%), renal tubular necrosis (3%), enlarged prostate (3%) Hepatic: Ascites (3%), hepatitis Neuromuscular & skeletal: Tremor (3%), leg weakness (3%), hyporeflexia, dysarthria, facial paralysis, hemiplegia, flank pain, asterixis, abnormal gait (3%), bone inflammation (3%) Ocular: Dry eyes, visual acuity change (6%), visual field deficit (3%) Otic: Hearing loss Renal: Acute renal failure, renal tubular necrosis Respiratory: Lower respiratory tract disorders (9%), pulmonary infiltration (6%), bronchial asthma (3%), pulmonary/larynx edema Miscellaneous: Face edema
<1% (Limited to important or life-threatening): Arterial thrombosis, basophilia, cataracts, conjunctivitis, erythema nodosum, hypercalcemia, hyperuricemia, inflammatory bowel syndrome, irreversible hearing loss, pancreatitis, pseudomotor cerebri, renal infarct, Sweet's syndrome, vasculitis, venous thrombosis
CONTRAINDICATIONS — Sensitivity to parabens, vitamin A, other retinoids, or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS Box warnings: Acute promyelocytic leukemia (APL): See "Disease-related concerns" below. Experienced physician: See "Other warnings/precautions" below. Leukocytosis: See "Concerns related to adverse effects" below. Pregnancy: See "Special populations" below.
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Leukocytosis: [U.S. Boxed Warning]: During treatment, ~40% of patients will develop rapidly evolving leukocytosis; may be associated with a higher risk of life-threatening complications. Lipid effects: Up to 60% of patients experienced hypercholesterolemia or hypertriglyceridemia, which were reversible upon completion of treatment. Liver function test abnormalities: Elevated liver function test results occur in 50% to 60% of patients during treatment. Carefully monitor liver function test results during treatment and give consideration to a temporary withdrawal of tretinoin if test results reach >5 times the upper limit of normal. Pseudotumor cerebri: Retinoids have been associated with pseudotumor cerebri (benign intracranial hypertension), especially in children. Concurrent use of other drugs associated with this effect (eg, tetracyclines) may increase risk. Early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Disease-related concerns: Acute promyelocytic leukemia (APL): [U.S. Boxed Warning]: Patients with APL are at high risk and can have severe adverse reactions to tretinoin. About 25% of patients with APL and treated with tretinoin, have experienced retinoic acid-APL (RA-APL) syndrome, characterized by fever, dyspnea, acute respiratory distress, weight gain, radiographic pulmonary infiltrates and pleural or pericardial effusions, edema, and hepatic, renal, and/or multiorgan failure. This syndrome has occasionally been accompanied by impaired myocardial contractility and episodic hypotension. It has been observed with or without concomitant leukocytosis. Endotracheal intubation and mechanical ventilation have been required in some cases due to progressive hypoxemia, and several patients have expired with multiorgan failure. The syndrome usually occurs during the first month of treatment, with some cases reported following the first dose. Management of the syndrome has not been defined, but high-dose steroids given at the first suspicion of RA-APL syndrome appear to reduce morbidity and mortality. At the first signs suggestive of the syndrome, immediately initiate high-dose steroids (dexamethasone 10 mg I.V.) every 12 hours for 3 days or until resolution of symptoms, regardless of the leukocyte count. The majority of patients do not require termination of tretinoin therapy during treatment of the RA-APL syndrome. If signs and symptoms of the RA-APL syndrome are present together with leukocytosis, initiate treatment with high-dose steroids immediately. Consider adding full-dose chemotherapy (including an anthracycline, if not contraindicated) to the tretinoin therapy on day 1 or 2 for patients presenting with a WBC count of >5 x 109/L or immediately, for patients presenting with a WBC count of <5 x 109/L, if the WBC count reaches 6 x 109/L by day 5, or 10 x 109/L by day 10 or 15 x 109/L by day 28.
Special populations: Pregnancy: [U.S. Boxed Warning]: High risk of teratogenicity; not to be used in women of childbearing potential unless the woman is capable of complying with effective contraceptive measures. Repeat pregnancy testing and contraception counseling monthly throughout the period of treatment.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
DRUG INTERACTIONS — Substrate of CYP2A6 (minor), 2B6 (minor), 2C8 (major), 2C9 (minor); Inhibits CYP2C9 (weak); Induces CYP2E1 (weak)
Antifibrinolytic agents (eg, aminocaproic acid, aprotinin, tranexamic acid): Concurrent use may increase risk of thrombosis.
CYP2C8 Inhibitors may increase the levels/effects of tretinoin. Example inhibitors include atazanavir, gemfibrozil, and ritonavir.
Ketoconazole: Increases the mean plasma AUC of tretinoin.
Tetracyclines: Concurrent use may increase risk of pseudotumor cerebri.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol (may increase CNS depression).
Food: Absorption of retinoids has been shown to be enhanced when taken with food.
Herb/Nutraceutical: St John's wort may decrease tretinoin levels. Avoid dong quai, St John's wort (may also cause photosensitization). Avoid additional vitamin A supplementation. May lead to vitamin A toxicity.
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Oral tretinoin is teratogenic and fetotoxic in rats at doses 1000 and 500 times the topical human dose, respectively.
LACTATION — Enters breast milk/not recommended
DIETARY CONSIDERATIONS — To enhance absorption, some clinicians recommend giving with a fatty meal. Capsule contains soybean oil.
PRICING — (data from drugstore.com)Capsules (Vesanoid) 10 mg (30): $554.88
MONITORING PARAMETERS — Monitor the patient's hematologic profile, coagulation profile, liver function test results and triglyceride and cholesterol levels frequently
TOXICOLOGY / OVERDOSE COMPREHENSIVE — The maximum tolerated dose in adult patients with myelodysplastic syndrome in solid tumors was 195 mg/m2/day; the maximum tolerated dose in pediatric patients was lower at 60 mg/m2/day. Overdosage with other retinoids has been associated with transient headache, facial flushing, cheilosis, abdominal pain, dizziness, and ataxia. These symptoms resolved quickly without residual effects.
CANADIAN BRAND NAMES — Vesanoid®
INTERNATIONAL BRAND NAMES — Vesanoid (CA. PL)
MECHANISM OF ACTION — Tretinoin appears to bind one or more nuclear receptors and inhibits clonal proliferation and/or granulocyte differentiation
PHARMACODYNAMICS / KINETICS Protein binding: >95%
Metabolism: Hepatic via CYP; primary metabolite: 4-oxo-all-trans-retinoic acid
Half-life elimination: Terminal: Parent drug: 0.5-2 hours
Time to peak, serum: 1-2 hours
Excretion: Urine (63%); feces (30%)
PATIENT INFORMATION — Take with food; do not crush, chew, or dissolve capsules. You will need frequent blood tests while taking this medication. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake), avoid alcohol and foods containing vitamin A, and foods with high fat content. You may experience lethargy, dizziness, visual changes, confusion, anxiety (avoid driving or engaging in tasks requiring alertness until response to drug is known). For nausea/vomiting, loss of appetite, or dry mouth, small frequent meals, chewing gum, or sucking lozenges may help. You may experience photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). You may experience dry, itchy, skin, and dry or irritated eyes (avoid contact lenses). Report persistent vomiting or diarrhea, difficulty breathing, unusual bleeding or bruising, acute GI pain, bone pain, or vision changes immediately.
PHARMACOLOGIC CATEGORY Antineoplastic Agent, Miscellaneous
DOSING: ADULTS Acute promyelocytic leukemia (APL): Oral: Remission induction: 45 mg/m2/day in 2-3 divided doses for up to 30 days after complete remission (maximum duration of treatment: 90 days) Remission maintenance: 45-200 mg/m2/day in 2-3 divided doses for up to 12 months.
DOSING: PEDIATRIC — APL induction of remission, remission maintenance: Oral: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 10 mg [contains soybean oil and parabens]
DOSAGE FORMS: CONCISE Capsule: Vesanoid®: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer with meals; do not crush capsules
USE — Induction of remission in patients with acute promyelocytic leukemia (APL), French American British (FAB) classification M3 (including the M3 variant)
ADVERSE REACTIONS SIGNIFICANT — Virtually all patients experience some drug-related toxicity, especially headache, fever, weakness and fatigue. These adverse effects are seldom permanent or irreversible nor do they usually require therapy interruption.
>10%: Cardiovascular: Peripheral edema (52%), chest discomfort (32%), edema (29%), arrhythmias (23%), flushing (23%), hypotension (14%), hypertension (11%) Central nervous system: Headache (86%), fever (83%), malaise (66%), pain (37%), dizziness (20%), anxiety (17%), insomnia (14%), depression (14%), confusion (11%) Dermatologic: Skin/mucous membrane dryness (77%), pruritus (20%), rash (54%), alopecia (14%) Endocrine & metabolic: Hypercholesterolemia and/or hypertriglyceridemia (60%) Gastrointestinal: Nausea/vomiting (57%), liver function tests increased (50% to 60%), GI hemorrhage (34%), abdominal pain (31%), mucositis (26%), diarrhea (23%), constipation (17%), dyspepsia (14%), abdominal distention (11%), weight gain (23%), weight loss (17%), xerostomia, anorexia (17%) Hematologic: Hemorrhage (60%), leukocytosis (40%), disseminated intravascular coagulation (DIC) (26%) Local: Phlebitis (11%), injection site reactions (17%) Neuromuscular & skeletal: Bone pain (77%), myalgia (14%), paresthesia (17%) Ocular: Visual disturbances (17%) Otic: Earache/ear fullness (23%) Renal: Renal insufficiency (11%) Respiratory: Upper respiratory tract disorders (63%), dyspnea (60%), respiratory insufficiency (26%), pleural effusion (20%), pneumonia (14%), rales (14%), expiratory wheezing (14%), dry nose Miscellaneous: Infection (58%), shivering (63%), retinoic acid-acute promyelocytic leukemia syndrome (25%), diaphoresis increased (20%)
1% to 10%: Cardiovascular: Cerebral hemorrhage (9%), pallor (6%), cardiac failure (6%), cardiac arrest (3%), enlarged heart (3%), heart murmur (3%), ischemia, stroke (3%), MI (93%), myocarditis (3%), pericarditis (3%), pulmonary hypertension (3%), secondary cardiomyopathy (3%) Central nervous system: Intracranial hypertension (9%), agitation (9%), hallucination (6%), agnosia (3%), aphasia (3%), cerebellar edema (3%), cerebral hemorrhage (9%), seizure (3%), coma (3%), CNS depression (3%), dysarthria (3%), encephalopathy (3%), hypotaxia (3%), light reflex absent (3%), spinal cord disorder (3%), unconsciousness (3%), dementia (3%), forgetfulness (3%), somnolence (3%), slow speech (3%), hypothermia (3%) Dermatologic: Cellulitis (8%), photosensitivity Endocrine & metabolic: Acidosis (3%) Gastrointestinal: Hepatosplenomegaly (9%), hepatitis (3%), ulcer (3%) Genitourinary: Dysuria (9%), acute renal failure (3%), micturition frequency (3%), renal tubular necrosis (3%), enlarged prostate (3%) Hepatic: Ascites (3%), hepatitis Neuromuscular & skeletal: Tremor (3%), leg weakness (3%), hyporeflexia, dysarthria, facial paralysis, hemiplegia, flank pain, asterixis, abnormal gait (3%), bone inflammation (3%) Ocular: Dry eyes, visual acuity change (6%), visual field deficit (3%) Otic: Hearing loss Renal: Acute renal failure, renal tubular necrosis Respiratory: Lower respiratory tract disorders (9%), pulmonary infiltration (6%), bronchial asthma (3%), pulmonary/larynx edema Miscellaneous: Face edema
<1% (Limited to important or life-threatening): Arterial thrombosis, basophilia, cataracts, conjunctivitis, erythema nodosum, hypercalcemia, hyperuricemia, inflammatory bowel syndrome, irreversible hearing loss, pancreatitis, pseudomotor cerebri, renal infarct, Sweet's syndrome, vasculitis, venous thrombosis
CONTRAINDICATIONS — Sensitivity to parabens, vitamin A, other retinoids, or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS Box warnings: Acute promyelocytic leukemia (APL): See "Disease-related concerns" below. Experienced physician: See "Other warnings/precautions" below. Leukocytosis: See "Concerns related to adverse effects" below. Pregnancy: See "Special populations" below.
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Leukocytosis: [U.S. Boxed Warning]: During treatment, ~40% of patients will develop rapidly evolving leukocytosis; may be associated with a higher risk of life-threatening complications. Lipid effects: Up to 60% of patients experienced hypercholesterolemia or hypertriglyceridemia, which were reversible upon completion of treatment. Liver function test abnormalities: Elevated liver function test results occur in 50% to 60% of patients during treatment. Carefully monitor liver function test results during treatment and give consideration to a temporary withdrawal of tretinoin if test results reach >5 times the upper limit of normal. Pseudotumor cerebri: Retinoids have been associated with pseudotumor cerebri (benign intracranial hypertension), especially in children. Concurrent use of other drugs associated with this effect (eg, tetracyclines) may increase risk. Early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Disease-related concerns: Acute promyelocytic leukemia (APL): [U.S. Boxed Warning]: Patients with APL are at high risk and can have severe adverse reactions to tretinoin. About 25% of patients with APL and treated with tretinoin, have experienced retinoic acid-APL (RA-APL) syndrome, characterized by fever, dyspnea, acute respiratory distress, weight gain, radiographic pulmonary infiltrates and pleural or pericardial effusions, edema, and hepatic, renal, and/or multiorgan failure. This syndrome has occasionally been accompanied by impaired myocardial contractility and episodic hypotension. It has been observed with or without concomitant leukocytosis. Endotracheal intubation and mechanical ventilation have been required in some cases due to progressive hypoxemia, and several patients have expired with multiorgan failure. The syndrome usually occurs during the first month of treatment, with some cases reported following the first dose. Management of the syndrome has not been defined, but high-dose steroids given at the first suspicion of RA-APL syndrome appear to reduce morbidity and mortality. At the first signs suggestive of the syndrome, immediately initiate high-dose steroids (dexamethasone 10 mg I.V.) every 12 hours for 3 days or until resolution of symptoms, regardless of the leukocyte count. The majority of patients do not require termination of tretinoin therapy during treatment of the RA-APL syndrome. If signs and symptoms of the RA-APL syndrome are present together with leukocytosis, initiate treatment with high-dose steroids immediately. Consider adding full-dose chemotherapy (including an anthracycline, if not contraindicated) to the tretinoin therapy on day 1 or 2 for patients presenting with a WBC count of >5 x 109/L or immediately, for patients presenting with a WBC count of <5 x 109/L, if the WBC count reaches 6 x 109/L by day 5, or 10 x 109/L by day 10 or 15 x 109/L by day 28.
Special populations: Pregnancy: [U.S. Boxed Warning]: High risk of teratogenicity; not to be used in women of childbearing potential unless the woman is capable of complying with effective contraceptive measures. Repeat pregnancy testing and contraception counseling monthly throughout the period of treatment.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
DRUG INTERACTIONS — Substrate of CYP2A6 (minor), 2B6 (minor), 2C8 (major), 2C9 (minor); Inhibits CYP2C9 (weak); Induces CYP2E1 (weak)
Antifibrinolytic agents (eg, aminocaproic acid, aprotinin, tranexamic acid): Concurrent use may increase risk of thrombosis.
CYP2C8 Inhibitors may increase the levels/effects of tretinoin. Example inhibitors include atazanavir, gemfibrozil, and ritonavir.
Ketoconazole: Increases the mean plasma AUC of tretinoin.
Tetracyclines: Concurrent use may increase risk of pseudotumor cerebri.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol (may increase CNS depression).
Food: Absorption of retinoids has been shown to be enhanced when taken with food.
Herb/Nutraceutical: St John's wort may decrease tretinoin levels. Avoid dong quai, St John's wort (may also cause photosensitization). Avoid additional vitamin A supplementation. May lead to vitamin A toxicity.
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Oral tretinoin is teratogenic and fetotoxic in rats at doses 1000 and 500 times the topical human dose, respectively.
LACTATION — Enters breast milk/not recommended
DIETARY CONSIDERATIONS — To enhance absorption, some clinicians recommend giving with a fatty meal. Capsule contains soybean oil.
PRICING — (data from drugstore.com)Capsules (Vesanoid) 10 mg (30): $554.88
MONITORING PARAMETERS — Monitor the patient's hematologic profile, coagulation profile, liver function test results and triglyceride and cholesterol levels frequently
TOXICOLOGY / OVERDOSE COMPREHENSIVE — The maximum tolerated dose in adult patients with myelodysplastic syndrome in solid tumors was 195 mg/m2/day; the maximum tolerated dose in pediatric patients was lower at 60 mg/m2/day. Overdosage with other retinoids has been associated with transient headache, facial flushing, cheilosis, abdominal pain, dizziness, and ataxia. These symptoms resolved quickly without residual effects.
CANADIAN BRAND NAMES — Vesanoid®
INTERNATIONAL BRAND NAMES — Vesanoid (CA. PL)
MECHANISM OF ACTION — Tretinoin appears to bind one or more nuclear receptors and inhibits clonal proliferation and/or granulocyte differentiation
PHARMACODYNAMICS / KINETICS Protein binding: >95%
Metabolism: Hepatic via CYP; primary metabolite: 4-oxo-all-trans-retinoic acid
Half-life elimination: Terminal: Parent drug: 0.5-2 hours
Time to peak, serum: 1-2 hours
Excretion: Urine (63%); feces (30%)
PATIENT INFORMATION — Take with food; do not crush, chew, or dissolve capsules. You will need frequent blood tests while taking this medication. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake), avoid alcohol and foods containing vitamin A, and foods with high fat content. You may experience lethargy, dizziness, visual changes, confusion, anxiety (avoid driving or engaging in tasks requiring alertness until response to drug is known). For nausea/vomiting, loss of appetite, or dry mouth, small frequent meals, chewing gum, or sucking lozenges may help. You may experience photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). You may experience dry, itchy, skin, and dry or irritated eyes (avoid contact lenses). Report persistent vomiting or diarrhea, difficulty breathing, unusual bleeding or bruising, acute GI pain, bone pain, or vision changes immediately.
Alitretinoin
U.S. BRAND NAMES — Panretin®
PHARMACOLOGIC CATEGORY Antineoplastic Agent, Miscellaneous
DOSING: ADULTS Kaposi's sarcoma: Topical: Apply gel twice daily to cutaneous lesions.
T-cell lymphomas (unlabeled use): Topical: Apply gel twice daily to cutaneous lesions.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel: 0.1% (60 g tube)
DOSAGE FORMS: CONCISE Gel: Panretin®: 0.1% (60 g tube)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Do not use occlusive dressings.
USE — Orphan drug: Topical treatment of cutaneous lesions in AIDS-related Kaposi's sarcoma
USE - UNLABELED / INVESTIGATIONAL — Cutaneous T-cell lymphomas
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Pain (0% to 34%) Dermatologic: Rash (25% to 77%), pruritus (8% to 11%) Neuromuscular & skeletal: Paresthesia (3% to 22%)
5% to 10%: Cardiovascular: Edema (3% to 8%) Dermatologic: Exfoliative dermatitis (3% to 9%), skin disorder (0% to 8%)
CONTRAINDICATIONS — Hypersensitivity to alitretinoin, other retinoids, or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Photosensitivity: May be photosensitizing (based on experience with other retinoids); minimize sun or other UV exposure of treated areas.
Concurrent drug therapy issues: Products containing DEET: Do not use concurrently with topical products containing DEET.
Special populations: Elderly: Safety has not been established in the elderly. Pediatrics: Safety has not been established in children. Pregnancy: May cause fetal harm if absorbed by a woman who is pregnant.
DRUG INTERACTIONS — Increased toxicity of DEET may occur if products containing this compound are used concurrently with alitretinoin. Due to limited absorption after topical application, interaction with systemic medications is unlikely.
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Potentially teratogenic and/or embryotoxic; limb, craniofacial, or skeletal defects have been observed in animal models. If used during pregnancy or if the patient becomes pregnant while using alitretinoin, the woman should be advised of potential harm to the fetus. Women of childbearing potential should avoid becoming pregnant.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Excretion in human breast milk is unknown; women are advised to discontinue breast-feeding prior to using this medication.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — There has been no experience with human overdosage of alitretinoin, and overdose is unlikely following topical application. Treatment is symptomatic and supportive.
CANADIAN BRAND NAMES — Panretin®
INTERNATIONAL BRAND NAMES — Panretin (AR, AT, BE, BG, CA, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Binds to retinoid receptors to inhibit growth of Kaposi's sarcoma
PHARMACODYNAMICS / KINETICS — Absorption: Not extensive
PATIENT INFORMATION — For external use only; avoid UV light exposure (sun or sunlamps) of treated areas; avoid DEET-containing products
PHARMACOLOGIC CATEGORY Antineoplastic Agent, Miscellaneous
DOSING: ADULTS Kaposi's sarcoma: Topical: Apply gel twice daily to cutaneous lesions.
T-cell lymphomas (unlabeled use): Topical: Apply gel twice daily to cutaneous lesions.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel: 0.1% (60 g tube)
DOSAGE FORMS: CONCISE Gel: Panretin®: 0.1% (60 g tube)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Do not use occlusive dressings.
USE — Orphan drug: Topical treatment of cutaneous lesions in AIDS-related Kaposi's sarcoma
USE - UNLABELED / INVESTIGATIONAL — Cutaneous T-cell lymphomas
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Pain (0% to 34%) Dermatologic: Rash (25% to 77%), pruritus (8% to 11%) Neuromuscular & skeletal: Paresthesia (3% to 22%)
5% to 10%: Cardiovascular: Edema (3% to 8%) Dermatologic: Exfoliative dermatitis (3% to 9%), skin disorder (0% to 8%)
CONTRAINDICATIONS — Hypersensitivity to alitretinoin, other retinoids, or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Photosensitivity: May be photosensitizing (based on experience with other retinoids); minimize sun or other UV exposure of treated areas.
Concurrent drug therapy issues: Products containing DEET: Do not use concurrently with topical products containing DEET.
Special populations: Elderly: Safety has not been established in the elderly. Pediatrics: Safety has not been established in children. Pregnancy: May cause fetal harm if absorbed by a woman who is pregnant.
DRUG INTERACTIONS — Increased toxicity of DEET may occur if products containing this compound are used concurrently with alitretinoin. Due to limited absorption after topical application, interaction with systemic medications is unlikely.
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Potentially teratogenic and/or embryotoxic; limb, craniofacial, or skeletal defects have been observed in animal models. If used during pregnancy or if the patient becomes pregnant while using alitretinoin, the woman should be advised of potential harm to the fetus. Women of childbearing potential should avoid becoming pregnant.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Excretion in human breast milk is unknown; women are advised to discontinue breast-feeding prior to using this medication.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — There has been no experience with human overdosage of alitretinoin, and overdose is unlikely following topical application. Treatment is symptomatic and supportive.
CANADIAN BRAND NAMES — Panretin®
INTERNATIONAL BRAND NAMES — Panretin (AR, AT, BE, BG, CA, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Binds to retinoid receptors to inhibit growth of Kaposi's sarcoma
PHARMACODYNAMICS / KINETICS — Absorption: Not extensive
PATIENT INFORMATION — For external use only; avoid UV light exposure (sun or sunlamps) of treated areas; avoid DEET-containing products
Aliskiren
U.S. BRAND NAMES — Tekturna®
PHARMACOLOGIC CATEGORY Renin Inhibitor
DOSING: ADULTS Hypertension: Initial: 150 mg once daily; may increase to 300 mg once daily (maximum: 300 mg/day). Note: Prior to initiation, correct hypovolemia and/or closely monitor volume status in patients on concurrent diuretics during treatment initiation.
DOSING: PEDIATRIC — Children <18 years: Dosage not established.
DOSING: ELDERLY Refer to adult dosing. No initial dosage adjustment required.
DOSING: RENAL IMPAIRMENT Mild-to-moderate impairment [GFR >30 mL/minute and/or Scr <1.7 mg/dL (women); Scr <2 mg/dL (men)]: No dose adjustment required
Severe impairment [GFR<30>1.7 mg/dL (women); Scr >2 mg/dL (men)]: Use caution; not studied in severe renal impairment
DOSING: HEPATIC IMPAIRMENT — No dosage adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Tekturna®: 150 mg, 300 mg
DOSAGE FORMS: CONCISE Tablet: Tekturna®: 150 mg, 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer at the same time daily; may take with or without a meal, but consistent administration with regards to meals is recommended. Avoid taking with high-fat meals.
USE — Treatment of hypertension, alone or in combination with other antihypertensive agents
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Dizziness (2%) Dermatologic: Rash (1%) Endocrine and metabolic: Hyperkalemia (monotherapy 1%; concurrent with ACE inhibitor in diabetic patients 6%) Gastrointestinal: Diarrhea (1% to 2%) Hematologic: Creatine kinase increased (>300%: 1%) Renal: BUN increased (7%), serum creatinine increased (7%) Respiratory: Cough (1% to 5%)
<1% (Limited to important or life-threatening): Abdominal pain, anemia, angina, angioedema, dyspepsia, gastroesophageal reflux, gout, myositis, renal stone formation, rhabdomyolysis, seizure, severe hypotension, uric acid increased
CONTRAINDICATIONS — Hypersensitivity to aliskiren or any component of the formulation; history of idiopathic or hereditary angioedema; history of ACE inhibitor- or ARB-related angioedema; bilateral renal artery stenosis; pregnancy
WARNINGS / PRECAUTIONS Box warnings: Pregnancy: See "Special populations" below.
Concerns related to adverse effects: Angioedema: At any time during treatment (especially following first dose) angioedema can occur; it may involve head and neck (potentially affecting the airway) or the extremities. Prolonged monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Discontinue immediately following any signs and symptoms of angioedema. Hyperkalemia: May occur (rarely) during monotherapy; risk may increase in patients with predisposing factors (eg, renal dysfunction, diabetes mellitus or concomitant use with ACE inhibitors, potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts). Hypotension: During the initiation of therapy, symptomatic hypotension may occur (rarely), particularly in patients with an activated renin-angiotensin system (ie, volume or salt-depleted patients)
Disease-related concerns: Renal impairment: Use with caution in patients with severe renal impairment; not studied in patients with severe renal impairment [GFR <30>1.7 mg/dL (women); Scr >2 mg/dL (men)], history of dialysis, nephrotic syndrome, or renovascular hypertension. Use with caution or avoid in patients with deteriorating renal function or renal artery stenosis (bilateral or unilateral).
Special populations: Pediatrics: Safety and efficacy have not been established in children. Pregnancy: [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Aliskiren should be discontinued as soon as possible once pregnancy is detected.
DRUG INTERACTIONS — Substrate of CYP3A4 (minor)
Atorvastatin: May increase the level/effect of aliskiren; monitor blood pressure.
Furosemide: Aliskiren may decrease the level/effect of furosemide.
Ketoconazole: May increase the level/effect of aliskerin; monitor blood pressure.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: High-fat meals decreases absorption.
PREGNANCY RISK FACTOR — C (show table) (1st trimester)/D (2nd and 3rd trimesters)
PREGNANCY IMPLICATIONS — Medications which act on the renin-angiotensin system are reported to have the following fetal/neonatal effects: Hypotension, neonatal skull hypoplasia, anuria, renal failure, and death; oligohydramnios is also reported. These effects are reported to occur with exposure during the 2nd and 3rd trimesters. There are no adequate and well-controlled studies in pregnant women. Discontinue aliskiren as soon as possible after pregnancy is detected.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — May be taken with or without food; however, a high-fat meal reduces absorption
MONITORING PARAMETERS — Serum potassium, BUN, serum creatinine
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Limited experience with overdosage. Treatment is symptom-directed and supportive.
MECHANISM OF ACTION — Aliskerin is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Ang II also functions within the Renin-Angiotensin-Aldosterone System (RAAS) as a negative inhibitory feedback mediator within the renal parenchyma to suppress the further release of renin. Thus, reductions in Ang II levels suppress this feedback loop, leading to further increased plasma renin concentrations (PRC) and subsequent activity (PRA). This disinhibition effect can be potentially problematic for ACE inhibitor and ARB therapy, as increased PRA could partially overcome the pharmacologic inhibition of the RAAS. As aliskerin is a direct inhibitor of renin activity, blunting of PRA despite the increased PRC (from loss of the negative feedback) may be clinically advantageous.
PHARMACODYNAMICS / KINETICS Onset of action: Maximum antihypertensive effect: Within 2 weeks
Absorption: Poor; absorption decreased by high-fat meal
Metabolism: Extent of metabolism unknown; in vitro studies indicate metabolism via CYP3A4
Bioavailability: ~3%
Half-life elimination: ~24 hours (range: 16-32 hours)
Time to peak, plasma: 1-3 hours
Excretion: Urine (~25% of absorbed dose excreted unchanged in urine); feces (unchanged via biliary excretion)
PHARMACOLOGIC CATEGORY Renin Inhibitor
DOSING: ADULTS Hypertension: Initial: 150 mg once daily; may increase to 300 mg once daily (maximum: 300 mg/day). Note: Prior to initiation, correct hypovolemia and/or closely monitor volume status in patients on concurrent diuretics during treatment initiation.
DOSING: PEDIATRIC — Children <18 years: Dosage not established.
DOSING: ELDERLY Refer to adult dosing. No initial dosage adjustment required.
DOSING: RENAL IMPAIRMENT Mild-to-moderate impairment [GFR >30 mL/minute and/or Scr <1.7 mg/dL (women); Scr <2 mg/dL (men)]: No dose adjustment required
Severe impairment [GFR<30>1.7 mg/dL (women); Scr >2 mg/dL (men)]: Use caution; not studied in severe renal impairment
DOSING: HEPATIC IMPAIRMENT — No dosage adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Tekturna®: 150 mg, 300 mg
DOSAGE FORMS: CONCISE Tablet: Tekturna®: 150 mg, 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer at the same time daily; may take with or without a meal, but consistent administration with regards to meals is recommended. Avoid taking with high-fat meals.
USE — Treatment of hypertension, alone or in combination with other antihypertensive agents
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Dizziness (2%) Dermatologic: Rash (1%) Endocrine and metabolic: Hyperkalemia (monotherapy 1%; concurrent with ACE inhibitor in diabetic patients 6%) Gastrointestinal: Diarrhea (1% to 2%) Hematologic: Creatine kinase increased (>300%: 1%) Renal: BUN increased (7%), serum creatinine increased (7%) Respiratory: Cough (1% to 5%)
<1% (Limited to important or life-threatening): Abdominal pain, anemia, angina, angioedema, dyspepsia, gastroesophageal reflux, gout, myositis, renal stone formation, rhabdomyolysis, seizure, severe hypotension, uric acid increased
CONTRAINDICATIONS — Hypersensitivity to aliskiren or any component of the formulation; history of idiopathic or hereditary angioedema; history of ACE inhibitor- or ARB-related angioedema; bilateral renal artery stenosis; pregnancy
WARNINGS / PRECAUTIONS Box warnings: Pregnancy: See "Special populations" below.
Concerns related to adverse effects: Angioedema: At any time during treatment (especially following first dose) angioedema can occur; it may involve head and neck (potentially affecting the airway) or the extremities. Prolonged monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Discontinue immediately following any signs and symptoms of angioedema. Hyperkalemia: May occur (rarely) during monotherapy; risk may increase in patients with predisposing factors (eg, renal dysfunction, diabetes mellitus or concomitant use with ACE inhibitors, potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts). Hypotension: During the initiation of therapy, symptomatic hypotension may occur (rarely), particularly in patients with an activated renin-angiotensin system (ie, volume or salt-depleted patients)
Disease-related concerns: Renal impairment: Use with caution in patients with severe renal impairment; not studied in patients with severe renal impairment [GFR <30>1.7 mg/dL (women); Scr >2 mg/dL (men)], history of dialysis, nephrotic syndrome, or renovascular hypertension. Use with caution or avoid in patients with deteriorating renal function or renal artery stenosis (bilateral or unilateral).
Special populations: Pediatrics: Safety and efficacy have not been established in children. Pregnancy: [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Aliskiren should be discontinued as soon as possible once pregnancy is detected.
DRUG INTERACTIONS — Substrate of CYP3A4 (minor)
Atorvastatin: May increase the level/effect of aliskiren; monitor blood pressure.
Furosemide: Aliskiren may decrease the level/effect of furosemide.
Ketoconazole: May increase the level/effect of aliskerin; monitor blood pressure.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: High-fat meals decreases absorption.
PREGNANCY RISK FACTOR — C (show table) (1st trimester)/D (2nd and 3rd trimesters)
PREGNANCY IMPLICATIONS — Medications which act on the renin-angiotensin system are reported to have the following fetal/neonatal effects: Hypotension, neonatal skull hypoplasia, anuria, renal failure, and death; oligohydramnios is also reported. These effects are reported to occur with exposure during the 2nd and 3rd trimesters. There are no adequate and well-controlled studies in pregnant women. Discontinue aliskiren as soon as possible after pregnancy is detected.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — May be taken with or without food; however, a high-fat meal reduces absorption
MONITORING PARAMETERS — Serum potassium, BUN, serum creatinine
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Limited experience with overdosage. Treatment is symptom-directed and supportive.
MECHANISM OF ACTION — Aliskerin is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Ang II also functions within the Renin-Angiotensin-Aldosterone System (RAAS) as a negative inhibitory feedback mediator within the renal parenchyma to suppress the further release of renin. Thus, reductions in Ang II levels suppress this feedback loop, leading to further increased plasma renin concentrations (PRC) and subsequent activity (PRA). This disinhibition effect can be potentially problematic for ACE inhibitor and ARB therapy, as increased PRA could partially overcome the pharmacologic inhibition of the RAAS. As aliskerin is a direct inhibitor of renin activity, blunting of PRA despite the increased PRC (from loss of the negative feedback) may be clinically advantageous.
PHARMACODYNAMICS / KINETICS Onset of action: Maximum antihypertensive effect: Within 2 weeks
Absorption: Poor; absorption decreased by high-fat meal
Metabolism: Extent of metabolism unknown; in vitro studies indicate metabolism via CYP3A4
Bioavailability: ~3%
Half-life elimination: ~24 hours (range: 16-32 hours)
Time to peak, plasma: 1-3 hours
Excretion: Urine (~25% of absorbed dose excreted unchanged in urine); feces (unchanged via biliary excretion)
Alglucerase glucocerebrosidase
U.S. BRAND NAMES — Ceredase®
PHARMACOLOGIC CATEGORY Enzyme
DOSING: ADULTS — Gaucher's disease: I.V.: Initial: 30-60 units/kg every 2 weeks; dosing is individualized based on disease severity; average dose: 60 units/kg every 2 weeks. Range: 2.5 units/kg 3 times/week to 60 units/kg once weekly to every 4 weeks. Once patient response is well established, dose may be reduced every 3-6 months to determine maintenance therapy.
DOSING: PEDIATRIC — Refer to adult dosing.
(For additional information see "Alglucerase (glucocerebrosidase): Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: Ceredase®: 80 units/mL (5 mL) [contains human albumin 1%]
DOSAGE FORMS: CONCISE Injection, solution [preservative free]: Ceredase®: 80 units/mL (5 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — I.V.: Infuse I.V. over 1-2 hours. Use of an in-line filter is recommended. Do not shake solution as it denatures the enzyme.
COMPATIBILITY — Stable in NS; do not mix with any other additives.
USE — Replacement therapy for Gaucher's disease (type 1)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Peripheral edema
Central nervous system: Chills, fatigue, fever, headache, lightheadedness
Endocrine & metabolic: Hot flashes, menstrual abnormalities
Gastrointestinal: Abdominal discomfort, diarrhea, nausea, oral ulcerations, vomiting
Local: Injection site: Abscess, burning, discomfort, pruritus, swelling
Neuromuscular & skeletal: Backache, weakness
Miscellaneous: Dysosmia; hypersensitivity reactions (abdominal cramping, angioedema, chest discomfort, flushing, hypotension, nausea, pruritus, respiratory symptoms, urticaria); IgG antibody formation (~13%)
CONTRAINDICATIONS — Hypersensitivity to any component of the formulation
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Hypersensitivity reactions: Patients who develop IgG antibodies may be at a higher risk for developing hypersensitivity. Use with caution in patients with prior allergies to hCG.
Disease-related concerns: Androgen-sensitive malignancies: Use with caution in patients with androgen-sensitive malignancies.
Special populations: Pediatrics: Safety and efficacy have not been established in children <2 years of age. May cause early virilization in males <10 years of age.
Other warnings/precautions: Placental tissue: Prepared from pooled human placental tissue that may contain the causative agents of some viral diseases.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have not been conducted.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — CBC, platelets, liver function tests, IgG antibody formation, acid phosphatase (AP); MRI or CT of liver and spleen, skeletal x-rays, physical exam every 6-12 months
TOXICOLOGY / OVERDOSE COMPREHENSIVE — No obvious toxicity was detected after single doses of up to 234 units/kg.
MECHANISM OF ACTION — Alglucerase is a modified form of glucocerebrosidase; it is prepared from human placental tissue. Glucocerebrosidase is an enzyme deficient in Gaucher's disease. It is needed to catalyze the hydrolysis of glucocerebroside to glucose and ceramide.
PHARMACODYNAMICS / KINETICS — Half-life elimination: ~3-11 minutes
PHARMACOLOGIC CATEGORY Enzyme
DOSING: ADULTS — Gaucher's disease: I.V.: Initial: 30-60 units/kg every 2 weeks; dosing is individualized based on disease severity; average dose: 60 units/kg every 2 weeks. Range: 2.5 units/kg 3 times/week to 60 units/kg once weekly to every 4 weeks. Once patient response is well established, dose may be reduced every 3-6 months to determine maintenance therapy.
DOSING: PEDIATRIC — Refer to adult dosing.
(For additional information see "Alglucerase (glucocerebrosidase): Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: Ceredase®: 80 units/mL (5 mL) [contains human albumin 1%]
DOSAGE FORMS: CONCISE Injection, solution [preservative free]: Ceredase®: 80 units/mL (5 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — I.V.: Infuse I.V. over 1-2 hours. Use of an in-line filter is recommended. Do not shake solution as it denatures the enzyme.
COMPATIBILITY — Stable in NS; do not mix with any other additives.
USE — Replacement therapy for Gaucher's disease (type 1)
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Peripheral edema
Central nervous system: Chills, fatigue, fever, headache, lightheadedness
Endocrine & metabolic: Hot flashes, menstrual abnormalities
Gastrointestinal: Abdominal discomfort, diarrhea, nausea, oral ulcerations, vomiting
Local: Injection site: Abscess, burning, discomfort, pruritus, swelling
Neuromuscular & skeletal: Backache, weakness
Miscellaneous: Dysosmia; hypersensitivity reactions (abdominal cramping, angioedema, chest discomfort, flushing, hypotension, nausea, pruritus, respiratory symptoms, urticaria); IgG antibody formation (~13%)
CONTRAINDICATIONS — Hypersensitivity to any component of the formulation
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Hypersensitivity reactions: Patients who develop IgG antibodies may be at a higher risk for developing hypersensitivity. Use with caution in patients with prior allergies to hCG.
Disease-related concerns: Androgen-sensitive malignancies: Use with caution in patients with androgen-sensitive malignancies.
Special populations: Pediatrics: Safety and efficacy have not been established in children <2 years of age. May cause early virilization in males <10 years of age.
Other warnings/precautions: Placental tissue: Prepared from pooled human placental tissue that may contain the causative agents of some viral diseases.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have not been conducted.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — CBC, platelets, liver function tests, IgG antibody formation, acid phosphatase (AP); MRI or CT of liver and spleen, skeletal x-rays, physical exam every 6-12 months
TOXICOLOGY / OVERDOSE COMPREHENSIVE — No obvious toxicity was detected after single doses of up to 234 units/kg.
MECHANISM OF ACTION — Alglucerase is a modified form of glucocerebrosidase; it is prepared from human placental tissue. Glucocerebrosidase is an enzyme deficient in Gaucher's disease. It is needed to catalyze the hydrolysis of glucocerebroside to glucose and ceramide.
PHARMACODYNAMICS / KINETICS — Half-life elimination: ~3-11 minutes
Alglucosidase alfa
U.S. BRAND NAMES — Myozyme®
PHARMACOLOGIC CATEGORY Enzyme
DOSING: PEDIATRIC — Replacement therapy for Pompe disease (infantile onset): Children 1 month to 3.5 years (at first infusion): I.V.: 20 mg/kg over ~4 hours every 2 weeks
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution [preservative free]: Myozyme®: 50 mg [contains mannitol 210 mg; polysorbate 80; derived from Chinese hamster ovary cells]
DOSAGE FORMS: CONCISE Injection, powder for reconstitution [preservative free]: Myozyme®: 50 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Infuse over ~4 hours; initiate at 1 mg/kg/hour. If tolerated, increase by 2 mg/kg/hour every 30 minutes to a maximum rate of 7 mg/kg/hour. Decrease rate or temporarily hold for infusion reactions. Infuse through a low protein-binding, 0.2 micron in-line filter.
COMPATIBILITY — Stable in NS; do not infuse with other products.
USE — Replacement therapy for Pompe disease (infantile onset)
ADVERSE REACTIONS SIGNIFICANT >20%: Cardiovascular: Tachycardia (23%), bradycardia (21%), flushing (21%) Central nervous system: Fever (92%), pain (postprocedural: 26%) Dermatologic: Rash (54%), diaper dermatitis (36%), urticaria (21%) Gastrointestinal: Diarrhea (62%), vomiting (49%), gastroenteritis (41%), oral candidiasis (31%), gastroesophageal reflux (26%), constipation (23%) Hematologic: Anemia (31%) Local: Catheter-related infections (28%) Otic: Otitis media (33% to 44%) Respiratory: Cough (46%), pneumonia (46%), upper respiratory tract infection (44%), oxygen saturation decreased (41%), pharyngitis (36%), respiratory distress (33%), respiratory failure (31%), rhinorrhea (28%), bronchiolitis (23%), nasopharyngitis (23%), tachypnea (23%) Miscellaneous: Infusion reaction (51%)
Frequency not reported and/or case reports: Abdominal pain, agitation, anaphylactic reactions, bronchospasm, cardiorespiratory failure, cyanosis, erythema, face edema, facial erythema, fluid overload, headache, hyperhydrosis, hypersensitivity, hyper-/hypotension, irritability, lacrimation increased, livedo reticularis, malaise, nausea, pallor, periorbital edema, pruritus, respiratory syncytial virus infection, restlessness, retching, rhinitis, rigors, tremor, wheezing
CONTRAINDICATIONS — Hypersensitivity to alglucosidase alfa or any component of the formulation
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Anaphylaxis/hypersensitivity/infusion reactions: Severe hypersensitivity reactions, including anaphylactic reactions and anaphylactic shock have been reported during infusion. Infusion-related reactions are common; discontinue immediately for severe hypersensitivity or anaphylactic reaction; mild-to-moderate reactions may be managed by reducing the infusion rate and/or administering antihistamines and/or antipyretics. Appropriate medical support for the management of infusion reactions should be readily available. Use caution with subsequent infusions; infusion reactions have occurred despite premedication with antihistamines, antipyretics, and/or steroids. Patients with acute underlying illness are at greater risk for infusion reactions.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease. Pompe disease: Safety and efficacy have not been established in juvenile-onset and adult-onset Pompe disease. Patients with Pompe disease are at increased risk for infusion-related cardiorespiratory failure (possibly due to fluid overload); monitor closely during infusion. Respiratory disease: Use with caution in patients with respiratory disease.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Animal studies have not demonstrated teratogenicity or fertility impairment. There are no adequate and well-controlled studies in pregnant women. A registry has been established for Pompe patients; women of childbearing potential are encouraged to enroll in the registry (www.pomperegistry.com or 1-800-745-4447).
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — A registry has been established for Pompe patients; women who are nursing are encouraged to enroll in the registry (www.pomperegistry.com or 1-800-745-4447)
MONITORING PARAMETERS — Liver enzymes (baseline and periodically; elevation may be due to disease process); vital signs during and following infusion; volume overload
TOXICOLOGY / OVERDOSE COMPREHENSIVE — There have been no reports of overdose. Doses of up to 40 mg/kg were administered in clinical trials. Treatment of overdose is symptom-directed and supportive.
MECHANISM OF ACTION — Alglucosidase alfa is a recombinant form of the enzyme acid alpha-glucosidase (GAA), which is required for glycogen cleavage. Due to an inherited GAA deficiency, glycogen accumulates in the tissues of patients with Pompe disease, leading to progressive muscle weakness. In infantile-onset Pompe disease, glycogen accumulates in cardiac and skeletal muscles and hepatic tissue, leading to cardiomyopathy and respiratory failure. Juvenile- and adult-onset Pompe disease are limited to glycogen accumulation in skeletal muscle, leading to respiratory failure. Alglucosidase alfa binds to mannose-6-phosphate receptors on the cell surface, becomes internalized and transported to lysosomes resulting in increased enzymatic activity and glycogen cleavage.
PHARMACODYNAMICS / KINETICS Distribution: Vss: 80-112 mL/kg
Half-life elimination: 2.3 hours
PHARMACOLOGIC CATEGORY Enzyme
DOSING: PEDIATRIC — Replacement therapy for Pompe disease (infantile onset): Children 1 month to 3.5 years (at first infusion): I.V.: 20 mg/kg over ~4 hours every 2 weeks
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution [preservative free]: Myozyme®: 50 mg [contains mannitol 210 mg; polysorbate 80; derived from Chinese hamster ovary cells]
DOSAGE FORMS: CONCISE Injection, powder for reconstitution [preservative free]: Myozyme®: 50 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Infuse over ~4 hours; initiate at 1 mg/kg/hour. If tolerated, increase by 2 mg/kg/hour every 30 minutes to a maximum rate of 7 mg/kg/hour. Decrease rate or temporarily hold for infusion reactions. Infuse through a low protein-binding, 0.2 micron in-line filter.
COMPATIBILITY — Stable in NS; do not infuse with other products.
USE — Replacement therapy for Pompe disease (infantile onset)
ADVERSE REACTIONS SIGNIFICANT >20%: Cardiovascular: Tachycardia (23%), bradycardia (21%), flushing (21%) Central nervous system: Fever (92%), pain (postprocedural: 26%) Dermatologic: Rash (54%), diaper dermatitis (36%), urticaria (21%) Gastrointestinal: Diarrhea (62%), vomiting (49%), gastroenteritis (41%), oral candidiasis (31%), gastroesophageal reflux (26%), constipation (23%) Hematologic: Anemia (31%) Local: Catheter-related infections (28%) Otic: Otitis media (33% to 44%) Respiratory: Cough (46%), pneumonia (46%), upper respiratory tract infection (44%), oxygen saturation decreased (41%), pharyngitis (36%), respiratory distress (33%), respiratory failure (31%), rhinorrhea (28%), bronchiolitis (23%), nasopharyngitis (23%), tachypnea (23%) Miscellaneous: Infusion reaction (51%)
Frequency not reported and/or case reports: Abdominal pain, agitation, anaphylactic reactions, bronchospasm, cardiorespiratory failure, cyanosis, erythema, face edema, facial erythema, fluid overload, headache, hyperhydrosis, hypersensitivity, hyper-/hypotension, irritability, lacrimation increased, livedo reticularis, malaise, nausea, pallor, periorbital edema, pruritus, respiratory syncytial virus infection, restlessness, retching, rhinitis, rigors, tremor, wheezing
CONTRAINDICATIONS — Hypersensitivity to alglucosidase alfa or any component of the formulation
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Anaphylaxis/hypersensitivity/infusion reactions: Severe hypersensitivity reactions, including anaphylactic reactions and anaphylactic shock have been reported during infusion. Infusion-related reactions are common; discontinue immediately for severe hypersensitivity or anaphylactic reaction; mild-to-moderate reactions may be managed by reducing the infusion rate and/or administering antihistamines and/or antipyretics. Appropriate medical support for the management of infusion reactions should be readily available. Use caution with subsequent infusions; infusion reactions have occurred despite premedication with antihistamines, antipyretics, and/or steroids. Patients with acute underlying illness are at greater risk for infusion reactions.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease. Pompe disease: Safety and efficacy have not been established in juvenile-onset and adult-onset Pompe disease. Patients with Pompe disease are at increased risk for infusion-related cardiorespiratory failure (possibly due to fluid overload); monitor closely during infusion. Respiratory disease: Use with caution in patients with respiratory disease.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Animal studies have not demonstrated teratogenicity or fertility impairment. There are no adequate and well-controlled studies in pregnant women. A registry has been established for Pompe patients; women of childbearing potential are encouraged to enroll in the registry (www.pomperegistry.com or 1-800-745-4447).
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — A registry has been established for Pompe patients; women who are nursing are encouraged to enroll in the registry (www.pomperegistry.com or 1-800-745-4447)
MONITORING PARAMETERS — Liver enzymes (baseline and periodically; elevation may be due to disease process); vital signs during and following infusion; volume overload
TOXICOLOGY / OVERDOSE COMPREHENSIVE — There have been no reports of overdose. Doses of up to 40 mg/kg were administered in clinical trials. Treatment of overdose is symptom-directed and supportive.
MECHANISM OF ACTION — Alglucosidase alfa is a recombinant form of the enzyme acid alpha-glucosidase (GAA), which is required for glycogen cleavage. Due to an inherited GAA deficiency, glycogen accumulates in the tissues of patients with Pompe disease, leading to progressive muscle weakness. In infantile-onset Pompe disease, glycogen accumulates in cardiac and skeletal muscles and hepatic tissue, leading to cardiomyopathy and respiratory failure. Juvenile- and adult-onset Pompe disease are limited to glycogen accumulation in skeletal muscle, leading to respiratory failure. Alglucosidase alfa binds to mannose-6-phosphate receptors on the cell surface, becomes internalized and transported to lysosomes resulting in increased enzymatic activity and glycogen cleavage.
PHARMACODYNAMICS / KINETICS Distribution: Vss: 80-112 mL/kg
Half-life elimination: 2.3 hours
Alfuzosin:
U.S. BRAND NAMES — Uroxatral®
PHARMACOLOGIC CATEGORY Alpha1 Blocker
DOSING: ADULTS — Benign prostatic hyperplasia (BPH): Oral: 10 mg once daily
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Bioavailability and maximum serum concentrations are increased by ~50% with mild, moderate, or severe renal impairment.
Note: Safety has not been evaluated in patients with creatinine clearances <30 mL/minute.
DOSING: HEPATIC IMPAIRMENT Mild hepatic impairment: Use has not been studied.
Moderate or severe hepatic impairment (Child-Pugh class B and C): Clearance is decreased 1/3 to 1/4 and serum concentration is increased three- to fourfold; use is contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, extended release, as hydrochloride: 10 mg
DOSAGE FORMS: CONCISE Tablet, extended release: Uroxatral™: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Tablet should be swallowed whole; do not crush or chew. Administer once daily (with a meal); should be taken at the same time each day.
USE — Treatment of the functional symptoms of benign prostatic hyperplasia (BPH)
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Dizziness (6%), fatigue (3%), headache (3%), pain (1% to 2%) Gastrointestinal: Abdominal pain (1% to 2%), constipation (1% to 2%), dyspepsia (1% to 2%), nausea (1% to 2%) Genitourinary: Impotence (1% to 2%) Respiratory: Upper respiratory tract infection (3%), bronchitis (1% to 2%), pharyngitis (1% to 2%), sinusitis (1% to 2%)
<1% (Limited to important or life-threatening): Angina pectoris (pre-existing CAD), angioedema, chest pain, diarrhea, edema, flushing, intraoperative floppy iris syndrome (with cataract surgery), priapism, pruritis, rash, rhinitis, tachycardia, urticaria
CONTRAINDICATIONS — Hypersensitivity to alfuzosin or any component of the formulation; moderate or severe hepatic insufficiency (Child-Pugh class B and C); potent CYP3A4 inhibitors (eg, itraconazole, ketoconazole, ritonavir)
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Angina: Discontinue if symptoms of angina occur or worsen. Floppy iris syndrome: Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; causality has not been established and there appears to be no benefit in discontinuing alpha-blocker therapy prior to surgery. Orthostatic hypotension/syncope: May cause significant orthostatic hypotension and syncope, especially with first dose; anticipate a similar effect if therapy is interrupted for a few days, if dosage is rapidly increased, or if another antihypertensive drug (particularly vasodilators) or a PDE5 inhibitor is introduced. Patients should be cautioned about performing hazardous tasks when starting new therapy or adjusting dosage upward.
Disease-related concerns: Hepatic impairment: Use with caution in patients with mild hepatic impairment; not recommended in moderate to severe impairment. Prostate cancer: Should rule out prostatic carcinoma before beginning therapy. Renal impairment: Use with caution in patients with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warning/precautions: Antihypertensive agent: Not intended for use as an antihypertensive drug.
DRUG INTERACTIONS — Substrate of CYP3A4 (major)
CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of alfuzosin. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.
CYP3A4 inhibitors: May increase the levels/effects of alfuzosin. Example inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil. Concurrent use of itraconazole, ketoconazole, or ritonavir is contraindicated.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Food increases the extent of absorption.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies; however, alfuzosin is not indicated for use in women.
LACTATION — Not indicated for use in women
DIETARY CONSIDERATIONS — Take following a meal at the same time each day.
PRICING — (data from drugstore.com)Tablet, 24-hour (Uroxatral) 10 mg (30): $76.49
MONITORING PARAMETERS — Urine flow; blood pressure
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Hypotension would be expected in case of overdose. Treatment is symptom-directed and supportive. Dialysis not likely to benefit.
CANADIAN BRAND NAMES — Xatral
INTERNATIONAL BRAND NAMES — Alfetim (HU); Alfusin (IN); Dalfaz (AR, ES, PL); Uroxatral (CL); Uroxatral OD (AR, UY); Uroxatral uno (DE); Xatral (AT, BE, BF, BJ, CA, CH, CI, CN, CZ, DK, ET, FI, FR, GB, GH, GM, GN, IE, IL, IT, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, SC, SD, SE, SL, SN, TZ, UG, ZA, ZM, ZW); Xatral LP (EC, FR, HK); Xatral OD (BR, CO, CR, DO, GT, HN, MX, NI, PA, PE, PH, PY, SV, VE); Xatral SR (AT, BG, EE, EG, IL, PK, SG); Xatral XL (ID, IL, KR, SG, TH); Xatral XR 10 (SG)
MECHANISM OF ACTION — An antagonist of alpha1-adrenoreceptors in the lower urinary tract. Smooth muscle tone is mediated by the sympathetic nervous stimulation of alpha1-adrenoreceptors, which are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck. Blockade of these adrenoreceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH.
PHARMACODYNAMICS / KINETICS Absorption: Decreased 50% under fasting conditions
Distribution: Vd: 3.2 L/kg
Protein binding: 82% to 90%
Metabolism: Hepatic, primarily via CYP3A4; metabolism includes oxidation, O-demethylation, and N-dealkylation; forms metabolites (inactive)
Bioavailability: 49% following a meal
Half-life elimination: 10 hours
Time to peak, plasma: 8 hours following a meal
Excretion: Feces (69%); urine (24%)
PATIENT INFORMATION — Do not take any new medication during therapy without consulting prescriber. Take exactly as directed, with a meal at the same time each day. Swallow tablet whole; do not crush or chew. May cause drowsiness, dizziness, impaired judgment (use caution when driving or engaging in tasks that require alertness until response to drug is known), or postural hypotension (use caution when rising from sitting or lying position or when climbing stairs). Report unusual chest pain, respiratory difficulty, or any persistent adverse reactions.
PHARMACOLOGIC CATEGORY Alpha1 Blocker
DOSING: ADULTS — Benign prostatic hyperplasia (BPH): Oral: 10 mg once daily
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Bioavailability and maximum serum concentrations are increased by ~50% with mild, moderate, or severe renal impairment.
Note: Safety has not been evaluated in patients with creatinine clearances <30 mL/minute.
DOSING: HEPATIC IMPAIRMENT Mild hepatic impairment: Use has not been studied.
Moderate or severe hepatic impairment (Child-Pugh class B and C): Clearance is decreased 1/3 to 1/4 and serum concentration is increased three- to fourfold; use is contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, extended release, as hydrochloride: 10 mg
DOSAGE FORMS: CONCISE Tablet, extended release: Uroxatral™: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Tablet should be swallowed whole; do not crush or chew. Administer once daily (with a meal); should be taken at the same time each day.
USE — Treatment of the functional symptoms of benign prostatic hyperplasia (BPH)
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Dizziness (6%), fatigue (3%), headache (3%), pain (1% to 2%) Gastrointestinal: Abdominal pain (1% to 2%), constipation (1% to 2%), dyspepsia (1% to 2%), nausea (1% to 2%) Genitourinary: Impotence (1% to 2%) Respiratory: Upper respiratory tract infection (3%), bronchitis (1% to 2%), pharyngitis (1% to 2%), sinusitis (1% to 2%)
<1% (Limited to important or life-threatening): Angina pectoris (pre-existing CAD), angioedema, chest pain, diarrhea, edema, flushing, intraoperative floppy iris syndrome (with cataract surgery), priapism, pruritis, rash, rhinitis, tachycardia, urticaria
CONTRAINDICATIONS — Hypersensitivity to alfuzosin or any component of the formulation; moderate or severe hepatic insufficiency (Child-Pugh class B and C); potent CYP3A4 inhibitors (eg, itraconazole, ketoconazole, ritonavir)
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Angina: Discontinue if symptoms of angina occur or worsen. Floppy iris syndrome: Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; causality has not been established and there appears to be no benefit in discontinuing alpha-blocker therapy prior to surgery. Orthostatic hypotension/syncope: May cause significant orthostatic hypotension and syncope, especially with first dose; anticipate a similar effect if therapy is interrupted for a few days, if dosage is rapidly increased, or if another antihypertensive drug (particularly vasodilators) or a PDE5 inhibitor is introduced. Patients should be cautioned about performing hazardous tasks when starting new therapy or adjusting dosage upward.
Disease-related concerns: Hepatic impairment: Use with caution in patients with mild hepatic impairment; not recommended in moderate to severe impairment. Prostate cancer: Should rule out prostatic carcinoma before beginning therapy. Renal impairment: Use with caution in patients with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warning/precautions: Antihypertensive agent: Not intended for use as an antihypertensive drug.
DRUG INTERACTIONS — Substrate of CYP3A4 (major)
CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of alfuzosin. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.
CYP3A4 inhibitors: May increase the levels/effects of alfuzosin. Example inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil. Concurrent use of itraconazole, ketoconazole, or ritonavir is contraindicated.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Food increases the extent of absorption.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies; however, alfuzosin is not indicated for use in women.
LACTATION — Not indicated for use in women
DIETARY CONSIDERATIONS — Take following a meal at the same time each day.
PRICING — (data from drugstore.com)Tablet, 24-hour (Uroxatral) 10 mg (30): $76.49
MONITORING PARAMETERS — Urine flow; blood pressure
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Hypotension would be expected in case of overdose. Treatment is symptom-directed and supportive. Dialysis not likely to benefit.
CANADIAN BRAND NAMES — Xatral
INTERNATIONAL BRAND NAMES — Alfetim (HU); Alfusin (IN); Dalfaz (AR, ES, PL); Uroxatral (CL); Uroxatral OD (AR, UY); Uroxatral uno (DE); Xatral (AT, BE, BF, BJ, CA, CH, CI, CN, CZ, DK, ET, FI, FR, GB, GH, GM, GN, IE, IL, IT, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, SC, SD, SE, SL, SN, TZ, UG, ZA, ZM, ZW); Xatral LP (EC, FR, HK); Xatral OD (BR, CO, CR, DO, GT, HN, MX, NI, PA, PE, PH, PY, SV, VE); Xatral SR (AT, BG, EE, EG, IL, PK, SG); Xatral XL (ID, IL, KR, SG, TH); Xatral XR 10 (SG)
MECHANISM OF ACTION — An antagonist of alpha1-adrenoreceptors in the lower urinary tract. Smooth muscle tone is mediated by the sympathetic nervous stimulation of alpha1-adrenoreceptors, which are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck. Blockade of these adrenoreceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH.
PHARMACODYNAMICS / KINETICS Absorption: Decreased 50% under fasting conditions
Distribution: Vd: 3.2 L/kg
Protein binding: 82% to 90%
Metabolism: Hepatic, primarily via CYP3A4; metabolism includes oxidation, O-demethylation, and N-dealkylation; forms metabolites (inactive)
Bioavailability: 49% following a meal
Half-life elimination: 10 hours
Time to peak, plasma: 8 hours following a meal
Excretion: Feces (69%); urine (24%)
PATIENT INFORMATION — Do not take any new medication during therapy without consulting prescriber. Take exactly as directed, with a meal at the same time each day. Swallow tablet whole; do not crush or chew. May cause drowsiness, dizziness, impaired judgment (use caution when driving or engaging in tasks that require alertness until response to drug is known), or postural hypotension (use caution when rising from sitting or lying position or when climbing stairs). Report unusual chest pain, respiratory difficulty, or any persistent adverse reactions.
Alendronate and cholecalciferol
U.S. BRAND NAMES — Fosamax Plus D™
PHARMACOLOGIC CATEGORY Bisphosphonate DerivativeVitamin D Analog
DOSING: ADULTS — Osteoporosis: Oral: One tablet once weekly
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Clcr <35 mL/minute: Not recommended
DOSING: HEPATIC IMPAIRMENT — Alendronate: None necessary. Cholecalciferol: May not be adequately absorbed in patients who have malabsorption due to inadequate bile production.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Fosamax Plus D™: 70/2800: Alendronate 70 mg and cholecalciferol 2800 int. units
DOSAGE FORMS: CONCISE Tablet: Fosamax Plus D™: 70/2800: Alendronate 70 mg and cholecalciferol 2800 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Alendronate must be taken with plain water (6-8 oz) first thing in the morning and 30 minutes before the first food, beverage, or other medication of the day. Patient should be instructed to stay upright (not to lie down) for at least 30 minutes and until after first food of the day (to reduce esophageal irritation).
USE — Treatment of osteoporosis in postmenopausal females; increase bone mass in males with osteoporosis
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to alendronate, other bisphosphonates, vitamin D derivatives, or any component of the formulation; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; malabsorption syndrome; evidence of vitamin D toxicity
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy. Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Osteonecrosis of the jaw: Bisphosphonate therapy has been associated with osteonecrosis, primarily of the jaw; this has been observed mostly in cancer patients, but also in patients with postmenopausal osteoporosis and other diagnoses. Risk factors include a diagnosis of cancer, with concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, coagulopathy, infection or pre-existing dental disease. Symptoms included nonhealing extraction socket or an exposed jawbone. There are no data addressing whether discontinuation of therapy reduces the risk of developing osteonecrosis. However, as a precautionary measure, dental exams and preventative dentistry should be performed prior to placing patients with risk factors on chronic bisphosphonate therapy. Invasive dental procedures should be avoided during treatment.
Disease-related concerns: Hypocalcemia/vitamin D deficiency: Before therapy initiation hypocalcemia and/or vitamin D deficiency must be corrected; ensure adequate calcium and vitamin D intake. Do not use to treat vitamin D deficiency. Hypercalcemia: May exacerbate hypercalcemia in certain disease states (eg, leukemia, lymphoma, sarcoidosis); monitor serum calcium levels. Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with Clcr <35 mL/minute).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS — See individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — See individual agents.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. No animal data are available for the use of cholecalciferol in pregnancy; however, high-dose ergocalciferol has demonstrated abortifacient properties and aortic abnormalities in rabbits. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Cholecalciferol enters breast milk; excretion of alendronate in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Ensure adequate calcium and vitamin D intake. May require additional vitamin D supplementation, particularly in patients at risk for vitamin D deficiency (eg, malabsorption syndromes, chronically ill, >70 years of age). Wait at least 30 minutes after taking alendronate with cholecalciferol before taking any supplement. Must be taken with plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day.
PRICING — (data from drugstore.com)Tablets (Fosamax Plus D) 70-2800 MG-UNIT (4): $79.70
MONITORING PARAMETERS — Alkaline phosphatase (measured periodically); urine and serum calcium, serum phosphorus, serum 25-hydroxy vitamin D; monitor pain and fracture rate; hormonal status (male and female) prior to therapy; bone mineral density (should be done prior to initiation of therapy and after 6-12 months of combined glucocorticoid and alendronate treatment)
REFERENCE RANGE Calcium (total): Adults: 9.0-11.0 mg/dL (2.05-2.54 mmol/L), may slightly decrease with aging
Phosphorus: 2.5-4.5 mg/dL (0.81-1.45 mmol/L)
25-hydroxyvitamin D: 10-80 ng/mL (higher during summer)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms may include anorexia, polyuria, polydipsia, lethargy, hypo-/hypercalcemia, hypophosphatemia, and upper GI adverse effects (eg, upset stomach, heartburn, esophagitis, gastritis, or ulcer). Treat with milk or antacids to bind alendronate. Hydration, systemic glucocorticoids, and reduction of calcium intake may be beneficial in correcting hypercalcemia. Dialysis would not be beneficial.
CANADIAN BRAND NAMES — Fosavance
INTERNATIONAL BRAND NAMES — Fosamax Plus (AR, HK, MX); Fosavance (AT, BE, BG, CA, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PH, PT, RU, SE, TR); Maximus (PE)
MECHANISM OF ACTION — See individual agents.
PATIENT INFORMATION — Do not take more than the recommended amount. While taking this medication, your prescriber may want you to follow a special diet or take a calcium supplement. Follow this diet closely. Avoid taking magnesium supplements or magnesium-containing antacids. Early symptoms of hypercalcemia include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, cramps, diarrhea, muscle pain, bone pain, and irritability.
PHARMACOLOGIC CATEGORY Bisphosphonate DerivativeVitamin D Analog
DOSING: ADULTS — Osteoporosis: Oral: One tablet once weekly
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Clcr <35 mL/minute: Not recommended
DOSING: HEPATIC IMPAIRMENT — Alendronate: None necessary. Cholecalciferol: May not be adequately absorbed in patients who have malabsorption due to inadequate bile production.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Fosamax Plus D™: 70/2800: Alendronate 70 mg and cholecalciferol 2800 int. units
DOSAGE FORMS: CONCISE Tablet: Fosamax Plus D™: 70/2800: Alendronate 70 mg and cholecalciferol 2800 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Alendronate must be taken with plain water (6-8 oz) first thing in the morning and 30 minutes before the first food, beverage, or other medication of the day. Patient should be instructed to stay upright (not to lie down) for at least 30 minutes and until after first food of the day (to reduce esophageal irritation).
USE — Treatment of osteoporosis in postmenopausal females; increase bone mass in males with osteoporosis
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to alendronate, other bisphosphonates, vitamin D derivatives, or any component of the formulation; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; malabsorption syndrome; evidence of vitamin D toxicity
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy. Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Osteonecrosis of the jaw: Bisphosphonate therapy has been associated with osteonecrosis, primarily of the jaw; this has been observed mostly in cancer patients, but also in patients with postmenopausal osteoporosis and other diagnoses. Risk factors include a diagnosis of cancer, with concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, coagulopathy, infection or pre-existing dental disease. Symptoms included nonhealing extraction socket or an exposed jawbone. There are no data addressing whether discontinuation of therapy reduces the risk of developing osteonecrosis. However, as a precautionary measure, dental exams and preventative dentistry should be performed prior to placing patients with risk factors on chronic bisphosphonate therapy. Invasive dental procedures should be avoided during treatment.
Disease-related concerns: Hypocalcemia/vitamin D deficiency: Before therapy initiation hypocalcemia and/or vitamin D deficiency must be corrected; ensure adequate calcium and vitamin D intake. Do not use to treat vitamin D deficiency. Hypercalcemia: May exacerbate hypercalcemia in certain disease states (eg, leukemia, lymphoma, sarcoidosis); monitor serum calcium levels. Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with Clcr <35 mL/minute).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS — See individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — See individual agents.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. No animal data are available for the use of cholecalciferol in pregnancy; however, high-dose ergocalciferol has demonstrated abortifacient properties and aortic abnormalities in rabbits. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Cholecalciferol enters breast milk; excretion of alendronate in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Ensure adequate calcium and vitamin D intake. May require additional vitamin D supplementation, particularly in patients at risk for vitamin D deficiency (eg, malabsorption syndromes, chronically ill, >70 years of age). Wait at least 30 minutes after taking alendronate with cholecalciferol before taking any supplement. Must be taken with plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day.
PRICING — (data from drugstore.com)Tablets (Fosamax Plus D) 70-2800 MG-UNIT (4): $79.70
MONITORING PARAMETERS — Alkaline phosphatase (measured periodically); urine and serum calcium, serum phosphorus, serum 25-hydroxy vitamin D; monitor pain and fracture rate; hormonal status (male and female) prior to therapy; bone mineral density (should be done prior to initiation of therapy and after 6-12 months of combined glucocorticoid and alendronate treatment)
REFERENCE RANGE Calcium (total): Adults: 9.0-11.0 mg/dL (2.05-2.54 mmol/L), may slightly decrease with aging
Phosphorus: 2.5-4.5 mg/dL (0.81-1.45 mmol/L)
25-hydroxyvitamin D: 10-80 ng/mL (higher during summer)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms may include anorexia, polyuria, polydipsia, lethargy, hypo-/hypercalcemia, hypophosphatemia, and upper GI adverse effects (eg, upset stomach, heartburn, esophagitis, gastritis, or ulcer). Treat with milk or antacids to bind alendronate. Hydration, systemic glucocorticoids, and reduction of calcium intake may be beneficial in correcting hypercalcemia. Dialysis would not be beneficial.
CANADIAN BRAND NAMES — Fosavance
INTERNATIONAL BRAND NAMES — Fosamax Plus (AR, HK, MX); Fosavance (AT, BE, BG, CA, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PH, PT, RU, SE, TR); Maximus (PE)
MECHANISM OF ACTION — See individual agents.
PATIENT INFORMATION — Do not take more than the recommended amount. While taking this medication, your prescriber may want you to follow a special diet or take a calcium supplement. Follow this diet closely. Avoid taking magnesium supplements or magnesium-containing antacids. Early symptoms of hypercalcemia include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, cramps, diarrhea, muscle pain, bone pain, and irritability.
Alfentanil
U.S. BRAND NAMES — Alfenta®
PHARMACOLOGIC CATEGORY Analgesic, Opioid
DOSING: ADULTS — Doses should be titrated to appropriate effects; wide range of doses is dependent upon desired degree of analgesia/anesthesia
Anesthesia: I.V.: Dose should be based on ideal body weight as follows (see table).
Adult Dosage Adjustments
Incremental injection in anesthesia 30 minutes: Initial dose (induction period): 8-20 mcg/kg Maintenance period (increments/infusion): 3-5 mcg/kg or 0.5-1 mcg/kg/minute Total dose: 8-40 mcg/kg Appropriate effects: Spontaneously breathing or assisted ventilation when required
Incremental injection in anesthesia of 30-60 minutes: Initial dose (induction period): 20-50 mcg/kg Maintenance period (increments/infusion): 5-15 mcg/kg Total dose: Up to 75 mcg/kg Appropriate effects: Assisted or controlled ventilation required. Attenuation of response to laryngoscopy and intubation.
Continuous infusion >45 minutes: Initial dose (induction period): 50-75 mcg/kg Maintenance period (increments/infusion): 0.5-3 mcg/kg/minute; average infusion rate: 1-1.5 mcg/kg/minute Total dose: Dependent on duration of procedure Appropriate effects: Assisted or controlled ventilation required. Some attenuation of response to intubation and incision, with intraoperative stability.
Anesthetic induction >45 minutes: Initial dose (induction period): 130-245 mcg/kg Maintenance period (increments/infusion): 0.5-1.5 mcg/kg/minute or general anesthetic Total dose: Dependent on duration of procedure Appropriate effects: Assisted or controlled ventilation required. Administer slowly (over 3 minutes). Concentration of inhalation agents reduced by 30% to 50% for initial hour.
DOSING: PEDIATRIC
(For additional information see "Alfentanil: Pediatric drug information")Children <12 years: Dose has not been established.
Children 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 500 mcg/mL (2 mL, 5 mL, 10 mL) Alfenta®: 500 mcg/mL (2 mL, 5 mL, 10 mL, 20 mL)
DOSAGE FORMS: CONCISE Injection, solution [preservative free]: 500 mcg/mL (2 mL, 5 mL, 10 mL) Alfenta®: 500 mcg/mL (2 mL, 5 mL, 10 mL, 20 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer I.V. slowly over 3-5 minutes or by I.V. continuous infusion.
COMPATIBILITY — Stable in D5W, NS, LR, D5NS.
Y-site administration: Compatible: Cisatracurium, etomidate, gatifloxacin, linezolid, propofol, remifentanil. Incompatible: Amphotericin B cholesteryl sulfate complex, thiopental.
Compatibility in syringe: Compatible: Atracurium, midazolam, ondansetron.
USE — Analgesic adjunct given by continuous infusion or in incremental doses in maintenance of anesthesia with barbiturate or N2O or a primary anesthetic agent for the induction of anesthesia in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required
ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Bradycardia, peripheral vasodilation Central nervous system: Drowsiness, sedation, intracranial pressure increased Endocrine & metabolic: Antidiuretic hormone release Gastrointestinal: Nausea, vomiting, constipation Ocular: Miosis
1% to 10%: Cardiovascular: Cardiac arrhythmia, orthostatic hypotension Central nervous system: Confusion, CNS depression Ocular: Blurred vision
<1% (Limited to important or life-threatening): Convulsions, mental depression, paradoxical CNS excitation or delirium, dizziness, dysesthesia, rash, urticaria, itching, biliary tract spasm, urinary tract spasm, respiratory depression, bronchospasm, laryngospasm, physical and psychological dependence with prolonged use; cold, clammy skin
CONTRAINDICATIONS — Hypersensitivity to alfentanil hydrochloride, to narcotics, or any component of the formulation; increased intracranial pressure, severe respiratory depression
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Opioid agonist toxicities: Shares the toxic potentials of opiate agonists, and precautions of opiate agonist therapy should be observed.
Disease-related concerns: Bradyarrhythmias: Use with caution when administering to patients with bradyarrhythmias. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Obesity: Use with caution in patients who are morbidly obese. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function.
Special populations: Neonates: Hypotension has occurred in neonates with respiratory distress syndrome. Pediatrics: Safety and efficacy have not been established in children <12 years old.
Other warnings/precautions: Rapid infusion: Inject slowly over 3-5 minutes; rapid I.V. infusion may result in skeletal muscle and chest wall rigidity, impaired ventilation, or respiratory distress/arrest; nondepolarizing skeletal muscle relaxant may be required. Trained individuals: Due to the high incidence of apnea, hypotension, tachycardia and muscle rigidity; it should be administered by individuals specifically trained in the use of anesthetic agents and should not be used in diagnostic or therapeutic procedures outside the monitored anesthesia setting; resuscitative and intubation equipment should be readily available.
RESTRICTIONS — C-II
DRUG INTERACTIONS — Substrate of CYP3A4 (major)
Dextroamphetamine: May enhance the analgesic effect of morphine and other opiate agonists.
Increased toxicity with CNS depressants (eg, benzodiazepines, barbiturates, tricyclic antidepressants), erythromycin, reserpine, beta-blockers.
CYP3A4 inhibitors: May increase the levels/effects of alfentanil. Example inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil.
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Respiratory rate, blood pressure, heart rate
REFERENCE RANGE — 100-340 ng/mL (depending upon procedure)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include miosis, respiratory depression, seizures, and CNS depression. Treatment includes naloxone 2 mg I.V. (0.01 mg/kg for children), with repeat administration as necessary, up to a total of 10 mg. May precipitate withdrawal.
CANADIAN BRAND NAMES — Alfentanil Injection, USP; Alfenta®
INTERNATIONAL BRAND NAMES — Alfenil (KR); Alfenta (BR, CA); Alfentanil Injection, USP (CA); Brevafen (AR); Fanaxal (ES); Fentalim (IT); Rapifen (AE, AT, AU, BE, BG, BH, BR, CH, CL, CY, CZ, DE, DK, EG, FI, FR, GB, GR, HK, HR, HU, IE, IL, IQ, IR, IT, JO, KW, LB, LY, NL, NO, NZ, OM, PL, PT, PY, QA, RU, SA, SE, SY, TW, UY, VE, YE, ZA)
MECHANISM OF ACTION — Binds with stereospecific receptors at many sites within the CNS, increases pain threshold, alters pain perception, inhibits ascending pain pathways; is an ultra short-acting narcotic
PHARMACODYNAMICS / KINETICS Onset of action: Rapid
Duration (dose dependent): 30-60 minutes
Distribution: Vd: Newborns, premature: 1 L/kg; Children: 0.163-0.48 L/kg; Adults: 0.46 L/kg
Half-life elimination: Newborns, premature: 5.33-8.75 hours; Children: 40-60 minutes; Adults: 83-97 minutes
PHARMACOLOGIC CATEGORY Analgesic, Opioid
DOSING: ADULTS — Doses should be titrated to appropriate effects; wide range of doses is dependent upon desired degree of analgesia/anesthesia
Anesthesia: I.V.: Dose should be based on ideal body weight as follows (see table).
Adult Dosage Adjustments
Incremental injection in anesthesia 30 minutes: Initial dose (induction period): 8-20 mcg/kg Maintenance period (increments/infusion): 3-5 mcg/kg or 0.5-1 mcg/kg/minute Total dose: 8-40 mcg/kg Appropriate effects: Spontaneously breathing or assisted ventilation when required
Incremental injection in anesthesia of 30-60 minutes: Initial dose (induction period): 20-50 mcg/kg Maintenance period (increments/infusion): 5-15 mcg/kg Total dose: Up to 75 mcg/kg Appropriate effects: Assisted or controlled ventilation required. Attenuation of response to laryngoscopy and intubation.
Continuous infusion >45 minutes: Initial dose (induction period): 50-75 mcg/kg Maintenance period (increments/infusion): 0.5-3 mcg/kg/minute; average infusion rate: 1-1.5 mcg/kg/minute Total dose: Dependent on duration of procedure Appropriate effects: Assisted or controlled ventilation required. Some attenuation of response to intubation and incision, with intraoperative stability.
Anesthetic induction >45 minutes: Initial dose (induction period): 130-245 mcg/kg Maintenance period (increments/infusion): 0.5-1.5 mcg/kg/minute or general anesthetic Total dose: Dependent on duration of procedure Appropriate effects: Assisted or controlled ventilation required. Administer slowly (over 3 minutes). Concentration of inhalation agents reduced by 30% to 50% for initial hour.
DOSING: PEDIATRIC
(For additional information see "Alfentanil: Pediatric drug information")Children <12 years: Dose has not been established.
Children 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 500 mcg/mL (2 mL, 5 mL, 10 mL) Alfenta®: 500 mcg/mL (2 mL, 5 mL, 10 mL, 20 mL)
DOSAGE FORMS: CONCISE Injection, solution [preservative free]: 500 mcg/mL (2 mL, 5 mL, 10 mL) Alfenta®: 500 mcg/mL (2 mL, 5 mL, 10 mL, 20 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer I.V. slowly over 3-5 minutes or by I.V. continuous infusion.
COMPATIBILITY — Stable in D5W, NS, LR, D5NS.
Y-site administration: Compatible: Cisatracurium, etomidate, gatifloxacin, linezolid, propofol, remifentanil. Incompatible: Amphotericin B cholesteryl sulfate complex, thiopental.
Compatibility in syringe: Compatible: Atracurium, midazolam, ondansetron.
USE — Analgesic adjunct given by continuous infusion or in incremental doses in maintenance of anesthesia with barbiturate or N2O or a primary anesthetic agent for the induction of anesthesia in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required
ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Bradycardia, peripheral vasodilation Central nervous system: Drowsiness, sedation, intracranial pressure increased Endocrine & metabolic: Antidiuretic hormone release Gastrointestinal: Nausea, vomiting, constipation Ocular: Miosis
1% to 10%: Cardiovascular: Cardiac arrhythmia, orthostatic hypotension Central nervous system: Confusion, CNS depression Ocular: Blurred vision
<1% (Limited to important or life-threatening): Convulsions, mental depression, paradoxical CNS excitation or delirium, dizziness, dysesthesia, rash, urticaria, itching, biliary tract spasm, urinary tract spasm, respiratory depression, bronchospasm, laryngospasm, physical and psychological dependence with prolonged use; cold, clammy skin
CONTRAINDICATIONS — Hypersensitivity to alfentanil hydrochloride, to narcotics, or any component of the formulation; increased intracranial pressure, severe respiratory depression
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Opioid agonist toxicities: Shares the toxic potentials of opiate agonists, and precautions of opiate agonist therapy should be observed.
Disease-related concerns: Bradyarrhythmias: Use with caution when administering to patients with bradyarrhythmias. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Obesity: Use with caution in patients who are morbidly obese. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function.
Special populations: Neonates: Hypotension has occurred in neonates with respiratory distress syndrome. Pediatrics: Safety and efficacy have not been established in children <12 years old.
Other warnings/precautions: Rapid infusion: Inject slowly over 3-5 minutes; rapid I.V. infusion may result in skeletal muscle and chest wall rigidity, impaired ventilation, or respiratory distress/arrest; nondepolarizing skeletal muscle relaxant may be required. Trained individuals: Due to the high incidence of apnea, hypotension, tachycardia and muscle rigidity; it should be administered by individuals specifically trained in the use of anesthetic agents and should not be used in diagnostic or therapeutic procedures outside the monitored anesthesia setting; resuscitative and intubation equipment should be readily available.
RESTRICTIONS — C-II
DRUG INTERACTIONS — Substrate of CYP3A4 (major)
Dextroamphetamine: May enhance the analgesic effect of morphine and other opiate agonists.
Increased toxicity with CNS depressants (eg, benzodiazepines, barbiturates, tricyclic antidepressants), erythromycin, reserpine, beta-blockers.
CYP3A4 inhibitors: May increase the levels/effects of alfentanil. Example inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil.
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Respiratory rate, blood pressure, heart rate
REFERENCE RANGE — 100-340 ng/mL (depending upon procedure)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include miosis, respiratory depression, seizures, and CNS depression. Treatment includes naloxone 2 mg I.V. (0.01 mg/kg for children), with repeat administration as necessary, up to a total of 10 mg. May precipitate withdrawal.
CANADIAN BRAND NAMES — Alfentanil Injection, USP; Alfenta®
INTERNATIONAL BRAND NAMES — Alfenil (KR); Alfenta (BR, CA); Alfentanil Injection, USP (CA); Brevafen (AR); Fanaxal (ES); Fentalim (IT); Rapifen (AE, AT, AU, BE, BG, BH, BR, CH, CL, CY, CZ, DE, DK, EG, FI, FR, GB, GR, HK, HR, HU, IE, IL, IQ, IR, IT, JO, KW, LB, LY, NL, NO, NZ, OM, PL, PT, PY, QA, RU, SA, SE, SY, TW, UY, VE, YE, ZA)
MECHANISM OF ACTION — Binds with stereospecific receptors at many sites within the CNS, increases pain threshold, alters pain perception, inhibits ascending pain pathways; is an ultra short-acting narcotic
PHARMACODYNAMICS / KINETICS Onset of action: Rapid
Duration (dose dependent): 30-60 minutes
Distribution: Vd: Newborns, premature: 1 L/kg; Children: 0.163-0.48 L/kg; Adults: 0.46 L/kg
Half-life elimination: Newborns, premature: 5.33-8.75 hours; Children: 40-60 minutes; Adults: 83-97 minutes
Alendronate
U.S. BRAND NAMES — Fosamax®
PHARMACOLOGIC CATEGORY Bisphosphonate Derivative
DOSING: ADULTS — Note: Patients treated with glucocorticoids and those with Paget's disease should receive adequate amounts of calcium and vitamin D.
Osteoporosis in postmenopausal females: Oral: Prophylaxis: 5 mg once daily or 35 mg once weekly Treatment: 10 mg once daily or 70 mg once weekly
Osteoporosis in males: Oral: 10 mg once daily or 70 mg once weekly
Osteoporosis secondary to glucocorticoids in males and females: Oral: Treatment: 5 mg once daily; a dose of 10 mg once daily should be used in postmenopausal females who are not receiving estrogen.
Paget's disease of bone in males and females: Oral: 40 mg once daily for 6 months Retreatment: Relapses during the 12 months following therapy occurred in 9% of patients who responded to treatment. Specific retreatment data are not available. Following a 6-month post-treatment evaluation period, treatment with alendronate may be considered in patients who have relapsed based on increases in serum alkaline phosphatase, which should be measured periodically. Retreatment may also be considered in those who failed to normalize their serum alkaline phosphatase.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Clcr 35-60 mL/minute: None necessary.
Clcr <35 mL/minute: Alendronate is not recommended due to lack of experience.
DOSING: HEPATIC IMPAIRMENT — No adjustment necessary.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Note: Strength expressed as free acid
Solution, oral, as monosodium trihydrate: Fosamax™: 70 mg/75 mL [contains parabens; raspberry flavor]
Tablet, as sodium: Fosamax™: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg
DOSAGE FORMS: CONCISE — Note: Strength expressed as free acid
Solution, oral: Fosamax®: 70 mg/75 mL
Tablet: Fosamax®: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Alendronate must be taken with plain water (tablets 6-8 oz; oral solution follow with 2 oz) first thing in the morning and 30 minutes before the first food, beverage, or other medication of the day. Do not take with mineral water or with other beverages. Patients should be instructed to stay upright (not to lie down) for at least 30 minutes and until after first food of the day (to reduce esophageal irritation). Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.
USE — Treatment and prevention of osteoporosis in postmenopausal females; treatment of osteoporosis in males; Paget's disease of the bone in patients who are symptomatic, at risk for future complications, or with alkaline phosphatase 2 times the upper limit of normal; treatment of glucocorticoid-induced osteoporosis in males and females with low bone mineral density who are receiving a daily dosage 7.5 mg of prednisone (or equivalent)
ADVERSE REACTIONS SIGNIFICANT — Note: Incidence of adverse effects (mostly GI) increases significantly in patients treated for Paget's disease at 40 mg/day.
>10%: Endocrine & metabolic: Hypocalcemia (transient, mild, 18%); hypophosphatemia (transient, mild, 10%)
1% to 10%: Central nervous system: Headache (up to 3%) Gastrointestinal: Abdominal pain (1% to 7%), acid reflux (1% to 4%), dyspepsia (1% to 4%), nausea (1% to 4%), flatulence (up to 4%), diarrhea (1% to 3%), gastroesophageal reflux disease (1% to 3%), constipation (up to 3%), esophageal ulcer (up to 2%), abdominal distension (up to 1%), gastritis (up to 1%), vomiting (up to 1%), dysphagia (up to 1%), gastric ulcer (1%), melena (1%) Neuromuscular & skeletal: Musculoskeletal pain (up to 6%), muscle cramps (up to 1%)
<1% (Limited to important or life-threatening): Anastomotic ulcer, angioedema; bone, muscle, or joint pain (occasionally severe, considered incapacitating in rare cases); dizziness, duodenal ulcer, episcleritis, erythema, esophageal erosions, esophageal perforation, esophageal stricture, esophagitis, fever, flu-like syndrome, hypersensitivity reactions, hypocalcemia (symptomatic), joint swelling, lymphocytopenia, malaise, myalgia, oropharyngeal ulceration, osteonecrosis (jaw), peripheral edema, photosensitivity (rare), pruritus, rash, scleritis (rare), Stevens-Johnson syndrome, taste perversion, toxic epidermal necrolysis, urticaria, uveitis (rare), vertigo, weakness
CONTRAINDICATIONS — Hypersensitivity to alendronate, other bisphosphonates, or any component of the formulation; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; oral solution should not be used in patients at risk of aspiration
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy. Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Osteonecrosis of the jaw: Bisphosphonate therapy has been associated with osteonecrosis, primarily of the jaw; this has been observed mostly in cancer patients, but also in patients with postmenopausal osteoporosis and other diagnoses. Risk factors include a diagnosis of cancer, with concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, coagulopathy, infection, or pre-existing dental disease. Symptoms included nonhealing extraction socket or an exposed jawbone. There are no data addressing whether discontinuation of therapy reduces the risk of developing osteonecrosis; however, as a precautionary measure, dental exams and preventative dentistry should be performed prior to placing patients with risk factors on chronic bisphosphonate therapy. Invasive dental procedures should be avoided during treatment.
Disease-related concerns: Hypocalcemia: Before therapy initiation hypocalcemia must be corrected; ensure adequate calcium and vitamin D intake. Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with Clcr <35 mL/minute).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS Aminoglycosides: May lower serum calcium levels with prolonged administration. Concomitant use may have an additive hypocalcemic effect.
Antacids: May decrease the absorption of bisphosphonate derivatives; should be administered at a different time of the day. Antacids containing aluminum, calcium, or magnesium are of specific concern.
Aspirin: May enhance the adverse/toxic effect of alendronate; specifically gastrointestinal adverse events.
Calcium salts: May decrease the absorption of bisphosphonate derivatives. Separate oral dosing in order to minimize risk of interaction.
Iron salts: May decrease the absorption of bisphosphonate derivatives. Only oral iron salts and oral bisphosphonates are of concern.
Magnesium salts: May decrease the absorption of bisphosphonate derivatives. Only oral magnesium salts and oral bisphosphonates are of concern.
Nonsteroidal anti-inflammatory drugs (NSAIDs): May enhance the gastrointestinal adverse/toxic effects (increased incidence of GI ulcers) of bisphosphonate derivatives.
Phosphate supplements: Bisphosphonate derivatives may enhance the hypocalcemic effect of phosphate supplements.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol (may increase risk of osteoporosis and gastric irritation).
Food: All food and beverages interfere with absorption. Coadministration with caffeine may reduce alendronate efficacy. Coadministration with dairy products may decrease alendronate absorption. Beverages (especially orange juice and coffee) and food may reduce the absorption of alendronate as much as 60%.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Safety and efficacy have not been established in pregnant women. Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. Based on limited case reports with pamidronate, serum calcium levels in the newborn may be altered if administered during pregnancy.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Ensure adequate calcium and vitamin D intake; however, wait at least 30 minutes after taking alendronate before taking any supplement. Alendronate must be taken with plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day.
PRICING — (data from drugstore.com)Solution (Fosamax) 70 mg/75mL (75): $27.99
Tablets (Fosamax) 5 mg (30): $79.31 10 mg (30): $85.99 35 mg (4): $72.99 70 mg (4): $77.61
MONITORING PARAMETERS — Alkaline phosphatase should be periodically measured; serum calcium and phosphorus; monitor pain and fracture rate; hormonal status (male and female) prior to therapy; bone mineral density (should be done prior to initiation of therapy and after 6-12 months of combined glucocorticoid and alendronate treatment)
REFERENCE RANGE — Calcium (total): Adults: 9.0-11.0 mg/dL (2.05-2.54 mmol/L), may slightly decrease with aging; phosphorus: 2.5-4.5 mg/dL (0.81-1.45 mmol/L)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include hypocalcemia, hypophosphatemia, and upper GI adverse events (upset stomach, heartburn, esophagitis, gastritis or ulcer). Treat with milk or antacids to bind alendronate. Dialysis would not be beneficial. Do not induce vomiting (due to the risk of esophageal irritation); keep fully upright.
CANADIAN BRAND NAMES — Apo-Alendronate®; CO Alendronate; Fosamax®; Gen-Alendronate; Novo-Alendronate; PMS-Alendronate; ratio-Alendronate; Riva-Alendronate
INTERNATIONAL BRAND NAMES — Aldrox (CL); Alenato (AR); Alend (KR); Alenmax (KR); Alexonal (ID); Alnax (PY); Apo-Alendronate (CA); Arendal (PE); Armol (CO); Bifemelan (CO); Bifosa (IN); Bolend (KR); Bonapex (EG); CO Alendronate (CA); Endronax (BR); Eucalen (CO); Fixopan (EC); Fosalan (IL); Fosamax (AN, AR, AT, AU, BB, BE, BG, BM, BR, BS, BZ, CA, CH, CL, CR, CZ, DE, DK, EC, EE, EG, ES, FI, FR, GB, GT, GY, HK, HN, HU, ID, IE, IT, JM, KR, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PK, SE, SG, SR, SV, TH, TT, TW, VE, ZA); Fosaqueen (KR); Fosmin (PE); Fosval (PY); Gen-Alendronate (CA); Marvil (PE, UY); MaxiBone (IL); MaxiBone 70 (IL); Neobon (CO); Novo-Alendronate (CA); Osdron (BR); Osdronat (CO); Oseotenk (AR); Osficar (CO); Osteofar (ID); Osteofos (HK); Osteopor (UY); Osteosan (CL); Osteovan (CR); Osticalcin (CO); PMS-Alendronate (CA); Porosal (VE); ratio-Alendronate (CA); Riva-Alendronate (CA); Tibolene (CO); Voroste (ID)
MECHANISM OF ACTION — A bisphosphonate which inhibits bone resorption via actions on osteoclasts or on osteoclast precursors; decreases the rate of bone resorption, leading to an indirect increase in bone mineral density. In Paget's disease, characterized by disordered resorption and formation of bone, inhibition of resorption leads to an indirect decrease in bone formation; but the newly-formed bone has a more normal architecture.
PHARMACODYNAMICS / KINETICS Distribution: 28 L (exclusive of bone)
Protein binding: ~78%
Metabolism: None
Bioavailability: Fasting: 0.6%; reduced 60% with food or drink
Half-life elimination: Exceeds 10 years
Excretion: Urine; feces (as unabsorbed drug)
PATIENT INFORMATION — Take as directed, with a full glass of water first thing in the morning and at least 30 minutes before the first food or beverage of the day. Wait at least 30 minutes after taking alendronate before taking anything else. Stay in sitting or standing position for 30 minutes following administration and until after the first food of the day to reduce potential for esophageal irritation. Consult prescriber to determine necessity of lifestyle changes (eg, decreased smoking, decreased alcohol intake, dietary supplements of calcium, or increased dietary vitamin D).
PHARMACOLOGIC CATEGORY Bisphosphonate Derivative
DOSING: ADULTS — Note: Patients treated with glucocorticoids and those with Paget's disease should receive adequate amounts of calcium and vitamin D.
Osteoporosis in postmenopausal females: Oral: Prophylaxis: 5 mg once daily or 35 mg once weekly Treatment: 10 mg once daily or 70 mg once weekly
Osteoporosis in males: Oral: 10 mg once daily or 70 mg once weekly
Osteoporosis secondary to glucocorticoids in males and females: Oral: Treatment: 5 mg once daily; a dose of 10 mg once daily should be used in postmenopausal females who are not receiving estrogen.
Paget's disease of bone in males and females: Oral: 40 mg once daily for 6 months Retreatment: Relapses during the 12 months following therapy occurred in 9% of patients who responded to treatment. Specific retreatment data are not available. Following a 6-month post-treatment evaluation period, treatment with alendronate may be considered in patients who have relapsed based on increases in serum alkaline phosphatase, which should be measured periodically. Retreatment may also be considered in those who failed to normalize their serum alkaline phosphatase.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Clcr 35-60 mL/minute: None necessary.
Clcr <35 mL/minute: Alendronate is not recommended due to lack of experience.
DOSING: HEPATIC IMPAIRMENT — No adjustment necessary.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Note: Strength expressed as free acid
Solution, oral, as monosodium trihydrate: Fosamax™: 70 mg/75 mL [contains parabens; raspberry flavor]
Tablet, as sodium: Fosamax™: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg
DOSAGE FORMS: CONCISE — Note: Strength expressed as free acid
Solution, oral: Fosamax®: 70 mg/75 mL
Tablet: Fosamax®: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Alendronate must be taken with plain water (tablets 6-8 oz; oral solution follow with 2 oz) first thing in the morning and 30 minutes before the first food, beverage, or other medication of the day. Do not take with mineral water or with other beverages. Patients should be instructed to stay upright (not to lie down) for at least 30 minutes and until after first food of the day (to reduce esophageal irritation). Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.
USE — Treatment and prevention of osteoporosis in postmenopausal females; treatment of osteoporosis in males; Paget's disease of the bone in patients who are symptomatic, at risk for future complications, or with alkaline phosphatase 2 times the upper limit of normal; treatment of glucocorticoid-induced osteoporosis in males and females with low bone mineral density who are receiving a daily dosage 7.5 mg of prednisone (or equivalent)
ADVERSE REACTIONS SIGNIFICANT — Note: Incidence of adverse effects (mostly GI) increases significantly in patients treated for Paget's disease at 40 mg/day.
>10%: Endocrine & metabolic: Hypocalcemia (transient, mild, 18%); hypophosphatemia (transient, mild, 10%)
1% to 10%: Central nervous system: Headache (up to 3%) Gastrointestinal: Abdominal pain (1% to 7%), acid reflux (1% to 4%), dyspepsia (1% to 4%), nausea (1% to 4%), flatulence (up to 4%), diarrhea (1% to 3%), gastroesophageal reflux disease (1% to 3%), constipation (up to 3%), esophageal ulcer (up to 2%), abdominal distension (up to 1%), gastritis (up to 1%), vomiting (up to 1%), dysphagia (up to 1%), gastric ulcer (1%), melena (1%) Neuromuscular & skeletal: Musculoskeletal pain (up to 6%), muscle cramps (up to 1%)
<1% (Limited to important or life-threatening): Anastomotic ulcer, angioedema; bone, muscle, or joint pain (occasionally severe, considered incapacitating in rare cases); dizziness, duodenal ulcer, episcleritis, erythema, esophageal erosions, esophageal perforation, esophageal stricture, esophagitis, fever, flu-like syndrome, hypersensitivity reactions, hypocalcemia (symptomatic), joint swelling, lymphocytopenia, malaise, myalgia, oropharyngeal ulceration, osteonecrosis (jaw), peripheral edema, photosensitivity (rare), pruritus, rash, scleritis (rare), Stevens-Johnson syndrome, taste perversion, toxic epidermal necrolysis, urticaria, uveitis (rare), vertigo, weakness
CONTRAINDICATIONS — Hypersensitivity to alendronate, other bisphosphonates, or any component of the formulation; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; oral solution should not be used in patients at risk of aspiration
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy. Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Osteonecrosis of the jaw: Bisphosphonate therapy has been associated with osteonecrosis, primarily of the jaw; this has been observed mostly in cancer patients, but also in patients with postmenopausal osteoporosis and other diagnoses. Risk factors include a diagnosis of cancer, with concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, coagulopathy, infection, or pre-existing dental disease. Symptoms included nonhealing extraction socket or an exposed jawbone. There are no data addressing whether discontinuation of therapy reduces the risk of developing osteonecrosis; however, as a precautionary measure, dental exams and preventative dentistry should be performed prior to placing patients with risk factors on chronic bisphosphonate therapy. Invasive dental procedures should be avoided during treatment.
Disease-related concerns: Hypocalcemia: Before therapy initiation hypocalcemia must be corrected; ensure adequate calcium and vitamin D intake. Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with Clcr <35 mL/minute).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS Aminoglycosides: May lower serum calcium levels with prolonged administration. Concomitant use may have an additive hypocalcemic effect.
Antacids: May decrease the absorption of bisphosphonate derivatives; should be administered at a different time of the day. Antacids containing aluminum, calcium, or magnesium are of specific concern.
Aspirin: May enhance the adverse/toxic effect of alendronate; specifically gastrointestinal adverse events.
Calcium salts: May decrease the absorption of bisphosphonate derivatives. Separate oral dosing in order to minimize risk of interaction.
Iron salts: May decrease the absorption of bisphosphonate derivatives. Only oral iron salts and oral bisphosphonates are of concern.
Magnesium salts: May decrease the absorption of bisphosphonate derivatives. Only oral magnesium salts and oral bisphosphonates are of concern.
Nonsteroidal anti-inflammatory drugs (NSAIDs): May enhance the gastrointestinal adverse/toxic effects (increased incidence of GI ulcers) of bisphosphonate derivatives.
Phosphate supplements: Bisphosphonate derivatives may enhance the hypocalcemic effect of phosphate supplements.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol (may increase risk of osteoporosis and gastric irritation).
Food: All food and beverages interfere with absorption. Coadministration with caffeine may reduce alendronate efficacy. Coadministration with dairy products may decrease alendronate absorption. Beverages (especially orange juice and coffee) and food may reduce the absorption of alendronate as much as 60%.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Safety and efficacy have not been established in pregnant women. Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. Based on limited case reports with pamidronate, serum calcium levels in the newborn may be altered if administered during pregnancy.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Ensure adequate calcium and vitamin D intake; however, wait at least 30 minutes after taking alendronate before taking any supplement. Alendronate must be taken with plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day.
PRICING — (data from drugstore.com)Solution (Fosamax) 70 mg/75mL (75): $27.99
Tablets (Fosamax) 5 mg (30): $79.31 10 mg (30): $85.99 35 mg (4): $72.99 70 mg (4): $77.61
MONITORING PARAMETERS — Alkaline phosphatase should be periodically measured; serum calcium and phosphorus; monitor pain and fracture rate; hormonal status (male and female) prior to therapy; bone mineral density (should be done prior to initiation of therapy and after 6-12 months of combined glucocorticoid and alendronate treatment)
REFERENCE RANGE — Calcium (total): Adults: 9.0-11.0 mg/dL (2.05-2.54 mmol/L), may slightly decrease with aging; phosphorus: 2.5-4.5 mg/dL (0.81-1.45 mmol/L)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include hypocalcemia, hypophosphatemia, and upper GI adverse events (upset stomach, heartburn, esophagitis, gastritis or ulcer). Treat with milk or antacids to bind alendronate. Dialysis would not be beneficial. Do not induce vomiting (due to the risk of esophageal irritation); keep fully upright.
CANADIAN BRAND NAMES — Apo-Alendronate®; CO Alendronate; Fosamax®; Gen-Alendronate; Novo-Alendronate; PMS-Alendronate; ratio-Alendronate; Riva-Alendronate
INTERNATIONAL BRAND NAMES — Aldrox (CL); Alenato (AR); Alend (KR); Alenmax (KR); Alexonal (ID); Alnax (PY); Apo-Alendronate (CA); Arendal (PE); Armol (CO); Bifemelan (CO); Bifosa (IN); Bolend (KR); Bonapex (EG); CO Alendronate (CA); Endronax (BR); Eucalen (CO); Fixopan (EC); Fosalan (IL); Fosamax (AN, AR, AT, AU, BB, BE, BG, BM, BR, BS, BZ, CA, CH, CL, CR, CZ, DE, DK, EC, EE, EG, ES, FI, FR, GB, GT, GY, HK, HN, HU, ID, IE, IT, JM, KR, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PK, SE, SG, SR, SV, TH, TT, TW, VE, ZA); Fosaqueen (KR); Fosmin (PE); Fosval (PY); Gen-Alendronate (CA); Marvil (PE, UY); MaxiBone (IL); MaxiBone 70 (IL); Neobon (CO); Novo-Alendronate (CA); Osdron (BR); Osdronat (CO); Oseotenk (AR); Osficar (CO); Osteofar (ID); Osteofos (HK); Osteopor (UY); Osteosan (CL); Osteovan (CR); Osticalcin (CO); PMS-Alendronate (CA); Porosal (VE); ratio-Alendronate (CA); Riva-Alendronate (CA); Tibolene (CO); Voroste (ID)
MECHANISM OF ACTION — A bisphosphonate which inhibits bone resorption via actions on osteoclasts or on osteoclast precursors; decreases the rate of bone resorption, leading to an indirect increase in bone mineral density. In Paget's disease, characterized by disordered resorption and formation of bone, inhibition of resorption leads to an indirect decrease in bone formation; but the newly-formed bone has a more normal architecture.
PHARMACODYNAMICS / KINETICS Distribution: 28 L (exclusive of bone)
Protein binding: ~78%
Metabolism: None
Bioavailability: Fasting: 0.6%; reduced 60% with food or drink
Half-life elimination: Exceeds 10 years
Excretion: Urine; feces (as unabsorbed drug)
PATIENT INFORMATION — Take as directed, with a full glass of water first thing in the morning and at least 30 minutes before the first food or beverage of the day. Wait at least 30 minutes after taking alendronate before taking anything else. Stay in sitting or standing position for 30 minutes following administration and until after the first food of the day to reduce potential for esophageal irritation. Consult prescriber to determine necessity of lifestyle changes (eg, decreased smoking, decreased alcohol intake, dietary supplements of calcium, or increased dietary vitamin D).
Bidding For Buyers---Lessons From The Auction Block
If you think that E-bay has nothing to teach you, think again. Itdoesn’t matter much that you aren’t in the auction business andthat your website is entirely different in scope. What matters isthat the first place phenomenon of the Internet Revolution isE-bay. Its evolution is not just as a profitable e-business but anew culture of society. The lessons learned at E-bay might justget you off the surfboard and onto that ship you have been waitingto come in. This on-the-edge idea broke ground out of a humbleSilicon Valley apartment into a reality model of more than 10million registered users and sales to the tune of more than $100 anano-second. In other words, while you spent ten seconds readingthis sentence, they sold $1000 worth of merchandise. Yes, E-bayhas something to teach us all. For within their model are lessonsyou can learn and adopt in your own business, no matter what yourbusiness is.Practicality dictates a certain model in order for entrepreneurs toachieve success. Until, of course, a titan in thinking comes alongto blow that model to kingdom come and put in it’s place a newparadigm of thinking. Enter E-bay. Enter the non-conventional.But enter, ready to learn.The Courage of Ideas-E-bay started out as an idea in the brain of someone not sodifferent than you. One man, in an apartment got a creativeinspiration that he turned into the biggest reality of success theInternet has yet to see. What does this tell us? That it canhappen to you. I’m sure that the idea had its obstacles toovercome before it ever arrived at its current glory, but throughpersistence became real. Ideas have power once we fuel them.Believe in the future of your ideas and surround yourself withpeople that can support and nuture that belief.The Journey With Out A RoadmapSome business journey’s are not by the book, complete with businessplan and a clear vision of its destination. Many ideas evolve,change, and grow through continued inspiration and perspiration.This isn’t to say that the business plan is not important, butrather that flexibility is. Be ready to take a new road when theone you’re started down is not achieving your vision. Realize thatthis is the evolution of an inspired idea.Taking the Old, and Incorporating The NewBe prepared to blend both new E-commerce ideas with oldtried-and-true principles for a net result that will equal success.Don’t banish all of one theory for another, but rather mix whatworks. Affiliate programs with established marketing plans,advertising venues with email, etc. Be courageous, but wise.>From Business to CommunityCreate a place that others will talk about. It is the nature ofpeople to want to gather, so create a gathering place for people toshare ideas, make the deal, and communicate. The dynamics of theInternet is in its community and E-bay saw the value of this andbecame not just a community, but a society of it’s own.Body Parts Are Not For Sale—Making Good with Bad TimesWhile E-bay got press over body parts that were put on it’s sitefor sale, it wasn’t all bad. Yes, they obviously pulled theseauctions from the site once it came to their attention, but thepress it created did not hurt E-bay. In fact, it solidified themas THE online community of our time. The place to be, to go, tobookmark, and return. It drove more people to the site. Thelesson? Make good with bad times. Weather the situation, butcreate an event.Evolving ForwardRemember above all that change is what creates a forward moving,successful business. Never stay stagnant. Be aware of consumer’stastes, the change of trends in behavior, and constantly evolveyour plan.E-bay was an idea. We all have them. The question is what will youdo with the next one that pops into your head? You know thepotential now, and if you doubt it, visit E-bay to becomeconvinced.
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