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.
Saturday, March 15, 2008
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
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