MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
ALPRAZolam may be confused with alprostadil, LORazepam, triazolam
Xanax® may be confused with Lanoxin®, Tenex®, Tylox®, Xopenex®, Zantac®, Zyrtec®
U.S. BRAND NAMES — Alprazolam Intensol®; Niravam™ ; Xanax XR®; Xanax®
PHARMACOLOGIC CATEGORY
Benzodiazepine
DOSING: ADULTS — Note: Treatment >4 months should be re-evaluated to determine the patient's continued need for the drug
Anxiety: Oral: Immediate release: Effective doses are 0.5-4 mg/day in divided doses; the manufacturer recommends starting at 0.25-0.5 mg 3 times/day; titrate dose upward; usual maximum: 4 mg/day. Patients requiring doses >4 mg/day should be increased cautiously. Periodic reassessment and consideration of dosage reduction is recommended.
Anxiety associated with depression: Oral: Immediate release: Average dose required: 2.5-3 mg/day in divided doses
Ethanol withdrawal (unlabeled use): Oral: Immediate release: Usual dose: 2-2.5 mg/day in divided doses
Panic disorder: Oral:
Immediate release: Initial: 0.5 mg 3 times/day; dose may be increased every 3-4 days in increments ≤ 1 mg/day. Mean effective dosage: 5-6 mg/day; many patients obtain relief at 2 mg/day, as much as 10 mg/day may be required
Extended release: 0.5-1 mg once daily; may increase dose every 3-4 days in increments ≤ 1 mg/day (range: 3-6 mg/day)
Switching from immediate release to extended release: Patients may be switched to extended release tablets by taking the total daily dose of the immediate release tablets and giving it once daily using the extended release preparation.
Preoperative sedation: Oral: 0.5 mg in evening at bedtime and 0.5 mg 1 hour before procedure
Dose reduction: Abrupt discontinuation should be avoided. Daily dose may be decreased by 0.5 mg every 3 days, however, some patients may require a slower reduction. If withdrawal symptoms occur, resume previous dose and discontinue on a less rapid schedule.
DOSING: PEDIATRIC
(For additional information see "Alprazolam: Pediatric drug information")
Anxiety (unlabeled use): Oral: Immediate release: Initial: 0.005 mg/kg/dose or 0.125 mg/dose 3 times/day; increase in increments of 0.125-0.25 mg, up to a maximum of 0.02 mg/kg/dose or 0.06 mg/kg/day (0.375-3 mg/day). See "Dose Reduction" comment in adult dosing.
Note: Treatment >4 months should be re-evaluated to determine the patient's continued need for the drug.
DOSING: ELDERLY — Initial: 0.125-0.25 mg twice daily; increase by 0.125 mg/day as needed. The smallest effective dose should be used.
Immediate release: Initial 0.25 mg 2-3 times/day
Extended release: Initial: 0.5 mg once daily
DOSING: RENAL IMPAIRMENT — No guidelines for adjustment; use caution.
DOSING: HEPATIC IMPAIRMENT — Oral: Reduce dose by 50% to 60% or avoid in cirrhosis.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral [concentrate]:
Alprazolam Intensol®: 1 mg/mL (30 mL) [alcohol free, dye free, sugar free; contains propylene glycol]
Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Xanax®: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Tablet, extended release: 0.5 mg, 1 mg, 2 mg, 3 mg
Xanax XR®: 0.5 mg, 1 mg, 2 mg, 3 mg
Tablet, orally disintegrating [scored]: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Niravam™ : 0.25 mg, 0.5 mg, 1 mg, 2 mg [orange flavor]
DOSAGE FORMS: CONCISE
Solution, oral [concentrate]:
Alprazolam Intensol®: 1 mg/mL
Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Xanax®: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Tablet, extended release: 0.5 mg, 1 mg, 2 mg, 3 mg
Xanax XR®: 0.5 mg, 1 mg, 2 mg, 3 mg
Tablet, orally disintegrating [scored]: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Niravam™ : 0.25 mg, 0.5 mg, 1 mg, 2 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes oral solution
ADMINISTRATION
Immediate release preparations: Can be administered sublingually with comparable onset and completeness of absorption.
Extended release tablet: Should be taken once daily in the morning; do not crush, break, or chew.
Orally-disintegrating tablets: Using dry hands, place tablet on top of tongue. If using one-half of tablet, immediately discard remaining half (may not remain stable). Administration with water is not necessary.
USE — Treatment of anxiety disorder (GAD); panic disorder, with or without agoraphobia; anxiety associated with depression
USE - UNLABELED / INVESTIGATIONAL — Anxiety in children
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Abnormal coordination, cognitive disorder, depression, drowsiness, fatigue, irritability, lightheadedness, memory impairment, sedation, somnolence
Gastrointestinal: Appetite increased/decreased, constipation, salivation decreased, weight gain/loss, xerostomia
Genitourinary: Micturition difficulty
Neuromuscular & skeletal: Dysarthria
1% to 10%:
Cardiovascular: Hypotension
Central nervous system: Agitation, attention disturbance, confusion, depersonalization, derealization, disorientation, disinhibition, dizziness, dream abnormalities, fear, hallucinations, hypersomnia, nightmares, seizure, talkativeness
Dermatologic: Dermatitis, pruritus, rash
Endocrine & metabolic: Libido decreased/increased, menstrual disorders
Gastrointestinal: Salivation increased
Genitourinary: Incontinence
Hepatic: Bilirubin increased, jaundice, liver enzymes increased
Neuromuscular & skeletal: Arthralgia, ataxia, myalgia, paresthesia
Ocular: Diplopia
Respiratory: Allergic rhinitis, dyspnea
<1% (Limited to important or life-threatening): Amnesia, falls, galactorrhea, gynecomastia, hepatic failure, hepatitis, hyperprolactinemia, Stevens-Johnson syndrome
CONTRAINDICATIONS — Hypersensitivity to alprazolam or any component of the formulation (cross-sensitivity with other benzodiazepines may exist); narrow-angle glaucoma; concurrent use with ketoconazole or itraconazole; pregnancy
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia. CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients.
Disease-related concerns: Depression: Use caution in patients with depression, particularly if suicidal risk may be present; episodes of mania or hypomania have occurred in depressed patients treated with alprazolam. 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 (generally >10 days). Hepatic impairment: Use with caution in patients with hepatic impairment. Impaired gag reflux: Use with caution in patients with an impaired gag reflux. Renal impairment: Use with caution in patients with renal impairment or predisposition to urate nephropathy; has weak uricosuric properties. Respiratory disease: Use with caution in patients with respiratory disease.
Concurrent drug therapy issues: CNS depressants/psychoactive medications: Use with caution in patients receiving other CNS depressants or psychoactive medication; effects with other sedative drugs or ethanol may be potentiated. High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors, moderate or strong CYP3A4 inducers and major CYP3A4 substrates (see Drug Interactions); consider alternative agents that avoid or lessen the potential for CYP-mediated interactions.
Special populations: Debilitated patients: Use with caution in debilitated patients. Elderly: Use with caution in the elderly; benzodiazepines have been associated with falls and traumatic injury. Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury. Obese patients: Use with caution in obese patients; may have prolonged action when discontinued.
Other warnings/precautions: Appropriate use: Does not have analgesic, antidepressant, or antipsychotic properties. Breakthrough anxiety: At the end of dosing interval, breakthrough anxiety may occur. Withdrawal: Rebound or withdrawal symptoms, including seizures, may occur 18 hours to 3 days following abrupt discontinuation or large decreases in dose (more common in patients receiving >4 mg/day or prolonged treatment). Use caution when reducing dose or withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.
RESTRICTIONS — C-IV
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP3A4 (major)
DRUG INTERACTIONS
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Aprepitant: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
CarBAMazepine: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Cimetidine: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Clozapine: Benzodiazepines may enhance the adverse/toxic effect of Clozapine. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Disulfiram: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Fosaprepitant: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Specifically, the active metabolite aprepitant is likely responsible for this effect. Risk C: Monitor therapy
Grapefruit Juice: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Isoniazid: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce dosage of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Nefazodone: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Oral Contraceptive (Estrogens): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Oral Contraceptive (Progestins): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Protease Inhibitors: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Management: Amprenavir, atazanavir, darunavir, indinavir, nelfinavir, ritonavir, and tipranavir are contraindicated with midazolam and triazolam according to each protease inhibitor's prescribing information. Risk D: Consider therapy modification
Proton Pump Inhibitors: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Exceptions: Lansoprazole; Pantoprazole; Rabeprazole. Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Exceptions: Citalopram; Escitalopram; PARoxetine; Sertraline. Risk C: Monitor therapy
St Johns Wort: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Risk D: Consider therapy modification
Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS
Cigarette smoking: May decrease alprazolam concentrations up to 50%.
Ethanol: Avoid ethanol (may increase CNS depression).
Food: Alprazolam serum concentration is unlikely to be increased by grapefruit juice because of alprazolam's high oral bioavailability. The Cmax of the extended release formulation is increased by 25% when a high-fat meal is given 2 hours before dosing. Tmax is decreased 30% when food is given immediately prior to dose. Tmax is increased by 30% when food is given ≥ 1 hour after dose.
Herb/Nutraceutical: St John's wort may decrease alprazolam levels. Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Benzodiazepines have the potential to cause harm to the fetus, particularly when administered during the first trimester. In addition, withdrawal symptoms may occur in the neonate following in utero exposure. Use during pregnancy should be avoided.
LACTATION — Enters breast milk/not recommended (AAP rates "of concern")
BREAST-FEEDING CONSIDERATIONS — Symptoms of withdrawal, lethargy, and loss of body weight have been reported in infants exposed to alprazolam and/or benzodiazepines while nursing. Breast-feeding is not recommended.
PRICING — (data from drugstore.com)
Concentrate (ALPRAZolam Intensol)
1 mg/mL (30): $67.03
Tablet, 24-hour (ALPRAZolam)
0.5 mg (30): $31.99
1 mg (30): $69.99
2 mg (30): $76.00
3 mg (30): $109.98
Tablet, 24-hour (Xanax XR)
0.5 mg (30): $81.58
1 mg (30): $104.06
2 mg (30): $135.16
3 mg (30): $202.73
Tablet, orally-disintegrating (Niravam)
0.25 mg (30): $86.32
0.5 mg (30): $104.93
1 mg (30): $135.40
2 mg (30): $213.26
Tablets (ALPRAZolam)
0.25 mg (30): $11.99
0.5 mg (30): $11.99
1 mg (30): $11.99
2 mg (30): $13.99
Tablets (Xanax)
0.25 mg (30): $48.29
0.5 mg (30): $54.01
1 mg (30): $68.34
2 mg (30): $111.29
MONITORING PARAMETERS — Respiratory and cardiovascular status
CANADIAN BRAND NAMES — Alti-Alprazolam; Apo-Alpraz®; Apo-Alpraz® TS; Gen-Alprazolam; Novo-Alprazol; Nu-Alprax; Xanax TS™ ; Xanax®
INTERNATIONAL BRAND NAMES — Aceprax (PY, UY); Actazolam (ID); Afobam (PL); Alcelam (TH); Alganax (ID); Alnax (TH); Alpaz (PE); Alplax (AR); Alpralid (IL); Alpraline (MY); Alpram (KP); Alpranax (MY); Alprax (AU, HK, IN, TH); Alpraz (LU); Alprazomerck (PL); Alprocontin (IN); Alprox (HU, IL, PL); Altrox (PH); Alviz (ID); Alzam (MX, ZA); Alzax (KP); Alzolam (IN); Anax (TH); Anpress (TH); Apo-Alpraz (SG); Apraz (BR); Aprazo (TW); Azor (ZA); Cassadan (DE); Constan (JP); Daclor (DO); Dixin (CO); Farmapram (MX); Feprax (ID); Frontal (BR); Frontin (HU, PL); Helex (HR); Irizz. (MX); Kalma (AU); Kinax (TW); Marzolam (TH); Neupax (MX); Neurol (PL); Pacyl (IN); Pharnax (TH); Prazol (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Prazovex (MY); Prinox (AR); Solanax (JP); Soxietas (ID); Tafil (CR, DE, DK, DO, GT, HN, MX, NI, PA, SV, VE); Tafil D (MU); Tazun (MX); Tensivan (CO); Trankimazin Retard (ES); Tranquinal (BR, DO, EC, GT, HN, NI, PA, PE, PY, SV, UY); Tricalma (CN); Valeans (IT); Xanacine (TH); Xanagis (IL); Xanax (AE, AR, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CO, CY, CZ, DE, EC, EE, EG, ET, FR, GB, GH, GM, GN, GR, GY, HK, HN, HR, HU, IE, IL, IQ, IR, IT, JM, JO, KE, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, OM, PE, PK, PL, PT, QA, SA, SC, SD, SL, SN, SR, SY, TH, TN, TT, TW, TZ, UG, YE, ZA, ZM, ZW); Xanax SR (SG); Xanax XR (IL, TH, TW); Xanor (AT, FI, NO, PH, SE, ZA); Xanor XR (PH); Zacetin (KP); Zamhexal (AU); Zanapam (AE, BH, CY, EG, IL, IQ, IR, JO, KP, KW, LB, LY, OM, QA, SA, SY, YE); Zolam (IN); Zolarem (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Zolastin (ID); Zoldac (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Zomiren (PL); Zopax (ZA); Zotran (CN); Zypraz (ID); Zyren (KP)
MECHANISM OF ACTION — Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization.
PHARMACODYNAMICS / KINETICS
Onset of action: Immediate release and extended release formulations: 1 hour
Duration: Immediate release: 5.1 +/- 1.7 hours; Extended release: 11.3 +/- 4.2 hours
Absorption: Extended release: Slower relative to immediate release formulation resulting in a concentration that is maintained 5-11 hours after dosing
Distribution: Vd: 0.9-1.2 L/kg; enters breast milk
Protein binding: 80%; primarily to albumin
Metabolism: Hepatic via CYP3A4; forms two active metabolites (4-hydroxyalprazolam and alpha-hydroxyalprazolam)
Bioavailability: 90%
Half-life elimination:
Adults: 11.2 hours (immediate release range: 6.3-26.9; extended release range: 10.7-15.8)
Elderly: 16.3 hours (range: 9-26.9 hours)
Alcoholic liver disease: 19.7 hours (range: 5.8-65.3 hours)
Obesity: 21.8 hours (range: 9.9-40.4 hours)
Time to peak, serum: Immediate release: 1-2 hours; Extended release: ~9 hours; decreased by 1 hour following bedtime dosing compared to morning dosing
Excretion: Urine (as unchanged drug and metabolites)
PATIENT INFORMATION — Avoid alcohol and other CNS depressants; avoid activities needing good psychomotor coordination until CNS effects are known; drug may cause physical or psychological dependence; avoid abrupt discontinuation after prolonged use; do not crush, break, or chew extended release tablets
Saturday, June 12, 2010
Alprazolam
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
ALPRAZolam may be confused with alprostadil, LORazepam, triazolam
Xanax® may be confused with Lanoxin®, Tenex®, Tylox®, Xopenex®, Zantac®, Zyrtec®
U.S. BRAND NAMES — Alprazolam Intensol®; Niravam™ ; Xanax XR®; Xanax®
PHARMACOLOGIC CATEGORY
Benzodiazepine
DOSING: ADULTS — Note: Treatment >4 months should be re-evaluated to determine the patient's continued need for the drug
Anxiety: Oral: Immediate release: Effective doses are 0.5-4 mg/day in divided doses; the manufacturer recommends starting at 0.25-0.5 mg 3 times/day; titrate dose upward; usual maximum: 4 mg/day. Patients requiring doses >4 mg/day should be increased cautiously. Periodic reassessment and consideration of dosage reduction is recommended.
Anxiety associated with depression: Oral: Immediate release: Average dose required: 2.5-3 mg/day in divided doses
Ethanol withdrawal (unlabeled use): Oral: Immediate release: Usual dose: 2-2.5 mg/day in divided doses
Panic disorder: Oral:
Immediate release: Initial: 0.5 mg 3 times/day; dose may be increased every 3-4 days in increments ≤ 1 mg/day. Mean effective dosage: 5-6 mg/day; many patients obtain relief at 2 mg/day, as much as 10 mg/day may be required
Extended release: 0.5-1 mg once daily; may increase dose every 3-4 days in increments ≤ 1 mg/day (range: 3-6 mg/day)
Switching from immediate release to extended release: Patients may be switched to extended release tablets by taking the total daily dose of the immediate release tablets and giving it once daily using the extended release preparation.
Preoperative sedation: Oral: 0.5 mg in evening at bedtime and 0.5 mg 1 hour before procedure
Dose reduction: Abrupt discontinuation should be avoided. Daily dose may be decreased by 0.5 mg every 3 days, however, some patients may require a slower reduction. If withdrawal symptoms occur, resume previous dose and discontinue on a less rapid schedule.
DOSING: PEDIATRIC
(For additional information see "Alprazolam: Pediatric drug information")
Anxiety (unlabeled use): Oral: Immediate release: Initial: 0.005 mg/kg/dose or 0.125 mg/dose 3 times/day; increase in increments of 0.125-0.25 mg, up to a maximum of 0.02 mg/kg/dose or 0.06 mg/kg/day (0.375-3 mg/day). See "Dose Reduction" comment in adult dosing.
Note: Treatment >4 months should be re-evaluated to determine the patient's continued need for the drug.
DOSING: ELDERLY — Initial: 0.125-0.25 mg twice daily; increase by 0.125 mg/day as needed. The smallest effective dose should be used.
Immediate release: Initial 0.25 mg 2-3 times/day
Extended release: Initial: 0.5 mg once daily
DOSING: RENAL IMPAIRMENT — No guidelines for adjustment; use caution.
DOSING: HEPATIC IMPAIRMENT — Oral: Reduce dose by 50% to 60% or avoid in cirrhosis.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral [concentrate]:
Alprazolam Intensol®: 1 mg/mL (30 mL) [alcohol free, dye free, sugar free; contains propylene glycol]
Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Xanax®: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Tablet, extended release: 0.5 mg, 1 mg, 2 mg, 3 mg
Xanax XR®: 0.5 mg, 1 mg, 2 mg, 3 mg
Tablet, orally disintegrating [scored]: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Niravam™ : 0.25 mg, 0.5 mg, 1 mg, 2 mg [orange flavor]
DOSAGE FORMS: CONCISE
Solution, oral [concentrate]:
Alprazolam Intensol®: 1 mg/mL
Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Xanax®: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Tablet, extended release: 0.5 mg, 1 mg, 2 mg, 3 mg
Xanax XR®: 0.5 mg, 1 mg, 2 mg, 3 mg
Tablet, orally disintegrating [scored]: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Niravam™ : 0.25 mg, 0.5 mg, 1 mg, 2 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes oral solution
ADMINISTRATION
Immediate release preparations: Can be administered sublingually with comparable onset and completeness of absorption.
Extended release tablet: Should be taken once daily in the morning; do not crush, break, or chew.
Orally-disintegrating tablets: Using dry hands, place tablet on top of tongue. If using one-half of tablet, immediately discard remaining half (may not remain stable). Administration with water is not necessary.
USE — Treatment of anxiety disorder (GAD); panic disorder, with or without agoraphobia; anxiety associated with depression
USE - UNLABELED / INVESTIGATIONAL — Anxiety in children
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Abnormal coordination, cognitive disorder, depression, drowsiness, fatigue, irritability, lightheadedness, memory impairment, sedation, somnolence
Gastrointestinal: Appetite increased/decreased, constipation, salivation decreased, weight gain/loss, xerostomia
Genitourinary: Micturition difficulty
Neuromuscular & skeletal: Dysarthria
1% to 10%:
Cardiovascular: Hypotension
Central nervous system: Agitation, attention disturbance, confusion, depersonalization, derealization, disorientation, disinhibition, dizziness, dream abnormalities, fear, hallucinations, hypersomnia, nightmares, seizure, talkativeness
Dermatologic: Dermatitis, pruritus, rash
Endocrine & metabolic: Libido decreased/increased, menstrual disorders
Gastrointestinal: Salivation increased
Genitourinary: Incontinence
Hepatic: Bilirubin increased, jaundice, liver enzymes increased
Neuromuscular & skeletal: Arthralgia, ataxia, myalgia, paresthesia
Ocular: Diplopia
Respiratory: Allergic rhinitis, dyspnea
<1% (Limited to important or life-threatening): Amnesia, falls, galactorrhea, gynecomastia, hepatic failure, hepatitis, hyperprolactinemia, Stevens-Johnson syndrome
CONTRAINDICATIONS — Hypersensitivity to alprazolam or any component of the formulation (cross-sensitivity with other benzodiazepines may exist); narrow-angle glaucoma; concurrent use with ketoconazole or itraconazole; pregnancy
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia. CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients.
Disease-related concerns: Depression: Use caution in patients with depression, particularly if suicidal risk may be present; episodes of mania or hypomania have occurred in depressed patients treated with alprazolam. 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 (generally >10 days). Hepatic impairment: Use with caution in patients with hepatic impairment. Impaired gag reflux: Use with caution in patients with an impaired gag reflux. Renal impairment: Use with caution in patients with renal impairment or predisposition to urate nephropathy; has weak uricosuric properties. Respiratory disease: Use with caution in patients with respiratory disease.
Concurrent drug therapy issues: CNS depressants/psychoactive medications: Use with caution in patients receiving other CNS depressants or psychoactive medication; effects with other sedative drugs or ethanol may be potentiated. High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors, moderate or strong CYP3A4 inducers and major CYP3A4 substrates (see Drug Interactions); consider alternative agents that avoid or lessen the potential for CYP-mediated interactions.
Special populations: Debilitated patients: Use with caution in debilitated patients. Elderly: Use with caution in the elderly; benzodiazepines have been associated with falls and traumatic injury. Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury. Obese patients: Use with caution in obese patients; may have prolonged action when discontinued.
Other warnings/precautions: Appropriate use: Does not have analgesic, antidepressant, or antipsychotic properties. Breakthrough anxiety: At the end of dosing interval, breakthrough anxiety may occur. Withdrawal: Rebound or withdrawal symptoms, including seizures, may occur 18 hours to 3 days following abrupt discontinuation or large decreases in dose (more common in patients receiving >4 mg/day or prolonged treatment). Use caution when reducing dose or withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.
RESTRICTIONS — C-IV
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP3A4 (major)
DRUG INTERACTIONS
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Aprepitant: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
CarBAMazepine: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Cimetidine: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Clozapine: Benzodiazepines may enhance the adverse/toxic effect of Clozapine. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Disulfiram: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Fosaprepitant: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Specifically, the active metabolite aprepitant is likely responsible for this effect. Risk C: Monitor therapy
Grapefruit Juice: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Isoniazid: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce dosage of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Nefazodone: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Oral Contraceptive (Estrogens): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Oral Contraceptive (Progestins): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Protease Inhibitors: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Management: Amprenavir, atazanavir, darunavir, indinavir, nelfinavir, ritonavir, and tipranavir are contraindicated with midazolam and triazolam according to each protease inhibitor's prescribing information. Risk D: Consider therapy modification
Proton Pump Inhibitors: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Exceptions: Lansoprazole; Pantoprazole; Rabeprazole. Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Exceptions: Citalopram; Escitalopram; PARoxetine; Sertraline. Risk C: Monitor therapy
St Johns Wort: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Risk D: Consider therapy modification
Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS
Cigarette smoking: May decrease alprazolam concentrations up to 50%.
Ethanol: Avoid ethanol (may increase CNS depression).
Food: Alprazolam serum concentration is unlikely to be increased by grapefruit juice because of alprazolam's high oral bioavailability. The Cmax of the extended release formulation is increased by 25% when a high-fat meal is given 2 hours before dosing. Tmax is decreased 30% when food is given immediately prior to dose. Tmax is increased by 30% when food is given ≥ 1 hour after dose.
Herb/Nutraceutical: St John's wort may decrease alprazolam levels. Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Benzodiazepines have the potential to cause harm to the fetus, particularly when administered during the first trimester. In addition, withdrawal symptoms may occur in the neonate following in utero exposure. Use during pregnancy should be avoided.
LACTATION — Enters breast milk/not recommended (AAP rates "of concern")
BREAST-FEEDING CONSIDERATIONS — Symptoms of withdrawal, lethargy, and loss of body weight have been reported in infants exposed to alprazolam and/or benzodiazepines while nursing. Breast-feeding is not recommended.
PRICING — (data from drugstore.com)
Concentrate (ALPRAZolam Intensol)
1 mg/mL (30): $67.03
Tablet, 24-hour (ALPRAZolam)
0.5 mg (30): $31.99
1 mg (30): $69.99
2 mg (30): $76.00
3 mg (30): $109.98
Tablet, 24-hour (Xanax XR)
0.5 mg (30): $81.58
1 mg (30): $104.06
2 mg (30): $135.16
3 mg (30): $202.73
Tablet, orally-disintegrating (Niravam)
0.25 mg (30): $86.32
0.5 mg (30): $104.93
1 mg (30): $135.40
2 mg (30): $213.26
Tablets (ALPRAZolam)
0.25 mg (30): $11.99
0.5 mg (30): $11.99
1 mg (30): $11.99
2 mg (30): $13.99
Tablets (Xanax)
0.25 mg (30): $48.29
0.5 mg (30): $54.01
1 mg (30): $68.34
2 mg (30): $111.29
MONITORING PARAMETERS — Respiratory and cardiovascular status
CANADIAN BRAND NAMES — Alti-Alprazolam; Apo-Alpraz®; Apo-Alpraz® TS; Gen-Alprazolam; Novo-Alprazol; Nu-Alprax; Xanax TS™ ; Xanax®
INTERNATIONAL BRAND NAMES — Aceprax (PY, UY); Actazolam (ID); Afobam (PL); Alcelam (TH); Alganax (ID); Alnax (TH); Alpaz (PE); Alplax (AR); Alpralid (IL); Alpraline (MY); Alpram (KP); Alpranax (MY); Alprax (AU, HK, IN, TH); Alpraz (LU); Alprazomerck (PL); Alprocontin (IN); Alprox (HU, IL, PL); Altrox (PH); Alviz (ID); Alzam (MX, ZA); Alzax (KP); Alzolam (IN); Anax (TH); Anpress (TH); Apo-Alpraz (SG); Apraz (BR); Aprazo (TW); Azor (ZA); Cassadan (DE); Constan (JP); Daclor (DO); Dixin (CO); Farmapram (MX); Feprax (ID); Frontal (BR); Frontin (HU, PL); Helex (HR); Irizz. (MX); Kalma (AU); Kinax (TW); Marzolam (TH); Neupax (MX); Neurol (PL); Pacyl (IN); Pharnax (TH); Prazol (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Prazovex (MY); Prinox (AR); Solanax (JP); Soxietas (ID); Tafil (CR, DE, DK, DO, GT, HN, MX, NI, PA, SV, VE); Tafil D (MU); Tazun (MX); Tensivan (CO); Trankimazin Retard (ES); Tranquinal (BR, DO, EC, GT, HN, NI, PA, PE, PY, SV, UY); Tricalma (CN); Valeans (IT); Xanacine (TH); Xanagis (IL); Xanax (AE, AR, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CO, CY, CZ, DE, EC, EE, EG, ET, FR, GB, GH, GM, GN, GR, GY, HK, HN, HR, HU, IE, IL, IQ, IR, IT, JM, JO, KE, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, OM, PE, PK, PL, PT, QA, SA, SC, SD, SL, SN, SR, SY, TH, TN, TT, TW, TZ, UG, YE, ZA, ZM, ZW); Xanax SR (SG); Xanax XR (IL, TH, TW); Xanor (AT, FI, NO, PH, SE, ZA); Xanor XR (PH); Zacetin (KP); Zamhexal (AU); Zanapam (AE, BH, CY, EG, IL, IQ, IR, JO, KP, KW, LB, LY, OM, QA, SA, SY, YE); Zolam (IN); Zolarem (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Zolastin (ID); Zoldac (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Zomiren (PL); Zopax (ZA); Zotran (CN); Zypraz (ID); Zyren (KP)
MECHANISM OF ACTION — Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization.
PHARMACODYNAMICS / KINETICS
Onset of action: Immediate release and extended release formulations: 1 hour
Duration: Immediate release: 5.1 +/- 1.7 hours; Extended release: 11.3 +/- 4.2 hours
Absorption: Extended release: Slower relative to immediate release formulation resulting in a concentration that is maintained 5-11 hours after dosing
Distribution: Vd: 0.9-1.2 L/kg; enters breast milk
Protein binding: 80%; primarily to albumin
Metabolism: Hepatic via CYP3A4; forms two active metabolites (4-hydroxyalprazolam and alpha-hydroxyalprazolam)
Bioavailability: 90%
Half-life elimination:
Adults: 11.2 hours (immediate release range: 6.3-26.9; extended release range: 10.7-15.8)
Elderly: 16.3 hours (range: 9-26.9 hours)
Alcoholic liver disease: 19.7 hours (range: 5.8-65.3 hours)
Obesity: 21.8 hours (range: 9.9-40.4 hours)
Time to peak, serum: Immediate release: 1-2 hours; Extended release: ~9 hours; decreased by 1 hour following bedtime dosing compared to morning dosing
Excretion: Urine (as unchanged drug and metabolites)
PATIENT INFORMATION — Avoid alcohol and other CNS depressants; avoid activities needing good psychomotor coordination until CNS effects are known; drug may cause physical or psychological dependence; avoid abrupt discontinuation after prolonged use; do not crush, break, or chew extended release tablets
Sound-alike/look-alike issues:
ALPRAZolam may be confused with alprostadil, LORazepam, triazolam
Xanax® may be confused with Lanoxin®, Tenex®, Tylox®, Xopenex®, Zantac®, Zyrtec®
U.S. BRAND NAMES — Alprazolam Intensol®; Niravam™ ; Xanax XR®; Xanax®
PHARMACOLOGIC CATEGORY
Benzodiazepine
DOSING: ADULTS — Note: Treatment >4 months should be re-evaluated to determine the patient's continued need for the drug
Anxiety: Oral: Immediate release: Effective doses are 0.5-4 mg/day in divided doses; the manufacturer recommends starting at 0.25-0.5 mg 3 times/day; titrate dose upward; usual maximum: 4 mg/day. Patients requiring doses >4 mg/day should be increased cautiously. Periodic reassessment and consideration of dosage reduction is recommended.
Anxiety associated with depression: Oral: Immediate release: Average dose required: 2.5-3 mg/day in divided doses
Ethanol withdrawal (unlabeled use): Oral: Immediate release: Usual dose: 2-2.5 mg/day in divided doses
Panic disorder: Oral:
Immediate release: Initial: 0.5 mg 3 times/day; dose may be increased every 3-4 days in increments ≤ 1 mg/day. Mean effective dosage: 5-6 mg/day; many patients obtain relief at 2 mg/day, as much as 10 mg/day may be required
Extended release: 0.5-1 mg once daily; may increase dose every 3-4 days in increments ≤ 1 mg/day (range: 3-6 mg/day)
Switching from immediate release to extended release: Patients may be switched to extended release tablets by taking the total daily dose of the immediate release tablets and giving it once daily using the extended release preparation.
Preoperative sedation: Oral: 0.5 mg in evening at bedtime and 0.5 mg 1 hour before procedure
Dose reduction: Abrupt discontinuation should be avoided. Daily dose may be decreased by 0.5 mg every 3 days, however, some patients may require a slower reduction. If withdrawal symptoms occur, resume previous dose and discontinue on a less rapid schedule.
DOSING: PEDIATRIC
(For additional information see "Alprazolam: Pediatric drug information")
Anxiety (unlabeled use): Oral: Immediate release: Initial: 0.005 mg/kg/dose or 0.125 mg/dose 3 times/day; increase in increments of 0.125-0.25 mg, up to a maximum of 0.02 mg/kg/dose or 0.06 mg/kg/day (0.375-3 mg/day). See "Dose Reduction" comment in adult dosing.
Note: Treatment >4 months should be re-evaluated to determine the patient's continued need for the drug.
DOSING: ELDERLY — Initial: 0.125-0.25 mg twice daily; increase by 0.125 mg/day as needed. The smallest effective dose should be used.
Immediate release: Initial 0.25 mg 2-3 times/day
Extended release: Initial: 0.5 mg once daily
DOSING: RENAL IMPAIRMENT — No guidelines for adjustment; use caution.
DOSING: HEPATIC IMPAIRMENT — Oral: Reduce dose by 50% to 60% or avoid in cirrhosis.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral [concentrate]:
Alprazolam Intensol®: 1 mg/mL (30 mL) [alcohol free, dye free, sugar free; contains propylene glycol]
Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Xanax®: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Tablet, extended release: 0.5 mg, 1 mg, 2 mg, 3 mg
Xanax XR®: 0.5 mg, 1 mg, 2 mg, 3 mg
Tablet, orally disintegrating [scored]: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Niravam™ : 0.25 mg, 0.5 mg, 1 mg, 2 mg [orange flavor]
DOSAGE FORMS: CONCISE
Solution, oral [concentrate]:
Alprazolam Intensol®: 1 mg/mL
Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Xanax®: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Tablet, extended release: 0.5 mg, 1 mg, 2 mg, 3 mg
Xanax XR®: 0.5 mg, 1 mg, 2 mg, 3 mg
Tablet, orally disintegrating [scored]: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Niravam™ : 0.25 mg, 0.5 mg, 1 mg, 2 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes oral solution
ADMINISTRATION
Immediate release preparations: Can be administered sublingually with comparable onset and completeness of absorption.
Extended release tablet: Should be taken once daily in the morning; do not crush, break, or chew.
Orally-disintegrating tablets: Using dry hands, place tablet on top of tongue. If using one-half of tablet, immediately discard remaining half (may not remain stable). Administration with water is not necessary.
USE — Treatment of anxiety disorder (GAD); panic disorder, with or without agoraphobia; anxiety associated with depression
USE - UNLABELED / INVESTIGATIONAL — Anxiety in children
ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Abnormal coordination, cognitive disorder, depression, drowsiness, fatigue, irritability, lightheadedness, memory impairment, sedation, somnolence
Gastrointestinal: Appetite increased/decreased, constipation, salivation decreased, weight gain/loss, xerostomia
Genitourinary: Micturition difficulty
Neuromuscular & skeletal: Dysarthria
1% to 10%:
Cardiovascular: Hypotension
Central nervous system: Agitation, attention disturbance, confusion, depersonalization, derealization, disorientation, disinhibition, dizziness, dream abnormalities, fear, hallucinations, hypersomnia, nightmares, seizure, talkativeness
Dermatologic: Dermatitis, pruritus, rash
Endocrine & metabolic: Libido decreased/increased, menstrual disorders
Gastrointestinal: Salivation increased
Genitourinary: Incontinence
Hepatic: Bilirubin increased, jaundice, liver enzymes increased
Neuromuscular & skeletal: Arthralgia, ataxia, myalgia, paresthesia
Ocular: Diplopia
Respiratory: Allergic rhinitis, dyspnea
<1% (Limited to important or life-threatening): Amnesia, falls, galactorrhea, gynecomastia, hepatic failure, hepatitis, hyperprolactinemia, Stevens-Johnson syndrome
CONTRAINDICATIONS — Hypersensitivity to alprazolam or any component of the formulation (cross-sensitivity with other benzodiazepines may exist); narrow-angle glaucoma; concurrent use with ketoconazole or itraconazole; pregnancy
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia. CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients.
Disease-related concerns: Depression: Use caution in patients with depression, particularly if suicidal risk may be present; episodes of mania or hypomania have occurred in depressed patients treated with alprazolam. 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 (generally >10 days). Hepatic impairment: Use with caution in patients with hepatic impairment. Impaired gag reflux: Use with caution in patients with an impaired gag reflux. Renal impairment: Use with caution in patients with renal impairment or predisposition to urate nephropathy; has weak uricosuric properties. Respiratory disease: Use with caution in patients with respiratory disease.
Concurrent drug therapy issues: CNS depressants/psychoactive medications: Use with caution in patients receiving other CNS depressants or psychoactive medication; effects with other sedative drugs or ethanol may be potentiated. High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors, moderate or strong CYP3A4 inducers and major CYP3A4 substrates (see Drug Interactions); consider alternative agents that avoid or lessen the potential for CYP-mediated interactions.
Special populations: Debilitated patients: Use with caution in debilitated patients. Elderly: Use with caution in the elderly; benzodiazepines have been associated with falls and traumatic injury. Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury. Obese patients: Use with caution in obese patients; may have prolonged action when discontinued.
Other warnings/precautions: Appropriate use: Does not have analgesic, antidepressant, or antipsychotic properties. Breakthrough anxiety: At the end of dosing interval, breakthrough anxiety may occur. Withdrawal: Rebound or withdrawal symptoms, including seizures, may occur 18 hours to 3 days following abrupt discontinuation or large decreases in dose (more common in patients receiving >4 mg/day or prolonged treatment). Use caution when reducing dose or withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.
RESTRICTIONS — C-IV
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP3A4 (major)
DRUG INTERACTIONS
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Aprepitant: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
CarBAMazepine: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Cimetidine: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Clozapine: Benzodiazepines may enhance the adverse/toxic effect of Clozapine. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Disulfiram: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Fosaprepitant: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Specifically, the active metabolite aprepitant is likely responsible for this effect. Risk C: Monitor therapy
Grapefruit Juice: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Isoniazid: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce dosage of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Nefazodone: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Oral Contraceptive (Estrogens): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Oral Contraceptive (Progestins): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Protease Inhibitors: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Management: Amprenavir, atazanavir, darunavir, indinavir, nelfinavir, ritonavir, and tipranavir are contraindicated with midazolam and triazolam according to each protease inhibitor's prescribing information. Risk D: Consider therapy modification
Proton Pump Inhibitors: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Exceptions: Lansoprazole; Pantoprazole; Rabeprazole. Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Exceptions: Citalopram; Escitalopram; PARoxetine; Sertraline. Risk C: Monitor therapy
St Johns Wort: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Risk D: Consider therapy modification
Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS
Cigarette smoking: May decrease alprazolam concentrations up to 50%.
Ethanol: Avoid ethanol (may increase CNS depression).
Food: Alprazolam serum concentration is unlikely to be increased by grapefruit juice because of alprazolam's high oral bioavailability. The Cmax of the extended release formulation is increased by 25% when a high-fat meal is given 2 hours before dosing. Tmax is decreased 30% when food is given immediately prior to dose. Tmax is increased by 30% when food is given ≥ 1 hour after dose.
Herb/Nutraceutical: St John's wort may decrease alprazolam levels. Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Benzodiazepines have the potential to cause harm to the fetus, particularly when administered during the first trimester. In addition, withdrawal symptoms may occur in the neonate following in utero exposure. Use during pregnancy should be avoided.
LACTATION — Enters breast milk/not recommended (AAP rates "of concern")
BREAST-FEEDING CONSIDERATIONS — Symptoms of withdrawal, lethargy, and loss of body weight have been reported in infants exposed to alprazolam and/or benzodiazepines while nursing. Breast-feeding is not recommended.
PRICING — (data from drugstore.com)
Concentrate (ALPRAZolam Intensol)
1 mg/mL (30): $67.03
Tablet, 24-hour (ALPRAZolam)
0.5 mg (30): $31.99
1 mg (30): $69.99
2 mg (30): $76.00
3 mg (30): $109.98
Tablet, 24-hour (Xanax XR)
0.5 mg (30): $81.58
1 mg (30): $104.06
2 mg (30): $135.16
3 mg (30): $202.73
Tablet, orally-disintegrating (Niravam)
0.25 mg (30): $86.32
0.5 mg (30): $104.93
1 mg (30): $135.40
2 mg (30): $213.26
Tablets (ALPRAZolam)
0.25 mg (30): $11.99
0.5 mg (30): $11.99
1 mg (30): $11.99
2 mg (30): $13.99
Tablets (Xanax)
0.25 mg (30): $48.29
0.5 mg (30): $54.01
1 mg (30): $68.34
2 mg (30): $111.29
MONITORING PARAMETERS — Respiratory and cardiovascular status
CANADIAN BRAND NAMES — Alti-Alprazolam; Apo-Alpraz®; Apo-Alpraz® TS; Gen-Alprazolam; Novo-Alprazol; Nu-Alprax; Xanax TS™ ; Xanax®
INTERNATIONAL BRAND NAMES — Aceprax (PY, UY); Actazolam (ID); Afobam (PL); Alcelam (TH); Alganax (ID); Alnax (TH); Alpaz (PE); Alplax (AR); Alpralid (IL); Alpraline (MY); Alpram (KP); Alpranax (MY); Alprax (AU, HK, IN, TH); Alpraz (LU); Alprazomerck (PL); Alprocontin (IN); Alprox (HU, IL, PL); Altrox (PH); Alviz (ID); Alzam (MX, ZA); Alzax (KP); Alzolam (IN); Anax (TH); Anpress (TH); Apo-Alpraz (SG); Apraz (BR); Aprazo (TW); Azor (ZA); Cassadan (DE); Constan (JP); Daclor (DO); Dixin (CO); Farmapram (MX); Feprax (ID); Frontal (BR); Frontin (HU, PL); Helex (HR); Irizz. (MX); Kalma (AU); Kinax (TW); Marzolam (TH); Neupax (MX); Neurol (PL); Pacyl (IN); Pharnax (TH); Prazol (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Prazovex (MY); Prinox (AR); Solanax (JP); Soxietas (ID); Tafil (CR, DE, DK, DO, GT, HN, MX, NI, PA, SV, VE); Tafil D (MU); Tazun (MX); Tensivan (CO); Trankimazin Retard (ES); Tranquinal (BR, DO, EC, GT, HN, NI, PA, PE, PY, SV, UY); Tricalma (CN); Valeans (IT); Xanacine (TH); Xanagis (IL); Xanax (AE, AR, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CO, CY, CZ, DE, EC, EE, EG, ET, FR, GB, GH, GM, GN, GR, GY, HK, HN, HR, HU, IE, IL, IQ, IR, IT, JM, JO, KE, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, OM, PE, PK, PL, PT, QA, SA, SC, SD, SL, SN, SR, SY, TH, TN, TT, TW, TZ, UG, YE, ZA, ZM, ZW); Xanax SR (SG); Xanax XR (IL, TH, TW); Xanor (AT, FI, NO, PH, SE, ZA); Xanor XR (PH); Zacetin (KP); Zamhexal (AU); Zanapam (AE, BH, CY, EG, IL, IQ, IR, JO, KP, KW, LB, LY, OM, QA, SA, SY, YE); Zolam (IN); Zolarem (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Zolastin (ID); Zoldac (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Zomiren (PL); Zopax (ZA); Zotran (CN); Zypraz (ID); Zyren (KP)
MECHANISM OF ACTION — Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization.
PHARMACODYNAMICS / KINETICS
Onset of action: Immediate release and extended release formulations: 1 hour
Duration: Immediate release: 5.1 +/- 1.7 hours; Extended release: 11.3 +/- 4.2 hours
Absorption: Extended release: Slower relative to immediate release formulation resulting in a concentration that is maintained 5-11 hours after dosing
Distribution: Vd: 0.9-1.2 L/kg; enters breast milk
Protein binding: 80%; primarily to albumin
Metabolism: Hepatic via CYP3A4; forms two active metabolites (4-hydroxyalprazolam and alpha-hydroxyalprazolam)
Bioavailability: 90%
Half-life elimination:
Adults: 11.2 hours (immediate release range: 6.3-26.9; extended release range: 10.7-15.8)
Elderly: 16.3 hours (range: 9-26.9 hours)
Alcoholic liver disease: 19.7 hours (range: 5.8-65.3 hours)
Obesity: 21.8 hours (range: 9.9-40.4 hours)
Time to peak, serum: Immediate release: 1-2 hours; Extended release: ~9 hours; decreased by 1 hour following bedtime dosing compared to morning dosing
Excretion: Urine (as unchanged drug and metabolites)
PATIENT INFORMATION — Avoid alcohol and other CNS depressants; avoid activities needing good psychomotor coordination until CNS effects are known; drug may cause physical or psychological dependence; avoid abrupt discontinuation after prolonged use; do not crush, break, or chew extended release tablets
Sunday, May 30, 2010
Alosetron
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Lotronex® may be confused with Lovenox®, Protonix®
International issues:
Lotronex® may be confused with Lotanax® which is a brand name for terfenadine in the Czech Republic
MEDICATION GUIDE — An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088624.pdf, must be dispensed with this medication for each new outpatient prescription and refill.
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: 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. Contraindicated in severe hepatic dysfunction (Child-Pugh score ≥ 10).
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Lotronex®: 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 without food; however, when administered with food, 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%)
2% to 10%: Gastrointestinal: Abdominal discomfort and pain (7%), nausea (6%), gastrointestinal discomfort and pain (5%), abdominal distention (2%), hemorrhoids (2%), regurgitation and reflux (2%)
≤ 1% (Limited to important or life-threatening): Allergic skin reactions, alopecia, anxiety, arrhythmia, bilirubin level changes, bladder inflammation, bone pain, breathing disorder, cholecystitis, cognitive function disorders, confusion, cramps, colitis, depression, dermatitis, diaphoresis, diverticulitis, dyspepsia, extrasystoles, fatigue, fluid disturbances, gastroenteritis, GI impaction, GI intussusception, GI lesions, GI motility decreased, GI obstructions, GI perforation, GI spasms, GI ulceration, headache, hematoma, hemorrhage, hepatitis, hyperacidity, hyper-/hypoglycemia, hypertension, hypnagogic effects, hypoesthesia, hypothalamus/pituitary dysfunction, ileus, ischemic colitis, memory effects, muscle pain/stiffness, occult stools, pain, proctitis, rash, RBC/hemoglobin defects, sedation, sexual dysfunction, skeletal pain, small bowel mesenteric ischemia, tachyarrhythmia, temperature regulation impairment, tremor, 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 or sequelae from constipation; history of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation and/or adhesions; diverticulitis, current or history of Crohn's disease, or ulcerative colitis; severe hepatic impairment; 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
Boxed warnings: Appropriate use: See "Other warnings/precautions" below. 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 who develop constipation; serious complications of constipation have been infrequently reported (obstruction, ileus, perforation, impaction, toxic megacolon, secondary ischemia). Constipation is a frequent, dose-related side effect; risk for complications from constipation 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. Do not initiate in patients with constipation. Do not initiate in patients with constipation. Ischemic colitis: [U.S. Boxed Warning]: Acute ischemic colitis has been reported during treatment. Discontinue and evaluate 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); contraindicated in severe impairment (Child-Pugh score ≥ 10).
Special populations: Elderly: Use with caution in the elderly due to increased risk of complications from constipation. Males: Safety and efficacy have not been established in males. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: Only indicated for women with severe diarrhea-predominant irritable bowel syndrome with inadequate response to conventional therapy. Patient-Physician agreement: [U.S. Boxed Warning]: Should only be prescribed by physicians enrolled in the Prometheus' Prescribing Program for Lotronex®. Patients must read and sign a "Patient-Physician" agreement before receiving the initial prescription.
RESTRICTIONS — Only physicians enrolled in Prometheus' 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.
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP1A2 (major), 2C9 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 2E1 (weak)
DRUG INTERACTIONS
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Alosetron. Risk C: Monitor therapy
Fluvoxamine: May decrease the metabolism of Alosetron. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Antiemetics (5HT3 Antagonists). Risk C: Monitor therapy
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)
1 mg (30): $428.32
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.
Sound-alike/look-alike issues:
Lotronex® may be confused with Lovenox®, Protonix®
International issues:
Lotronex® may be confused with Lotanax® which is a brand name for terfenadine in the Czech Republic
MEDICATION GUIDE — An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088624.pdf, must be dispensed with this medication for each new outpatient prescription and refill.
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: 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. Contraindicated in severe hepatic dysfunction (Child-Pugh score ≥ 10).
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Lotronex®: 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 without food; however, when administered with food, 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%)
2% to 10%: Gastrointestinal: Abdominal discomfort and pain (7%), nausea (6%), gastrointestinal discomfort and pain (5%), abdominal distention (2%), hemorrhoids (2%), regurgitation and reflux (2%)
≤ 1% (Limited to important or life-threatening): Allergic skin reactions, alopecia, anxiety, arrhythmia, bilirubin level changes, bladder inflammation, bone pain, breathing disorder, cholecystitis, cognitive function disorders, confusion, cramps, colitis, depression, dermatitis, diaphoresis, diverticulitis, dyspepsia, extrasystoles, fatigue, fluid disturbances, gastroenteritis, GI impaction, GI intussusception, GI lesions, GI motility decreased, GI obstructions, GI perforation, GI spasms, GI ulceration, headache, hematoma, hemorrhage, hepatitis, hyperacidity, hyper-/hypoglycemia, hypertension, hypnagogic effects, hypoesthesia, hypothalamus/pituitary dysfunction, ileus, ischemic colitis, memory effects, muscle pain/stiffness, occult stools, pain, proctitis, rash, RBC/hemoglobin defects, sedation, sexual dysfunction, skeletal pain, small bowel mesenteric ischemia, tachyarrhythmia, temperature regulation impairment, tremor, 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 or sequelae from constipation; history of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation and/or adhesions; diverticulitis, current or history of Crohn's disease, or ulcerative colitis; severe hepatic impairment; 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
Boxed warnings: Appropriate use: See "Other warnings/precautions" below. 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 who develop constipation; serious complications of constipation have been infrequently reported (obstruction, ileus, perforation, impaction, toxic megacolon, secondary ischemia). Constipation is a frequent, dose-related side effect; risk for complications from constipation 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. Do not initiate in patients with constipation. Do not initiate in patients with constipation. Ischemic colitis: [U.S. Boxed Warning]: Acute ischemic colitis has been reported during treatment. Discontinue and evaluate 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); contraindicated in severe impairment (Child-Pugh score ≥ 10).
Special populations: Elderly: Use with caution in the elderly due to increased risk of complications from constipation. Males: Safety and efficacy have not been established in males. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: Only indicated for women with severe diarrhea-predominant irritable bowel syndrome with inadequate response to conventional therapy. Patient-Physician agreement: [U.S. Boxed Warning]: Should only be prescribed by physicians enrolled in the Prometheus' Prescribing Program for Lotronex®. Patients must read and sign a "Patient-Physician" agreement before receiving the initial prescription.
RESTRICTIONS — Only physicians enrolled in Prometheus' 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.
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP1A2 (major), 2C9 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 2E1 (weak)
DRUG INTERACTIONS
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Alosetron. Risk C: Monitor therapy
Fluvoxamine: May decrease the metabolism of Alosetron. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Antiemetics (5HT3 Antagonists). Risk C: Monitor therapy
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)
1 mg (30): $428.32
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.
Alosetron
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Lotronex® may be confused with Lovenox®, Protonix®
International issues:
Lotronex® may be confused with Lotanax® which is a brand name for terfenadine in the Czech Republic
MEDICATION GUIDE — An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088624.pdf, must be dispensed with this medication for each new outpatient prescription and refill.
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: 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. Contraindicated in severe hepatic dysfunction (Child-Pugh score ≥ 10).
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Lotronex®: 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 without food; however, when administered with food, 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%)
2% to 10%: Gastrointestinal: Abdominal discomfort and pain (7%), nausea (6%), gastrointestinal discomfort and pain (5%), abdominal distention (2%), hemorrhoids (2%), regurgitation and reflux (2%)
≤ 1% (Limited to important or life-threatening): Allergic skin reactions, alopecia, anxiety, arrhythmia, bilirubin level changes, bladder inflammation, bone pain, breathing disorder, cholecystitis, cognitive function disorders, confusion, cramps, colitis, depression, dermatitis, diaphoresis, diverticulitis, dyspepsia, extrasystoles, fatigue, fluid disturbances, gastroenteritis, GI impaction, GI intussusception, GI lesions, GI motility decreased, GI obstructions, GI perforation, GI spasms, GI ulceration, headache, hematoma, hemorrhage, hepatitis, hyperacidity, hyper-/hypoglycemia, hypertension, hypnagogic effects, hypoesthesia, hypothalamus/pituitary dysfunction, ileus, ischemic colitis, memory effects, muscle pain/stiffness, occult stools, pain, proctitis, rash, RBC/hemoglobin defects, sedation, sexual dysfunction, skeletal pain, small bowel mesenteric ischemia, tachyarrhythmia, temperature regulation impairment, tremor, 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 or sequelae from constipation; history of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation and/or adhesions; diverticulitis, current or history of Crohn's disease, or ulcerative colitis; severe hepatic impairment; 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
Boxed warnings: Appropriate use: See "Other warnings/precautions" below. 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 who develop constipation; serious complications of constipation have been infrequently reported (obstruction, ileus, perforation, impaction, toxic megacolon, secondary ischemia). Constipation is a frequent, dose-related side effect; risk for complications from constipation 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. Do not initiate in patients with constipation. Do not initiate in patients with constipation. Ischemic colitis: [U.S. Boxed Warning]: Acute ischemic colitis has been reported during treatment. Discontinue and evaluate 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); contraindicated in severe impairment (Child-Pugh score ≥ 10).
Special populations: Elderly: Use with caution in the elderly due to increased risk of complications from constipation. Males: Safety and efficacy have not been established in males. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: Only indicated for women with severe diarrhea-predominant irritable bowel syndrome with inadequate response to conventional therapy. Patient-Physician agreement: [U.S. Boxed Warning]: Should only be prescribed by physicians enrolled in the Prometheus' Prescribing Program for Lotronex®. Patients must read and sign a "Patient-Physician" agreement before receiving the initial prescription.
RESTRICTIONS — Only physicians enrolled in Prometheus' 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.
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP1A2 (major), 2C9 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 2E1 (weak)
DRUG INTERACTIONS
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Alosetron. Risk C: Monitor therapy
Fluvoxamine: May decrease the metabolism of Alosetron. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Antiemetics (5HT3 Antagonists). Risk C: Monitor therapy
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)
1 mg (30): $428.32
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.
Sound-alike/look-alike issues:
Lotronex® may be confused with Lovenox®, Protonix®
International issues:
Lotronex® may be confused with Lotanax® which is a brand name for terfenadine in the Czech Republic
MEDICATION GUIDE — An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088624.pdf, must be dispensed with this medication for each new outpatient prescription and refill.
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: 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. Contraindicated in severe hepatic dysfunction (Child-Pugh score ≥ 10).
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Lotronex®: 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 without food; however, when administered with food, 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%)
2% to 10%: Gastrointestinal: Abdominal discomfort and pain (7%), nausea (6%), gastrointestinal discomfort and pain (5%), abdominal distention (2%), hemorrhoids (2%), regurgitation and reflux (2%)
≤ 1% (Limited to important or life-threatening): Allergic skin reactions, alopecia, anxiety, arrhythmia, bilirubin level changes, bladder inflammation, bone pain, breathing disorder, cholecystitis, cognitive function disorders, confusion, cramps, colitis, depression, dermatitis, diaphoresis, diverticulitis, dyspepsia, extrasystoles, fatigue, fluid disturbances, gastroenteritis, GI impaction, GI intussusception, GI lesions, GI motility decreased, GI obstructions, GI perforation, GI spasms, GI ulceration, headache, hematoma, hemorrhage, hepatitis, hyperacidity, hyper-/hypoglycemia, hypertension, hypnagogic effects, hypoesthesia, hypothalamus/pituitary dysfunction, ileus, ischemic colitis, memory effects, muscle pain/stiffness, occult stools, pain, proctitis, rash, RBC/hemoglobin defects, sedation, sexual dysfunction, skeletal pain, small bowel mesenteric ischemia, tachyarrhythmia, temperature regulation impairment, tremor, 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 or sequelae from constipation; history of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation and/or adhesions; diverticulitis, current or history of Crohn's disease, or ulcerative colitis; severe hepatic impairment; 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
Boxed warnings: Appropriate use: See "Other warnings/precautions" below. 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 who develop constipation; serious complications of constipation have been infrequently reported (obstruction, ileus, perforation, impaction, toxic megacolon, secondary ischemia). Constipation is a frequent, dose-related side effect; risk for complications from constipation 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. Do not initiate in patients with constipation. Do not initiate in patients with constipation. Ischemic colitis: [U.S. Boxed Warning]: Acute ischemic colitis has been reported during treatment. Discontinue and evaluate 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); contraindicated in severe impairment (Child-Pugh score ≥ 10).
Special populations: Elderly: Use with caution in the elderly due to increased risk of complications from constipation. Males: Safety and efficacy have not been established in males. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Appropriate use: [U.S. Boxed Warning]: Only indicated for women with severe diarrhea-predominant irritable bowel syndrome with inadequate response to conventional therapy. Patient-Physician agreement: [U.S. Boxed Warning]: Should only be prescribed by physicians enrolled in the Prometheus' Prescribing Program for Lotronex®. Patients must read and sign a "Patient-Physician" agreement before receiving the initial prescription.
RESTRICTIONS — Only physicians enrolled in Prometheus' 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.
METABOLISM / TRANSPORT EFFECTS — Substrate of CYP1A2 (major), 2C9 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 2E1 (weak)
DRUG INTERACTIONS
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Alosetron. Risk C: Monitor therapy
Fluvoxamine: May decrease the metabolism of Alosetron. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Antiemetics (5HT3 Antagonists). Risk C: Monitor therapy
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)
1 mg (30): $428.32
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
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Axert® may be confused with Antivert®
U.S. BRAND NAMES — Axert®
PHARMACOLOGIC CATEGORY
Antimigraine Agent
Serotonin 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 (maximum daily dose: 25 mg)
Note: The safety of treating more than 4 migraines/month has not been established.
Dosage adjustment with concomitant use of an enzyme inhibitor:
Patients receiving a potent CYP3A4 inhibitor: Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
Patients with renal impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
Patients with hepatic impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
DOSING: PEDIATRIC — Migraine: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Severe renal impairment (Clcr ≤ 30 mL/minute): 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:
Axert®: 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 in adults (with a history of migraine) and adolescents (with a history of migraine lasting ≥ 4 hours when left untreated)
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Somnolence (≤ 5%), dizziness (≤ 4%), headache (≤ 2%)
Gastrointestinal: Nausea (1% to 3%), vomiting (≤ 2%), xerostomia (1%)
Neuromuscular & skeletal: Paresthesia (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylactic shock, angina, angioedema, breast pain, colitis, coronary artery vasospasm, hemiplegia, hypertension, myocardial ischemia, MI, neuropathy, rash, seizure, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo
CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; hemiplegic or basilar migraine; known or suspected ischemic heart disease (eg, angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); cerebrovascular syndromes (eg, stroke, transient ischemic attacks); peripheral vascular disease (eg, ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivatives and/or ergotamine-containing medications (eg, dihydroergotamine, ergotamine)
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 been reported on rare occasions following 5-HT1 agonist administration in patients with and without a history of hypertension. Ocular effects: Transient and permanent blindness and partial vision loss have been reported (rare) with 5-HT1 agonist administration. Sulfonamide allergy: Almotriptan contains a sulfonyl group which is structurally different from a sulfonamide. Cross-reactivity in patients with sulfonamide allergy has not been evaluated; however, the manufacturer recommends that caution be exercised in this patient population. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist administration.
Disease-related concerns: Coronary artery disease: Almotriptan should not be given to patients with documented ischemic or vasospastic CAD. Patients with risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) should undergo adequate cardiac evaluation prior to administration; if the cardiac evaluation is "satisfactory," the first dose of almotriptan should be given in the healthcare provider's office. All patients should undergo periodic evaluation of cardiovascular status during treatment. 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. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended for severe renal impairment.
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 <12 years of age. Efficacy has not been demonstrated in improvement of migraine-associated symptoms (eg, phonophobia, nausea, photophobia) in patients aged 12-17 years (Linder, 2008).
Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; it is not indicated for migraine prophylaxis, or for the treatment of cluster headaches, hemiplegic migraine, or basilar migraine. If a patient does not respond to the first dose, the diagnosis of acute migraine should be reconsidered.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP2D6, 3A4
DRUG INTERACTIONS
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
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): $130.08
12.5 mg (12): $238.94
CANADIAN BRAND NAMES — Axert®
INTERNATIONAL BRAND NAMES — Almogran (BE, CH, DE, DK, ES, FI, FR, GB, IE, IS, IT, JP, NL, NO, PT, SE)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes vasoconstriction and reduces 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: Via MAO type A oxidative deamination (~27% of dose) and CYP3A4 and 2D6 (~12% of dose) to inactive metabolites
Bioavailability: ~70%
Half-life elimination: 3-4 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (~75%; ~40% of total dose as unchanged drug); feces (~13% of total dose as unchanged drug and metabolites)
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.
Sound-alike/look-alike issues:
Axert® may be confused with Antivert®
U.S. BRAND NAMES — Axert®
PHARMACOLOGIC CATEGORY
Antimigraine Agent
Serotonin 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 (maximum daily dose: 25 mg)
Note: The safety of treating more than 4 migraines/month has not been established.
Dosage adjustment with concomitant use of an enzyme inhibitor:
Patients receiving a potent CYP3A4 inhibitor: Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
Patients with renal impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
Patients with hepatic impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
DOSING: PEDIATRIC — Migraine: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Severe renal impairment (Clcr ≤ 30 mL/minute): 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:
Axert®: 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 in adults (with a history of migraine) and adolescents (with a history of migraine lasting ≥ 4 hours when left untreated)
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Somnolence (≤ 5%), dizziness (≤ 4%), headache (≤ 2%)
Gastrointestinal: Nausea (1% to 3%), vomiting (≤ 2%), xerostomia (1%)
Neuromuscular & skeletal: Paresthesia (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylactic shock, angina, angioedema, breast pain, colitis, coronary artery vasospasm, hemiplegia, hypertension, myocardial ischemia, MI, neuropathy, rash, seizure, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo
CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; hemiplegic or basilar migraine; known or suspected ischemic heart disease (eg, angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); cerebrovascular syndromes (eg, stroke, transient ischemic attacks); peripheral vascular disease (eg, ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivatives and/or ergotamine-containing medications (eg, dihydroergotamine, ergotamine)
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 been reported on rare occasions following 5-HT1 agonist administration in patients with and without a history of hypertension. Ocular effects: Transient and permanent blindness and partial vision loss have been reported (rare) with 5-HT1 agonist administration. Sulfonamide allergy: Almotriptan contains a sulfonyl group which is structurally different from a sulfonamide. Cross-reactivity in patients with sulfonamide allergy has not been evaluated; however, the manufacturer recommends that caution be exercised in this patient population. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist administration.
Disease-related concerns: Coronary artery disease: Almotriptan should not be given to patients with documented ischemic or vasospastic CAD. Patients with risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) should undergo adequate cardiac evaluation prior to administration; if the cardiac evaluation is "satisfactory," the first dose of almotriptan should be given in the healthcare provider's office. All patients should undergo periodic evaluation of cardiovascular status during treatment. 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. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended for severe renal impairment.
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 <12 years of age. Efficacy has not been demonstrated in improvement of migraine-associated symptoms (eg, phonophobia, nausea, photophobia) in patients aged 12-17 years (Linder, 2008).
Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; it is not indicated for migraine prophylaxis, or for the treatment of cluster headaches, hemiplegic migraine, or basilar migraine. If a patient does not respond to the first dose, the diagnosis of acute migraine should be reconsidered.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP2D6, 3A4
DRUG INTERACTIONS
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
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): $130.08
12.5 mg (12): $238.94
CANADIAN BRAND NAMES — Axert®
INTERNATIONAL BRAND NAMES — Almogran (BE, CH, DE, DK, ES, FI, FR, GB, IE, IS, IT, JP, NL, NO, PT, SE)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes vasoconstriction and reduces 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: Via MAO type A oxidative deamination (~27% of dose) and CYP3A4 and 2D6 (~12% of dose) to inactive metabolites
Bioavailability: ~70%
Half-life elimination: 3-4 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (~75%; ~40% of total dose as unchanged drug); feces (~13% of total dose as unchanged drug and metabolites)
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.
Almotriptan
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Axert® may be confused with Antivert®
U.S. BRAND NAMES — Axert®
PHARMACOLOGIC CATEGORY
Antimigraine Agent
Serotonin 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 (maximum daily dose: 25 mg)
Note: The safety of treating more than 4 migraines/month has not been established.
Dosage adjustment with concomitant use of an enzyme inhibitor:
Patients receiving a potent CYP3A4 inhibitor: Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
Patients with renal impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
Patients with hepatic impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
DOSING: PEDIATRIC — Migraine: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Severe renal impairment (Clcr ≤ 30 mL/minute): 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:
Axert®: 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 in adults (with a history of migraine) and adolescents (with a history of migraine lasting ≥ 4 hours when left untreated)
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Somnolence (≤ 5%), dizziness (≤ 4%), headache (≤ 2%)
Gastrointestinal: Nausea (1% to 3%), vomiting (≤ 2%), xerostomia (1%)
Neuromuscular & skeletal: Paresthesia (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylactic shock, angina, angioedema, breast pain, colitis, coronary artery vasospasm, hemiplegia, hypertension, myocardial ischemia, MI, neuropathy, rash, seizure, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo
CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; hemiplegic or basilar migraine; known or suspected ischemic heart disease (eg, angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); cerebrovascular syndromes (eg, stroke, transient ischemic attacks); peripheral vascular disease (eg, ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivatives and/or ergotamine-containing medications (eg, dihydroergotamine, ergotamine)
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 been reported on rare occasions following 5-HT1 agonist administration in patients with and without a history of hypertension. Ocular effects: Transient and permanent blindness and partial vision loss have been reported (rare) with 5-HT1 agonist administration. Sulfonamide allergy: Almotriptan contains a sulfonyl group which is structurally different from a sulfonamide. Cross-reactivity in patients with sulfonamide allergy has not been evaluated; however, the manufacturer recommends that caution be exercised in this patient population. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist administration.
Disease-related concerns: Coronary artery disease: Almotriptan should not be given to patients with documented ischemic or vasospastic CAD. Patients with risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) should undergo adequate cardiac evaluation prior to administration; if the cardiac evaluation is "satisfactory," the first dose of almotriptan should be given in the healthcare provider's office. All patients should undergo periodic evaluation of cardiovascular status during treatment. 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. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended for severe renal impairment.
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 <12 years of age. Efficacy has not been demonstrated in improvement of migraine-associated symptoms (eg, phonophobia, nausea, photophobia) in patients aged 12-17 years (Linder, 2008).
Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; it is not indicated for migraine prophylaxis, or for the treatment of cluster headaches, hemiplegic migraine, or basilar migraine. If a patient does not respond to the first dose, the diagnosis of acute migraine should be reconsidered.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP2D6, 3A4
DRUG INTERACTIONS
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
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): $130.08
12.5 mg (12): $238.94
CANADIAN BRAND NAMES — Axert®
INTERNATIONAL BRAND NAMES — Almogran (BE, CH, DE, DK, ES, FI, FR, GB, IE, IS, IT, JP, NL, NO, PT, SE)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes vasoconstriction and reduces 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: Via MAO type A oxidative deamination (~27% of dose) and CYP3A4 and 2D6 (~12% of dose) to inactive metabolites
Bioavailability: ~70%
Half-life elimination: 3-4 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (~75%; ~40% of total dose as unchanged drug); feces (~13% of total dose as unchanged drug and metabolites)
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.
Sound-alike/look-alike issues:
Axert® may be confused with Antivert®
U.S. BRAND NAMES — Axert®
PHARMACOLOGIC CATEGORY
Antimigraine Agent
Serotonin 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 (maximum daily dose: 25 mg)
Note: The safety of treating more than 4 migraines/month has not been established.
Dosage adjustment with concomitant use of an enzyme inhibitor:
Patients receiving a potent CYP3A4 inhibitor: Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
Patients with renal impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
Patients with hepatic impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use
DOSING: PEDIATRIC — Migraine: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Severe renal impairment (Clcr ≤ 30 mL/minute): 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:
Axert®: 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 in adults (with a history of migraine) and adolescents (with a history of migraine lasting ≥ 4 hours when left untreated)
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Somnolence (≤ 5%), dizziness (≤ 4%), headache (≤ 2%)
Gastrointestinal: Nausea (1% to 3%), vomiting (≤ 2%), xerostomia (1%)
Neuromuscular & skeletal: Paresthesia (≤ 1%)
<1% (Limited to important or life-threatening): Anaphylactic shock, angina, angioedema, breast pain, colitis, coronary artery vasospasm, hemiplegia, hypertension, myocardial ischemia, MI, neuropathy, rash, seizure, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo
CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; hemiplegic or basilar migraine; known or suspected ischemic heart disease (eg, angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); cerebrovascular syndromes (eg, stroke, transient ischemic attacks); peripheral vascular disease (eg, ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivatives and/or ergotamine-containing medications (eg, dihydroergotamine, ergotamine)
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 been reported on rare occasions following 5-HT1 agonist administration in patients with and without a history of hypertension. Ocular effects: Transient and permanent blindness and partial vision loss have been reported (rare) with 5-HT1 agonist administration. Sulfonamide allergy: Almotriptan contains a sulfonyl group which is structurally different from a sulfonamide. Cross-reactivity in patients with sulfonamide allergy has not been evaluated; however, the manufacturer recommends that caution be exercised in this patient population. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist administration.
Disease-related concerns: Coronary artery disease: Almotriptan should not be given to patients with documented ischemic or vasospastic CAD. Patients with risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) should undergo adequate cardiac evaluation prior to administration; if the cardiac evaluation is "satisfactory," the first dose of almotriptan should be given in the healthcare provider's office. All patients should undergo periodic evaluation of cardiovascular status during treatment. 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. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended for severe renal impairment.
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 <12 years of age. Efficacy has not been demonstrated in improvement of migraine-associated symptoms (eg, phonophobia, nausea, photophobia) in patients aged 12-17 years (Linder, 2008).
Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; it is not indicated for migraine prophylaxis, or for the treatment of cluster headaches, hemiplegic migraine, or basilar migraine. If a patient does not respond to the first dose, the diagnosis of acute migraine should be reconsidered.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP2D6, 3A4
DRUG INTERACTIONS
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
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): $130.08
12.5 mg (12): $238.94
CANADIAN BRAND NAMES — Axert®
INTERNATIONAL BRAND NAMES — Almogran (BE, CH, DE, DK, ES, FI, FR, GB, IE, IS, IT, JP, NL, NO, PT, SE)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes vasoconstriction and reduces 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: Via MAO type A oxidative deamination (~27% of dose) and CYP3A4 and 2D6 (~12% of dose) to inactive metabolites
Bioavailability: ~70%
Half-life elimination: 3-4 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (~75%; ~40% of total dose as unchanged drug); feces (~13% of total dose as unchanged drug and metabolites)
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 MEDICATION SAFETY ISSUES Sound-alike/look-alike issues: Allopurinol may be confused with Apresoline Zyloprim® may be confused with X
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Allopurinol may be confused with Apresoline
Zyloprim® may be confused with Xylo-Pfan®, ZORprin®, Zovirax®
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 years: 150 mg/day in 3 divided doses
6-10 years: 300 mg/day in 2-3 divided doses
>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
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.
Hemodialysis: Administer dose after hemodialysis or administer 50% supplemental dose.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium: 500 mg
Aloprim™ : 500 mg
Tablet: 100 mg, 300 mg
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
Dermatologic: Rash
Endocrine & metabolic: Gout (acute)
Gastrointestinal: Diarrhea, nausea
Hepatic: Alkaline phosphatase increased, liver enzymes increased
<1% (Limited to important or life-threatening): Abdominal pain, agranulocytosis, alopecia, angioedema, aplastic anemia, arthralgia, bronchospasm, cataracts, cholestatic jaundice, dermatitis (eczematoid, exfoliative, vascular bullous), dyspepsia, ecchymosis, eosinophilia, epistaxis, fever, gastritis, granuloma annulare, hepatitis, gynecomastia, headache, hepatic necrosis, hepatomegaly, hyperbilirubinemia, hypersensitivity reactions, leukocytosis, leukopenia, lichen planus, loss of taste perception, macular retinitis, myopathy, necrotizing angiitis, nephritis, neuritis, neuropathy, onycholysis, pancreatitis, paresthesia, purpura, pruritus, renal failure, somnolence, Stevens-Johnson syndrome, taste perversion, thrombocytopenia, toxic epidermal necrolysis, toxic pustuloderma, uremia, vasculitis, vomiting
CONTRAINDICATIONS — Hypersensitivity to allopurinol or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Allergic reaction: Has been associated with a number of hypersensitivity reactions, including severe reactions (vasculitis and Stevens-Johnson syndrome); discontinue at first sign of rash. Bone marrow suppression: Has been reported; use caution with other drugs causing myelosuppression. Hepatotoxicity: Reversible hepatotoxicity has been reported; use with caution in patients with pre-existing hepatic impairment.
Disease-related concerns: Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia. Renal impairment: Use with caution in patients with renal impairment; may be at increased risk for hypersensitivity reactions. 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; dosage adjustment necessary. Diuretics: Use with caution in patients taking diuretics concurrently. The risk of hypersensitivity may be increased in patients receiving thiazides.
DRUG INTERACTIONS
ACE Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk D: Consider therapy modification
Amoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Ampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Antacids: May decrease the absorption of Allopurinol. Exceptions: Sodium Bicarbonate. Risk D: Consider therapy modification
AzaTHIOprine: Allopurinol may decrease the metabolism of AzaTHIOprine. Risk D: Consider therapy modification
CarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
ChlorproPAMIDE: Allopurinol may increase the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy
Cyclophosphamide: Allopurinol may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, bone marrow suppression. Risk C: Monitor therapy
Didanosine: Allopurinol may increase the serum concentration of Didanosine. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Mercaptopurine: Allopurinol may decrease the metabolism of Mercaptopurine. Risk D: Consider therapy modification
Pivampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Pivampicillin. Risk C: Monitor therapy
Theophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Thiazide Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
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): $23.99
300 mg (30): $56.04
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.
CANADIAN BRAND NAMES — Alloprin®; Apo-Allopurinol®; Novo-Purol; Zyloprim®
INTERNATIONAL BRAND NAMES — Adenock (JP); AL (PH); Alinol (TH); Allo (CO); Allo 300 (DE); Allo-Puren (DE); Allobeta (AU); Allohexal (AU); Allopin (TH); Allopur (CH, NO); Allopurinol (PL); Allopurinol-ratiopharm (LU); Alloratio (PL); Alloril (IL); Allorin (NZ); Allosig (AU); Allozym (JP); Allpargin (LU); Allupol (PL); Allurase (PH); Allurit (IT); Alopron (BB, BM, BS, BZ, GY, JM, NL, PR, SR, TT); Alopurinol (HR); Alositol (JP); Alpurase (PH); Alpuric (LU); Alurin (GT); Aluron (VE); Anoprolin (JP); Anzief (JP); Apo-Allopurinol (PL); Aprinol (JP); Apurin (FI, GR); Atisuril (MX); Benoxuric (ID); Bleminal (DE); Caplenal (GB); 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, TN, TZ, UG, ZA, ZM, ZW); Etindrax (MX); Foligan (DE); Genozyl (MX); Gichtex (AT); Hamarin (GB); Hexanurat (DK); Huma-Purol (HU); Isoric (ID); Ketanrift (JP); Ketobun-A (JP); Licoric (ID); Litinol (VE); Llanol (PH); Masaton (JP); Mephanol (AE, BF, BH, BJ, CH, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Milurit (BG, HK, HN, HU, PL); Miniplanor (JP); Neufan (JP); Nilapur (ID); Nipurol (VE); No-Uric (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Pritanol (ID); Progout (AU, HK, SG); Proxuric (ID); Puribel 300 (MX); Puricemia (ID); Puricos (ZA); Purinol (MY); Puristen (PH); Remid (DE); Riball (JP); Rinolic (ID); Salterprim (ZA); Sinoric (ID); Takanarumin (JP); Trianol (PH); Unizuric 300 (MX); Uric (JP); Uricad (TH); Uricnol (ID); Uriconorm (CH); Urinol (MY); Uripurinol (DE); Urogquad (AR); Uroquad (BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, ID, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, PR, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZA, ZM, ZW); Urosin (AT, DE, EC, LU); Xandase (TH); Xanturic (FR); Xanurace (PH); Zylapour (GR); Zyloprim (AU, BB, BM, BS, BZ, CR, DO, GY, JM, MX, NI, NL, PA, PH, PY, SR, SV, TT); Zyloric (AE, AT, BE, BF, BG, BH, BJ, BR, CH, CI, CN, CY, CZ, DE, DK, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, HN, ID, IE, IL, IN, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, NO, OM, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SY, TH, TN, TR, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Zyroric (KP)
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
Sound-alike/look-alike issues:
Allopurinol may be confused with Apresoline
Zyloprim® may be confused with Xylo-Pfan®, ZORprin®, Zovirax®
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 years: 150 mg/day in 3 divided doses
6-10 years: 300 mg/day in 2-3 divided doses
>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
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.
Hemodialysis: Administer dose after hemodialysis or administer 50% supplemental dose.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium: 500 mg
Aloprim™ : 500 mg
Tablet: 100 mg, 300 mg
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
Dermatologic: Rash
Endocrine & metabolic: Gout (acute)
Gastrointestinal: Diarrhea, nausea
Hepatic: Alkaline phosphatase increased, liver enzymes increased
<1% (Limited to important or life-threatening): Abdominal pain, agranulocytosis, alopecia, angioedema, aplastic anemia, arthralgia, bronchospasm, cataracts, cholestatic jaundice, dermatitis (eczematoid, exfoliative, vascular bullous), dyspepsia, ecchymosis, eosinophilia, epistaxis, fever, gastritis, granuloma annulare, hepatitis, gynecomastia, headache, hepatic necrosis, hepatomegaly, hyperbilirubinemia, hypersensitivity reactions, leukocytosis, leukopenia, lichen planus, loss of taste perception, macular retinitis, myopathy, necrotizing angiitis, nephritis, neuritis, neuropathy, onycholysis, pancreatitis, paresthesia, purpura, pruritus, renal failure, somnolence, Stevens-Johnson syndrome, taste perversion, thrombocytopenia, toxic epidermal necrolysis, toxic pustuloderma, uremia, vasculitis, vomiting
CONTRAINDICATIONS — Hypersensitivity to allopurinol or any component of the formulation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Allergic reaction: Has been associated with a number of hypersensitivity reactions, including severe reactions (vasculitis and Stevens-Johnson syndrome); discontinue at first sign of rash. Bone marrow suppression: Has been reported; use caution with other drugs causing myelosuppression. Hepatotoxicity: Reversible hepatotoxicity has been reported; use with caution in patients with pre-existing hepatic impairment.
Disease-related concerns: Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia. Renal impairment: Use with caution in patients with renal impairment; may be at increased risk for hypersensitivity reactions. 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; dosage adjustment necessary. Diuretics: Use with caution in patients taking diuretics concurrently. The risk of hypersensitivity may be increased in patients receiving thiazides.
DRUG INTERACTIONS
ACE Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk D: Consider therapy modification
Amoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Ampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Antacids: May decrease the absorption of Allopurinol. Exceptions: Sodium Bicarbonate. Risk D: Consider therapy modification
AzaTHIOprine: Allopurinol may decrease the metabolism of AzaTHIOprine. Risk D: Consider therapy modification
CarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
ChlorproPAMIDE: Allopurinol may increase the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy
Cyclophosphamide: Allopurinol may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, bone marrow suppression. Risk C: Monitor therapy
Didanosine: Allopurinol may increase the serum concentration of Didanosine. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Mercaptopurine: Allopurinol may decrease the metabolism of Mercaptopurine. Risk D: Consider therapy modification
Pivampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Pivampicillin. Risk C: Monitor therapy
Theophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Thiazide Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
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): $23.99
300 mg (30): $56.04
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.
CANADIAN BRAND NAMES — Alloprin®; Apo-Allopurinol®; Novo-Purol; Zyloprim®
INTERNATIONAL BRAND NAMES — Adenock (JP); AL (PH); Alinol (TH); Allo (CO); Allo 300 (DE); Allo-Puren (DE); Allobeta (AU); Allohexal (AU); Allopin (TH); Allopur (CH, NO); Allopurinol (PL); Allopurinol-ratiopharm (LU); Alloratio (PL); Alloril (IL); Allorin (NZ); Allosig (AU); Allozym (JP); Allpargin (LU); Allupol (PL); Allurase (PH); Allurit (IT); Alopron (BB, BM, BS, BZ, GY, JM, NL, PR, SR, TT); Alopurinol (HR); Alositol (JP); Alpurase (PH); Alpuric (LU); Alurin (GT); Aluron (VE); Anoprolin (JP); Anzief (JP); Apo-Allopurinol (PL); Aprinol (JP); Apurin (FI, GR); Atisuril (MX); Benoxuric (ID); Bleminal (DE); Caplenal (GB); 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, TN, TZ, UG, ZA, ZM, ZW); Etindrax (MX); Foligan (DE); Genozyl (MX); Gichtex (AT); Hamarin (GB); Hexanurat (DK); Huma-Purol (HU); Isoric (ID); Ketanrift (JP); Ketobun-A (JP); Licoric (ID); Litinol (VE); Llanol (PH); Masaton (JP); Mephanol (AE, BF, BH, BJ, CH, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Milurit (BG, HK, HN, HU, PL); Miniplanor (JP); Neufan (JP); Nilapur (ID); Nipurol (VE); No-Uric (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Pritanol (ID); Progout (AU, HK, SG); Proxuric (ID); Puribel 300 (MX); Puricemia (ID); Puricos (ZA); Purinol (MY); Puristen (PH); Remid (DE); Riball (JP); Rinolic (ID); Salterprim (ZA); Sinoric (ID); Takanarumin (JP); Trianol (PH); Unizuric 300 (MX); Uric (JP); Uricad (TH); Uricnol (ID); Uriconorm (CH); Urinol (MY); Uripurinol (DE); Urogquad (AR); Uroquad (BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, ID, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, PR, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZA, ZM, ZW); Urosin (AT, DE, EC, LU); Xandase (TH); Xanturic (FR); Xanurace (PH); Zylapour (GR); Zyloprim (AU, BB, BM, BS, BZ, CR, DO, GY, JM, MX, NI, NL, PA, PH, PY, SR, SV, TT); Zyloric (AE, AT, BE, BF, BG, BH, BJ, BR, CH, CI, CN, CY, CZ, DE, DK, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, HN, ID, IE, IL, IN, IQ, IR, IT, JO, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, NO, OM, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SY, TH, TN, TR, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Zyroric (KP)
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
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