Pronunciation:

(METH a done)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Restrictions:

Treatment of narcotic addiction: May only be dispensed by pharmacies or maintenance programs approved by the FDA and designated state authority. Prior approval must be obtained for doses >120 mg administered at a clinic or >100 mg to be taken at home.

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

May prolong the QT interval; use caution in patients at risk for QT prolongation, with medications known to prolong the QT interval, or history of conduction abnormalities. QT interval prolongation and torsade de pointes may be associated with doses >200 mg/day, but have also been observed with lower doses. May cause severe hypotension; use caution with severe volume depletion or other conditions which may compromise maintenance of normal blood pressure. Use caution with cardiovascular disease or patients predisposed to dysrhythmias.

Methadone has a long half-life and risk of accumulation; because methadone's effects on respiration last much longer than its analgesic effects, the dose must be titrated slowly. May cause respiratory depression; use caution in patients with respiratory disease or pre-existing respiratory depression. Potential for drug dependency exists, abrupt cessation may precipitate withdrawal. Use caution in elderly, debilitated, or pediatric patients. Use with caution in patients with depression or suicidal tendencies, or in patients with a history of drug abuse. Tolerance or psychological and physical dependence may occur with prolonged use.

Use with caution in patients with hepatic, pulmonary, or renal function impairment. 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). Effects with other sedative drugs or ethanol may be potentiated. Elderly may be more sensitive to CNS depressant and constipating effects. Use with caution in patients with head injury or increased ICP, biliary tract dysfunction or pancreatitis; history of ileus or bowel obstruction, glaucoma, hyperthyroidism, hypothyroidism, adrenal insufficiency, prostatic hyperplasia or urinary stricture, CNS depression, toxic psychosis, alcoholism, delirium tremens, or kyphoscoliosis. Tablets contain excipients to deter use by injection.

Adverse Reactions:

Cardiovascular: Bradycardia, peripheral vasodilation, cardiac arrest, syncope, faintness, shock, hypotension, edema, arrhythmia, bigeminal rhythms, extrasystoles, tachycardia, torsade de pointes, ventricular fibrillation, ventricular tachycardia, ECG changes, QT interval prolonged, T-wave inversion, cardiomyopathy, flushing, heart failure, palpitation, phlebitis, orthostatic hypotension,

Central nervous system: Euphoria, dysphoria, headache, insomnia, agitation, disorientation, drowsiness, dizziness, lightheadedness, sedation, confusion, seizure

Dermatologic: Pruritus, urticaria, rash, hemorrhagic urticaria

Endocrine & metabolic: Libido decreased, hypokalemia, hypomagnesemia, antidiuretic effect, amenorrhea

Gastrointestinal: Nausea, vomiting, constipation, anorexia, stomach cramps, xerostomia, biliary tract spasm, abdominal pain, glossitis, weight gain

Genitourinary: Urinary retention or hesitancy, impotence

Hematologic: Thrombocytopenia (reversible, reported in patients with chronic hepatitis)

Neuromuscular & skeletal: Weakness

Local: I.M./SubQ injection: Pain, erythema, swelling; I.V. injection: pruritus, urticaria, rash, hemorrhagic urticaria (rare)

Ocular: Miosis, visual disturbances

Respiratory: Respiratory depression, respiratory arrest, pulmonary edema

Miscellaneous: Physical and psychological dependence, death, diaphoresis

Overdosage/Toxicology:

Drug Interactions:

Agonist/antagonist analgesics (buprenorphine, butorphanol, nalbuphine, pentazocine): May decrease analgesic effect of methadone and precipitate withdrawal symptoms; use is not recommended.

Antiretroviral agents, NNRTI: May decrease levels of methadone, opioid withdrawal syndrome has been reported. Effect reported with efavirenz and nevirapine.

Antiretroviral agent, NRTI: Methadone may increase bioavailability and toxic effects of zidovudine. Methadone may decrease bioavailability of didanosine and stavudine.

Antiretroviral agent, PI: Ritonavir (and combinations) may decrease levels of methadone; withdrawal symptoms have inconsistently been observed, monitor.

CNS depressants (including but not limited to opioid analgesics, general anesthetics, sedatives, hypnotics, ethanol): May cause respiratory depression, hypotension, profound sedation, or coma.

CYP2D6 substrates: Methadone may increase the levels/effects of CYP2D6 substrates. Example substrates include amphetamines, selected beta-blockers, dextromethorphan, fluoxetine, lidocaine, mirtazapine, nefazodone, paroxetine, risperidone, ritonavir, thioridazine, tricyclic antidepressants, and venlafaxine.

CYP2D6 prodrug substrates: Methadone may decrease the levels/effects of CYP2D6 prodrug substrates. Example prodrug substrates include codeine, hydrocodone, oxycodone, and tramadol.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of methadone. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of methadone. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

Desipramine: Levels of desipramine may be increased by methadone.

QTc interval-prolonging agents (including but may not be limited to amitriptyline, astemizole, bepridil, disopyramide, erythromycin, haloperidol, imipramine, quinidine, pimozide, procainamide, sotalol, and thioridazine): Effect/toxicity increased; use with caution.

Somatostatin: Therapeutic effect of methadone may be decreased; limited documentation; monitor

Zidovudine: serum concentrations may be increased by methadone; monitor

Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid ethanol (may increase CNS effects). Watch for sedation.

Herb/Nutraceutical: Avoid St John's wort (may decrease methadone levels; may increase CNS depression). Avoid valerian, kava kava, gotu kola (may increase CNS depression). Methadone is metabolized by CYP3A4 in the intestines; avoid concurrent use of grapefruit juice.

Stability:

Injection: Store at controlled room temperature of 15°C to 30°C (59°F to 86°F); protect from light

Oral concentrate, oral solution, tablet: Store at controlled room temperature of 15°C to 30°C (59°F to 86°F)

Compatibility:

Mechanism of Action:

Pharmacodynamics/Kinetics:

Onset of action: Oral: Analgesic: 0.5-1 hour; Parenteral: 10-20 minutes

Peak effect: Parenteral: 1-2 hours

Duration: Oral: 6-8 hours, increases to 22-48 hours with repeated doses

Distribution: Vd: 2-6 L/kg; crosses placenta; enters breast milk

Protein binding: 85% to 90%

Metabolism: Hepatic; N-demethylation via CYP3A4 and 2D6 to inactive metabolites

Half-life elimination: 8-59 hours; may be prolonged with alkaline pH, decreased during pregnancy

Excretion: Urine (<10% as unchanged drug); increased with urine pH <6

Dosage:

Children:

Pain (analgesia):

Oral (unlabeled use): Initial: 0.1-0.2 mg/kg 4-8 hours initially for 2-3 doses, then every 6-12 hours as needed. Dosing interval may range from 4-12 hours during initial therapy; decrease in dose or frequency may be required (~ days 2-5) due to accumulation with repeated doses (maximum dose: 5-10 mg)

I.V. (unlabeled use): 0.1 mg/kg every 4-8 hours initially for 2-3 doses, then every 6-12 hours as needed. Dosing interval may range from 4-12 hours during initial therapy; decrease in dose or frequency may be required (~ days 2-5) due to accumulation with repeated doses (maximum dose: 5-8 mg)

Iatrogenic narcotic dependency (unlabeled): Oral: General guidelines: Initial: 0.05-0.1 mg/kg/dose every 6 hours; increase by 0.05 mg/kg/dose until withdrawal symptoms are controlled; after 24-48 hours, the dosing interval can be lengthened to every 12-24 hours; to taper dose, wean by 0.05 mg/kg/day; if withdrawal symptoms recur, taper at a slower rate

Adults:

Pain (analgesia):

Oral: Initial: 5-10 mg; dosing interval may range from 4-12 hours during initial therapy; decrease in dose or frequency may be required (~days 2-5) due to accumulation with repeated doses

Manufacturer's labeling: 2.5-10 mg every 3-4 hours as needed

I.V.: Manufacturers labeling: Initial: 2.5-10 mg every 8-12 hours in opioid-naive patients; titrate slowly to effect; may also be administered by SubQ or I.M. injection

Conversion from oral to parenteral dose: Initial dose: Oral: parenteral: 2:1 ratio

Detoxification: Oral: 15-40 mg/day

Maintenance treatment of opiate dependence: Oral: 20-120 mg/day

Dosage adjustment in renal impairment: Clcr<10 mL/minute: Administer 50% to 75% of normal dose

Dosage adjustment in hepatic impairment: Avoid in severe liver disease

Administration:

Monitoring Parameters:

Reference Range:

Patient Education:

Anesthesia and Critical Care Concerns/Other Considerations:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Oncology: Vesicant:

Dosage Forms:

Injection, solution, as hydrochloride: 10 mg/mL (20 mL)

Solution, oral, as hydrochloride: 5 mg/5 mL (500 mL); 10 mg/5 mL (500 mL) [contains alcohol 8%; citrus flavor]

Solution, oral concentrate, as hydrochloride: 10 mg/mL (30 mL)

Methadone Intensol™: 10 mg/mL (30 mL)

Methadose®: 10 mg/mL (30 mL) [cherry flavor]

Tablet, as hydrochloride (Dolophine®, Methadose®): 5 mg, 10 mg

Tablet, dispersible, as hydrochloride:

Methadose®: 40 mg

Methadone Diskets®: 40 mg [orange-pineapple flavor]

International Brand Names: