Yes

Analgesic, Narcotic

Management of severe pain; detoxification and maintenance treatment of narcotic addiction

C-II

B/D (if used for prolonged periods or in high doses at term)

Hypersensitivity to methadone or any component

Because methadone's effects on respiration last much longer than its analgesic effects, the dose must be titrated slowly; because of its long half-life and risk of accumulation, it is not considered a drug of first choice in the elderly, who may be particularly susceptible to its CNS depressant and constipating effects. 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 (ie, 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, adrenal insufficiency, prostatic hypertrophy or urinary stricture, CNS depression, toxic psychosis, alcoholism, delirium tremens, or kyphoscoliosis. Tablets are to be used only for oral administration and must not be used for injection.

Cardiovascular: Bradycardia, peripheral vasodilation, cardiac arrest, syncope, faintness

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

Dermatologic: Pruritus, urticaria, rash

Endocrine & metabolic: Decreased libido

Gastrointestinal: Nausea, vomiting, constipation, anorexia, stomach cramps, xerostomia, biliary tract spasm

Genitourinary: Urinary retention or hesitancy, antidiuretic effect, impotence

Neuromuscular & skeletal: Weakness

Ocular: Miosis, visual disturbances

Respiratory: Respiratory depression, respiratory arrest

Miscellaneous: Physical and psychological dependence

Symptoms of overdose include respiratory depression, CNS depression, miosis, hypothermia, circulatory collapse, convulsions

Naloxone 2 mg I.V. (0.01 mg/kg for children) with repeat administration as necessary up to a total of 10 mg

CYP1A2, 2D6, and 3A3/4 enzyme substrate; CYP2D6 inhibitor

Fluconazole, itraconazole, and ketoconazole increase serum methadone concentrations via CYP3A4 inhibition; an increased narcotic effect may be experienced

Highly incompatible with all other I.V. agents when mixed together

Binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression

Oral: Onset of analgesia: Within 0.5-1 hour; Duration: 6-8 hours, increases to 22-48 hours with repeated doses

Parenteral: Onset of effect: Within 10-20 minutes; Peak effect: Within 1-2 hours

Distribution: Crosses the placenta; appears in breast milk

Protein binding: 80% to 85%

Metabolism: In the liver (N-demethylation)

Half-life: 15-29 hours, may be prolonged with alkaline pH

Elimination: In urine (<10% as unchanged drug); increased renal excretion with urine pH <6

Doses should be titrated to appropriate effects

Oral, I.M., S.C.: 0.7 mg/kg/24 hours divided every 4-6 hours as needed or 0.1-0.2 mg/kg every 4-12 hours as needed; maximum: 10 mg/dose

I.V.: 0.1 mg/kg every 4 hours initially for 2-3 doses, then every 6-12 hours as needed; maximum: 10 mg/dose

Adults:

Analgesia: Oral, I.M., S.C.: 2.5-10 mg every 3-8 hours as needed, up to 5-20 mg every 6-8 hours

Detoxification: Oral: 15-40 mg/day; should not exceed 21 days and may not be repeated earlier than 4 weeks after completion of preceding course

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

Dosing adjustment in renal impairment: Cl_cr <10 mL/minute: Administer at 50% to 75% of normal dose

Dosing adjustment/comments in hepatic disease: Avoid in severe liver disease

Important note: Methadone accumulates with repeated doses and dosage may need to be adjusted downward after 3-5 days to prevent toxic effects. Some patients may benefit from every 8- to 12-hour dosing interval (pain control).

Alcohol: Additive CNS effects, avoid or limit alcohol; watch for sedation

Food: Glucose may cause hyperglycemia; monitor blood glucose concentrations

Pain relief, respiratory and mental status, blood pressure

Therapeutic: 100-400 ng/mL (SI: 0.32-1.29 mmol/L); Toxic: >2 mg/mL (SI: >6.46 mmol/L)

No information available to require special precautions

1% to 10% of patients experience significant dry mouth which will disappear with cessation of drug therapy

If self-administered, use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. While using this medication, do not use alcohol and other prescription or OTC medications (especially sedatives, tranquilizers, antihistamines, or pain medications) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). May cause hypotension, dizziness, drowsiness, impaired coordination, or blurred vision (use caution when driving, climbing stairs, or changing position - rising from sitting or lying to standing, or when engaging in tasks requiring alertness until response to drug is known); loss of appetite, nausea, or vomiting (frequent mouth care, small frequent meals, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help - if constipation remains an unresolved problem, consult prescriber about use of stool softeners). Report chest pain, slow or rapid heartbeat, acute dizziness or persistent headache; changes in mental status; swelling of extremities or unusual weight gain; changes in urinary elimination; acute headache; back or flank pain or muscle spasms; blurred vision; skin rash; or shortness of breath. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. If you are breast-feeding, take medication immediately after breast-feeding or 3-4 hours prior to next feeding.

Observe patient for excessive sedation, respiratory depression, implement safety measures, assist with ambulation

Injection, as hydrochloride: 10 mg/mL (1 mL, 10 mL, 20 mL)

Solution, as hydrochloride:

Oral: 5 mg/5 mL (5 mL, 500 mL); 10 mg/5 mL (500 mL)

Oral, concentrate: 10 mg/mL (30 mL)

Tablet, as hydrochloride: 5 mg, 10 mg

Tablet, dispersible, as hydrochloride: 40 mg

Anand KJ and Arnold JH, "Opioid Tolerance and Dependence in Infants and Children," Crit Care Med, 1994, 22(2):334-42.

Berde C, Ablin A, Glazer J, et al, "American Academy of Pediatrics Report of the Subcommittee on Disease-Related Pain in Childhood Cancer," Pediatrics, 1990, 86(5 Pt 2):818-25.

"Drugs for Pain," Med Lett Drugs Ther, 1998, 40(1033):79-84.

Ferrell BA, "Pain Management in Elderly People," J Am Geriatr Soc, 1991, 39(1):64-73.

Gayle MO, Ryan CA, and Nazarali S, "Unusual Cause of Methadone Poisoning," Acta Paediatr Scand, 1991, 80(4):486-7.

Lauriault G, LeBelle MJ, Lodge BA, et al, "Stability of Methadone in Four Vehicles for Oral Administration," Am J Hosp Pharm, 1991, 48(6):1252-6.

Molyneux E, Ahern R, and Baldwin B, "Accidental Ingestion of Methadone," BMJ, 1991, 303(6807):922-3.

Olkkola KT, Hamunen K, and Maunuksela EL, "Clinical Pharmacokinetics and Pharmacodynamics of Opioid Analgesics in Infants and Children," Clin Pharmacokinet, 1995, 28(5):385-404.

Wasserman S and Yahr MD, "Choreic Movements Induced by the Use of Methadone," Arch Neurol, 1980, 37(11):727-8.

Wu CH and Henry JA, "Deaths of Heroin Addicts Starting on Methadone Maintenance," Lancet, 1990, 335(8686):424.