methadone hydrochloride
Dolophine, Methadose, Physeptone ◆

Available forms
Available by prescription only
Injection: 10 mg/ml
Oral solution: 5 mg/5 ml, 10 mg/5 ml, 10 mg/ml (concentrate)
Tablets: 5 mg, 10 mg, 40 mg for oral solution (for narcotic abstinence syndrome)

Indications and dosages
 Severe pain. Adults: 2.5 to 10 mg P.O., I.M., or S.C. q 3 to 4 hours, p.r.n., or around-the-clock.
Children ◇: 0.7 mg/kg P.O. daily in divided doses q 4 to 6 hours
 Relief of severe, chronic pain. Adults: 5 to 20 mg P.O. q 6 to 8 hours.
 Narcotic abstinence syndrome. Adults: 15 to 40 mg P.O. daily (highly individualized).
 Maintenance dosage is 20 to 120 mg P.O. daily. Adjust dose, p.r.n. Daily doses above 120 mg require special state and federal approval. If patient feels nauseated, give one-fourth of total P.O. dose in two injections, S.C. or I.M. Treatment is 30 (short-term) to 180 (long-term) days.

Pharmacodynamics
Analgesic action: Methadone is an opiate agonist that has analgesic activity via an affinity for the opiate receptors similar to that of morphine. It’s recommended for severe, chronic pain and is also used in detoxification and maintenance of patients with opiate abstinence syndrome.

Pharmacokinetics
Absorption: Well absorbed from the GI tract. Oral administration delays onset and prolongs duration of action as compared to parenteral administration.
Distribution: Highly bound to tissue protein, which may explain its cumulative effects and slow elimination.
Metabolism: Metabolized primarily in the liver by N-demethylation.
Excretion: Half-life is prolonged (7 to 11 hours) in patients with hepatic dysfunction. Urinary excretion, the major route, is dose-dependent. Methadone metabolites are also excreted in the feces via the bile.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in geriatric or debilitated patients and in those with severe renal or hepatic impairment, acute abdominal conditions, hypothyroidism, Addison’s disease, prostatic hyperplasia, urethral stricture, head injury, increased intracranial pressure, asthma, or other respiratory disorders.

Interactions
Drug-drug. CNS depressants, such as antidepressants, antihistamines, barbiturates, benzodiazepines, general anesthetics, muscle relaxants, narcotic analgesics, phenothiazines, and sedative-hypnotics: Potentiates respiratory and CNS depression, sedation, and hypotensive effects. Use together cautiously.
Cimetidine: Increases respiratory and CNS depression, causing confusion, disorientation, apnea, or seizures. Such use usually requires reduced dosage of methadone.
Efavirenz, nelfinavir, nevirapine, ritonavir: May decrease action of methadone. Increased methadone dose may be needed.
Fosphenytoin, phenytoin, primidone, rifampin: May reduce blood methadone level. Monitor patient.
Opioid antagonists: Patients who become physically dependent on methadone may experience acute withdrawal syndrome if given these drugs. Use cautiously, and monitor patient closely.
Drug-lifestyle. Alcohol use: Potentiates respiratory and CNS depression, sedation, and hypotensive effects. Discourage alcohol use.

Adverse reactions
CNS: sedation, somnolence, clouded sensorium, euphoria, dizziness, choreic movements, seizures, headache, insomnia, agitation, light-headedness, syncope.
CV: hypotension, bradycardia, shock, cardiac arrest, arrhythmias, palpitations, edema.
EENT: visual disturbances.
GI: nausea, vomiting, constipation, ileus, dry mouth, anorexia, biliary tract spasm.
GU: urine retention.
Respiratory: respiratory depression, respiratory arrest.
Skin: diaphoresis; pruritus; urticaria; pain at injection site; tissue irritation and induration after S.C. injection.
Other: physical dependence, decreased libido.

Effects on lab test results
• May increase amylase levels.

Overdose and treatment
The most common signs and symptoms of overdose are CNS depression, respiratory depression, and miosis (pinpoint pupils). Others include hypotension, bradycardia, hypothermia, shock, apnea, cardiopulmonary arrest, circulatory collapse, pulmonary edema, and seizures. Toxicity may result from accumulation of drug over several weeks.
 To treat acute overdose, first establish adequate respiratory exchange by way of a patent airway and ventilation as needed; administer an opioid antagonist (naloxone) to reverse respiratory depression. Because the duration of action of methadone is longer than that of naloxone, repeated naloxone dosing is needed. The antagonist naloxone shouldn’t be given unless the patient has clinically significant respiratory or CV depression. Monitor vital signs closely.
 If patient is seen within 2 hours of ingestion of an oral overdose, empty the stomach immediately by inducing emesis (ipecac syrup) or using gastric lavage. Use cautiously to avoid risk of aspiration. Administer activated charcoal through nasogastric tube for further removal of drug in an oral overdose.
 Provide symptomatic and supportive treatment (continued respiratory support, correction of fluid or electrolyte imbalance). Monitor laboratory values, vital signs, and neurologic status closely.

Special considerations
• Verify that patient is in a methadone maintenance program for management of narcotic addiction and, if so, at what dosage, and continue that program appropriately.
• Dispersible tablets must be dissolved in 4 ounces (120 ml) of water or fruit juice; oral concentrate must be diluted to at least 30 ml, but when used for detoxification, must be diluted with at least 3 ounces (90 ml) of water before use.
 ALERT Diluents used for diluting methadone and levomethadyl acetate should differ in color and taste to avoid confusion.
• Oral liquid form (not tablet form) is legally required and is the only form available in drug maintenance programs.
• Regimented scheduling (around-the-clock) is beneficial in severe, chronic pain. Tolerance may develop with long-term use, requiring a higher dose to achieve the same degree of analgesia.
• Patient treated for narcotic abstinence syndrome usually requires an additional analgesic if pain control is needed.
• Physical and psychological tolerance or dependence may occur. Be aware of potential for abuse.
 ALERT Very high doses may cause prolongation of QT interval and torsades de pointes.
Breast-feeding patients
• Methadone appears in breast milk. It may cause physical dependence in breast-feeding infants of women on methadone maintenance therapy.
Pediatric patients
• Drug isn’t recommended for use in children. Safe use as maintenance drug in adolescent addicts hasn’t been established.
Geriatric patients
• Lower doses are usually indicated for geriatric patients because they may be more sensitive to the therapeutic and adverse effects of drug.

Patient education
• If appropriate, tell patient that constipation is often severe during maintenance with methadone. Instruct him to take a stool softener or other laxative.
• Caution patient to avoid activities that require full alertness, such as driving and operating machinery, because of potential for drowsiness.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use