Methadone

Methadone Brand Names

Dolophine (US), Methadone Diskets, Methadone Intensol, Methadose, Metadol (Canadian)

Methadone is the Generic Name

Methadone Hydrochloride is belonged to analgesic and opioid pharmacologic category.

Indication / Use

Methadone is used to manage moderate-to-severe pain. Besides, it is also commonly used for detoxification and maintenance treatment of opioid addiction. However, it must be part of an FDA-approved program if it is intended to be used for the latter purpose.

Restrictions

When methadone is purposed for treatment of opioid addiction, it may only be dispensed in accordance to guidelines established by the Substance Abuse and Mental Health Services Administrations's (SAMHSA) Center for substance Abuse Treatment (CSAT).

However, regulations regarding methadone use may vary by state or different country. Advice should be obtained from appropriate regulatory agencies or consult with pain management care specialists before dispensing methadone.

There are regulatory exceptions to the General Requirement to Provide Opioid Agonist Treatment in which:

1. During inpatient care, when the patient was admitted for any condition other than concurrent opioid addiction, with the purpose to facilitate the treatment of the primary admitting diagnosis.

2. During an emergency period of no longer than 3 days while definitive care for the addiction is being sought in an  appropriately licensed facility

Pregnancy Risk Factor Category: C/D (dangerous especially in prolonged used or at high doses)

Some animal studies have shown teratogenic effects, however, the data collected by Teratogen Information System are complicated by other factors including maternal use of illicit drugs, nutrition supplement, concurrent infections and psychosocial circumstances.

Though, there is improvement being observed in pregnant women with methadone treatment compared to pregnant women using illicit drugs.

Methadone can be detected in the amniotic fluid, cord plasma, and newborn urine. Fetal growth, birth weight, length, head or other s may be affected and decreased in infants born to narcotic-addicted mothers with methadone treatment during pregnancy. Growth deficits do not appear to persist but decreased performance on psychometric and behavioural tests has been found to continue into childhood.

Besides, there is also report of abnormal fetal nonstress tests where withdrawal symptoms in the neonate may be observed up to 2-4 weeks after delivery.

Hence, methadone should be only used during pregnancy when clearly needed where benefits outweigh risk.

Since methadone clearance is increased and half-life is decreased during 2nd and 3rd trimesters of pregnancy, withdrawal symptoms may be observed in the mother and thus, methadone dosage may need to be increased and adjusted or decreasing dosing interval during pregnancy.

Methadone may enter into breast milk and is not recommended to be used during lactation.

Safety issues

Methadone is always confused with sound or look alike drugs such as dexmethylphenidate or methylphenidate.

Methadone has been listed in the drug classes under the Institute for Safe Medication Practices (ISMP) which may post heightened risk or harm to patient when used in error.

Contraindications

Respiratory depression in which in the absence of resuscitative equipment or in an unmonitored condition, acute bronchial asthma or hypercarbia, paralytic ileus, concurrent use of selegiline

Precautions

As with other opioid-containing analgesic regimen, methadone should be tailored to each patient's needs and based on the type of pain being managed, such as the factors of acute versus chronic, route of administration, degree of tolerance for opioids, age, weight, and other medical conditions. Also, the optimal analgesic dose varies widely among different individuals and methadone doses should be titrated to pain relief. Patients on stable maintenance doses of methadone may require higher doses in case of acute pain, for example during postoperative pain and physical trauma. It is noted that methadone is ineffective for anxiety relief.

Methadone may prolong the QT interval and increase risk of torsade de pointes. Before starting methadone treatment, patients should be informed of the potential arrhythmia risk, and assessed for history of structural heart disease, arrhythmia, syncope, or any potential drug interactions including drugs that prolong QT interval, induce hypokalemia, hypomagnesemia, or hypocalcemia, or reduce methadone clearance. ECG baseline should be obtained for all patients and evaluate the risk according to QT interval monitoring.

Methadone must be used iwth caution in patients at risk for QT prolongation, taking medications that would prolong the QT interval, electrolyte depletion inducer or history of conduction abnormalities. Normally QT interval prolongation and torsade de pointes is associated with high doses or greater 100 mg/day, however, it has also been observed with lower doses used.

Methadone may also cause severe hypotension and should be used cautiously  in case of severe volume depletion or abnormal blood pressure, cardiovascular disease or dysrhythmias.

Methadone may also cause respiratory depression and care must be taken when used in patinets with respiratory disease or pre-existing respiratory conditions such as severe obesity, asthma, COPD, sleep apnea, or CNS depression. Since the respiratory effects last longer than the analgesic effects, slow titration of methadone doses is required. Attention and care should be emphasized when initiating methadone treatment on dose titration and conversion from other opioid agonists. Incomplete cross tolerance may occur patient may not be tolerant to methadone even though tolerant to other mu opioid agonists. Abrupt cessation must be avoided as may precipitate withdrawal symptoms.

Methadone may cause CNS depression which impair physical or mental abilities and thus should be cautioned in performing tasks requiring mental alertness such as operating machinery or driving after taking methadone. Sedative drugs or ethanol may potentiate methadone effects. Use with caution in patients with depression or suicidal tendencies or history or drug abuse. Psychological and physical dependence may occur with prolonged use.

Also, patient with head injury or increased intracranial pressure must be taken extra care. Patients with acute abdominal conditions may obscure diagnosis or clinical course.. Elderly patients is more susceptible to methadone side effects such as CNS, respiratory and gastrointestinal effects and hence, lower initial dose should be used in elderly or debilitated,  or in patients with abnormal thyroid metabolism, obesity, adrenal insufficiency, prostatic hyperplasia or urethral stricture and also in impaired renal and hepatic function.

It must be noted that safety and efficacy of methadone use has not been established in children.

Methadone Adverse Reactions

Adverse effects of methadone may decrease over several weeks with prolonged administration. However, constipation and sweating may persist.

Cardiovascular: arrhythmia, bigeminal rhythms, radycardia, cardiac arrest, cardiomyopathy, 


ECG changes, edema, extrasystoles, faintness, flushing, heart failure, hypotension, palpitation, peripheral vasodilation, phlebitis, orthostatic hypotension, QT interval prolonged, shock, syncope, tachycardia, torsade de pointes, T-wave inversion, ventricular fibrillation, ventricular tachycardia

Central nervous system: Agitation, confusion, disorientation, dizziness, drowsiness, dysphoria, euphoria, hallucination, headache, insomnia, light-headedness, sedation, seizure

Dermatologic: Hemorhagic urticaria, pruritus, rash, urticaria (more common when administered intravenously but are rare side effects)

Endocrine & metabolic: Antidiuretic effect, amenorrhea, hypokalemia, hypomagnesemia, decreased libido

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

Hematologic: Thrombocytopenia which is reversible, reported in patients with chronic hepatitis

Neuromuscular & skeletal: weakness

Local (intramuscular or subcutaneous injection): Erythema, pain or swelling.

Ocular Miosis, visual disturbances

Respiratory: Pulmonary edema, respiratory depression, respiratory arrest

Miscellaneous: Death, diaphoresis, physical and psychological dependence

Reference:

Charles F. Lacy, Lora L. Armstrong, Morton P. Goldman, Leonard L.Lance. Drug Information Handbook 18^th Edition. 2009-2010.

Lexi-Comp is the official drug reference for the American Pharmacists Association.