Methadone

Mechanism :

Methadone is a mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine, the most prominent of which involves the central nervous system and organs composed of smooth muscle. The principal therapeutic uses for methadone are for analgesia and for detoxification or maintenance in opioid addiction. The methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe. Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone's efficacy is unknown.

Indication :

• It is used in the treatment of opiate withdrawal. It blocks the euphoric action of heroin and other narcotics. Used for analgesia, to wane neonates of opioid dependence.

Contraindications :

Hypersensitivity to drug/class/component

Respiratory depression, acute or severe Asthma, Paralytic ileus, GI obstruction or stricture, Coma or impaired consciousness, Labor and delivery, Avoid abrupt withdrawal.

Dosing :

Adverse Effect :

Common Reactions: Light-headedness, dizziness and nausea, vomiting.

Serious Reactions: Respiratory depression, respiratory arrest, apnea, hypotension leading to shock, bradycardia cardiac arrest, cardiomyopathy, myocardial infarction, QT prolongation leading to torsades de pointes, arrhythmias, ventricular tachycardia and fibrillation, ICP increased, seizures, paralytic ileus, neonatal opioid withdrawal syndrome (long-term maternal use).

Other Reactions: Dry mouth, palpitation, tachycardia, sedation, urinary retention, pruritus urticaria, weakness.

Interaction :

Alvimopan: Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Amobarbital, Butabarbital, Butethal, Butalbital and all barbitone derivatives: Decreases the effect of methadone.
Amprenavir: The protease inhibitor, amprenavir, may decrease the effect of methadone.
Carbamazepine: May decrease the serum level of methadone. Monitor for changes in the therapeutic and adverse effects of methadone.
Cimetidine: Cimetidine, a moderate CYP3A4 inhibitor, may increase the serum concentration of methadone, a CYP3A4 substrate.
Fluvoxamine: Increases the effect and toxicity of methadone.
Fosamprenavir: The protease inhibitor, fosamprenavir, may decrease the effect of methadone.
Hydantoin Derivatives: Decreases the effect of methadone.
Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Nelfinavir: Nelfinavir decreases the effect of methadone.
Nevirapine: The antiretroviral agent decreases the effect of methadone.
Rifabutin, Rifampin: The rifamycin decreases the effect of methadone.
Rilpivirine: Dose adjustment and clinical monitoring for rilpivirine may be necessary if coadministered with methadone.
Ritonavir: The protease inhibitor, ritonavir, may decrease the effect of methadone.
Secobarbital: The barbiturate, secobarbital, decreases the effect of methadone.
St. John's Wort: St. John's Wort decreases levels/effect of methadone.
Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution .
Talbutal: The barbiturate, talbutal, decreases the effect of methadone.
Tamoxifen: Methadone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Tamsulosin: Methadone, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Methadone is initiated, discontinued, or dose changed.
Telaprevir: Telaprevir decreases exposure of methane by 30% however opioid withdrawal was not observed in patients.
Telithromycin: Telithromycin may reduce clearance of Methadone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Methadone if Telithromycin is initiated, discontinued or dose changed.
Thiopental: Thiopental may decrease the effect of Methadone by increasing Methadone metabolism. Methadone withdrawal may occur.
Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Tipranavir: Tipranavir, co-administered with Ritonavir, decreases the Methadone concentration. Monitor for symptoms of opiate withdrawal.
Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Tramadol: Methadone may decrease the effect of Tramadol by decreasing active metabolite production.
Triprolidine: The CNS depressants, Triprolidine and Methadone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of methadone by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of methadone if voriconazole is initiated, discontinued or dose changed.
Zidovudine: Methadone increases the effect and toxicity of zidovudine
Trimipramine, Vorinostat, Ziprasidone, Zuclopenthixol: Additive QTc prolongation may occur, can lead to Torsade de Pointes.

Renal Dose :

Hepatic Dose :