Methadone

Clinical dataTrade namesDolophine, Methadose, othersOther namesMethadone HydrochlorideAHFS/Drugs.comMonographMedlinePlusa682134License dataPregnancy
categoryAddiction
liabilityHighRoutes of
administrationBy mouth, intravenous, insufflation, sublingual, rectalDrug classOpioidATC codeLegal statusLegal statusPharmacokinetic dataBioavailabilityRectal: 76%

SC: 79%
Oral: 41–99%

IV/IM: 100% Protein binding85–90%MetabolismLiver (CYP3A4, CYP2B6 and CYP2D6-mediated)Metabolites• EDDP

• EDMP

• para-HydroxymethadoneOnset of actionRapidElimination half-life15–55 hoursDuration of actionSingle dose: 4–8 h
Prolonged use:
• Withdrawal prevention: 1–2 days
• Pain relief: 8–12 hoursExcretionUrine, faecesIdentifiersCAS NumberPubChemCIDIUPHAR/BPSDrugBankChemSpiderUNIIKEGGChEBIChEMBLCompTox Dashboard(EPA)ECHA InfoCard100.000.907Chemical and physical dataFormulaC₂₁H₂₇NOMolar mass309.453 g·mol3D model (JSmol)ChiralityRacemic mixture(verify)

Methadone, sold under the brand names Dolophine and Methadose, among others, is a potent synthetic opioid used medically to treat chronic pain and opioid use disorder. Prescribed for daily use, the medicine relieves cravings and opioid withdrawal symptoms. Withdrawal management using methadone can be accomplished in less than a month, or it may be done gradually over a longer period of time, or simply maintained for the rest of the patient's life. While a single dose has a rapid effect, maximum effect can take up to five days of use. After long-term use, in people with normal liver function, effects last 8 to 36 hours. Methadone is usually taken by mouth and rarely by injection into a muscle or vein.

Side effects are similar to those of other opioids. These frequently include dizziness, sleepiness, nausea, vomiting, and sweating. Serious risks include opioid abuse and respiratory depression. Abnormal heart rhythms may also occur due to a prolonged QT interval. The number of deaths in the United States involving methadone poisoning declined from 4,418 in 2011 to 3,300 in 2015. Risks are greater with higher doses. Methadone is made by chemical synthesis and acts on opioid receptors.

Methadone was developed in Germany in the late 1930s by Gustav Ehrhart and Max Bockmühl. It was approved for use as an analgesic in the United States in 1947, and has been used in the treatment of addiction since the 1960s. It is on the World Health Organization's List of Essential Medicines.