rifampicin and methadone

Rifampicin is a potent inducer of hepatic cytochrome P450 enzymes, particularly CYP3A4, and also induces P-glycoprotein. Methadone is extensively metabolised by CYP3A4, CYP2B6 and other enzymes. Induction increases methadone metabolism and reduces its plasma concentration.

Co-administration can lead to significantly reduced methadone exposure, precipitating opioid withdrawal symptoms such as anxiety, sweating, diarrhoea, and myalgia. This may compromise methadone maintenance therapy and increase the risk of relapse or illicit opioid use.

Avoid concomitant use if possible. If co-prescription is essential, consider increasing the methadone dose guided by clinical response and monitor for withdrawal symptoms. Monitor plasma methadone concentrations if available. If rifampicin is stopped, reduce the methadone dose as appropriate to prevent toxicity.

Well established by clinical studies and case reports. Rifampicin has been shown to reduce methadone plasma concentrations by 50% or more, leading to withdrawal symptoms in many patients.