Methadone × Rifampicin

Rifampicin strongly induces liver enzymes, including CYP3A4 and CYP2B6, which mainly clear methadone (rifampicin SmPC). Rifampicin 600 mg/day reduced the oral bioavailability of methadone from 70% to 50% (rifampicin SmPC), and in patients stable on methadone, serum levels fell markedly and withdrawal symptoms appeared (US Food and Drug Administration (FDA) methadone label). After rifampicin is stopped, the induction fades and methadone levels rise again (methadone FDA label).

Opioid withdrawal on the previous methadone dose: restlessness, lacrimation, rhinorrhoea, yawning, sweating, chills, myalgia, mydriasis, and also irritability, anxiety, back and joint pain, abdominal cramps, insomnia, nausea, vomiting, diarrhoea, and increased blood pressure, respiratory rate or heart rate. After rifampicin is stopped, if the methadone dose is not reduced, sedation and respiratory depression can follow, up to a fatal overdose.

The pair is not banned. While the patient takes rifampicin, a higher methadone dose may be needed (methadone and rifampicin SmPCs). The US Food and Drug Administration (FDA) methadone label advises, if the combination is necessary, to consider raising the methadone dose until stable effects are reached and to watch for withdrawal signs. After rifampicin is stopped, a lower methadone dose is considered and the patient is seen at frequent intervals to catch sedation and respiratory depression early (methadone FDA label). The rifampicin SmPC warns that doses of other drugs may need adjusting both when rifampicin is started and when it is stopped.