Pethidine Ritonavir

METHADONE, PETHIDINE PROTEASE INHIBITORS 1 efficacy of methadone, with risk of withdrawal, when coadministered with amprenavir, nelfinavir, ritonavir (with or without lopinavir) or saquinavir Uncertain possibly due to induction of CYP3A4 and CYP2D6 Monitor closely for opioid withdrawal, and t dose of methadone as necessary. This advice includes co-administration of methadone with low-dose ritonavir. Short-term use of pethidine is unlikely to cause a problem... 

Ritonavir decreases pethidine (meperidine) and increases norpethidine levels, which may possibly increase toxicity on long-term use. Similarly, ritonavir and other protease inhibitors increase buprenorphine levels. Ritonavir may increase the metabolism of morphine, and decrease the metabolism of dextropropoxyphene (CYP3A4 substrate) and tramadol or other CYP2D6 substrates (such as codeine). 

Ritonavir 500 mg twice daily for 10 days decreased the AUC of a single 50-mg dose of oral pethidine by 62% and increased the AUC of norpethi-dine by 47% in 8 healthy subjects. Norpethidine is pharmaeologieally aetive, and is possibly less effective an analgesic than the parent eom-pound, and more likely to cause CNS effects such as seizures. 

The manufacturers of pethidine oral preparations and injection contraindicate or advise against its use with ritonavir because of the risk of norpethidine toxicity. Long-term use of pethidine with other protease inhibitors e.g. tipranavir, which are given with low-dose ritonavir is also not recommended. ... 

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See also in sourсe #XX -- [ ]

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