Methadone Lopinavir

Nevirapine is a moderate inducer of CYP3A metabolism, resulting in decreased levels of amprenavir, indinavir, lopinavir, saquinavir, efavirenz, and methadone (Table 49-4). Drugs that induce the CYP3A system, such as tipranavir, rifampin, rifabutin, and St. John s wort, can decrease levels of nevirapine, whereas those that inhibit CYP3A activity, such as fluconazole, ketoconazole, and clarithromycin, can increase nevirapine levels. 

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... 

McCance-Bvatz EF, Rainey PM, Friedland G, Jatlow P (2003) The protease inhibitor lopinavir-ritonavir may produce opiate withdrawal in methadone-maintained padents. Clin hifect Dis 37 476 82. 

Methadone serum levels can be reduced by amprenavir, nelfina-vir, lopinavir/ritonavir, saquinavir/ritonavir, tipranavir/ritona-vir, and possibly ritonavir. In addition, amprenavir levels may be reduced by methadone. No interaction appears to occur between methadone and indinavir, or possibly atazanavir or saquinavir, alone. 

In a further study, methadone appeared to have no effect on the pharmacokinetics of lopinavir or ritonavir (given as a combined preparation). "... 

In a further study, methadone apparently increased ritonavir exposure by 60%, when given alone, but had no effect on ritonavir pharmacokinetics when it was given with lopinavir. "... 

Stevens RC, Rapaport S, Maroldo-CoimeUy L, Patterson JB, Bertz R. Lack of methadone dose alterations or withdrawal symptoms during therapy with lopinavir/ritonavir. J Acquir Immune Defic Syndr (2003) 33,650-1. 

Smith P, McCance-Katz E, Sarlo J, Di Francesco R, Morse GD. Methadone increases riton-av ir exposure when adm blistered alone but not lopinavir/RT V combination. Intersci ConfAn-timicrob Agents Chemother (2003) 43,339. 

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