Tipranavir Methadone

The buffer in didanosine tablets and powder interferes with absorption of indinavir, delavirdine, atazanavir, dapsone, itraconazole, and fluoroquinolone agents therefore, administration should be separated in time. Serum levels of didanosine are increased when -administered with tenofovir or ganciclovir, and are decreased by atazanavir, delavirdine, ritonavir, tipranavir, and methadone (Table 49-4). 

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. 

Zidovudine (AZT) is an HIV reverse transcriptase inhibitor and chain terminator that is extensively glucuronidated (70% of the dose) primarily by UGT2B7. Metabolism of AZT is induced by rifampin (PXR), ritonavir, tipranavir, and efavirenz. Zidovudine clearance is inhibited by methadone (McCance-Katz, 1998) (opiates like codeine and morphine are UGT2B7 substrates), fluconazole Trapnell, 1998, atovaquone (Lee, 1996), and valproate (Lertora, 1994). Rifampin increased the formation clearance to AZT-glucuronide by twofold (Gallicano, 1999). 

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. 

The manufacturers of tipranavir state that use of methadone with tiprana-vir boosted by low-dose ritonavir (200 mg) can result in a decrease in methadone levels of about 50%, which may require dose increase in some patients. " ... 

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