Tipranavir Fluconazole

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. 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

Drug interactions occur between tipranavir and fluconazole and between tipranavir and clarithromycin, increasing the AUC over a 12 hour period for tipranavir by 56 and 59%, respectively. Care should be taken when administering tipranavir with CYP450 inhibitors and inducers, because clinically significant interactions are possible. Coadministration of tipranavir with antacids decreases the tripranavir AUC by up to 33%. 

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). 

Fluconazole increased the AUC of tipranavir, and its maximum and minimum levels by 50%, 32%, and 69%, respectively, when tiprana-vir/ritonavir 500/200 mg was given twice daily. Fluconazole levels were not affeeted. ... 

The small to modest changes in protease inhibitor pharmacokinetics seen with fluconazole are unlikely to be of clinical significance. Because fluconazole causes a more significant increase in tipranavir levels, the manufacturer of tipranavir states that fluconazole, in doses of greater than... 

Tipranavir + ritonavir In a controlled, two-period study in 20 healthy volunteers who took tipranavir + ritonavir 500/ 200 mg, fluconazole 100 mg increased the AUC of tipranavir by 50% [50/]. However, the authors concluded that no dosage adjustments are necessary when tipranavir + ritonavir is combined with fluconazole. 

---

See also in sourсe #XX -- [ ]

---