APTIVUS

In order to achieve effective tipranavir plasma concentrations and a twice-daily dosing regimen, co-administration of APTIVUS with ritonavir is essential [see Dosage and Administration (2) ]. Ritonavir inhibits hepatic cytochrome P450 3A (CYP3A), the intestinal P-gp efflux pump and possibly intestinal CYP3A. In a dose-ranging evaluation in 113 HIV-1 negative male and female volunteers, there was a 29-fold increase in the geometric mean morning steady-state trough plasma concentrations of tipran...

14.1 Clinical Trials in Adults The following clinical data is derived from analyses of 48-week data from studies measuring effects on plasma HIV-1 RNA levels and CD4+ cell counts. At present there are no results from controlled studies evaluating the effect of APTIVUS/ritonavir on clinical progression of HIV-1. APTIVUS/ritonavir 500 mg/200 mg BID + optimized background regimen (OBR) vs. Comparator Protease Inhibitor/ritonavir BID + OBR The two clinical trials 1182.12 and 1182.48 (RESIST 1 and RESIST 2) are ongoing, randomized, controlled, open-label, multicenter studies in HIV-1 positive, trip...

The following adverse reactions are described, in greater detail, in other sections: Hepatic Impairment and Toxicity [see Warnings and Precautions (5.2) ] Intracranial Hemorrhage [see Warnings and Precautions (5.3) ] Rash [see Warnings and Precautions (5.6) ] Due to the need for co-administration of APTIVUS with ritonavir, please refer to ritonavir prescribing information for ritonavir-associated adverse reactions. Because clinical trials are conducted under widely varying conditions, adverse...

APTIVUS is contraindicated in patients with moderate or severe (Child-Pugh Class B or C, respectively) hepatic impairment [see Warnings and Precautions (5.2) ]. APTIVUS/ritonavir is contraindicated when co-administered with drugs that are highly dependent on CYP3A for clearance or are potent CYP3A inducers (see Table 1 ) [see Drug Interactions (7.2) ].

Table 1Drugs that are Contraindicated with...

Co-administration with Ritonavir: APTIVUS must be co-administered with ritonavir and food to achieve the desired antiviral effect. Failure to administer APTIVUS with ritonavir and food may result in a loss of efficacy of tipranavir. ( 5.1 ) Hepatic Impairment: Discontinue for signs and symptoms of clinical hepatitis or asymptomatic increases in ALT/AST >10 times ULN or asymptomatic increases in ALT/AST 5-10 times ULN with concomitant increases in total bilirubin. Monitor liver function tests pri...

7 DRUG INTERACTIONS Co-administration of APTIVUS can alter the concentrations of other drugs and other drugs may alter the concentration of tipranavir. The potential for drug-drug interactions must be considered prior to and during therapy. ( 4 , 5.4 , 7 ) 7.1 Potential for APTIVUS/ritonavir to Affect Other Drugs APTIVUS co-administered with ritonavir at the recommended dose is a net inhibitor of ...