|
ipranavir plasma concentrations. Co-administration of APTIVUS/ritonavir and drugs that inhibit P-gp may increase tipranavir plasma concentrations. Co-administration of APTIVUS/ritonavir with drugs that inhibit CYP 3A may not further increase tipranavir plasma concentrations, because the level of metabolites is low following steady-state administration of APTIVUS/ritonavir 500/200 mg twice daily.
Clinically significant drug-drug interactions of APTIVUS co-administered with ritonavir are summarized in Table 4 below.
Table 4 Established and Other Potentially Significant Drug Interactions: Alterations in Dose or Regimen May be Recommended Based on Drug Interaction Studies or Predicted Interaction
Concomitant Drug Class:
Drug name |
Effect on Concentration of Tipranavir or
Concomitant Drug |
Clinical Comment |
|
↑ increase, ↓ decrease, ↔ no change, ↕ unable to predict |
HIV-1 Antiviral Agents |
Fusion Inhibitors:
|
|
|
Enfuvirtide |
↑ Tipranavir |
At steady state, tipranavir trough concentrations were approximately 45% higher in patients co-administered enfuvirtide in the Phase 3 trials. The mechanism for this increase is not known. Dose adjustments are not recommended. |
Nucleoside Reverse Transcriptase Inhibitors:
|
|
|
Abacavir |
↓ Abacavir AUC by approximately 40% |
Clinical relevance of reduction in abacavir levels not established. Dose adjustment of abacavir cannot be recommended at this time. |
|
|
|
Didanosine (EC) |
↓ Didanosine |
Clinical relevance of reduction in didanosine levels not established. For optimal absorption, didanosine should be separated from APTIVUS/ritonavir dosing by at least 2 hours. |
|
|
|
Zidovudine |
↓ Zidovudine AUC by approximately 35%. ZDV glucuronide concentrations were unaltered. |
Clinical relevance of reduction in zidovudine levels not established. Dose adjustment of zidovudine cannot be recommended at this time. |
Protease Inhibitors (co-administered with 200 mg of ritonavir):
|
|
Fosamprenavir
Lopinavir
Saquinavir |
↓ Amprenavir
↓ Lopinavir
↓ Saquinavir |
Combining a protease inhibitor with APTIVUS/ritonavir is not recommended. |
Protease Inhibitors (co-administered with 100 mg of ritonavir):
|
|
|
Atazanavir |
↓ Atazanavir
↑ Tipranavir |
|
Agents for Opportunistic Infections |
|
Antifungals:
|
|
|
Fluconazole |
↑ Tipranavir, ↔ Fluconazole |
Fluconazole increases tipranavir concentrations but dose adjustments are not needed. Fluconazole doses >200 mg/day are not recommended. |
|
|
Itraconazole
|
|
