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Hepatitis C NS3 Protease Inhibitors and Antiretroviral Drugs

for Health Care Providers

Hepatitis C NS3 Protease Inhibitors and Antiretroviral Drugs

Boceprevir and telaprevir, 2 NS3 protease inhibitors for the treatment of hepatitis C, were recently approved by the FDA. These agents are CYP 3A4 substrates and inhibitors (as well as P-glycoprotein substrates), so they may have significant pharmacokinetic interactions with ARVs. To date, few studies have examined these potential drug-drug interactions, but 2 presentations at CROI earlier this year did provide data on select interactions.

Boceprevir1

Compared with monotherapy levels:

  • Efavirenz
    Boceprevir: AUC decreased 19%, Cmin decreased 44%
    EFV: AUC increased 20%, Cmax increased 11%
  • Ritonavir (100 mg QD)
    Boceprevir: AUC decreased 19%
  • Tenofovir
    TDF: Cmax increased 32%

Telaprevir2

Compared with monotherapy levels:

  • Efavirenz
    Telaprevir (dosed at 750 mg Q8H): AUC decreased 26%, Cmin decreased 47%
    EFV: no significant change (previous data)
    • With telaprevir 1,125 mg Q8H: telaprevir AUC decreased 18%,
      Cmin decreased 25%; EFV AUC decreased 18%, Cmin decreased 10%
  • Atazanavir/r (300/100 mg QD)
    Telaprevir: AUC decreased 20%, Cmin decreased 15%
    ATV: AUC increased 17%, Cmin increased 85%
  • Darunavir/r (600/100 mg BID)
    Telaprevir: AUC decreased 35%, Cmin decreased 32%
    DRV: AUC decreased 40%, Cmin decreased 42%
  • Fosamprenavir/r (700/100 mg BID)
    Telaprevir: AUC decreased 32%, Cmin decreased 30%
    Amprenavir: AUC decreased 47%, Cmin decreased 56%
  • Lopinavir/r (400/100 mg BID)
    Telaprevir: AUC decreased 54%, Cmin decreased 52%
    LPV: no significant changes
  • Tenofovir
    Telaprevir: no significant changes
    TDF: AUC increased 30%, Cmin increased 41%

Clinical bottom line

Unfortunately, interactions between telaprevir and many PIs and NNRTIs are expected to be clinically significant. Dosage adjustments may be possible in some cases (eg, increasing telaprevir dosage to compensate for the 3A4 induction attributable to efavirenz), but in many cases, appropriate adjustments have not been established. Some combinations should be avoided (eg, most PIs with telaprevir). Studies of boceprevir in combination with ARVs are lacking.


References

  1. Kasserra C, Hughes E, Treitel M, et al. Clinical pharmacology of BOC: metabolism, excretion and drug-drug interactions. In: Program and abstracts of the 18th Conference on Retroviruses and Opportunistic Infections; February 27-March 2, 2011; Boston. Abstract 118.
  2. van Heeswijk R, Vandevoorde A, Boogaerts G, et al. Pharmacokinetic interactions between ARV agents and the investigational HCV protease inhibitor TVR in healthy volunteers. In: Program and abstracts of the 18th Conference on Retroviruses and Opportunistic Infections; February 27-March 2, 2011; Boston. Abstract 119.