Cobicistat versus ritonavir boosting and differences in the drug-drug interaction profiles with co-medications

J Antimicrob Chemother. 2016 Jul;71(7):1755-8. doi: 10.1093/jac/dkw032. Epub 2016 Mar 5.

Abstract

Nearly all HIV PIs and the integrase inhibitor elvitegravir require a pharmacokinetic enhancer in order to achieve therapeutic plasma concentrations at the desired dose and frequency. Whereas ritonavir has been the only available pharmacokinetic enhancer for more than a decade, cobicistat has recently emerged as an alternative boosting agent. Cobicistat and ritonavir are equally strong inhibitors of cytochrome P450 (CYP) 3A4 and consequently were shown to be equivalent pharmacokinetic enhancers for elvitegravir and for the PIs atazanavir and darunavir. Since cobicistat is a more selective CYP inhibitor than ritonavir and is devoid of enzyme-inducing properties, differences are expected in their interaction profiles with some co-medications. Drugs whose exposure might be altered by ritonavir but unaltered by cobicistat are drugs primarily metabolized by CYP1A2, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 or drugs undergoing mainly glucuronidation. Thus, co-medications should be systematically reviewed when switching the pharmacokinetic enhancer to anticipate potential dosage adjustments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacokinetics*
  • Atazanavir Sulfate / administration & dosage
  • Atazanavir Sulfate / pharmacokinetics
  • Cobicistat / administration & dosage*
  • Cobicistat / pharmacokinetics*
  • Cobicistat / pharmacology
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A Inhibitors / administration & dosage*
  • Cytochrome P-450 CYP3A Inhibitors / pharmacokinetics
  • Darunavir / administration & dosage
  • Darunavir / pharmacokinetics
  • Drug Interactions
  • Drug Therapy, Combination / adverse effects
  • HIV Infections / drug therapy
  • HIV Protease Inhibitors / administration & dosage*
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacokinetics
  • HIV-1 / drug effects
  • Humans
  • Ritonavir / administration & dosage*
  • Ritonavir / pharmacokinetics

Substances

  • Anti-HIV Agents
  • Cytochrome P-450 CYP3A Inhibitors
  • HIV Protease Inhibitors
  • Atazanavir Sulfate
  • Cytochrome P-450 CYP3A
  • Cobicistat
  • Ritonavir
  • Darunavir