Induction effects of ritonavir: implications for drug interactions.

Article Details

Citation

Foisy MM, Yakiwchuk EM, Hughes CA

Induction effects of ritonavir: implications for drug interactions.

Ann Pharmacother. 2008 Jul;42(7):1048-59. doi: 10.1345/aph.1K615. Epub 2008 Jun 24.

PubMed ID
18577765 [ View in PubMed
]
Abstract

OBJECTIVE: To review the literature on the induction effects of ritonavir on the cytochrome P450 enzyme system and glucuronyl transferase and identify resultant established and potential drug interactions. DATA SOURCES: Primary literature was identified from MEDLINE (1950-April 2008), EMBASE (1988-April 2008) and International Pharmaceutical Abstracts (1970-April 2008) using the search terms ritonavir, cytochrome P450 enzyme system, enzyme induction, glucuronyl transferase, and drug interactions. Additionally, relevant conference abstracts and references of relevant articles were reviewed. STUDY SELECTION AND DATA ABSTRACTION: All English-language articles and abstracts identified were reviewed. DATA SYNTHESIS: Ritonavir is a well-known inhibitor of the metabolism of numerous medications that are substrates of the CYP3A and CYP2D6 pathways. It also exhibits a biphasic, time-dependent effect on P-glycoprotein of inhibition followed by induction. Numerous pharmacokinetic studies suggested that ritonavir induces cytochrome P450 enzymes 3A, 1A2, 2B6, 2C9, and 2C19, as well as glucuronyl transferase. Additionally, several case reports described clinically significant subtherapeutic effects of drugs metabolized by these isoenzymes when coadministered with ritonavir. Both therapeutic and boosting doses of ritonavir appear to induce these enzymes; however, most of the studies of low-dose ritonavir involved a second protease inhibitor such as lopinavir, darunavir, or tipranavir. It is, therefore, difficult to distinguish the relative effects of additional medications unless well-designed, 3-way studies are conducted. CONCLUSIONS: At both therapeutic and boosting doses, ritonavir exhibits a clinically relevant induction effect on numerous drug-metabolizing enzymes. A decrease or loss of therapeutic effect may be observed when ritonavir is coadministered with medications that are substrates for these enzymes. It is important for clinicians to be aware of drugs potentially impacted by ritonavir therapy to identify and manage these interactions.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
RitonavirCytochrome P450 2C9ProteinHumans
Unknown
Inducer
Details
Drug Interactions
DrugsInteraction
Canagliflozin
Rifampicin
The serum concentration of Canagliflozin can be decreased when it is combined with Rifampicin.
Lamotrigine
Atazanavir
The serum concentration of Lamotrigine can be decreased when it is combined with Atazanavir.
Voriconazole
Ritonavir
The serum concentration of Voriconazole can be decreased when it is combined with Ritonavir.
Interactions
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