Cobicistat Versus Ritonavir: Similar Pharmacokinetic Enhancers But Some Important Differences.

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Tseng A, Hughes CA, Wu J, Seet J, Phillips EJ

Cobicistat Versus Ritonavir: Similar Pharmacokinetic Enhancers But Some Important Differences.

Ann Pharmacother. 2017 Nov;51(11):1008-1022. doi: 10.1177/1060028017717018. Epub 2017 Jun 19.

PubMed ID

28627229 [ View in PubMed

]

Abstract

OBJECTIVE: To describe properties of cobicistat and ritonavir; compare boosting data with atazanavir, darunavir, and elvitegravir; and summarize antiretroviral and comedication interaction studies, with a focus on similarities and differences between ritonavir and cobicistat. Considerations when switching from one booster to another are discussed. DATA SOURCES: A literature search of MEDLINE was performed (1985 to April 2017) using the following search terms: cobicistat, ritonavir, pharmacokinetic, drug interactions, booster, pharmacokinetic enhancer, HIV, antiretrovirals. Abstracts from conferences, article bibliographies, and product monographs were reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language studies or those conducted in humans were considered. DATA SYNTHESIS: Similar exposures of elvitegravir, darunavir, and atazanavir are achieved when combined with cobicistat or ritonavir. Cobicistat may not be as potent a CYP3A4 inhibitor as ritonavir in the presence of a concomitant inducer. Ritonavir induces CYP1A2, 2B6, 2C9, 2C19, and uridine 5'-diphospho-glucuronosyltransferase, whereas cobicistat does not. Therefore, recommendations for cobicistat with comedications that are extrapolated from studies using ritonavir may not be valid. Pharmacokinetic properties of the boosted antiretroviral can also affect interaction outcome with comedications. Problems can arise when switching patients from ritonavir to cobicistat regimens, particularly with medications that have a narrow therapeutic index such as warfarin. CONCLUSIONS: When assessing and managing potential interactions with ritonavir- or cobicistat-based regimens, clinicians need to be aware of important differences and distinctions between these agents. This is especially important for patients with multiple comorbidities and concomitant medications. Additional monitoring or medication dose adjustments may be needed when switching from one booster to another.

DrugBank Data that Cites this Article

Drugs

Ritonavir

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cobicistat	Cytochrome P450 3A5	Protein	Humans	Yes	Inhibitor	Details
Cobicistat	Cytochrome P450 3A7	Protein	Humans	Yes	Inhibitor	Details

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Cobicistat	Cytochrome P450 3A4	Protein	Humans	No	Substrate	Details
Ritonavir	Cytochrome P450 2C19	Protein	Humans	No	Inducer	Details
Ritonavir	UDP-glucuronosyltransferases (UGTs) (Protein Group)	Protein group	Humans	No	Inducer	Details

Drug Interactions

Drugs	Interaction
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Atazanavir Tenofovir disoproxil	The serum concentration of Atazanavir can be decreased when it is combined with Tenofovir disoproxil.
Atazanavir Tenofovir alafenamide	The serum concentration of Atazanavir can be decreased when it is combined with Tenofovir alafenamide.
Atazanavir Tenofovir	The serum concentration of Atazanavir can be decreased when it is combined with Tenofovir.
Elvitegravir Atazanavir	The serum concentration of Elvitegravir can be increased when it is combined with Atazanavir.