PMID: 11918509Mar 29, 2002Paper

Severe interaction between ritonavir and acenocoumarol

The Annals of Pharmacotherapy
Josep M LlibreGuillem Sirera

Abstract

To report a clinically severe interaction between ritonavir (RTV) and acenocoumarol resulting in a decrease in the anticoagulant effect severe enough to eventually preclude RTV administration. An asymptomatic, HIV-infected, 46-year-old man with mitraortic prosthetic valves receiving acenocoumarol therapy started stavudine, lamivudine, and RTV 600 mg twice daily. His international normalized ratio (INR) decreased dramatically (the opposite of what should be expected). Although the acenocoumarol dose was progressively increased to 3 times the original dose, it was impossible to achieve the previous INR and RTV was withdrawn. RTV is an inducer of the hepatic isoenzymes CYP1A2, CYP1A4, and CYP2C9/19 and leads to extensive metabolism of acenocoumarol that cannot be balanced by dose increases. This effect is the opposite of what was expected to occur, considering that RTV is also a strong inhibitor of most hepatic isoenzymes. RTV severely decreases the anticoagulant effect of acenocoumarol. It must be added to the list of drugs that affect the action of oral anticoagulants, and it probably should be avoided in patients receiving acenocoumarol.

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Citations

Feb 24, 2011·Expert Opinion on Drug Metabolism & Toxicology·Inmaculada Jiménez-NácherVincent Soriano
May 5, 2004·Psychosomatics·Gary H WynnKelly L Cozza
Feb 27, 2015·European Journal of Clinical Investigation·Michele CorrealeDonato Lacedonia
May 10, 2016·Journal of Clinical Pharmacy and Therapeutics·A de Lorenzo-PintoM Sanjurjo-Sáez
Jun 26, 2008·The Annals of Pharmacotherapy·Michelle M FoisyChristine A Hughes
Dec 5, 2002·Pharmacoepidemiology and Drug Safety
Aug 5, 2020·The Journal of Antimicrobial Chemotherapy·Catherine HodgeSaye Khoo
Sep 13, 2020·Cardiovascular Drugs and Therapy·Shubham Agarwal, Sanjeev Kumar Agarwal

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