Severe interaction between ritonavir and acenocoumarol.
OBJECTIVE
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.


METHODS
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was progressively increased to 3 times the original dose, it was impossible to achieve the previous INR and RTV was withdrawn.


CONCLUSIONS
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.


CONCLUSIONS
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.
Llibre
Josep M
JM
Internal Medicine Department, Hospital Sant Jaume, Barcelona, Spain. jmllibre@bcgest.scs.es
Romeu
Joan
J
López
Estibaliz
E
Sirera
Guillem
G
D000074:Acenocoumarol / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004347:Drug Interactions; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000627:therapeutic use*; D020246:Venous Thrombosis / Q000097:blood / Q000150:complications / Q000188:drug therapy
D000925:Anticoagulants; D065607:Cytochrome P-450 Enzyme Inhibitors; D017320:HIV Protease Inhibitors; D003577:Cytochrome P-450 Enzyme System; D000074:Acenocoumarol; D019438:Ritonavir