Drug interactions with antiretrovirals and warfarin.
BACKGROUND
Antiretroviral therapy exhibits significant potential to alter the metabolism of other medications. Warfarin is widely used for the management of clotting disorders and is prone to drug-drug interactions that can result in subtherapeutic anticoagulation or over-anticoagulation.


METHODS
The mechanism and clinical significance of drug-drug interactions between warfarin and individual antiretrovirals are discussed. Literature searches were conducted in August of 2009 using multiple databases including Medline (1950 - 2009), EMBASE (1980 - 2009), International Pharmaceutical Abstracts (1970 - 2009) and the Cochrane Database of Systematic Reviews. The following search terms were utilized: warfarin, HIV, antiretroviral, drug interaction, protease inhibitor (PI), non-nucleoside reverse-transcriptase inhibitor (NNRTI), cytochrome P450 (CYP450), CYP2C9 and individual antiretrovirals by name. The manufacturers of PIs and NNRTIs were also contacted regarding unpublished data.


RESULTS
Clinicians will gain an understanding of the antiretrovirals that are prone to alter warfarin metabolism and the implications for warfarin dose modification.


CONCLUSIONS
Metabolic interaction between warfarin and antiretrovirals is likely, particularly if NNRTIs or PIs are included in the antiretroviral regimen. Titration of warfarin dose should be conducted on the basis of close monitoring of the international normalized ratio. Empiric warfarin dose modifications should be considered for individual antiretrovirals.
Liedtke
Michelle D
MD
Department of Pharmacy, University of Oklahoma, Health Sciences Center, College of Pharmacy, 1110 N Stonewall, CPB 206, Oklahoma City, OK 73117, USA. Michelle-liedtke@ouhsc.edu
Rathbun
R Chris
RC
D000818:Animals; D044966:Anti-Retroviral Agents / Q000378:metabolism* / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D014859:Warfarin / Q000378:metabolism* / Q000627:therapeutic use*
D044966:Anti-Retroviral Agents; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System