Abstract
Sir: Warfarin is metabolized by cytochrome P450 2C9 (CYP2C9). 1,2 Due to drug interactions, warfarin dose modification is required when it is combined with other drugs. For example, antiretroviral drugs, nevirapine and lopinavir–ritonavir, reduce the serum concentration of warfarin, 3,4 while efavirenz increases the concentration, 4 probably via CYP2C9 induction and inhibition, respectively. No clinical data are currently available for other antiretrovirals. We describe three HIV-1-infected patients in whom the use of non-boosted fosamprenavir had a favourable outcome. Case 1 was a 60-year-old Japanese man who had been treated with a stable dose of warfarin (mean daily dose, 3 mg) for chronic atrial flutter. The international normalized ratio (INR) was maintained within the optimal range (1.5–2.5). One year later, antiretroviral therapy (ART) was started with abacavir, lamivudine and non-boosted fosamprenavir (1400 mg twice daily). In this patient, dose modification of warfarin was not necessary because INR was controlled within 1.46–3.01. Case 2 was a 33-year-old Japanese man who had been treated with abacavir, lamivudine and lopinavir/ritonavir. He developed deep vein thrombosis followed by pulmonary embolism. Warfarin was given initially at 7 mg/day to maintain INR within the optimal range (2–3). After several months, the control of INR became difficult; at 9 mg of warfarin, INR was 1.38–1.75. Therefore, ART was changed to abacavir, lamivudine and fosamprenavir (1400 mg twice daily), and warfarin dose was decreased to 4.25–5.00 mg/day. The new treatment allowed maintenance of INR within the optimal range. Case 3 was a 49-year-old Japanese man who had been treated with abacavir, lamivudine and fosamprenavir (1400 mg twice daily). He underwent mitral mechanical valve replacement for mitral incompetence and heart failure. After surgery, warfarin was given initially at 2–2.5 mg/day to almost maintain INR within the optimal range (2.5–3.5); at 2.5 mg of warfarin, INR was 2.85–3.65.
Amprenavir is mainly metabolized by CYP3A4 and to a lesser extent by CYP2D6, CYP2C19 and CYP2C9. 5 Interaction between fosamprenavir and warfarin is theoretically rare. Actually in our cases, non-boosted fosamprenavir showed favourable results. Along with the long-term use of ART, cardiovascular events are increasing. When warfarin co-administration is indispensable, non-boosted fosamprenavir can be an antiretroviral agent of choice.