Case reports describe reduced warfarin effects in a patient givenetretinate,and in a patient given isotretinoin. Acitretin did notsignificantly alter anticoagulant effects of phenprocoumon inhealthy subjects.
Acitretin 50mg daily for 10 days slightly increased Quick test of 10 healthy subjects stabilised on phenprocoumon, from 22 to 24%, and corresponding INR value decreased from 2.91 to 2.71. However,these changes were not considered to be significant (See reference number 1).
Etretinate. A man with T-cell lymphoma who had recently been given chemotherapy (cyclophosphamide,doxorubicin, vincristine and prednisolone) was anticoagulated with warfarin after developing a pulmonary embolism. About three weeks later,he started etretinate 40mg daily and it was found necessary to increase his warfarin dosage from 7 to 10mg daily. His liver function tests were normal (See reference number 2). This patient had also recently started taking co-proxamol,, tolbutamide, and cimetidine, ’, but all of these have been reported to only rarely increase the effect of warfarin.
Isotretinoin. A 61-year-old man stabilised on warfarin 2.5mg daily for 2 to 3 years had a decrease in his INR to below 2.5 after starting oral cefpodoxime proxetil 200mg twice daily and oral isotretinoin 30mg daily for inflammatory lesions of face. He required an increase in warfarin dose to 3.75mg daily. The cefpodoxime was stopped after 10 days without a further change in warfarin requirement. However, when isotretinoin was discontinued after 40 days, INR progressively increased and warfarin dose was eventually reduced to pretreatment dose of 2.5mg daily (See reference number 3).
It has been suggested that etretinate or isotretinoin may increase rate of metabolism of warfarin (See reference number 2,3)
The clinical relevance of two case reports of a modest increase in warfarin requirements on
starting etretinate or isotretinoin is uncertain, but, until more is known, consideration could be given to monitoring INR if patients are given warfarin and these retinoids. The study with acitretin suggests that no phenprocoumon dose adjustments are expected to be needed on starting acitretin.
Hartmann D,Mosberg H, Weber W. Lack of effect of acitretin on the hypoprothrombinemicaction of phenprocoumon in healthy volunteers. Dermatologica (1989) 178, 33–6.
Ostlere LS,Langtry JAA, Jones S, Staughton RCD. Reduced therapeutic effect of warfarincaused by etretinate. Br J Dermatol (1991) 124, 505–10.
Fiallo P. Reduced therapeutic activity of warfarin during treatment with oral isotretinoin. Br J Dermatol (2004) 150,164.