A woman taking warfarin with a stable INR (mean 2.2 over previous year) developed petechiae and purpura 55 days after starting duloxetine 30mg daily, and was found to have an INR of 5. Warfarin was stopped on day 58, but INR continued to rise to greater than 19 on day 85, and she was given vitamin K. On day 94 duloxetine was stopped. Warfarin was restarted on day 110 and by day 140 INR was 2.2 with thewarfarin dose stabilised at original level (See reference number 1).
The possible interactions of warfarin or other anticoagulants with venlafaxine do not appear to have been studied, but, as of May 2000, manufacturers had on record 6 case reports of increased prothrombin times, raised INRs and bleeding (haematuria, gastrointestinal bleeding, melaena, haemarthrosis) in patients taking warfarin with venlafaxine (See reference number 2).
Just why these adverse interactions should have occurred is not understood,especially as no pharmacokinetic interaction is thought likely. Venlafaxine alone may uncommonly cause ecchymosis and mucosal bleeding and,rarely, prolonged bleeding time and haemorrhage (See reference number 3). However, given many other factors that can influence anticoagulant control, reports of possible interactions could just represent idiosyncratic cases.
No interaction is established, and general relevance of these unpublished cases is uncertain. If one subscribes to view that increased monitoring is necessary when any drug is started or stopped in a patient on warfarin or related drugs, then it would be prudent to monitor prothrombin times with venlafaxine. More study is needed.
Glueck CJ,Khalil Q, Winiarska M, Wang P. Interaction of duloxetine and warfarin causing severe elevation of international normalized ratio. JAMA (2006) 295, 1517–18.
Wyeth Laboratories. Personal communication,May 2000.
Efexor (Venlafaxine hydrochloride). Wyeth Pharmaceuticals. UK Summary of product characteristics,May 2006.