Orlistat had no effect on pharmacodynamics or pharmacokinetics of single-dose warfarin in healthy subjects. However,orlistat reduces fat absorption, and might therefore reduce vitamin Kabsorption. There is a published report of a patient taking warfarin who developed a modest increase in INR after taking orlistat.Similar cases have been reported to regulatory authorities.
In a placebo-controlled,randomised, crossover study, 12 healthy subjects were given orlistat 120mg three times daily for 16 days, with a single 30mg dose of warfarin on day 11. The pharmacokinetics and pharmacodynamics of warfarin were not altered by orlistat, and markers of vitamin K nutritional status were not affected.(See reference number 1) However, regarding this study, manufacturers US prescribing information states that vitamin K levels did tend to decline in subjects taking orlistat.(See reference number 2) It is also noted that reports of “decreased prothrombin,increased INR and unbalanced anticoagulant treatment resulting in change of haemostatic parameters” have been reported in patients taking orlistat and anticoagulants.(See reference number 2) In addition, in 2001 Canadian regulatory authorities reported that unexpected increases in INR were noted after orlistat was given to patients taking either warfarin or acenocoumarol. These were managed by dosage adjustments of coumarin or dis-continuation of orlistat (See reference number 3).
In a published report,a 66-year-old man stabilised on warfarin for
2.5 years who started taking orlistat 120mg three times daily for weight reduction had a modest increase in his INR,from less than 3, to 4.7 within 18 days. Warfarin was withheld and he was later restabilised on approximately two-thirds of previous dose while continuing orlistat (See reference number 4).
Orlistat may reduce absorption of fat soluble vitamins including vitamin K,(See reference number 4,5) and a change to a lower fat diet associated with use of orlistat may also contribute to changes in balance between vitamin K and war
The manufacturers say that patients stabilised on anticoagulants and given orlistat should be closely monitored for changes in coagulation parameters (See reference number 2,5). Given reports of changes in INRs, and fact that changes in dietary vitamin K, are known to affect warfarin efficacy, this seems prudent in patients taking a coumarin or an indanedione.
Zhi J,Melia AT, Guerciolini R, Koss-Twardy SG, Passe SM, Rakhit A, Sadowski JA. The effect of orlistat on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. J Clin Pharmacol (1996) 36, 659–666.
Xenical (Orlistat). Roche Pharmaceuticals. US Prescribing information,January 2007.
Canadian Adverse Drug Reaction Monitoring Program. Communiqué. Orlistat (Xenical) interaction with coumarin derivatives: increased INR. Can Adverse Drug React News (2001) 11 (Jul),7.
MacWalter RS,Fraser HW, Armstrong KM. Orlistat enhances warfarin effect. Ann Pharmacother (2003) 37, 510–12.
Xenical (Orlistat). Roche Products Ltd. UK Summary of product characteristics,May 2006.