Orlistat enhances warfarin effect.
OBJECTIVE
To report a case of increased international normalized ratio (INR) associated with the addition of orlistat to the drug regimen of a patient receiving warfarin therapy.


METHODS
A 66-year-old white man with a history of chronic atrial fibrillation (treated with a stable dose of warfarin), hypertension, and diet-controlled type 2 diabetes mellitus was started on orlistat for weight reduction. An increased INR was reported after the introduction of orlistat; there had been no other recent changes to medication or medical conditions. Warfarin was withheld and the dose reduced to allow INR control to be reestablished. According to the Naranjo probability scale, this reaction was probable.


CONCLUSIONS
Control of the INR within therapeutic limits is always a challenge. Dietary intake of vitamin K, intercurrent illness, concomitant medication, herbal remedies, and other factors can interfere with warfarin dosing. Orlistat use may be associated with patient alteration of diet to compensate for adverse effects or other mechanisms by which orlistat alters warfarin control, including direct effect on absorption of vitamin K.


CONCLUSIONS
The introduction of chronic dosing of orlistat may reduce the absorption of fat-soluble vitamins, including vitamin K, with the result that a lower dose of warfarin may be required. This may be due in part to change to a lower fat diet with decreased amounts of vitamin K. It may also be due to an effect on vitamin K absorption. Caution should be exercised when these 2 drugs are used concurrently.
MacWalter
Ronald S
RS
Stroke Studies Centre, Ninewells Hospital and Medical School, Dundee, Scotland. ronald.macwalter@tuht.scot.nhs.uk
Fraser
Hazel W
HW
Armstrong
Katherine M
KM
D000368:Aged; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D019934:International Normalized Ratio; D007783:Lactones / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D000077403:Orlistat; D013997:Time Factors; D014812:Vitamin K / Q000378:metabolism; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*
D019440:Anti-Obesity Agents; D000925:Anticoagulants; D007783:Lactones; D014812:Vitamin K; D014859:Warfarin; D000077403:Orlistat