Orlistat Warfarin

Orlistat reduces the absorption of fat-soluble vitamins. Daily intake of a multivitamin containing vitamins A, D, E, and K, as well as 3-carotene, is recommended. Patients should take the multivitamin 2 hours prior to or after the dose of orlistat.31 Since availability of vitamin K may decline in patients receiving orlistat therapy, close monitoring of coagulation status should occur with concomitant administration of warfarin.31 Administration of orlistat in conjunction with cyclosporine can result in decreased cyclosporine plasma levels. To avoid this interaction, cyclosporine should be taken 2 hours preceding or following the dose of orlistat. Additionally, cyclosporine levels should be monitored more frequently.31... 

Drugs that may interact with orlistat include cyclosporine, fat-soluble vitamins, pravastatin, and warfarin. 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Ketoconazole doubled the AUC of rimonabant, and other potent CYP3A4 inhibitors are also expected to raise rimonabant levels. Potent CYP3A4 inducers are expected to lower rimonabant levels. Due to a lack of information the manufacturers suggest that rimonabant should not be taken with antidepressants. Rimonabant does not appear to affect the levels of oral contraceptives, di-goxin, midazolam or warfarin, and alcohol, lorazepam, and orlistat do not appear to alter rimonabant levels. 

Orlistat had no effect on the pharmacodynamics or pharmacokinetics of single-dose warfarin in healthy subjects. However, oriistat reduces fat absorption, and might therefore reduce vitamin K absorption. There is a published report of a patient taking warfarin who developed a modest increase in INR after taking oriistat Similar cases have been reported to regulatory authorities. 

In a published report, a 66-year-old man stabilised on warfarin for 2.5 years who started taking orlistat 120 mg three times daily for weight reduction had a modest increase in his ESTR, from less than 3, to 4.7 within 18 days. Warfarin was withheld and he was later restabilised on approximately two-thirds of the previous dose while continuing the orlistat. ... 

Orlistat may reduce the absorption of fat soluble vitamins including vitamin and a change to a lower fat diet associated with the use of orlistat may also contribute to changes in the balance between vitamin K and warfarin. ... 

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,... 

Mac Walter RS, Fraser HW, Armstrong KM. Orlistat enhances warfarin effect. Ann Pharma-cother (2003) 37,510-12. 

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