Warfarin Azathioprine

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

There are several important drug-drug interactions with allopurinol. The effects of both theophylline and warfarin may be potentiated by allopurinol. Azathioprine and 6-mercaptopurine are purines whose metabolism is inhibited... 

Cholestasis Oral contraceptives, ciclosporin, tamoxifen, warfarin, azathioprine, carbimazole... 

AZATHIOPRINE ANTICOAGULANTS-WARFARIN Possible 1 anticoagulant effect Induction of metabolism of warfarin Monitor INR closely... 

Azathioprine or mercaptopurine have been sometimes involved in reduced warfarin and acenocoumarol activity, and increased warfarin dosages may be necessary (103). Similar findings were found in a patient taking maintenance phenprocoumon (SEDA-21, 382). 

Rotenberg M, Levy Y, Shoenfeld Y, Almog S, Ezra D. Effect of azathioprine on the anticoagulant activity of warfarin. Ann Pharmacother 2000 34(l) 120-2. 

Rivier G, Khamashta MA, Hughes GR. Warfarin and azathioprine a drug interaction does exist. Am J Med 1993 95(3) 342. 

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... 

Yoshikawa N, Ito H. Combined therapy with prednisolone, azathioprine, heparin-warfarin, and dipyridamole for paediatric patients with severe IgA nephropathy Is it relevant for adult patients Nephrol Dial Transplant 1999 14 1097-1099. 

ANTICOAGULANTS-ORAL AZATHIOPRINE, MERCAPTOPURINE, MITOTANE Possible i anticoagulant effect induction of metaboiism of warfarin Monitor iNR cioseiy... 

A 47-year-old woman with multiple medical problems stabilised on warfarin (and also taking azathioprine, captopril, furosemide, insulin, capto-pril, prednisone, levothyroxine, valproic acid and zolpidem) had all her teeth removed under general anaesthetic. Sixteen days later she needed a dental abscess drained and was given oral clindamycin 300 mg four times daily with ibuprofen 600 mg for any discomfort. On day 17 she needed a suture to stop some bleeding and her INR was found to be 3.5. By day 20 she had developed more severe oral bleeding, which needed emergency room treatment. Her INR was found to have risen to 13 and her haemat-ocrit decreased to 18%. She was treated successfully with a blood transfusion and vitamin K. ... 

A number of case reports describe an increase in the effects of warfarin, accompanied by bleeding in some cases, caused by an-tineoplastic regimens containing carboplatin, chlormethine, cyclophosphamide, doxorubicin, etoposide, gefitinib, gemcitabine, ifosfamide with mesna, methotrexate, procarbazine, trastuzum-ab, vincristine or vindesine. A decrease in the effects of warfarin has been seen with azathioprine, cyclophosphamide, mercaptop-urine and mitotane, a decrease in the effects of acenocoumarol has been seen with mercaptopurine, and a decrease in the effects of phenprocoumon have l n seen with azathioprine. 

A survey of 103 patients with antiphospholipid syndrome found that azathioprine appear to increase warfarin requirements. A woman who... 

Singleton JD, Conyers L. Warfarin and azathioprine an important drug intcrsciion.AmJMed... 

Walker J, Mendelson H, McClure A Smith MD. Warfarin and azathioprine clinically significant drug n Axzc. on. J Rheumatol (2002) 29,398-9. 

Havrda DE, Rathbun S, Scheid D. A case report of warfarin resistance due to azathioprine and review of the literature. Pharmacotherapy (2001) 21, 355-7. 

Class 2 (High PermeabiUty, Low Solrrbility) Azathioprine, Azithromycin, Alprazolam, Warfarin, Haloperidol, Glipizide, Griseofulvinum, Danazol, Dapsone, Diclofenac, Indometacin, Itraconzol, Carbamazepine, Carvedilol, Ketoconazole, Lansoprazol, Mebendazole, Mefloqrrine, Nalidixic acid. Nevirapine, Piroxicam, Praziquantel, Ritonavir, Rifampicinirm, Spironolactone, Tamoxifen, Terfenadine, Trimethoprim, Ibnprofen, lopanoic add, Lovastatin, Naproxen, Oxaprozin, Flubiprofen, Cisapride. ... 

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