Metformin Warfarin

A 73-year-old woman taking metformin 1000 mg bd and warfarin 5 mg/day developed epistaxis, hematuria, gingival bleeding, a retroperitoneal hematoma, and bilateral perinephric blood with obstruction of both collecting systems (152). She received fresh frozen plasma, vitamin K, 10 mg, and packed erythrocytes. In the next 8 hours she developed a metabolic acidosis... 

Interference with warfarin by metformin has been described before (SED-14,1513). 

Schier JG, Hoffman RS. Metformin acidosis due to a warfarin adverse drug event. Ann Pharmacother 2003 37 1145. 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antipyrine, atenolol, atropine, azatadine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorcycUzine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthahdone, chlorzoxazone, cimeti-dine, cisapride, clomipramine, clonazepam, cloni e, clozapine, cocaine, codeine, colchicine, cyclizine, cyclobenzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, diphenoxylate, dipyridamole, disopyramide, do-butamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvox-amine, furosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydroxychloroquine, hydro-jQTzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, levorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, metformin, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyldopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, nedoxone, na-phazoline, naproxen, nifedipine, nizatidine, norepinephrine, oxazepam, oxycodone, oxymetazoline, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procychdine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethylperazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimepra-zine, trimethoprim, trimipramine, verapamil, warfarin, lometazoline, yohimbine, zopiclone... 

Rosiglitazone has been studied in combination with acarbose, digoxin, metformin, nifedipine, ranitidine, warfarin, and oral contraceptives [67,72] There have been no clinically significant effects on the pharmacokinetics of any of these agents in combination with rosiglitazone. 

One patient taking warfarin developed haematuria with a therapeutic prothrombin time three months after starting phenformin. Another patient developed metformin-induced lactic acidosis after warfarin-induced bleeding caused renal obstruction. However, these interactions are isolated and seem unlikely to be of general importance. 

The information about a biguanide interaction with warfarin appears to be limited to these isolated reports, neither of which definitively suggest that the biguanide altered anticoagulant effects. In general no interaction would be expected between metformin or phenformin and warfarin. 

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