Warfarin Acetaminophen

The effects of warfarin may increase when administered with acetaminophen, NSAIDs, beta blockers, disulfiram, isoniazid, chloral hydrate, loop diuretics, aminoglycosides, cimetidine, tetracyclines, and cephalosporins. Oral contraceptives, ascorbic acid, barbiturates, diuretics, and vitamin K decrease the effects of warfarin. Because die effects of warfarin are influenced by many drugp, die patient must notify die nurse or die primary healdi care provider when taking a new drug or discontinuing... 

Other potential adverse effects include impaired absorption of fat-soluble vitamins A, D, E, and K hypernatremia and hyperchloremia GI obstruction and reduced bioavailability of acidic drugs such as warfarin, nicotinic acid, thyroxine, acetaminophen, hydrocortisone, hydrochlorothiazide, loperamide, and possibly iron. Drug interactions may be avoided by alternating administration times with an interval of 6 hours or greater between the BAR and other drugs. 

A2 Acetaminophen, antipyrine, caffeine, clomipramine, phenacetin, tacrine, tamoxifen, theophylline, warfarin Smoking, charcoal-broiled foods, cruciferous vegetables, omeprazole Galangin, furafylline, fluvoxamine... 

A2 Phenacetin, theophylline, acetaminophen, warfarin, caffeine, cimetidine Aromatic amines, arylhydrocarbons, NNK,3 aflatoxin, estradiol Caffeine, [acetanilide, methoxyresorufin, ethoxyresorufin]... 

Carbamazepine can decrease piasma ieveis of acetaminophen, ciozapine, benzodiazepines, dicumaroi, doxycyciine, theophyiiine, warfarin, and haioperidoi as weii as other anticonvuisants such as phensuximide, methsuximide, ethosuximide, phenytoin, tiagabine, topiramate, iamotrigine, and vaiproate... 

It is instructive to examine which drugs are substrates for various isoforms of CYP enzymes. Table 11.2 lists some of the substrates for different CYP isoforms (10, 11). There are several examples of a single compound that is metabolized by multiple CYP enzymes (acetaminophen, diazepam, caffeine, halothane, warfarin, testosterone, zidovudine), and CYP enzymes that metabolize bioactive endogenous molecules (prostaglandins, steroids) as well as drugs. 

A4 34.1 Acetaminophen, caffeine carbamazepine, codeine, cortisol, erythromycin, cyclophosphamide, (S)-and (R)-warfarin, phenytoin, testosterone, halothane, zidovudine... 

In a prospective, case-control study, designed to determine causes of INRs over 6.0 in an outpatient anticoagulant unit, there was a clear dose-dependent association between the use of paracetamol (acetaminophen) and having an INR greater than 6.0 (212). The authors studied 93 patients with INRs over 6.0 (cases) and 196 patients with INRs of 1.7-3.3 (controls) during warfarin therapy. The likelihood of an INR greater than 6.0 increased from an odds ratio of 3.5 for doses of 2275 549 mg per week, to 6.9 for doses of 4550-9099 mg per week, to a 10-fold increase at a dose of over 9100 mg per week. 

Hylek EM, Heiman H, Skates SJ, Sheehan M A, Singer DE. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA 1998 279(9) 657-62. 

Bell WR. Acetaminophen and warfarin undesirable synergy. JAMA 1998 279(9) 702-3. 

Riser J, Gilroy C, Hudson P, McCay L, Willis TA. Acetaminophen and risk factors for excess anticoagulation with warfarin. JAMA 1998 280(8) 696. 

Kwan D, Bartle WR, Walker SE. The effects of acetaminophen on pharmacokinetics and pharmacodynamics of warfarin. J Clin Pharmacol 1999 39(l) 68-75. 

A 46-year-old woman is prescribed doxycycline for a diagnosis of community-acquired pneumonia. Her PMH is significant for iron-deficiency anemia, peptic ulcer disease, HTN, a recent DVT, and headaches. Her current medications include ferrous sulfate, ibuprofen, enalapril, acetaminophen, famotidine, and warfarin. Which of her following medications is most likely to result in decreased levels of doxycycline ... 

Clinically important, potentially hazardous interactions with acetaminophen, antibitoics, lovastatin, oral contraceptives, warfarin... 

CYP1A2 Acetaminophen Antipyrine Caffei ne Tacrine Theophylline R-Warfarin... 

Drug interactions with acetaminophen can occur for example, iso-niazid can increase the risk of hepatotoxicity. Chronic ingestion of maximal doses of acetaminophen may intensify the anticoagulant effect in patients taking warfarin, so that such individuals may require closer monitoring. Food decreases the maximum serum concentration of acetaminophen by approximately one-half. 

Acetaminophen, acetanilide, aminopyrine, antipyrine, aromatic amines, chlorzoxazone, clozapine, 17/3-estradiol, flutamide, imipramine,lidocaine,((S)-and (i )-mianserin, (S)- and (J )-naproxen, phenacetin, propafenone, tacrine, tamoxifen, theophylline, trimethadone, verapamil, (7 )-warfarin, zolpidem... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

Cronqvist, J. Nilsson-Ehle, I. Determination of acyclovir in human serum hy hi -performance liquid chromatography. J.Liq.Chromatogr., 1988, 11, 2593-2601 [serum non-interfering acetaminophen, allopurinol, baclofen, carbacholine, cefuroxime, chlorpropamide, cilastatin, cloxacillin, diazepam, di-cumarol, digoxin, flucloxacillm, furosemide, fusidic acid, fusidic, glipizide, heparin, hydrochlorothiazide, imipenem, insulin, isoniazid, ketoprofen, metronidazole, naproxen, perphenazine, phenytoin, prednisolone, propranolol, p3razinamide, p3ridoxine, ranitidine, rifampicin, rifampin, spironolactone, streptomycin, sulfamethoxazole, trimethoprim, warfarin]... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, 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, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

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