Nafcillin Warfarin

A patient experienced the effects of interactions of warfarin with nafcillin and dicloxacillin (333). During co-administration of nafcillin, warfarin doses were increased to as much as 4.5 times the previous amounts needed to provide adequate anticoagulation. During co-administration of dicloxacillin, warfarin doses gradually fell, but still stabilized at a higher maintenance dose than before. 

HeUker GM, Fowler JW Jr, Self TH. Possible nafcillin-warfarin interaction. Arch Intern Med 1994 154(7) 822-4. 

Ceftriaxone (A) Clindamycin (A) Clofibrate (A) Dexamethasone (N) Diazepam (B) Diazoxide (A) Dicloxacillin (N) Digitoxin (N) Etoposide (N) Ibuprofen (A) Indomethacin (A) Nafcillin (A) Naproxen (A) Oxacillin (A) Phenylbutazone (A) Phenytoin (A) Probenecid (A) Salicylic acid (A) Sulfisoxazole (A) Teniposide (N) Thiopental (A) Tolbutamide (A) Valproic acid (A) Warfarin (A)... 

In contrast, some penicillinase-resistant penicillins (dicloxacillin, nafcillin) provoke resistance to warfarin, lasting for up to 3 weeks after withdrawal of the antibiotic (331,332). 

Taylor AT, Pritchard DC, Goldstein AO, Fletcher JL Jr. Continuation of warfarin-nafcillin interaction during dicloxaciUin therapy. J Fam Pract 1994 39(2) 182-5. 

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... 

Noninterfering acetaminophen, N-acetylprocainamide, amikacin, amitriptyline, amlodi-pine, carbamazepine, cefotaxime, ceftazidime, chloramphenicol, ciprofloxacin, cisapride, clindamycin, clonidine, codeine, cyclosporine, digoxin, diphenhydramine, disopyramide, ethosuximide, fluconazole, gentamicin, gentamicin, heparin, labetalol, levothyroxine, li-docaine, lithium, methotrexate, metronidazole, minoxidil, nafcillin, nifedipine, phenobar-bital, phenobarbital, phenytoin, phenytoin, primidone, procainamide, propranolol, quini-dine, ranitidine, salicylic acid, theophylline, tobramycin, tobramycin, valproic acid, warfarin... 

In contrast, several cases of markedly reduced warfarin effects (warfarin resistance) have been seen with intravenous nafcillin, with a 75% reduction in warfarin half-life documented in one case. Similarly, other studies and cases suggest that dicloxacillin may cause a modest reduction in warfarin effects in many patients, and that some may experience greater reductions, with thrombosis being reported in one case. 

The prothrombin time of a 29-year-old patient stabilised on warfarin fell from a range of 20 to 25 seconds down to 16 seconds live days after intravenous nafcillin 2 g every 4 hours was started for endocarditis. Over the next 2 weeks the prothrombin time ranged between 14 and 17 seconds despite an eventual doubling of the warfarin dose, and heparin was substituted. In this patient the half-life of a single 30-mg dose of warfarin was 11 hours when nafcillin was taken, 17 hours 4 days after stopping nafcillin, and 44 hours eight months after the nafcillin was discontinued. At least 10 other cases of this warfarin resistance have been reported with high-dose nafcillin. " ... 

Not understood. The interaction between nafcillin and warfarin is possibly due to increases in the metabolism of warfarin by the liver. Dicloxacillin also possibly reduces serum warfarin levels. Other penicillins (ampicillin, benzylpenicillin, carbenicillin, methicillin, ticarcillin ) have caused increased bleeding times when given alone, principally due to platelet inhibition, which might be additive with the effects of oral anticoagulants. Broad-spectrum antibacterials may decrease the gut flora and thereby possibly decrease production of vitamin K. Other factors relating to the disease may be important, see Coumarins -i- Antibacterials p.365. 

The reduced effect of warfarin with dicloxacillin and nafcillin appears to be established. If these penicillins are used, increase monitoring of the INR and anticipate the need to increase the warfarin dose. Some patients taking nafcillin have been warfarin resistant, and needed heparin treatment. 

Qureshi GD, Reinders TP, Somori GJ, Evans HI. Warfarin resistance with nafcillin therapy. Ann Intern Med (19S4) 100, 527-9. 

Fraser GL, Miller M, Kane K. Warfarin resistance associated with nafcillin therai . AmJ Med( 9S9) 87, 237-8. 

Shovick VA, Rihn TL. Decreased hypoprothrombinemic response to warfarin secondary to the warfarin-nafcillin interaction. DICP Ann Pharmacother ( 99V) 25, 598-9. 

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