Warfarin Dicloxacillin

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. 

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). 

A 41-year-old man taking warfarin 22mg/week with a prothrombin time of 20.7 seconds was given dicloxacillin 500 mg qds for 10 days (331). The prothrombin time and S- and R-warfarin concentrations fell by 17, 25, and 20% respectively after 5 days. In a retrospective review of seven other patients, the mean prothrombin time fell by 17% (range 11-26%) within 4 days of starting dicloxacillin. 

MaiUoux AT, Gidal BE, Sorkness CA. Potential interaction between warfarin and dicloxacillin. Ann Pharmacother 1996 30(12) 1402-7. 

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... 

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. 

In a controlled study in 7 patients stabilised on warfarin and without infections, dicloxacillin 500 mg four times daily for 7 days reduced the mean prothrombin time by 1.9 seconds. One patient had a 5.6 second reduction. This study was conducted because the authors had noted a case of a patient receiving warfarin who had a decrease in prothrombin time when dicloxacillin was started. Another patient stabilised on warfarin had a 17% fall in prothrombin times within 4 to 5 days of starting dicloxacillin 500 mg four times daily, with a documented 20 to 25% reduction in both S- and R-warfarin levels. In a retrospective review, 7 other patients similarly treated were also identified as having a 17% reduction in pro-... 

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. 

---