Warfarin Disulfiram

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... 

Disulfiram inhibits several of the enzymes responsible for warfarin metabolism increased PT/INR have been noted if disulfiram is added to warfarin therapy, carefully monitor PT/INR the warfarin dose will probably have to be decreased. 

Metronidazole Nausea/vomiting Metallic taste Refrain from using alcoholic beverages potential for disulfiram-like reaction Substrate for CYP2C9 and inhibitor of CYP2C9, 3A3/4 and 3A5-7 potential interactions may include warfarin (enhanced prothrombin time) and lithium (increased concentrations)... 

Drugs that may interact with disulfiram include alcohol, benzodiazepines, caffeine, chlorzoxazone, cocaine, hydantoins, isoniazid, metronidazole, theophylline, tricyclic antidepressants, and warfarin. 

P450 system Drugs that may be affected by proton pump inhibitors include benzodiazepines, clarithromycin, cyclosporine, disulfiram, digoxin, azole antifungal agents, hydantoins, cilostazol, salicylates, sulfonylureas, and warfarin. 

Drugs that might be affected by lopinavir/ritonavir include ergot derivatives, oral contraceptives, antiarrhythmics, HMG-CoA reductase inhibitors, HIV protease inhibitors, atovaquone, calcium channel blockers, ketoconazole, itraconazole, pimozide, cisapride, clarithromycin, disulfiram, metronidazole, immunosuppressants, midazolam, triazolam, narcotic analgesics, rifabutin and rifabutin metabolite, sildenafil, warfarin, bupropion, clozapine, desipramine, piroxicam, quinidine, theophylline, and zolpidem. 

Interferes w/ DNA synth Dose Adults. Anaerobic Infxns 500 mg IV q6-8h Amebic dysentery 750 mg/d PO for 5-10 d Trichomoniasis 250 mg PO tid for 7 d or 2 g PO X 1 C. difficile 500 mg PO or IV qSh for 7-10 d (PO preferred IV only if pt NPO) Vaginosis 1 applicator-full intravag bid or 500 mg PO bid for 7 d Acne rosacea/skin Apply bid Peds. 30 mg/ kg PO/IV/d q6H, 4 g/d max-s-. Amebic dysentery 35-50 mg/kg/24 h PO in 3 -s- doses for 5-10 d Rx 7-10 d for C. difficile-, in hepatic impair Caution [B, M] Avoid EtOH Contra 1st tri of PRO Disp Tabs, caps, IV, topical lotion, intravag gel, cream SE Disulfiram-like Rxn dizziness, HA, GI upset, anorexia, urine discoloration Interactions t Effects W/ cimetidine T effects OF carbamazepine, fluorouracil, Li, warfarin -1- effects W/ barbiturates, cholestyramine, colestipol, phenytoin EMS t Effects of anticoagulants concurrent EtOH use can cause disulfiram-like Rxn (tach, N/V, sweating, flushing, headache, blurred vision, confusion) may cause a metallic taste and discolored urine OD May cause N/V/D, numbness in hands and feet, Szs, and loss of coordination symptomatic and supportive... 

Rx of pneumonia, skin, soft tissue Infxns, osteomyelitis caused by penicillinase-producing staphylococci Action Bactericidal X cell wall synth Dose Adults. 250-500 mg qid Feds <40 kg, 12.5-100 mg/kg/d - qid take on empty stomach Caution [B, ] Contra Component orPCN sensitivity Disp Caps 125, 250, 500 mg soln 62.5 mg/5 mL SE N/D, abd pain Interactions T Effects W/ disulfiram, probenecid T effects OF MRX, X effects W/ macrolides, tetracyclines, food X effects OF OCPs, warfarin EMS Monitor for signs of electrolyte disturbances and hypovolemia d/t D OD May cause N/V/D, behavior changes, urinary retention, skin rash and Szs symptomatic and supportive... 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

Correct choice = A. Rifampin induces the hepatic mixed function oxidases that metabolize warfarin. Platelet inhibitors, such as aspirin, increase the anticoagulant effect of warfarin. Phenylbutazone can transiently increase the level of free warfarin by displacing it from the plasma albumin binding site. Cimetidine inhibits warfarin metabolism and causes potentiation of the anticoagulant. Disulfiram inhibits warfarin metabolism. 

DISULFIRAM ANTICOAGULANTS -WARFARIN t anticoagulant effect Uncertain at present Monitor INR at least weekly until stable... 

O Reilly RA. Dynamic interaction between disulfiram and separated enantiomorphs of racemic warfarin. Chn Pharmacol Ther 1981 29(3) 332-6. 

Bad breath has been reported in patients taking disulfiram concurrently with warfarin (40). 

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... 

Clinically important, potentially hazardous interactions with alcohol, anisindione, anticoagulants, astemizole, dicumarol, disulfiram, fluorouracil, mycophenolate, warfarin... 

---