Warfarin (Adverse Reactions)

Warfarin is an oral anti-vitamin K anticoagulant. It prevents the formation in the liver of active coagulation factors II, VII, IX and X by inhibiting vitamin K-dependent gamma-carboxylation of precursor proteins.

CONTRAINDICATIONS

Warfarin is contraindicated in the following cases:

Hypersensitivity.

Pregnancy.

Lack of patient cooperation.

Hemorrhagic diathesis and/or blood dyscrasia. Organic lesions susceptible to bleeding. Recent or planned surgery on the CNS, ophthalmological operations, or those exposing large tissue surfaces.

Gastroduodenal ulcer or bleeding in the gastrointestinal, urogenital, or respiratory tracts, cerebrovascular bleeding, pericarditis, pericardial effusions, subacute bacterial endocarditis.

Severe arterial hypertension, severe lesions of the hepatic and renal parenchyma. Increased fibrinolytic activity.

High doses of NSAIDs (non-steroidal anti-inflammatory drugs), miconazole (systemic and oral gel), phenylbutazone (systemic), high doses of ASA and other salicylates.

PRECAUTIONS

Precautions should be taken when prescribing warfarin in the following circumstances:

If there is a risk of bleeding, necrosis (if present, substitute with heparin), release of emboli or atheromatous plaques.

Moderate-severe renal insufficiency, moderate-severe hepatic insufficiency, moderate-severe arterial hypertension, infectious diseases or alterations of intestinal flora, catheters, deficiency in anticoagulant response mediated by protein C or its cofactor, protein S (risk of tissue necrosis); monitor INR (from English, International Normalized Ratio of Warfarin).

There is no data to support its use in children; discontinue treatment if calciphylaxis appears (higher risk in renal disease on dialysis).

SIDE EFFECTS

Hemorrhage in any organ.

DRUG INTERACTIONS

The effect of warfarin is inhibited by: enzyme inducers (aminoglutethimide, carbamazepine, phenazone, griseofulvin, phenobarbital, secobarbital, rifampicin, H. perforatum), drugs that reduce its absorption (sucralfate, ascorbic acid), vitamin K, ginseng and foods rich in vitamin K (cereals, broccoli, cabbage, carrots, poultry offal).

The effect of warfarin is potentiated by:

• Enzyme inhibitors (allopurinol, dextropropoxyphene, tramadol, amiodarone, ciprofloxacin, clarithromycin, erythromycin, norfloxacin, ofloxacin, pefloxacin, cloranfenicol, cimetidine, omeprazole, ranitidine, cisapride, disulfiram, fluvastatin, lov
• Drugs that displace it from plasma protein binding (ethacrynic acid, nalidixic acid, diclofenac, phenylbutazone, feprazone, ibuprofen, ketoprofen, mefenamic acid, sulindac, benziodarone, bicalutamide, carnitine, gemfibrozil, hydr
• Decreased vitamin K availability (levothyroxine, neomycin, cefamandole, clofibrate, stanozolol).
• Drugs that decrease the synthesis of coagulation factors (danazol, paracetamol, quinidine, quinine, vitamin E, ethanol).
• ASA, diflunisal.
• Doxycycline, tetracycline (hypoprothrombinemic).
• Clindamycin: may increase anticoagulant activity with an increase in coagulation test values (PT-prothrombin time/INR) and/or bleeding.
• Others: benzbromarone, propranolol, piracetam.

Warfarin increases prothrombin time when prescribed concomitantly with: sulfamethoxazole, flutamide.

Warfarin decreases prothrombin time with: chlorthalidone, spironolactone.

The anticoagulant effect of warfarin may be variable due to intake of: oral contraceptives, phenytoin, disopyramide, cholestyramine.

TRADE NAMES

• Coumadin ®
• Aldocumar ®
• Jantoven ®