Contraindications Cautions and Drug Interactions

Oral anticoagulants are ordinarily contraindicated in the presence of active or past gastrointestinal ulceration; thrombocytopenia; hepatic or renal disease; malignant hypertension; recent brain, eye, or spinal cord surgery; bacterial endocarditis; chronic alcoholism; and pregnancy. These agents also should not be prescribed for individuals with physically hazardous occupations.

Minor hemorrhage caused by oral anticoagulant overdosage can be treated by discontinuing drug administration. Oral or parenteral vitamin K1 (phytona-dione) administration will return prothrombin time to normal by 24 hours. This period is required for de novo synthesis of biologically active coagulation factors. Serious hemorrhage may be stopped by administration of fresh frozen plasma or plasma concentrates containing vitamin K-dependent factors.

Dietary intake of vitamin K and prior or concomitant therapy with a large number of pharmacologically unrelated drugs can potentiate or inhibit the actions of oral anticoagulants. Laxatives and mineral oil may reduce the absorption of warfarin. The patient's pro-thrombin time and international normalized ratio (INR) should be monitored when a drug is added or removed from therapy. Selected drug interactions involving oral anticoagulants are summarized in Table 22.1.

TABLE 22.1 Drug Interactions Involving Oral Anticoagulants

Drugs That Increase Oral Anticoagulant Effects

TABLE 22.1 Drug Interactions Involving Oral Anticoagulants

Drugs That Increase Oral Anticoagulant Effects

Acetaminophen

Chloral hydrate

Fenoprofen

Lovastatin

Propranolol

Alcohol (acute intoxica-

Chlorpropamide

Fluconazole

Mefenamic acid

Quinidine, quinine

tion)

Chymotrypsin

Fluoroquinolones

Metronidazole

Ranitidine

Allopurinol

Cimetidine

Fluoxetine

Micolazole

Sulfamethoxazole-

Amiodarone

Clarithromycin

Fluvastatin

Nabumetone

trimethoprim

Anabolic and andro

Clofibrate

Gemcitabine

Nalidixic acid

Sulfinpyrazone

genic steroids

Cotrimoxazole

Gemfibrozil

Naproxen

Sulindac

Aspirin

Dextran

Glucagon

Omeprazole

Tamoxifen

Azapropazone

Diazoxide

Heparin

Oral hypoglycemics

Ticlopidine

Bromelains

Diflunisal

Ibuprofen

Pentoxifylline

Tolmetin

Cephalosporins

Disulfiram

Indomethacin

Phenylbutazone

Tolterodine

Carboplatin/Etoposide

Ethacrynic acid

Inhalation anesthetics

Phenytoin

Tricyclic antidepressants

Celecoxib

Felbamate

Isoniazid

Piroxicam

Troglitazone

Chenodiol

Fenofibrate

Levamisole/Fluorouracil

Propafenone

Vitamin E

Drugs That Decrease Oral Coagulant Effects

Alcohol (chronic abuse)

Barbiturates

Dextrothyroxine

Nafcillin

Sucralfate

Aminoglutethimide

Carbamazepine

Ginseng

Oral contraceptives

Trazodone

Antacids

Chlordiazepoxide

Griseofulvin

Penicillins (large doses)

Vitamin K (large doses)

Antihistamines

Cholestyramine

Haloperidol

Primidone

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