Apo-Warfarin

Apo-Warfarin Special Precautions

warfarin

Manufacturer:

Apotex

Distributor:

Pharmaforte
Full Prescribing Info
Special Precautions
Periodic determination of PT/INR or other suitable coagulation test is essential.
Numerous factors, alone or in combination, including travel, changes in diet, environment, physical state and medication may influence response of the patient to anticoagulants. It is generally good practice to monitor the patient's response with additional PT/INR determinations in the period immediately after discharge from the hospital, and whenever other medications are initiated, discontinued or taken irregularly. The following factors are listed for reference; however, other factors may also affect the anticoagulant response.
Drugs may interact with Apo-Warfarin through pharmacodynamic or pharmacokinetic mechanisms. Pharmacodynamic mechanisms for drug interactions with Apo-Warfarin are synergism (impaired hemostasis, reduced clotting factor synthesis), competitive antagonism (vitamin K), and altered physiological control loop for vitamin K metabolism (hereditary resistance). Pharmacokinetic mechanisms for drug interactions with Apo-Warfarin are mainly enzyme induction, enzyme inhibition and reduced plasma protein-binding. It is important to note that some drugs may interact by more than one mechanism.
The following factors, alone or in combination, may be responsible for increased PT/INR response: Endogenous Factors: Blood dyscrasias (see Contraindications); cancer; collagen vascular disease; congestive heart failure; diarrhea; elevated temperature; hepatic disorders (infectious hepatitis, jaundice); hyperthyroidism; poor nutritional state; steatorrhea; vitamin K deficiency.
Exogenous Factors: Potential drug interactions with Apo-Warfarin are listed as follows by drug class and by specific drugs.
Classes of Drugs: Adrenergic stimulants, central; Alcohol abuse reduction preparations; Analgesics; Anesthetics, inhalation; Antiarrhythmics*; Antibiotics*: Aminoglycosides (oral), Cephalosporins (parenteral), Macrolides, Miscellaneous, Penicillins (IV, high dose), Quinolones (fluoroquinolones), Sulfonamides (long-acting), Tetracyclines; Anticoagulants; Anticonvulsants*; Antidepressants*; Antimalarial Agents; Antineoplastics*; Antiparasitics/Antimicrobials; Antiplatelet drugs/effects; Antithyroid drugs*; β-adrenergic blockers; bromelains; Cholelitholytic agents; Diabetes agents, oral; Diuretics*; Fungal medications, systemic*; Gastric acidity and peptic ulcer agents*; Gastrointestinal, ulcerative colitis agents; gout treatment agents; hemorrheologic agents; hepatotoxic drugs; hyperglycemic agents; hypertensive emergency agents; hypnotics*; hypolipidemics*; monoamine oxidase inhibitors; narcotics, prolonged; nonsteroidal anti-inflammatory agents; psychostimulants; pyrazolones; salicylates; selective serotonin re-uptake inhibitors; steroids, adrenocortical*; steroids, anabolic (17-alkyl testosterone derivatives); thrombolytics; thyroid drugs; tuberculosis agents*; uricosuric agents; vaccines; vitamins*.
Specific Drugs Reported: Acetaminophen; alcohol*; allopurinol; aminosalicylic acid; amiodarone HCl; aspirin; atorvastatin; azithromycin; capecitabine; cefamandole; cefazolin; cefoperazone; cefotetan; cefoxitin; ceftriaxone; celecoxib; cerivastatin; chenodiol; chloramphenicol; chloral hydrate*; chlorpropamide; cholestyramine*; cimetidine; ciprofloxacin; cisapride; clarithromycin; clofibrate; Apo-Warfarin overdosage; cyclophosphamide*; danazol; dextran; dextrothyroxine; diazoxide; diclofenac; dicumarol; diflunisal; disulfiram; doxycycline; erythromycin; ethacrynic acid; fenofibrate; fenoprofen; fluconazole; fluorouracil; fluoxetine; flutamide; fluvastatin; fluvoxamine; gemfibrozil; glucagon; halothane; heparin; ibuprofen; ifosfamide; indomethacin; influenza virus vaccine; itraconazole; ketoprofen; ketorolac; levamisole; levofloxacin; levothyroxine; liothyronine; lovastatin; mefenamic acid; methimazole*; methyldopa; methylphenidate; methylsalicylate ointment (topical); metronidazole; miconazole; moricizine HCl*; nalidixic acid; naproxen; neomycin; norfloxacin; ofloxacin; olsalazine; omeprazole; oxaprozin; oxymetholone; paroxetine; penicillin G, IV; pentoxifylline; phenylbutazone; phenytoin*; piperacillin; piroxicam; pravastatin; prednisone*; propafenone; propoxyphene; propranolol; propylthiouracil*; quinidine; quinine; ranitidine*; rofecoxib; sertraline; simvastatin; stanozolol; streptokinase; sulfamethizole; sulfamethoxazole; sulfinpyrazone; sulfisoxazole; sulindac; tamoxifen; tetracycline; thyroid; ticarcillin; ticlopidine; tissue plasminogen activator (t-PA); tolbutamide; trimethoprim/sulfamethoxazole; urokinase; valproate; vitamin E; zafirlukast; zileuton.
Also: Other medications affecting blood elements which may modify hemostasis; dietary deficiencies; prolonged hot weather; unreliable PT/INR determinations.
The following factors, alone or in combination, may be responsible for decreased PT/INR response: Endogenous Factors: Edema; hereditary coumarin resistance; hyperlipidemia; hypothyroidism; nephrotic syndrome.
Exogenous Factors: Potential drug interactions with Apo-Warfarin (warfarin sodium) are as follows by drug class and by specific drugs.
Classes of Drugs: Adrenal cortical steroid inhibitors; antacids; antianxiety agents; antiarrhythmics*; antibiotics*; anticonvulsants*; antidepressants*; antihistamines; antineoplastics*; antipsychotic medications; antithyroid drugs*; barbiturates; diuretics*; enteral nutritional supplements; fungal medications, systemic*; gastric acidity and peptic ulcer agents*; hypnotics*; hypolipidemics*; immunosuppressives; oral contraceptives, estrogen-containing; steroids, adrenocortical*; tuberculosis agents*; vitamins*.
Specific Drugs Reported: Alcohol*; aminoglutethimide; amobarbital; atorvastain; azathioprine; butabarbital; butalbital; carbamazepine; chloral hydrate*; chlordiazepoxide; chlorthalidone; cholestyramine*; corticotropin; cortisone; Apo-Warfarin underdosage; cyclophosphamide*; dicloxacillin; ethchlorvynol; glutethimide; griseofulvin; haloperidol; meprobamate; 6-mercaptopurine; methimazole*; moricizine HCl*; nafcillin; paraldehyde; pentobarbital; phenobarbital; phenytoin*; pravastatin; prednisone*; primidone; propylthiouracil*; raloxifene; ranitidine*; rifampin; secobarbital; spironolactone; sucralfate; trazodone; vitamin C (high dose); vitamin K.
Also: Diet high in vitamin K; unreliable PT/INR determinations.
*Increased and decreased PT/INR responses have been reported.
Because a patient may be exposed to a combination of the previously mentioned factors, the net effect of Apo-Warfarin on PT/INR response may be unpredictable. More frequent PT/INR monitoring is therefore advisable. Medications of unknown interaction with coumarins are best regarded with caution. When these medications are started or stopped, more frequent PT/INR monitoring is advisable.
It has been reported that concomitant administration of warfarin and ticlopidine may be associated with cholestatic hepatitis.
Botanical (Herbal) Medicines: Caution should be exercised when botanical medicines (botanicals) are taken concomitantly with Apo-Warfarin. Few adequate, well-controlled studies exist evaluating the potential for metabolic and/or pharmacologic interactions between botanicals and Apo-Warfarin. Due to a lack of manufacturing standardization with botanical medicinal preparations, the amount of active ingredients may vary. This could further confound the ability to assess potential interactions and effects on anticoagulation. It is good practice to monitor the patient's response with additional PT/INR determinations when initiating or discontinuing botanicals.
Specific botanicals reported to affect Apo-Warfarin therapy include the following: Bromelains, danshen, dong quai (Angelica sinesis), garlic, Ginkgo biloba, and ginseng are associated most often with an INCREASE in the effects of Apo-Warfarin; Coenzyme Q10 (ubidecarenone) and St John's wort are associated most often with a DECREASE in the effects of Apo-Warfarin.
Some botanicals may cause bleeding events when taken alone (eg garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties. These effects would be expected to be additive to the anticoagulant effects of Apo-Warfarin. Conversely, other botanicals may have coagulant properties when taken alone or may decrease the effects of Apo-Warfarin.
Effect on Other Drugs: Coumarins may also affect the action of other drugs. Hypoglycaemic agents (chlorpropamide and tolbutamide) and anticonvulsants (phenytoin and phenobarbital) may accumulate in the body as a result of interference with either their metabolism or excretion.
Special Risk Patients: Apo-Warfarin is a narrow therapeutic range (index) drug, and caution should be observed when warfarin sodium is administered to certain patients eg, the elderly or debilitated or when administered in any situation or physical condition where added risk of hemorrhage is present.
IM injections of concomitant medications should be confined to the upper extremities which permits easy access for manual compression, inspections for bleeding and use of pressure bandages.
Caution should be observed when Apo-Warfarin (or warfarin) is administered concomitantly with non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, to be certain that no change in anticoagulation dosage is required. In addition to specific drug interactions that might affect PT/INR, NSAIDs, including aspirin can inhibit platelet aggregation and can cause gastrointestinal bleeding, peptic ulceration and/or perforation.
Acquired or inherited warfarin resistance should be suspected if large daily doses of Apo- Warfarin are required to maintain a patient's PT/INR within a normal therapeutic range.
Information for Patients: The objective of anticoagulant therapy is to decrease the clotting ability of the blood so that thrombosis is prevented, while avoiding spontaneous bleeding. Effective therapeutic levels with minimal complications are in part dependent upon cooperative and well-instructed patients who communicate effectively with their physician. Patients should be advised: Strict adherence to prescribed dosage schedule is necessary. Do not take or discontinue any other medication, including salicylates (eg, aspirin and topical analgesics) and other over-the-counter medications and botanical (herbal) products (eg bromelains, coenzyme Q10, danshen, dong quai, garlic, ginkgo biloba, ginseng, St John's wort) except on advice of the physician. Avoid alcohol consumption. Avoid any activity or sport that may result in traumatic injury. Prothrombin time tests and regular visits to physician or clinic are needed to monitor therapy. Carry identification stating that Apo-Warfarin is being taken. If the prescribed dose of Apo-Warfarin is forgotten, notify the physician immediately. Take the dose as soon as possible on the same day but do not take a double dose of Apo-Warfarin the next day to make up for missed doses. The amount of vitamin K in food may affect therapy with Apo-Warfarin. Eat a normal, balanced diet maintaining a consistent amount of vitamin K. Avoid drastic changes in dietary habits eg, eating large amounts of green leafy vegetables. Contact physician to report any illness eg, diarrhea, infection or fever. Notify physician immediately if any unusual bleeding or symptoms occur. Signs and symptoms of bleeding include: Pain, swelling or discomfort, prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or dark brown urine, red or tar black stools, headache, dizziness, or weakness. If therapy with Apo-Warfarin is discontinued, patients should be cautioned that the anticoagulant effects of Apo-Warfarin may persist for about 2-5 days. Patients should be advised that all warfarin products represent the same medication and should not be taken concomitantly as overdosage may result. Carcinogenicity, Mutagenicity & Impairment of Fertility: Carcinogenicity and mutagenicity studies have not been performed with Apo-Warfarin. The reproductive effects of Apo-Warfarin have not been evaluated.
Use in pregnancy: Pregnancy Category X: Do not take Apo-Warfarin during pregnancy and do not become pregnant while taking it (see Contraindications).
Use in children: Safety and effectiveness in pediatric patients <18 years have not been established in randomized, controlled clinical trials. However, the use of Apo-Warfarin in pediatric patients is well documented for the prevention and treatment of thromboembolic events. Difficulty achieving and maintaining therapeutic PT/INR ranges in the pediatric patient has been reported. More frequent PT/INR determinations are recommended because of possible changing warfarin requirements.
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