General: Periodic determination of prothrombin time or other suitable coagulation test is essential. The availability of suitable laboratory facilities to monitor therapy accurately with oral anticoagulants is mandatory, both to assure adequate anticoagulation and to avoid toxicity due to overdosage. The dosage of oral anticoagulants depends on the clinical response as monitored by prothrombin time determinations (see DOSAGE AND ADMINISTRATION). Since heparin prolongs the one-stage prothrombin time, a period of at least 5 hours should elapse after the last intravenous dose and after the last subcutaneous dose of heparin before drawing blood to determine the prothrombin time when heparin and anisindione have been given together. In addition to adequate laboratory facilities, a supply of oral or parenteral phytonadione (vitamin K1) and a source of whole blood or plasma should be available when emergency treatment of acute overdosage is required (see OVERDOSAGE).
A number of factors including environmental, mental, medical, and nutritional states may affect an individual's response to anticoagulant therapy. Factors which increase sensitivity to the drug and lengthen prothrombin time include:initial hypo-prothrombinemia, increased age, poor nutritional status, vitamin K deficiency or malabsorption, congestive heart failure or vascular damage, hepatic disorders including hepatitis or obstructive jaundice, biliary fistula, febrile states, hyperthyroidism, preparatory bowel sterilization, recent surgery, and X-ray therapy.
Factors which may decrease the response to oral anticoagulants and shorten the prothrombin time include: pregnancy, diabetes mellitus, hyper-lipidemia, hypothyroidism, hypercholesterolemia, and hereditary or acquired resistance.
Laboratory Tests: The need for careful control of the degree of anticoagulation, as determined by changes in prothrombin activity, cannot be overemphasized. It should be noted, however, that bleeding during anticoagulant therapy may not always correlate with prothrombin activity.
The stool guaiac test should be used to detect occult gastrointestinal bleeding.
In long-term therapy with anticoagulants, periodic laboratory evaluation of organ systems, including hematopoietic, renal, and hepatic studies, should be performed (see WARNINGS).
Please also refer to WARNINGS and PRECAUTIONS.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term dosing studies to determine the carcinogenic potential of oral anticoagulants, including anisindione, have not been done. Information on mutagenesis is unknown.
Pregnancy: Teratogenic and other effects — Pregnancy Category X: (See CONTRAINDICATIONS.)
Labor and Delivery: Anisindione is contraindicated in pregnancy. If oral anticoagulants are used in pregnant women, they should not be administered during the first trimester, and should be discontinued prior to labor and delivery.
Some clinicians suggest the replacement of oral anticoagulants with heparin therapy before term. Heparin is withheld during early labor and reinstituted 6 hours postpartum. After 5 to 7 days, therapy with oral anticoagulants may be resumed if indicated.
See CONTRAINDICATIONS for the use of oral anticoagulants in pregnancy.
Nursing Mothers: Oral anticoagulants or their metabolites are excreted in the milk of nursing mothers, possibly in amounts sufficient to cause a prothrombopenic state and bleeding in the newborn. As a general rule, nursing should not be undertaken while a patient is receiving an oral anticoagulant.
Pediatric Use: The use of oral anticoagulants in pediatric patients is not well documented. However, they may be beneficial in pediatric patients with rare thromboembolic disorder secondary to other disease states such as the nephrotic syndrome or congenital heart lesions. Heparin is probably the initial anticoagulant of choice because of its immediate onset of action.