Table 5: Range of Expected Therapeutic Warfarin Doses Based on CYP2C9 and VKORC1 Genotypes* *
Ranges are derived from multiple published clinical studies. Other clinical factors (e.g., age, race, body weight, sex, concomitant medications and comorbidities) are generally accounted for along with genotype in the ranges expressed in the Table. VKORC1 –1639 G→A (rs9923231) variant is used in this table. Other coinherited VKORC1 variants may also be important determinants of warfarin dose. Patients with CYP2C9 *1/*3, *2/*2, *2/*3 and *3/*3 may require more prolonged time (> 2 to 4 weeks) to achieve maximum INR effect for a given dosage regimen.
VKORC1 CYP2C9
*1/*1 *1/*2 *1/*3 *2/*2 *2/*3 *3/*3
GG 5 mg to 7 mg 5 mg to 7 mg 3 mg to 4 mg 3 mg to 4 mg 3 mg to 4 mg 0.5 mg to 2 mg
AG 5 mg to 7 mg 3 mg to 4 mg 3 mg to 4 mg 3 mg to 4 mg 0.5 mg to 2 mg 0.5 mg to 2 mg
AA 3 mg to 4 mg 3 mg to 4 mg 0.5 mg to 2 mg 0.5 mg to 2 mg 0.5 mg to 2 mg 0.5 mg to 2 mg

Maintenance
Most patients are satisfactorily maintained at a dose of 2 mg to 10 mg daily. Flexibility of dosage is provided by breaking scored tablets in half. The individual dose and interval should be gauged by the patient’s prothrombin response. Acquired or inherited warfarin resistance is rare, but should be suspected if large daily doses of warfarin sodium tablets are required to maintain a patient’s PT/INR within a normal therapeutic range. Lower maintenance doses are recommended for elderly and/or debilitated patients and patients with a potential to exhibit greater than expected PT/INR response to warfarin sodium tablets (see PRECAUTIONS).

Duration of Therapy
The duration of therapy in each patient should be individualized. In general, anticoagulant therapy should be continued until the danger of thrombosis and embolism has passed.14,15,17,18,21,22

Missed Dose
The anticoagulant effect of warfarin sodium tablets persists beyond 24 hours. If the patient forgets to take the prescribed dose of warfarin sodium tablets at the scheduled time, the dose should be taken as soon as possible on the same day. The patient should not take the missed dose by doubling the daily dose to make up for missed doses, but should refer back to his or her physician.

Intravenous Route of Administration
Warfarin sodium for Injection provides an alternate administration route for patients who cannot receive oral drugs. The IV dosages would be the same as those that would be used orally if the patient could take the drug by the oral route. Warfarin sodium for Injection should be administered as a slow bolus injection over 1 to 2 minutes into a peripheral vein. It is not recommended for intramuscular administration. The vial should be reconstituted with 2.7 mL of sterile water for injection and inspected for particulate matter and discoloration immediately prior to use. Do not use if either particulate matter and/or discoloration is noted. After reconstitution, warfarin sodium for injection is chemically and physically stable for 4 hours at room temperature. It does not contain any antimicrobial preservative and, thus, care must be taken to assure the sterility of the prepared solution. The vial is not recommended for multiple use and unused solution should be discarded.

Laboratory Control
The PT reflects the depression of vitamin K-dependent Factors VII, X and II. A system of standardizing the PT in oral anticoagulant control was introduced by the World Health Organizati