Coumadin

[Warfarin Sodium Tablets, USP]

The INR can be calculated as: INR = (observed PT ratio) ISI where the ISI (International Sensitivity Index) is the cor-rection factor in the equation that relates the PT ratio of the local reagent to the reference preparation and is a meas-ure of the sensitivity of a given thromboplastin to reduction of vitamin K-dependent coagulation factors; the lower the ISI, the more "sensitive" the reagent and the closer the derived INR will be to the observed PT ratio. 1

The proceedings and recommendations of the 1992 National Conference on Antithrombotic Therapy 2-4 review and evaluate issues related to oral anticoagulant therapy and the sensitivity of thromboplastin reagents and provide additional guidelines for defining the appropriate therapeutic regimen.

The conversion of the INR to PT ratios for the less-intense (INR 2.0-3.0) and more intense (INR 2.5-3.5) therapeu-tic range recommended by the ACCP for thromboplastins over a range of ISI values is shown in Table 3. 5
TABLE 3 Relationship Between INR and PT Ratios For Thromboplastins With Different ISI Values (Sensitivities)

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TREATMENT DURING DENTISTRY AND SURGERY

The management of patients who undergo dental and surgical procedures requires close liaison between attending physicians, surgeons and dentists. PT/ INR determination is recommended just prior to any dental or surgical procedure. In patients undergoing minimal invasive procedures who must be anticoagulated prior to, during, or immediately following these procedures, adjusting the dosage of COUMADIN (Warfarin Sodium) to maintain the PT/ INR at the low end of the therapeutic range may safely allow for continued anticoagulation.

The operative site should be sufficiently limited and accessible to permit the effective use of local procedures for hemostasis. Under these conditions, dental and minor surgical procedures may be performed without undue risk of hemorrhage. Some dental or surgical procedures may necessitate the interruption of COUMADIN therapy. When discontinuing COUMADIN even for a short period of time, the benefits and risks should be strongly considered.

CONVERSION FROM HEPARIN THERAPY

Since the anticoagulant effect of COUMADIN is delayed, heparin is preferred initially for rapid anticoagulation. Conversion to COUMADIN may begin concomitantly with heparin therapy or may be delayed 3 to 6 days. To ensure continuous anticoagulation, it is advisable to continue full dose heparin therapy and that COUMADIN therapy be overlapped with heparin for 4 to 5 days, until COUMADIN has produced the desired therapeutic response as determined by PT/ INR.

When COUMADIN has produced the desired PT/ INR or prothrombin activity, heparin may be discontinued. COUMADIN may increase the aPTT test, even in the absence of heparin. During initial therapy with COUMADIN, the interference with heparin anticoagulation is of minimal clinical significance.

As heparin may affect the PT/ INR, patients receiving both heparin and COUMADIN should have blood for PT/ INR determination drawn at least:

° 5 hours after the last IV bolus dose of heparin, or
° 4 hours after cessation of a continuous IV infusion of heparin, or
° 24 hours after the last subcutaneous heparin injection.

HOW SUPPLIED

Tablets: For oral use, single scored with one face imprinted numerically with 1, 2, 2-1/ 2, 3, 4, 5, 6, 7-1/ 2 or 10
superimposed and inscribed with "COUMADIN" and with the opposite face plain. COUMADIN is available in bottles and Hospital Unit-Dose Blister Packages with potencies and colors as follows:
Hospital Unit-Dose 100's 1000's Blister Package of 100
1 mg pink NDC 0056-0169-70 NDC 0056-0169-90 NDC 0056-0169-75 2 mg lavender NDC 0056-0170-70 NDC 0056-0170-90 NDC 0056-0170-75
2-1/ 2 mg green NDC 0056-0176-70 NDC 0056-0176-90 NDC 0056-0176-75 3 mg tan NDC 0056-0188-70 NDC 0056-0188-90 NDC 0056-0188-75
4 mg blue NDC 0056-0168-70 NDC 0056-0168-90 NDC 0056-0168-75 5 mg peach NDC 0056-0172-70 NDC 0056-0172-90 NDC 0056-0172-75
6 mg teal NDC 0056-0189-70 NDC 0056-0189-90 NDC 0056-0189-75 7-1/ 2 mg yellow NDC 0056-0173-70 NDC 0056-0173-75
10 mg white NDC 0056-0174-70 NDC 0056-0174-75 (Dye Free)
Protect from light. Store at controlled room temperature (59°-86° F, 15°-30° C). Dispense in a tight, light-resistant container as defined in the USP.

Hospital Unit-Dose Blister Packages are to be stored in carton until contents have been used.

Injection:

Available for intravenous use only. Not recommended for intramuscular administration. Reconstitute with 2.7 mL of sterile Water for Injection to yield 2 mg/ mL. Net contents 5.4 mg lyophilized powder. Maximum yield 2.5 mL.
5 mg vial (box of 6) NDC 0590-0324-35
Protect from light. Keep vial in box until used. Store at controlled room temperature (59°-86° F, 15°-30° C).
After reconstitution, store at controlled room temperature (59°-86° F, 15°-30° C) and use within 4 hours. Do not refrigerate. Discard any unused solution.
REFERENCES:

1. Poller, L.: Laboratory Control of Anticoagulant Therapy. Seminars in Thrombosis and Hemostasis, Vol. 12, No. 1, pp. 13-19, 1986.

2. Hirsh, J.: Is the Dose of Warfarin Prescribed by American Physicians Un-necessarily High? Arch Int Med, Vol. 147, pp. 769-771, 1987.

3. Cook, D. J., Guyatt, H. G., Laupacis, A., Sackett, D. L.: Rules of Evidence and Clinical Recommendations on the Use of Antithrombotic Agents. Chest ACCP Consensus Conference on Antithrombotic Therapy. Chest, Vol. 102( Suppl), pp. 305S-311S, 1992.

4. Hirsh, J., Dalen, J., Deykin, D., Poller, L.: Oral Anticoagulants Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range. Chest
ACCP Consensus Conference on Antithrombotic Therapy. Chest, Vol. 102( Suppl), pp. 312S-326S, 1992. 5. Hirsh, J., M. D., F. C. C. P.: Hamilton Civic Hospitals Research Center, Hamilton, Ontario, Personal Communication.

Distributed by:
COUMADIN ® and the color and configuration of COUMADIN tablets are trademarks of Bristol-Myers Squibb Company. Any unlicensed use of these trademarks is expressly prohibited under the U. S. Trademark Act.
Copyright © Bristol-Myers Squibb Company 2002
T1-B001-07-02 6572-01/ Rev. June 2002 Printed in U. S. A.
PT RATIOS
ISI ISI ISI ISI ISI 1.0 1.4 1.8 2.3 2.8
INR= 2.0-3.0 2.0-3.0 1.6-2.2 1.5-1.8 1.4-1.6 1.3-1.5
INR= 2.5-3.5 2.5-3.5 1. 9-2.4 1.7-2.0 1.5-1.7 1.4-1.6 4

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