Warik Dosage/Direction for Use

The dosage and administration of Warfarin must be individualized for each patient according to the particular patient's PT/INR response to the drug. The dosage should be adjusted based upon the patient's PT/INR. (See Table 1.)

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The best available information supports the following recommendations for dosing of WARFARIN.
Venous Thromboembolism (including deep venous thrombosis [DVT] and pulmonary embolism [PE]): For patients with a first episode of DVT or PE secondary to a transient (reversible) risk factor, treatment with Warfarin for 3 months is recommended. For patients with a first episode of idiopathic DVT or PE, Warfarin is recommended for at least 6 to 12 months. For patients with two or more episodes of documented DVT or PE, indefinite treatment with Warfarin is suggested. For patients with a first episode of DVT or PE who have documented antiphospholipid antibodies or who have two or more thrombophilic conditions, treatment for 12 months is recommended and indefinite therapy is suggested. For patients with a first episode of DVT or PE who have documented deficiency of antithrombin, deficiency of Protein C or Protein S, or the Factor V Leiden or prothrombin 20210 gene mutation, homocystinemia, or high factor VIII levels (>90^th percentile of normal), treatment for 6 to 12 months is recommended and indefinite therapy is suggested for idiopathic thrombosis. The risk-benefit should be reassessed periodically in patients who receive indefinite anticoagulant treatment. The dose of Warfarin should be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations.
Atrial Fibrillation: Oral anticoagulation therapy with Warfarin is recommended in patients with persistent or paroxysmal AF (PAF) (intermittent AF) at high risk of stroke (i.e., having any of the following features: prior ischemic stroke, transient ischemic attack, or systemic embolism, age >75 years, moderately or severely impaired left ventricular systolic function and/or congestive heart failure, history of hypertension, or diabetes mellitus). In patients with persistent AF or PAF, age 65 to 75 years, in the absence of other risk factors, but who are at intermediate risk of stroke, antithrombotic therapy with either oral Warfarin or aspirin, 325 mg/day, is recommended. For patients with AF and prosthetic heart valves, anticoagulation with oral Warfarin should be used; the target INR may be increased and aspirin added depending on valve type and position, and on patient factors.
Post-Myocardial Infarction: In most healthcare settings, moderate- and low-risk patients with a myocardial infarction should be treated with aspirin alone over oral vitamin-K antagonist (VKA) therapy plus aspirin. In healthcare settings in which meticulous INR monitoring is standard and routinely accessible, for both high- and low-risk patients after myocardial infarction (MI), long-term (up to 4 years) high-intensity oral Warfarin (target INR, 3.5; range, 3.0 to 4.0) without concomitant aspirin or moderate-intensity oral Warfarin (target INR, 2.5; range, 2.0 to 3.0) with aspirin is recommended. For high-risk patients with MI, including those with a large anterior MI, those with significant heart failure, those with intracardiac thrombus visible on echocardiography, and those with a history of a thromboembolic event, therapy with combined moderate-intensity (INR, 2.0 to 3.0) oral Warfarin plus low-dose aspirin (≤100 mg/day) for 3 months after the MI is suggested.
Mechanical or Bioprosthetic Heart Valves: For all patients with mechanical prosthetic heart valves, Warfarin is recommended. For patients with a St. Jude Medical (St. Paul, MN) bileaflet valve in the aortic position, a target INR of 2.5 (range, 2.0 to 3.0) is recommended. For patients with tilting disk valves and bileaflet mechanical valves in the mitral position, a target INR of 3.0 (range, 2.5 to 3.5) is recommended. For patients with caged ball or caged disk valves, a target INR of 3.0 (range, 2.5 to 3.5) in combination with aspirin, 75 to 100 mg/day is recommended. For patients with bioprosthetic valves, Warfarin therapy with a target INR of 2.5 (range, 2.0 to 3.0) is recommended for valves in the mitral position and is suggested for valves in the aortic position for the first 3 months after valve insertion.
Recurrent Systemic Embolism and Other Indications: Patients with valvular disease associated with atrial fibrillation, patients with mitral stenosis, and patients with recurrent systemic embolism of unknown etiology. A moderate dose regimen (INR 2.0 to 3.0) is recommended for these patients.
An INR greater than 4.0 appears to provide no additional therapeutic benefit in most patients and is associated with a higher risk of bleeding.
Initial dosage: The dosing of Warfarin must be individualized according to patient's sensitivity to the drug as indicated by PT/INR. Use of a large loading dose may increase the incidence of hemorrhagic and other complications, does not offer more rapid protection against thrombi formation, and is not recommended. It is recommended that Warfarin therapy be initiated with a dose of 2 to 5 mg per day with dosage adjustments based on the results of PT/INR determinations. The lower initiation doses should be considered for patients with certain genetic variations in CYP2C9 and VKORC1 enzymes as well as for elderly and/or debilitated patients and patients with potential to exhibit greater than expected PT/INR response to Warfarin.
Maintenance: Most patients are satisfactorily maintained at a dose of 2 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 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.
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.
Missed dose: The anticoagulant effect of Warfarin persists beyond 24 hours. If the patient forgets to take the prescribed dose of Warfarin 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.
Laboratory Control: The PT should be determined daily after the administration of the initial dose until PT/INR results stabilize in the therapeutic range. Intervals between subsequent PT/INR determinations should be based upon the physician's judgment of the patient's reliability and response to Warfarin in order to maintain the individual within the therapeutic range. Acceptable intervals for PT/INR determinations are normally within the range of 1 to 4 weeks after a stable dosage has been determined. To ensure adequate control, it is recommended additional PT tests be done when other Warfarin products are interchanged with Warfarin sodium tablets, USP, as well as whenever other medications are initiated, discontinued, or taken irregularly. Safety and efficacy of Warfarin therapy can be improved by increasing the quality of laboratory control. Reports suggest that in usual care monitoring, patients are in therapeutic range only 33%-64% of the time. Time in therapeutic range is significantly greater (56%-93%) in patients managed by anticoagulation clinics, among self-testing and self-monitoring patients, and in patients managed with the help of computer programs. Self-testing patients had fewer bleeding events than patients in usual care.
Treatment with 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 procedures. In patients undergoing minimal invasive procedures who must be anticoagulated prior to, during, or immediately following these procedures, adjusting the dosage of Warfarin 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 Warfarin therapy. When discontinuing Warfarin even for a short period of time, the benefits and risks should be strongly considered.
Conversion from Heparin Therapy: Since the anticoagulant effect of Warfarin is delayed, heparin is preferred initially for rapid anticoagulation. Conversion to Warfarin 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 Warfarin therapy be overlapped with heparin for 4 to 5 days, until Warfarin has produced the desired therapeutic response as determined by PT/INR. When Warfarin has produced the desired PT/INR or prothrombin activity, heparin may be discontinued.
Doses of Warfarin sodium should be given at the same time each day. Theoretically, sudden discontinuation of Warfarin may result in rebound hypercoagulability with risk of thrombosis. Therefore, some clinician's tail off long-term treatment over several weeks but the need for this is unclear.