Jantoven - Drug Monograph

Introduction

Jantoven (warfarin sodium) is an oral anticoagulant medication belonging to the class of vitamin K antagonists. It is the most widely prescribed anticoagulant in the United States for long-term prevention and treatment of thromboembolic disorders. As a narrow therapeutic index medication, Jantoven requires careful dosing and monitoring to balance efficacy with safety.

Mechanism of Action

Jantoven exerts its anticoagulant effect by interfering with the vitamin K-dependent synthesis of biologically active forms of clotting factors II, VII, IX, and X. It inhibits vitamin K epoxide reductase, preventing the reduction of vitamin K epoxide to its active hydroquinone form. This results in the production of partially carboxylated and decarboxylated proteins with reduced coagulant activity. The anticoagulant effect is delayed until functional clotting factors are depleted, typically requiring 36-72 hours for full therapeutic effect.

Indications

FDA-approved indications include:

• Prophylaxis and treatment of venous thrombosis and pulmonary embolism
• Prevention and treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement
• Reduction of risk of death, recurrent myocardial infarction, and thromboembolic events after myocardial infarction

Off-label uses may include:

• Prevention of stroke in patients with antiphospholipid syndrome
• Secondary prevention in patients with peripheral arterial disease

Dosage and Administration

• Elderly: May require lower doses due to increased sensitivity
• Renal impairment: No dosage adjustment typically needed
• Hepatic impairment: Use with caution; may require dose reduction
• Pediatric: Dosing based on body weight and monitoring requirements

Pharmacokinetics

Contraindications

• Hemorrhagic tendencies or blood dyscrasias
• Recent or planned surgery of central nervous system, eye, or traumatic surgery
• Bleeding diathesis
• Uncontrolled hypertension
• Pregnancy (except when benefit outweighs risk in mechanical heart valves)
• Hypersensitivity to warfarin or any component
• Major regional or lumbar block anesthesia
• Threatened abortion, eclampsia, or preeclampsia

Warnings and Precautions

• Risk of tissue necrosis (typically occurs within first few days of therapy)
• Increased risk in elderly patients
• Potential for acute kidney injury in patients with impaired renal function
• Cholesterol microembolization syndrome ("purple toes syndrome")
• Hepatic disease may potentiate response
• Diarrhea, fever, or poor nutritional status may increase sensitivity

Drug Interactions

• Antiplatelets (aspirin, clopidogrel): Increased bleeding risk
• NSAIDs: Increased bleeding risk
• SSRIs/SNRIs: Increased bleeding risk
• Antibiotics (particularly fluoroquinolones, macrolides, sulfonamides): Increased INR
• Antifungals (fluconazole, voriconazole): Increased INR
• Amiodarone: Potentiates warfarin effect
• Cholestyramine: Decreased warfarin absorption
• Vitamin K: Decreased warfarin effect
• CYP2C9 inducers (rifampin, carbamazepine): Decreased warfarin effect

Adverse Effects

• Bleeding (ecchymosis, epistaxis, gingival bleeding)
• Gastrointestinal disturbances
• Elevated liver enzymes

• Major hemorrhage (GI, intracranial, retroperitoneal)
• Skin necrosis and gangrene
• Purple toes syndrome
• Hypersensitivity reactions
• Tracheobronchial calcification with long-term use
• Systemic atheroemboli and cholesterol microembolization

Monitoring Parameters

• INR: Target range typically 2.0-3.0 for most indications; 2.5-3.5 for mechanical mitral valves
• Complete blood count with platelets
• Stool occult blood testing periodically
• Liver function tests regularly

• Signs and symptoms of bleeding
• Dietary vitamin K intake consistency
• Medication adherence and new prescriptions
• Renal function in patients with comorbidities

Patient Education

• Take medication at the same time each day
• Do not change brands without consulting healthcare provider
• Maintain consistent vitamin K intake in diet
• Recognize signs of bleeding (unusual bruising, blood in urine/stool, bleeding gums)
• Carry medical identification indicating anticoagulant use
• Inform all healthcare providers about warfarin therapy
• Avoid activities with high risk of trauma or bleeding
• Report any new medications, including over-the-counter products and supplements
• Attend all scheduled blood test appointments
• Avoid alcohol consumption
• Report planned surgical procedures or dental work

References

1. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-e88S.

2. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e152S-e184S.

3. Jantoven [package insert]. Minneapolis, MN: Upsher-Smith Laboratories, LLC; 2021.

4. Nutescu EA, Shapiro NL, Chevalier A. Warfarin and its interactions with foods, herbs, and other dietary supplements. Expert Opin Drug Saf. 2006;5(3):433-451.

5. Witt DM, Clark NP, Kaatz S, et al. Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):187-205.

6. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. J Am Coll Cardiol. 2019;74(1):104-132.