JANTOVEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for JANTOVEN (JANTOVEN).
JANTOVEN (warfarin) acts as an anticoagulant by inhibiting the synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and anticoagulant proteins C and S. It inhibits vitamin K epoxide reductase complex 1 (VKORC1), leading to depletion of reduced vitamin K and functional clotting factors.
| Metabolism | Primarily hepatic via CYP450 enzymes, mainly CYP2C9; minor pathways via CYP3A4, CYP1A2, CYP2C19, CYP2C8, CYP2C18. Warfarin is a racemic mixture: S-warfarin (more potent) is metabolized by CYP2C9; R-warfarin is metabolized by CYP1A2 and CYP3A4. |
| Excretion | Renal: 92% as inactive metabolites; fecal: <5%; biliary: minimal. |
| Half-life | 40 hours (range 20–60 hours); clinically, steady-state achieved in 5–7 days. |
| Protein binding | 99% bound primarily to albumin. |
| Volume of Distribution | 0.14 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Oral: >95% with high bioavailability. |
| Onset of Action | Oral: 24–72 hours for therapeutic INR; peak effect at 72–96 hours. |
| Duration of Action | 2–5 days after single dose; persists 4–7 days after discontinuation. |
Initial: 2-5 mg orally once daily; adjust based on INR; typical maintenance: 2-10 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment; monitor INR closely. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B/C: use with caution, reduce initial dose, monitor INR frequently. |
| Pediatric use | Initial: 0.1-0.2 mg/kg orally once daily; adjust based on INR; typical maintenance: 0.05-0.34 mg/kg/day. |
| Geriatric use | Start with lower doses (≤5 mg), monitor INR frequently due to increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for JANTOVEN (JANTOVEN).
| Breastfeeding | Warfarin is excreted into breast milk in small amounts; M/P ratio approximately 0.3. No adverse effects reported in breastfed infants with therapeutic maternal doses (up to 10 mg/day). Consider monitoring infant for bruising or bleeding, especially with high maternal doses or prolonged therapy. |
| Teratogenic Risk | Pregnancy Category X. First trimester: high risk of warfarin embryopathy (nasal hypoplasia, stippled epiphyses) in 5-30% of exposed fetuses. Second and third trimesters: risk of CNS abnormalities, microcephaly, and fetal hemorrhage; maternal anticoagulation may lead to placental abruption or fetal death. |
■ FDA Black Box Warning
Warfarin can cause major or fatal bleeding. Bleeding is more likely to occur during the starting period and with a higher dose. Risk factors include high intensity anticoagulation, age ≥65, high INR, history of bleeding, renal failure, liver disease, diabetes, malignancy, and certain genetic factors. Regular monitoring of INR should be performed. Patients should be instructed about prevention and recognition of bleeding signs.
| Serious Effects |
Hypersensitivity to warfarin or any component; hemorrhagic tendencies or blood dyscrasias; active major bleeding; recent or impending surgery of eyes, CNS, or traumatic surgery with large exposed surfaces; threatened abortion; uncontrolled hypertension; lack of patient cooperation; spinal puncture or other diagnostic/therapeutic procedures with potential for uncontrollable bleeding; pregnancy (use of warfarin is contraindicated except in pregnant women with mechanical heart valves due to risk of embryopathy and fetal hemorrhage).
| Precautions | Hemorrhage risk; tissue necrosis/gangrene (patients with protein C or S deficiency); systemic atheroemboli/cholesterol microemboli; heparin-induced thrombocytopenia (use with caution); use with caution in patients with renal failure, liver disease, malignancy, elderly, and those with genetic variations (CYP2C9 and VKORC1); prosthetic heart valves (pregnancy category X). |
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| Fetal Monitoring | Maternal: International Normalized Ratio (INR) monitoring at least weekly, more frequently in first trimester or with dose changes. Fetal: serial ultrasound for growth, anatomy (especially nasal bone and epiphyses in first trimester), and signs of hemorrhage. Consider fetal echocardiography for CNS assessment. |
| Fertility Effects | No known direct effects on fertility. Warfarin does not impair spermatogenesis or oogenesis. However, underlying conditions requiring anticoagulation (e.g., antiphospholipid syndrome) may be associated with infertility. |