ATHROMBIN-K
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ATHROMBIN-K (ATHROMBIN-K).
Antithrombin III (AT III) activation and factor Xa inhibition via heparin cofactor II binding.
| Metabolism | Hepatic desulfation via endothelial sulfatases; renal excretion of desulfated metabolites. |
| Excretion | Primarily renal (urinary) as unchanged drug and metabolites, accounting for ~60-70% of elimination; biliary/fecal excretion accounts for ~20-30%. |
| Half-life | Terminal elimination half-life is approximately 4-6 hours in patients with normal renal function; prolonged in renal impairment. |
| Protein binding | Approximately 80-90% bound primarily to albumin. |
| Volume of Distribution | Vd is 0.2-0.3 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Oral bioavailability is 50-70% due to first-pass metabolism. |
| Onset of Action | Oral: 1-2 hours; Intravenous: within 5-10 minutes. |
| Duration of Action | Oral: 8-12 hours; Intravenous: 4-6 hours; clinical effect correlates with plasma concentration. |
2.5-5 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 50%; GFR <30 mL/min: avoid use. |
| Liver impairment | Child-Pugh class A: standard dosing; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: avoid use. |
| Pediatric use | Not approved for pediatric use; no established dosing guidelines. |
| Geriatric use | Initiate at 2.5 mg once daily; titrate cautiously with monitoring of renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ATHROMBIN-K (ATHROMBIN-K).
| Breastfeeding | Warfarin does not pass into breast milk in clinically significant amounts. The milk-to-plasma (M/P) ratio is approximately 0.1. Breastfeeding is considered safe, but monitor infant for bruising or bleeding. No dose adjustment needed in lactating women. |
| Teratogenic Risk | ATHROMBIN-K (warfarin) is contraindicated in pregnancy due to high teratogenic risk. First trimester exposure causes warfarin embryopathy (nasal hypoplasia, stippled epiphyses) in up to 30% of cases. Second and third trimester exposure risks fetal intracranial hemorrhage, CNS abnormalities, and fetal death. Heparin is preferred anticoagulant during pregnancy. |
■ FDA Black Box Warning
Risk of bleeding including intracranial and retroperitoneal hemorrhage; do not use in patients with active major bleeding or history of heparin-induced thrombocytopenia.
| Serious Effects |
Active bleeding; history of heparin-induced thrombocytopenia; hypersensitivity to heparin or pork products.
| Precautions | Monitor platelet counts; increased bleeding risk with concurrent anticoagulants; use with caution in renal impairment. |
| Food/Dietary | Warfarin interacts with vitamin K-rich foods. Maintain consistent intake of foods high in vitamin K such as leafy green vegetables (spinach, kale, broccoli, Brussels sprouts), and avoid large fluctuations in dietary vitamin K. Cranberry products, grapefruit juice, and pomegranate may increase warfarin effect; avoid large amounts. Limit alcohol consumption. Avoid herbal supplements like St. John's Wort, ginseng, ginkgo, and coenzyme Q10, which may affect INR. |
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| Fetal Monitoring | Monitor maternal INR weekly during pregnancy if warfarin is used (rarely, for mechanical heart valves). Fetal ultrasound for anomalies after first trimester exposure. Assess fetal growth and signs of bleeding. Postnatal evaluation of neonate for any sequelae. |
| Fertility Effects | Warfarin does not directly impair fertility. However, anticoagulation may be necessary in women with thrombophilia who are attempting pregnancy; switch to heparin before conception to avoid teratogenicity. |
| Clinical Pearls | ATHROMBIN-K (warfarin) requires careful INR monitoring; target INR 2.0-3.0 for most indications. Beware of drug interactions: NSAIDs, antibiotics, antifungals, and antiplatelet agents increase bleeding risk. Initiate with 5 mg daily for most patients, adjust based on INR. Use lower doses in elderly, malnourished, or hepatic impairment. Reversal with vitamin K (1-2.5 mg PO) for supratherapeutic INR without bleeding; for serious bleeding, use prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP). |
| Patient Advice | Take warfarin exactly as prescribed at the same time each day. · Monitor for signs of bleeding: unusual bruising, nosebleeds, bleeding gums, dark stools, blood in urine, prolonged bleeding from cuts. · Avoid aspirin, ibuprofen, naproxen, and other NSAIDs unless prescribed by your doctor. · Keep all appointments for INR blood tests and dose adjustments. · Inform all healthcare providers you are taking warfarin, including dentists and surgeons. · Carry a medical ID card or bracelet stating you take warfarin. · Avoid alcohol or limit to 1-2 drinks occasionally, as alcohol can affect INR. · Do not start or stop any medications, including over-the-counter drugs and herbal supplements, without talking to your doctor. |