DICUMAROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DICUMAROL (DICUMAROL).
Dicumarol is a vitamin K antagonist that inhibits the synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and anticoagulant proteins C and S by blocking the reduction of vitamin K epoxide to vitamin K hydroquinone in the liver.
| Metabolism | Dicumarol is extensively metabolized in the liver primarily by cytochrome P450 (CYP) enzymes, including CYP2C9. |
| Excretion | Primarily renal as inactive metabolites; minimal biliary/fecal. ~95% renal, ~5% fecal. |
| Half-life | 24–48 hours; prolonged in hepatic impairment or with CYP2C9 polymorphisms. |
| Protein binding | 99% bound to albumin. |
| Volume of Distribution | 0.1–0.3 L/kg; reflects high protein binding and limited tissue distribution. |
| Bioavailability | Oral: nearly 100%. |
| Onset of Action | Oral: 24–72 hours for therapeutic INR (2.0–3.0). |
| Duration of Action | 2–5 days after cessation; effects persist until clotting factors synthesized. |
Initial oral dose 200-300 mg once daily for 2-3 days, then maintenance 25-200 mg once daily adjusted to target INR of 2.0-3.0 for most indications. Administered orally.
| Dosage form | CAPSULE |
| Renal impairment | No specific dose adjustment recommended for GFR >10 mL/min. For GFR <10 mL/min or hemodialysis, use with caution and monitor INR; dose reduction of 50% may be considered due to potential increased sensitivity. |
| Liver impairment | Child-Pugh Class A: No adjustment. Class B: Reduce dose by 50% and monitor INR. Class C: Avoid use or use with extreme caution with 75% dose reduction and close INR monitoring. |
| Pediatric use | Safety and efficacy not established. Use not recommended in pediatric patients. |
| Geriatric use | Start at lower end of dosing range (25-100 mg initial, then 25-150 mg maintenance) due to increased sensitivity. Monitor INR closely, target lower end of therapeutic range (e.g., INR 2.0-2.5) based on bleeding risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DICUMAROL (DICUMAROL).
| Breastfeeding | Dicumarol is excreted into breast milk in small amounts. The M/P (milk-to-plasma) ratio is approximately 0.2. While the American Academy of Pediatrics considers it compatible with breastfeeding, caution is warranted due to potential for anticoagulation in the infant. Monitor infant for bruising, bleeding, and prothrombin time. |
| Teratogenic Risk | First trimester: Exposure between 6-9 weeks gestation is associated with warfarin embryopathy (fetal warfarin syndrome) including nasal hypoplasia, stippled epiphyses, and central nervous system anomalies. Second and third trimesters: Risk of spontaneous abortion, stillbirth, prematurity, and fetal hemorrhage. All trimesters: Fetal intracerebral hemorrhage is possible. Dicumarol is a vitamin K antagonist and is considered teratogenic throughout pregnancy. |
■ FDA Black Box Warning
WARNING: BLEEDING RISK. Dicumarol can cause major or fatal bleeding. Regular monitoring of INR is required. Patients should be instructed about precautions to minimize bleeding risk. Use with caution in patients at high risk of bleeding.
| Serious Effects |
["Active bleeding or hemorrhagic tendencies","Recent or contemplated surgery of the central nervous system or eye","Threatened abortion","Severe uncontrolled hypertension","Bacterial endocarditis","Inability to obtain adequate coagulation monitoring","Hypersensitivity to dicumarol or any component of the formulation","Pregnancy (especially first trimester and last month)"]
| Precautions | ["Hemorrhage: risk factors include trauma, surgery, peptic ulcer disease, severe hypertension, renal insufficiency","Necrosis: rare but serious skin necrosis and gangrene due to paradoxical thrombosis and skin infarction","Purple toe syndrome: cholesterol microembolization presenting as purple discoloration of toes","Systemic atheroemboli: due to dislodgement of atherosclerotic plaques","Pregnancy: can cause fetal harm, especially in the first trimester"] |
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| Fetal Monitoring | Maternal: Prothrombin time (PT) and International Normalized Ratio (INR) should be monitored frequently (at least weekly) to maintain therapeutic range. Fetal: Serial ultrasound to assess for fetal growth, placental abruption, and signs of hemorrhage. Avoid Dicumarol near term due to risk of fetal hemorrhage; consider switching to heparin or low-molecular-weight heparin. |
| Fertility Effects | No known direct effects on fertility. However, the underlying condition requiring anticoagulation (e.g., thromboembolic disease) may impact fertility indirectly. Dicumarol is not known to impair spermatogenesis or ovulation. |