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. |
| Molecular Weight | 336.34 |
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 | Avoid; crosses placenta; risk of teratogenicity (fetal warfarin syndrome) but limited data. Use only if benefit outweighs risk for maternal thromboembolism. |
| 2nd trimester | Avoid; increased risk of fetal hemorrhage and placental abruption. Use only if necessary. |
| 3rd trimester | Avoid; high risk of fetal/neonatal hemorrhage, placental abruption, and preterm labor. Heparin preferred. |
Clinical note
Comprehensive clinical and safety monograph for DICUMAROL (DICUMAROL).
| Placental transfer | Crosses placenta; fetal levels approximately 50% of maternal levels. |
| Breastfeeding | Not detectable in breast milk due to high protein binding; considered compatible with breastfeeding. Monitor infant for bleeding. |
| Lactation Rating |
■ 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 |
HemophiliaThrombocytopeniaActive bleedingSevere hypertensionBacterial endocarditisRecent surgery with bleeding riskPregnancy (except mechanical heart valve in some guidelines)
| 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 |
| Food/Dietary | Foods high in vitamin K (e.g., kale, spinach, Brussels sprouts, broccoli, green tea, liver) can reduce the anticoagulant effect. Consistent intake is important; avoid large changes in consumption. Grapefruit juice may potentiate effect; avoid excessive intake. Cranberry juice may increase INR; avoid large amounts. |
Loading safety data…
| L2 (Probably Compatible) |
| 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. |
| 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. |
| Clinical Pearls | DICUMAROL is a vitamin K antagonist anticoagulant. Monitor INR closely, especially when initiating or discontinuing other medications. Use with caution in hepatic impairment, and avoid use in pregnancy. The effect of DICUMAROL can be reversed with vitamin K or fresh frozen plasma in cases of bleeding. |
| Patient Advice | Take exactly as prescribed; do not miss doses or take double doses. · Avoid abrupt changes in diet, especially foods high in vitamin K (e.g., leafy greens, broccoli, spinach). · Report any signs of bleeding (bruising, dark stools, blood in urine, prolonged bleeding from cuts) immediately. · Use soft toothbrush and electric razor to minimize bleeding risk. · Carry a medical alert card indicating you are taking DICUMAROL. · Inform all healthcare providers (including dentists) that you are on this medication. · Do not start or stop any other medications, including over-the-counter drugs or supplements, without consulting your doctor. · If you are of childbearing potential, discuss contraception and pregnancy planning with your doctor. |