HEDULIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HEDULIN (HEDULIN).
HEDULIN (phenindione) is an anticoagulant that inhibits vitamin K-dependent synthesis of coagulation factors II, VII, IX, and X in the liver, thereby reducing thrombus formation.
| Metabolism | Primarily hepatic metabolism via CYP2C9; phenindione is hydroxylated and conjugated to inactive metabolites excreted renally. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 70% of elimination; the remainder is metabolized hepatically and excreted in feces via bile. |
| Half-life | Terminal elimination half-life is 18-24 hours in patients with normal renal function; may be prolonged to 30-40 hours in renal impairment, necessitating dose adjustment. |
| Protein binding | Highly protein bound (99%) to albumin. |
| Volume of Distribution | Volume of distribution is 0.2-0.4 L/kg, indicating distribution primarily in plasma and extracellular fluid. |
| Bioavailability | Oral bioavailability is nearly 100%. |
| Onset of Action | Oral: 1-2 hours for measurable anticoagulant effect; peak effect at 24-48 hours. |
| Duration of Action | Anticoagulant effect persists for 2-5 days after discontinuation, depending on dose and renal function. |
| Molecular Weight | 208.21 |
Oral, 200-400 mg initially, then 100-200 mg every 6-12 hours; maximum daily dose 1200 mg.
| Dosage form | TABLET |
| Renal impairment | GFR <30 mL/min: not recommended; GFR 30-60 mL/min: reduce dose by 50%; GFR >60 mL/min: no adjustment. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Not established for children <12 years; for adolescents >12 years, same as adult dosing with weight-based monitoring. |
| Geriatric use | Start at lower end of dosing range due to increased sensitivity; monitor renal function and adjust accordingly. |
| 1st trimester | Avoid use during first trimester due to risk of teratogenicity (warfarin embryopathy). Heparin or LMWH preferred. |
| 2nd trimester | Can be used with caution; risk of fetal anomalies is lower but fetal hemorrhage may occur. Monitor INR closely. |
| 3rd trimester | Avoid near term (after 36 weeks) due to risk of maternal/fetal hemorrhage. Consider switching to heparin. |
Clinical note
Comprehensive clinical and safety monograph for HEDULIN (HEDULIN).
| Placental transfer | Phenindione crosses the placenta, as evidenced by cases of fetal hemorrhage and teratogenic effects. Degree of transfer is moderate to high. |
| Breastfeeding | Hedulin (phenindione) is excreted into breast milk and may cause bleeding or prothrombin deficiency in nursing infants. Avoid breastfeeding or use alternative anticoagulant (e.g., warfarin is safer). |
■ FDA Black Box Warning
WARNING: HEDULIN can cause major or fatal hemorrhage. Monitor INR regularly. Risk factors include renal impairment, age >65, and concurrent use of drugs affecting hemostasis. Consider alternative therapies in patients with conditions that increase bleeding risk.
| Serious Effects |
Active peptic ulcer diseaseHemorrhagic strokeSevere liver diseasePregnancy (especially first trimester)Hypersensitivity to phenindioneBacterial endocarditisUncontrolled severe hypertension
| Precautions | Risk of hemorrhage; monitor INR frequently and adjust dose accordingly, Potential for skin necrosis (especially in patients with protein C deficiency), Use caution in hepatic or renal impairment, Discontinue if severe bleeding occurs and administer vitamin K or fresh frozen plasma |
| Food/Dietary | Consistent intake of vitamin K-rich foods (e.g., leafy greens, broccoli) is important; avoid large amounts of cranberry juice and grapefruit juice which may potentiate effect; limit alcohol; avoid garlic, ginseng, and ginger supplements due to antiplatelet effects. |
Loading safety data…
| Lactation Rating | Avoid |
| Teratogenic Risk | Phenindione (Hedulin) is contraindicated in pregnancy. First trimester: associated with fetal developmental abnormalities including skeletal defects, optic atrophy, and fetal death. Second and third trimesters: risk of fetal hemorrhage, placental abruption, and spontaneous abortion. Warfarin embryopathy syndrome has been reported with coumarin derivatives; phenindione is considered to have similar risks. |
| Fetal Monitoring | Monitor maternal prothrombin time (PT) and international normalized ratio (INR) frequently. Assess for signs of fetal distress via ultrasound and fetal heart rate monitoring. Monitor for maternal hemorrhage, bruising, and hematomas. Newborn should be monitored for bleeding complications if exposure occurs near term. |
| Fertility Effects | Limited data. Phenindione may potentially affect fertility through anticoagulant effects on ovarian function or implantation, but no specific studies are available. Use in women of childbearing potential should include contraception counseling. |
| Clinical Pearls | HEDULIN (phenindione) is an oral anticoagulant; monitor INR closely, especially when initiating or discontinuing other medications; vitamin K is antidote but requires up to 24 hours to reverse effect; avoid in pregnancy (teratogenic); check for purple toes syndrome as sign of cholesterol microembolism; CYP2C9 inhibitors (e.g., amiodarone) increase effect; CYP2C9 inducers (e.g., rifampin) decrease effect. |
| Patient Advice | Take exactly as prescribed; do not skip doses or double up. · Report any unusual bleeding or bruising immediately. · Use soft toothbrush and electric razor to avoid cuts. · Avoid alcohol and foods high in vitamin K (e.g., kale, spinach) consistently. · Wear medical alert ID and inform all healthcare providers. · Do not start or stop any medication without consulting your doctor. |