HEDULIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HEDULIN (HEDULIN).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for HEDULIN (HEDULIN).

Breastfeeding

Phenindione is excreted into breast milk. The M/P ratio is not established. Due to risk of neonatal bleeding, breastfeeding is not recommended. Alternative anticoagulants such as heparin or low molecular weight heparin are preferred.

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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Active bleeding or bleeding disorders","Severe hepatic or renal impairment","Known hypersensitivity to phenindione","Inability to comply with INR monitoring","Pregnancy (teratogenic effects)"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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HEDULIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HEDULIN (HEDULIN).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for HEDULIN (HEDULIN).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Active bleeding or bleeding disorders","Severe hepatic or renal impairment","Known hypersensitivity to phenindione","Inability to comply with INR monitoring","Pregnancy (teratogenic effects)"]