PHENURONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHENURONE (PHENURONE).

How it works

Phenurone (phenacemide) is an anticonvulsant that reduces neuronal excitability by inhibiting voltage-gated sodium channels and potentiating GABAergic inhibition. It also has a structure similar to other hydantoins and may increase the seizure threshold.

What the body does with it

Metabolism	Primarily hepatic metabolism via hydrolysis and conjugation; involves CYP450 enzymes (minor contribution). Metabolites are excreted in urine.
Excretion	Phenurone is extensively metabolized in the liver; less than 1% is excreted unchanged in urine. The primary metabolite is 4-hydroxyphenylethylhydantoin (p-HPEH). Renal excretion accounts for approximately 70-80% of the dose, mainly as metabolites; the remainder is eliminated via bile/feces. Enterohepatic circulation may occur.
Half-life	The terminal elimination half-life is approximately 22-35 hours in adults. This long half-life supports once- or twice-daily dosing, but requires careful monitoring for accumulation.
Protein binding	Approximately 80-90% bound, primarily to serum albumin. The binding is saturable, which can lead to nonlinear pharmacokinetics at high doses.
Volume of Distribution	0.5-1.0 L/kg. This moderate Vd indicates distribution into total body water and some tissue binding. Vd may be increased in epilepsy or with co-administration of other anticonvulsants.
Bioavailability	Oral bioavailability is approximately 90-100% based on absorption studies. Food does not significantly affect absorption.
Onset of Action	Oral: therapeutic effect (seizure control) typically occurs within 2-4 days of initiating therapy, but clinical response may require 1-2 weeks for full antiepileptic effect.
Duration of Action	Seizure control persists for the dosing interval (12-24 hours) with regular dosing. The long half-life allows steady-state concentration after about 5-7 days.

Classification & Brands

Dosing & administration

Adults: 500 mg to 1 g orally twice daily, increased gradually up to 3 g/day in divided doses.

Dosage form	TABLET
Renal impairment	No specific guidelines; use with caution in renal impairment. Monitor for toxicity.
Liver impairment	Child-Pugh Class A: No adjustment; Class B: Reduce dose by 25-50%; Class C: Avoid use.
Pediatric use	Children: 10-20 mg/kg/day orally in 2-3 divided doses; maximum 1.5 g/day.
Geriatric use	Initiate at low end of dosing range (500 mg/day) and titrate slowly; monitor for neurotoxicity.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for PHENURONE (PHENURONE).

Breastfeeding	Excreted into breast milk; M/P ratio unknown. Avoid breastfeeding due to potential for adverse effects (e.g., sedation, poor feeding) in the infant.
Teratogenic Risk	Category D: Increased risk of neural tube defects, cleft palate, and congenital heart defects. Avoid in first trimester; use only if benefit outweighs risk in later trimesters.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Phenacemide may cause fatal hepatotoxicity and aplastic anemia. Patients must be closely monitored for signs of hepatic dysfunction and blood dyscrasias.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of liver disease or hepatic dysfunction. History of aplastic anemia or bone marrow depression. Hypersensitivity to phenacemide or other hydantoins. Concurrent use with other hepatotoxic drugs.

Clinical Precautions

Precautions

Hepatotoxicity: monitor liver function tests at baseline and periodically; discontinue if signs of hepatic injury. Aplastic anemia: advise patients to report unexplained bleeding, bruising, or signs of infection. Suicidal ideation: monitor for changes in mood or behavior. Withdrawal: do not discontinue abruptly.

Clinical Tips & Counseling

Drug interactions

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PHENURONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHENURONE (PHENURONE).

How it works

What the body does with it

Metabolism	Primarily hepatic metabolism via hydrolysis and conjugation; involves CYP450 enzymes (minor contribution). Metabolites are excreted in urine.
Excretion	Phenurone is extensively metabolized in the liver; less than 1% is excreted unchanged in urine. The primary metabolite is 4-hydroxyphenylethylhydantoin (p-HPEH). Renal excretion accounts for approximately 70-80% of the dose, mainly as metabolites; the remainder is eliminated via bile/feces. Enterohepatic circulation may occur.
Half-life	The terminal elimination half-life is approximately 22-35 hours in adults. This long half-life supports once- or twice-daily dosing, but requires careful monitoring for accumulation.
Protein binding	Approximately 80-90% bound, primarily to serum albumin. The binding is saturable, which can lead to nonlinear pharmacokinetics at high doses.
Volume of Distribution	0.5-1.0 L/kg. This moderate Vd indicates distribution into total body water and some tissue binding. Vd may be increased in epilepsy or with co-administration of other anticonvulsants.
Bioavailability	Oral bioavailability is approximately 90-100% based on absorption studies. Food does not significantly affect absorption.
Onset of Action	Oral: therapeutic effect (seizure control) typically occurs within 2-4 days of initiating therapy, but clinical response may require 1-2 weeks for full antiepileptic effect.
Duration of Action	Seizure control persists for the dosing interval (12-24 hours) with regular dosing. The long half-life allows steady-state concentration after about 5-7 days.

Classification & Brands

Dosing & administration

Adults: 500 mg to 1 g orally twice daily, increased gradually up to 3 g/day in divided doses.

Dosage form	TABLET
Renal impairment	No specific guidelines; use with caution in renal impairment. Monitor for toxicity.
Liver impairment	Child-Pugh Class A: No adjustment; Class B: Reduce dose by 25-50%; Class C: Avoid use.
Pediatric use	Children: 10-20 mg/kg/day orally in 2-3 divided doses; maximum 1.5 g/day.
Geriatric use	Initiate at low end of dosing range (500 mg/day) and titrate slowly; monitor for neurotoxicity.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for PHENURONE (PHENURONE).

Breastfeeding	Excreted into breast milk; M/P ratio unknown. Avoid breastfeeding due to potential for adverse effects (e.g., sedation, poor feeding) in the infant.
Teratogenic Risk	Category D: Increased risk of neural tube defects, cleft palate, and congenital heart defects. Avoid in first trimester; use only if benefit outweighs risk in later trimesters.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Phenacemide may cause fatal hepatotoxicity and aplastic anemia. Patients must be closely monitored for signs of hepatic dysfunction and blood dyscrasias.