PHENURONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PHENURONE (PHENURONE).
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.
| 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. |
| Molecular Weight | 246.21 |
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. |
| 1st trimester | Increased risk of neural tube defects and other major malformations. Use only if no alternative. |
| 2nd trimester | May cause fetal growth restriction and hemorrhagic disorders. Avoid unless essential. |
| 3rd trimester | Risk of neonatal coagulation abnormalities and withdrawal. Use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for PHENURONE (PHENURONE).
| Placental transfer | Phenurone crosses the placenta; fetal levels approximate maternal serum levels. |
| Breastfeeding | Phenurone is excreted in human milk; potential for serious adverse reactions in nursing infants. Decision to discontinue nursing or drug should consider importance of drug to mother. |
| Lactation Rating |
■ 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.
| Serious Effects |
Hypersensitivity to phenytoin or hydantoinsBradycardia, heart block, or other conduction abnormalitiesAdams-Stokes syndromeSinus node diseaseConcomitant use with delavirdine
| 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. |
| Food/Dietary | No significant food interactions documented. Avoid alcohol entirely due to additive CNS depression and potential hepatotoxicity. |
Loading safety data…
| Avoid |
| 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 | Monitor serum drug levels, liver function, complete blood count, and fetal ultrasound for anomalies. Assess for neural tube defects with alpha-fetoprotein screening. |
| Fertility Effects | May cause oligospermia or menstrual irregularities; limited data suggest reversible impairment of fertility in both males and females. |
| Clinical Pearls | Phenurone (phenacemide) is a last-line anticonvulsant due to high risk of hepatotoxicity and bone marrow suppression. Monitor LFTs and CBC monthly. Avoid in patients with liver disease or history of psychosis. Therapeutic drug monitoring: target serum phenacemide level 5-12 mcg/mL. May cause severe personality changes and suicidal ideation. |
| Patient Advice | Take exactly as prescribed; do not adjust dose without consulting your doctor. · Report signs of liver injury (yellow skin/eyes, dark urine, abdominal pain) or blood dyscrasias (fever, sore throat, easy bruising) immediately. · Avoid alcohol completely while taking this medication. · May cause drowsiness or dizziness; avoid driving until you know how this drug affects you. · Use reliable contraception; phenacemide can harm a fetus and decrease effectiveness of hormonal contraceptives. · Do not stop abruptly; withdrawal can precipitate seizures. |