PHENYTEK
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PHENYTEK (PHENYTEK).
Stabilizes neuronal membranes by promoting sodium efflux and inhibiting calcium influx, thereby reducing repetitive firing of action potentials. Enhances GABA-mediated inhibition and modulates voltage-gated sodium channels.
| Metabolism | Primarily hepatic via CYP2C9 and CYP2C19 isoenzymes. Undergoes saturable (Michaelis-Menten) kinetics. Minor metabolism via CYP3A4. |
| Excretion | Primarily hepatic metabolism; less than 5% excreted unchanged in urine. Renal excretion of inactive metabolites accounts for ~70-80%, with biliary/fecal elimination of ~20%. |
| Half-life | Terminal elimination half-life averages 22 hours (range 7-42 hours). Dose-dependent due to saturable metabolism; half-life increases with higher doses or in hepatic impairment. |
| Protein binding | Approximately 90-95% bound, primarily to serum albumin. Binding is saturable; decreased binding in uremia or hypoalbuminemia increases free fraction. |
| Volume of Distribution | Vd ~0.5-0.8 L/kg; indicates extensive tissue distribution, with high concentrations in brain and CSF. In neonates, Vd may be up to 1.2 L/kg. |
| Bioavailability | Oral: ~90-95% (PHENYTEK is a prodrug of fosphenytoin; fosphenytoin is rapidly converted to phenytoin with ~100% bioavailability). |
| Onset of Action | Oral: 0.5-2 hours for therapeutic antiepileptic effect; IV loading (if available): 10-30 minutes. |
| Duration of Action | Duration of anticonvulsant effect is approximately 12-24 hours for immediate-release oral; sustained-release formulations provide 24-hour coverage. Therapeutic serum levels (10-20 mcg/mL) correlate with effect. |
Initial dose: 100 mg orally 3 times daily; maintenance: 300-400 mg/day in 3-4 divided doses. Extended-release (ER) formulation: 300 mg orally once daily for once-daily dosing; may be increased to 400 mg once daily if needed.
| Dosage form | CAPSULE |
| Renal impairment | For GFR 10-50 mL/min: administer 75% of usual dose; for GFR <10 mL/min: administer 50% of usual dose. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: contraindicated or use with extreme caution, reduce dose by 75%. |
| Pediatric use | Loading dose: 15-20 mg/kg orally; maintenance: 5-10 mg/kg/day in 2-3 divided doses. Maximum daily dose: 300 mg. Extended-release not recommended for children under 12 years. |
| Geriatric use | Start at lower doses (e.g., 100 mg daily) with gradual titration; monitor for neurotoxicity (e.g., nystagmus, ataxia) due to decreased clearance; consider serum concentration monitoring. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PHENYTEK (PHENYTEK).
| Breastfeeding | Phenytoin is excreted into breast milk with an average milk-to-plasma (M/P) ratio of 0.18-0.45. Estimates of infant dose are approximately 2-5% of the maternal weight-adjusted dose, which is generally below the therapeutic range. Adverse effects are rare but include drowsiness, poor feeding, and methemoglobinemia in sensitive infants. Benefits of breastfeeding generally outweigh risks with maternal monitoring for infant sedation and feeding. |
| Teratogenic Risk | Phenytoin (PHENYTEK) is a known human teratogen. First trimester exposure is associated with a 2-3 fold increased risk of major congenital malformations, including orofacial clefts, congenital heart defects, and neural tube defects. A specific pattern of minor anomalies, known as fetal hydantoin syndrome (FHS), may occur. Second and third trimester exposure may be associated with growth restriction, neurodevelopmental delays, and cognitive impairment. The risk is dose-dependent and increases with polytherapy. |
■ FDA Black Box Warning
Intravenous administration may cause cardiovascular collapse, severe hypotension, and cardiac arrhythmias. Monitor cardiac function continuously during IV infusion. Risk of severe injection site reactions including purple glove syndrome.
| Serious Effects |
Hypersensitivity to phenytoin or hydantoins. Sinus bradycardia, sinoatrial block, second- and third-degree AV block, or Adams-Stokes syndrome (IV formulation). History of prior hepatotoxicity due to phenytoin. Coadministration with delavirdine (CYP3A4 substrate) due to potential loss of antiviral efficacy.
| Precautions | Risk of suicidal thoughts and behavior. Hepatotoxicity, blood dyscrasias (agranulocytosis, thrombocytopenia). Exacerbation of porphyria. Acute hypersensitivity reactions including Stevens-Johnson syndrome. Abrupt discontinuation may precipitate status epilepticus. Hyperglycemia and hypocalcemia. Lymphadenopathy requiring evaluation. Serum phenytoin levels should be monitored due to nonlinear pharmacokinetics. |
Loading safety data…
| Fetal Monitoring | Maternal monitoring: serum phenytoin concentrations (free and total) every 2-4 weeks; adjust dose to maintain therapeutic levels. Monitor for signs of toxicity (nystagmus, ataxia, sedation) and adverse effects (megaloblastic anemia, osteoporosis). Fetal monitoring: prenatal ultrasound for structural anomalies at 18-20 weeks; consider fetal echocardiography. Neonatal monitoring: assess for bleeding tendencies (vitamin K deficiency), signs of withdrawal (hyperactivity, feeding difficulties), and measure phenytoin levels if toxicity suspected. |
| Fertility Effects | Phenytoin may impair fertility in both sexes. In women, it can cause menstrual irregularities, anovulation, and reduced fertility due to enzyme induction affecting sex hormone metabolism. In men, it may cause decreased libido, erectile dysfunction, and abnormal sperm parameters. Effects are generally reversible upon dose reduction or discontinuation. |