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. |
| Molecular Weight | 252.27 |
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 | Phenytoin is associated with an increased risk of congenital malformations, including orofacial clefts, cardiac defects, and neural tube defects. The risk is dose-dependent. Use during the first trimester should be avoided unless no safer alternative is available. |
| 2nd trimester | Continued caution advised. Risk of fetal hydantoin syndrome persists with chronic use. Dose adjustment may be necessary due to altered pharmacokinetics during pregnancy. Monitor phenytoin levels and adjust dose to maintain therapeutic efficacy while minimizing fetal exposure. |
| 3rd trimester | Late pregnancy may increase the risk of neonatal hemorrhage due to vitamin K deficiency (phenytoin induces vitamin K metabolism). Administer vitamin K prophylaxis to the mother near term and to the neonate at birth. Withdrawal symptoms may occur in the neonate if the mother is on chronic therapy. |
Clinical note
Comprehensive clinical and safety monograph for PHENYTEK (PHENYTEK).
| Placental transfer | Phenytoin crosses the placenta extensively. Cord blood concentrations approximate maternal plasma levels. Fetal liver and tissues can accumulate drug. |
■ 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 any component of the formulationSinus bradycardiaSinoatrial blockSecond- or third-degree atrioventricular blockAdams-Stokes syndrome
| 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. |
| Food/Dietary | Enteral tube feedings can reduce phenytoin absorption; separate administration by 1-2 hours. Grapefruit juice may increase phenytoin levels via CYP inhibition, but effect is variable; avoid excessive consumption. High-protein diet may accelerate phenytoin metabolism. Folic acid supplementation may decrease phenytoin levels; monitor. Vitamin D and calcium supplementation recommended for osteoporosis prevention. |
Loading safety data…
| Breastfeeding | Phenytoin is excreted into breast milk in low concentrations. The estimated infant dose is less than 10% of the maternal weight-adjusted dose, which is generally considered compatible with breastfeeding. However, monitor the infant for potential adverse effects such as drowsiness, poor feeding, or rash. Use with caution in premature or ill infants. |
| Lactation Rating | L3 (Moderately Safe) - Limited data suggest risk is low in healthy, full-term infants; however, monitor infant for adverse effects. |
| 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. |
| 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. |
| Clinical Pearls | PHENYTEK is a fosphenytoin prodrug equivalent to phenytoin. Administer intravenously or intramuscularly at a rate not exceeding 150 mg PE/min (PE = phenytoin equivalents). Monitor ECG and blood pressure during IV infusion due to risk of hypotension and arrhythmias. Avoid IM administration if possible due to muscle necrosis risk. Therapeutic range is 10-20 mcg/mL for total phenytoin; free phenytoin levels (target 1-2 mcg/mL) are preferred in hypoalbuminemia or renal impairment. Use caution in porphyria, history of hypersensitivity to hydantoins, or sinus bradycardia. Phenytoin is highly protein bound; drug interactions are common via CYP2C9, CYP2C19, and CYP3A4 induction/inhibition. Long-term use may cause folate deficiency, peripheral neuropathy, and osteoporosis (consider vitamin D and folate supplementation). |
| Patient Advice | Take PHENYTEK exactly as prescribed; do not change dose without consulting your doctor. · Do not use during pregnancy unless clearly needed; it may cause fetal harm. Use effective contraception. · Avoid alcohol while taking this medication. · Report any skin rash, unusual bleeding or bruising, fever, swollen glands, or mouth sores immediately. · Practice good oral hygiene to prevent gingival hypertrophy. · Do not stop taking suddenly as it may cause withdrawal seizures. · You may need regular blood tests to check drug levels and liver function. · This medication may cause dizziness or drowsiness; avoid driving until you know how it affects you. · Notify all healthcare providers you are taking Phenytek, as it interacts with many drugs. · Wear a medical alert bracelet indicating you take PHENYTEK. |