DILANTIN-125
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DILANTIN-125 (DILANTIN-125).
Phenytoin stabilizes neuronal membranes by promoting voltage-gated sodium channel inactivation, reducing high-frequency neuronal firing and seizure propagation.
| Metabolism | Primarily hepatic via CYP2C9 and CYP2C19 isoenzymes; exhibits non-linear (saturable) kinetics; major metabolite is 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH). |
| Excretion | Renal: 70% as metabolites (mainly HPPA glucuronide and sulfate), 5-10% as unchanged drug. Fecal: 30% (minor). |
| Half-life | Terminal half-life: 7-42 hours (mean 22 hours) in adults; dose-dependent due to saturable metabolism. Steady-state reached in 7-10 days. |
| Protein binding | 90% (primarily albumin); increased free fraction in hypoalbuminemia (cirrhosis, nephrotic syndrome). |
| Volume of Distribution | 0.5-0.8 L/kg (total), 1.7 L/kg (free); low Vd reflects high protein binding. |
| Bioavailability | Oral: 85-95% for extended phenytoin sodium (Dilantin-125). IM: erratic and painful, not recommended (70-80%). |
| Onset of Action | Oral: 1-3 hours for seizure control; IV (fosphenytoin): 15-30 minutes. |
| Duration of Action | Oral: 24 hours for seizure control with therapeutic levels (10-20 mcg/mL). Clinical effect persists as long as levels maintained. |
| Molecular Weight | 252.27 |
300-400 mg per day orally in divided doses (e.g., 100 mg three times daily); loading dose 1 g orally divided into three doses given at 2-hour intervals, then 100 mg every 6-8 hours for first 24 hours.
| Dosage form | SUSPENSION |
| Renal impairment | Hemodialysis: supplemental dose of 50% of usual daily dose post-dialysis recommended. For GFR <10 mL/min: cautious use with monitoring of free phenytoin levels; dose reduction may be necessary. Peritoneal dialysis: no specific adjustment guidelines, but monitor levels. |
| Liver impairment | Child-Pugh Class A: no dose adjustment needed but monitor levels. Child-Pugh Class B: reduce dose by 25-50% due to decreased metabolism. Child-Pugh Class C: reduce dose by 50-75%, monitor free phenytoin levels closely. |
| Pediatric use | Loading dose: 15-20 mg/kg orally (divided into 2-3 doses); maintenance: 5-10 mg/kg/day orally in 2-3 divided doses, titrate to therapeutic serum levels (10-20 mcg/mL). Maximum dose: 300 mg/day for children <10 years old. |
| Geriatric use | Start at low end of adult dosing (100 mg twice daily) and titrate slowly, monitoring for neurotoxicity (ataxia, nystagmus) and drug interactions due to decreased protein binding and renal function. Target therapeutic levels at lower end (10-15 mcg/mL). |
| 1st trimester | Associated with increased risk of major congenital malformations, particularly cleft lip/palate and cardiac defects. Use only if benefit outweighs risk. |
| 2nd trimester | May cause fetal hydantoin syndrome, including growth retardation, microcephaly, and neurodevelopmental issues. Monitor fetal growth. |
| 3rd trimester | Risk of neonatal hemorrhage due to vitamin K depletion; administer vitamin K to neonate. Withdrawal symptoms may occur. |
Clinical note
Comprehensive clinical and safety monograph for DILANTIN-125 (DILANTIN-125).
| Placental transfer | Crosses the placenta extensively; fetal plasma concentrations approach maternal levels. Documented teratogen. |
| Breastfeeding | Phenytoin is excreted into breast milk in low concentrations (milk-to-plasma ratio approximately 0.18-0.45). Cases of drowsiness and poor sucking in infants have been reported. Weigh benefits against risks; monitor infant for adverse effects. |
■ FDA Black Box Warning
Intravenous administration may cause cardiovascular collapse and CNS depression; rapid infusion can cause hypotension, bradycardia, and cardiac arrest.
| Serious Effects |
Hypersensitivity to phenytoin or hydantoinsSinus bradycardiaSinoatrial blockSecond- or third-degree AV blockAdams-Stokes syndrome
| Precautions | Narrow therapeutic index; monitoring of serum concentrations required; risk of Stevens-Johnson syndrome, hepatotoxicity, lymphadenopathy, and hypersensitivity reactions; withdrawal-precipitated status epilepticus; cerebellar atrophy with chronic use; folate deficiency and megaloblastic anemia; gingival hyperplasia; osteomalacia; interaction with many drugs. |
| Food/Dietary | Avoid enteral tube feeding within 2 hours of dose; calcium-containing supplements or antacids may reduce absorption. Grapefruit juice may increase phenytoin levels. Folic acid supplementation may decrease phenytoin levels; monitor. High-protein or low-protein diets can alter phenytoin metabolism. |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Phenytoin (DILANTIN-125) is associated with fetal hydantoin syndrome, including craniofacial anomalies, nail hypoplasia, growth retardation, and neurodevelopmental deficits. First trimester exposure carries highest risk. Third trimester use may cause neonatal hemorrhage due to vitamin K deficiency. Risk of major malformations is approximately 2-3 times baseline. |
| Fetal Monitoring | Monitor maternal serum phenytoin levels (free and total) every 4-8 weeks during pregnancy and postpartum. Assess fetal growth via ultrasound. Perform maternal alpha-fetoprotein screening and high-resolution ultrasound for neural tube defects. Administer vitamin K 10 mg/day orally during last month to prevent neonatal hemorrhage. Monitor for signs of folate deficiency; supplement with folic acid 0.4-1 mg/day. |
| Fertility Effects | Phenytoin may reduce fertility by altering hypothalamic-pituitary-ovarian axis. It can induce hepatic metabolism of sex hormones, potentially causing menstrual irregularities, anovulation, and increased risk of polycystic ovary syndrome. Effects are reversible upon discontinuation. |
| Clinical Pearls | Dilantin-125 (phenytoin oral suspension) has erratic absorption; shake well before each dose. Narrow therapeutic index: target total phenytoin concentration 10-20 mcg/mL. Highly protein-bound; monitor free levels in hypoalbuminemia or renal impairment. Induces CYP450 enzymes, affecting many drug interactions. IV formulation contraindicated IM due to precipitation and tissue necrosis. |
| Patient Advice | Take exactly as prescribed; do not skip doses or double up. · Shake the bottle vigorously before each dose to ensure uniform suspension. · Use a calibrated measuring device; do not use household spoons. · Do not stop abruptly; sudden withdrawal can trigger seizures. · Report any rash immediately; it may indicate serious hypersensitivity (DRESS syndrome). · Avoid alcohol; it can interfere with drug levels and increase side effects. · Practice good oral hygiene; phenytoin can cause gingival hyperplasia. · Use reliable contraception; phenytoin reduces effectiveness of hormonal contraceptives. · Wear medical alert identification for epilepsy. |