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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DILANTIN-125 (DILANTIN-125).
| Breastfeeding | Phenytoin is excreted into breast milk with milk-to-plasma ratio (M/P) approximately 0.18-0.45. Infant serum levels are typically subtherapeutic (less than 10% of maternal levels). Breastfeeding is generally considered compatible, but monitor infant for drowsiness, poor feeding, and rash. |
| 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. |
■ 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 hydantoins; sinus bradycardia, sinoatrial block, second- or third-degree AV block, or Stokes-Adams syndrome (IV form); history of acute hepatotoxicity due to phenytoin.
| 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. |
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| 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. |