DILANTIN-30
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DILANTIN-30 (DILANTIN-30).
Stabilizes neuronal membranes by promoting sodium channel inactivation, thereby inhibiting repetitive firing of action potentials.
| Metabolism | Primarily hepatic via CYP2C9 and CYP2C19; exhibits saturable (Michaelis-Menten) pharmacokinetics. |
| Excretion | Renal: ~70% (primarily as inactive metabolites including p-HPPH glucuronide, with <5% unchanged); Biliary/fecal: ~30% (enterohepatic circulation contributes to biliary excretion of metabolites and a small amount of unchanged drug). |
| Half-life | Terminal elimination half-life averages 22 hours (range 7–42 hours) in adults; dose-dependent due to saturable metabolism (Michaelis-Menten kinetics). At low concentrations, half-life is approximately 10–15 hours; at high concentrations, half-life may exceed 30 hours. Clinical context: steady state achieved in 5–10 days; half-life prolonged in neonates, elderly, and hepatic impairment. |
| Protein binding | Approximately 90% bound to serum albumin. In uremic or hypoalbuminemic patients, free fraction increases (up to 20%) requiring monitoring of free phenytoin levels. |
| Volume of Distribution | Vd: 0.5–0.8 L/kg in adults (approximately 35–56 L in a 70 kg individual). Clinical meaning: reflects extensive tissue distribution, particularly to brain and adipose tissue; Vd is not significantly altered in obesity. |
| Bioavailability | Oral (immediate-release): 85–95%. Oral (extended-release): 85–95% (but rate of absorption is slower). Intramuscular: erratic and painful, not recommended (bioavailability highly variable, 50–90%). |
| Onset of Action | Oral (immediate-release): 2–4 hours for anticonvulsant effect (peak serum concentrations at 1.5–3 hours). Oral (extended-release): 4–12 hours (peak at 4–12 hours). Intravenous: 0.5–1 hour (rapid brain penetration). |
| Duration of Action | Oral: 12–24 hours (based on once or twice daily dosing; therapeutic serum levels 10–20 mcg/mL maintained with appropriate dosing). IV: 12–24 hours. Clinical note: duration follows terminal half-life; due to saturable kinetics, duration may be prolonged at higher doses. |
| Molecular Weight | 252.27 |
300 mg/day orally in 3 divided doses (100 mg three times daily) or 300 mg/day once daily as an extended-release capsule. Loading dose: 1 g orally divided into three doses (400 mg, 300 mg, 300 mg) given at 2-hour intervals. Intravenous fosphenytoin loading dose: 15-20 mg PE/kg; maintenance: 4-6 mg PE/kg/day IV.
| Dosage form | SUSPENSION |
| Renal impairment | No dose adjustment needed for mild to moderate renal impairment. In severe renal impairment (GFR <10 mL/min), consider increasing dose interval to every 8 hours or reduce dose by 25-50%. Monitor free phenytoin levels due to hypoalbuminemia. |
| Liver impairment | In Child-Pugh Class A: no adjustment. Class B: reduce dose by 25% and monitor levels. Class C: avoid use or reduce dose by 50% with close monitoring of total and free phenytoin levels. |
| Pediatric use | Loading dose: 15-20 mg/kg IV (fosphenytoin) or orally. Maintenance: 5 mg/kg/day in 2-3 divided doses initially, adjusting based on therapeutic levels (target 10-20 mcg/mL). Maximum: 300 mg/day. |
| Geriatric use | Start at lower end of dosing range (e.g., 100 mg orally once daily) due to reduced clearance and increased sensitivity. Titrate slowly to minimum effective dose. Monitor total and free phenytoin levels as hypoalbuminemia may cause toxicity at normal total levels. |
| 1st trimester | Associated with increased risk of congenital malformations including cleft palate, cardiac defects, and neural tube defects. Avoid unless no safer alternative. |
| 2nd trimester | Continued risk of fetal hydantoin syndrome and developmental delay. Monitor anticonvulsant levels closely due to physiological changes. |
| 3rd trimester | Risk of neonatal hemorrhage due to vitamin K deficiency; administer vitamin K to neonate. Risk of neonatal withdrawal syndrome. |
Clinical note
Comprehensive clinical and safety monograph for DILANTIN-30 (DILANTIN-30).
| Placental transfer | Phenytoin readily crosses the placenta; fetal plasma concentrations approximate maternal levels. |
| Breastfeeding | Phenytoin is excreted into breast milk in low concentrations (milk:plasma ratio ~0.18-0.45). Reports of drowsiness, poor sucking, and methemoglobinemia in infants. Monitor infant for adverse effects; generally considered compatible with caution. |
■ FDA Black Box Warning
Increased risk of suicidal thoughts or behavior; monitor for changes in mood or behavior.
| Serious Effects |
Hypersensitivity to phenytoin or hydantoinsSinus bradycardiaSA blockSecond- or third-degree AV blockAdam-Stokes syndrome
| Precautions | Cardiovascular effects including hypotension and arrhythmias; hepatotoxicity; hematologic effects (agranulocytosis, thrombocytopenia); lymphadenopathy; hypersensitivity reactions (DRESS); teratogenicity; gingival hyperplasia; osteomalacia; acute intermittent porphyria; slow IV administration to avoid purple glove syndrome. |
| Food/Dietary | Avoid grapefruit juice (increases phenytoin levels). Enteral tube feeding may reduce absorption; hold feedings 1-2 hours before and after dose. Calcium-containing foods or supplements may decrease absorption. Folate supplementation recommended due to drug-induced folate deficiency. Alcohol intake can alter phenytoin levels and reduce seizure control. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Phenytoin (DILANTIN-30) is associated with fetal hydantoin syndrome, including craniofacial abnormalities, growth restriction, and cognitive deficits. First trimester exposure carries the highest risk of major malformations (cleft palate, congenital heart defects). Third trimester use may cause neonatal coagulopathy due to vitamin K deficiency. Neural tube defects are also increased. |
| Fetal Monitoring | Monitor maternal serum phenytoin concentrations (target therapeutic range). Fetal ultrasound for structural anomalies. Assess fetal growth. Neonatal vitamin K administration at birth. Monitor for neonatal withdrawal/toxicity. |
| Fertility Effects | Phenytoin may reduce fertility in women by causing menstrual irregularities, anovulation, and possible alterations in sex hormone binding globulin levels. Reversible upon discontinuation. |
| Clinical Pearls | DILANTIN-30 contains phenytoin 30 mg, a class 1B antiarrhythmic and anticonvulsant. For seizure disorders, monitor therapeutic range (10-20 mcg/mL total phenytoin). Narrow therapeutic index; nonlinear kinetics due to hepatic saturation. Caution with hypoalbuminemia or renal impairment: adjust for free phenytoin levels. IV administration contraindicated; only oral. May cause gingival hyperplasia, nystagmus, ataxia, and lupus-like syndrome. Multiple drug interactions (CYP2C9/2C19 substrates). Fosphenytoin is prodrug for IV use. Avoid in pregnancy (fetal hydantoin syndrome). |
| Patient Advice | Take exactly as prescribed; do not skip or double doses. · Do not crush or chew capsules; swallow whole. · Avoid sudden discontinuation; may trigger seizures. · Report symptoms like rash, jaundice, fever, or swollen glands immediately. · Maintain good oral hygiene to prevent gum overgrowth. · Use birth control; phenytoin reduces oral contraceptive efficacy. · Avoid alcohol and grapefruit juice. · May cause dizziness; avoid driving until effects known. · Wear medical alert ID for epilepsy or arrhythmia. · Inform all healthcare providers of phenytoin use. |