DILANTIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DILANTIN (DILANTIN).
Phenytoin stabilizes neuronal membranes and decreases seizure activity by increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses. It acts by blocking voltage-dependent sodium channels, thereby inhibiting the spread of seizure activity.
| Metabolism | Primarily metabolized by hepatic cytochrome P450 enzymes CYP2C9 and CYP2C19. Phenytoin exhibits saturable (Michaelis-Menten) pharmacokinetics with dose-dependent elimination. Major metabolite is 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), which is glucuronidated and excreted in urine. |
| Excretion | Primarily hepatic metabolism to inactive metabolites (p-hydroxyphenyltoin and glucuronide conjugate). Less than 5% excreted unchanged in urine. Fecal excretion minimal (<2%). |
| Half-life | Average 22 hours (range 7-42 hours) in adults. Dose-dependent; increases with higher concentrations due to saturable metabolism. In neonates: 10-15 hours. In chronic use, half-life may increase. |
| Protein binding | 90-95% bound to albumin. Hypoalbuminemia or uremia can decrease binding, increasing free fraction. |
| Volume of Distribution | 0.6-0.8 L/kg. Reflects distribution into total body water and tissues; higher in neonates and children (up to 1 L/kg). |
| Bioavailability | Oral: 90-100% (capsules, chewable tablets). Extended-release: 85-95%. IM: poor and erratic; not for routine use. Suspension: 90-100% but absorption may be slower. |
| Onset of Action | IV: 0.5-1 hour (peak effect). Oral: 2-4 hours (therapeutic effect). IM: not recommended due to erratic absorption and tissue damage. |
| Duration of Action | 12-24 hours for seizure control after single dose; therapeutic effect persists with chronic dosing due to long half-life. |
| Molecular Weight | 252.27 |
| Action Class | Sodium channel modulators (AED) |
300–400 mg/day orally in 2–3 divided doses; IV loading dose 15–20 mg/kg at max 50 mg/min, then 300 mg/day IV divided 2–3 times daily.
| Dosage form | TABLET, CHEWABLE |
| Renal impairment | No dose adjustment required for GFR >10 mL/min. For GFR <10 mL/min, reduce dose by 25–50% and monitor levels. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: reduce dose by 75% or avoid use. |
| Pediatric use | Loading: 15–20 mg/kg IV. Maintenance: 5–10 mg/kg/day orally in 2–3 divided doses; max 300 mg/day. |
| Geriatric use | Start at 200 mg/day orally in 2 divided doses; titrate slowly; monitor free phenytoin levels (due to reduced albumin). |
| 1st trimester | Associated with major congenital malformations including cardiac defects and neural tube defects; folic acid supplementation recommended. |
| 2nd trimester | Risk of IUGR and cognitive impairment; adjust dose based on serum levels. |
| 3rd trimester | Neonatal hemorrhage risk due to vitamin K depletion; prophylactic vitamin K recommended. |
Clinical note
Comprehensive clinical and safety monograph for DILANTIN (DILANTIN).
| Placental transfer | Extensively crosses placenta; fetal concentrations approximate maternal levels. |
| Breastfeeding | Excreted into breast milk in low concentrations; monitor infant for sedation and poor suckling. Generally considered compatible with caution. |
| Lactation Rating |
■ FDA Black Box Warning
Intravenous administration of phenytoin may cause cardiovascular adverse reactions including severe hypotension and cardiac arrhythmias. Continuous monitoring of ECG and vital signs is required during IV administration. Parenteral phenytoin should not be given faster than 50 mg per minute in adults or 1-3 mg/kg per minute in neonates.
| Serious Effects |
Hypersensitivity to hydantoinsSinus bradycardiaSA blockSecond- or third-degree AV blockAdams-Stokes syndrome
| Precautions | Cardiovascular risk: hypotension, arrhythmias with IV administration, Neurological effects: sedation, ataxia, nystagmus, cognitive impairment, Hematological effects: agranulocytosis, thrombocytopenia, leukopenia, Dermatological reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome, Hepatic injury: acute hepatotoxicity, hepatitis, Teratogenicity: fetal hydantoin syndrome if used during pregnancy, Hyperglycemia, osteomalacia, lymphadenopathy, Supratherapeutic levels can cause toxicity; therapeutic monitoring required |
| Food/Dietary | Enteral tube feeding formulas may reduce phenytoin absorption; separate enteral feeds by at least 1 hour before and after dose. Calcium supplements, antacids, and dairy products may decrease absorption; avoid taking within 2 hours of dose. Chronic alcohol use increases phenytoin metabolism, reducing serum levels; acute alcohol intake inhibits metabolism, raising levels. Folic acid supplements may lower phenytoin levels; monitor if started. Grapefruit juice may increase phenytoin levels; avoid concurrent consumption. |
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| Teratogenic Risk | Phenytoin (DILANTIN) is classified as FDA Pregnancy Category D. First trimester exposure is associated with a 2-3 fold increased risk of major malformations, including orofacial clefts, congenital heart defects, and the fetal hydantoin syndrome (craniofacial dysmorphisms, nail hypoplasia, growth deficiency, neurodevelopmental delays). Second and third trimester exposure may cause decreased fetal growth, microcephaly, and cognitive deficits. Risk is dose-dependent and increased with polytherapy. |
| Fetal Monitoring | Monitor maternal phenytoin serum concentrations regularly (before and during pregnancy). Assess folate status and supplement with folic acid (0.4-5 mg/day) preconception and throughout pregnancy. Obtain maternal alpha-fetoprotein screening at 16-18 weeks. Perform targeted fetal ultrasound at 18-22 weeks for structural anomalies. Consider fetal echocardiogram. Monitor fetal growth by serial ultrasounds in third trimester. Monitor for neonatal bleeding and administer vitamin K (1 mg IM) at birth due to phenytoin-induced vitamin K deficiency. |
| Fertility Effects | Phenytoin may reduce fertility due to effects on sex hormones. It induces hepatic CYP450 enzymes, increasing clearance of estrogen and progesterone, potentially causing menstrual irregularities, amenorrhea, and ovulation dysfunction. This may impair fertility in women. In men, phenytoin may cause decreased sperm count and motility. Reversible upon discontinuation. |
| Clinical Pearls | Dilantin (phenytoin) is a sodium channel blocker used for generalized tonic-clonic and partial seizures. It has zero-order pharmacokinetics at therapeutic doses; small dose increases can cause disproportionate rises in serum concentration. Monitor free phenytoin in hypoalbuminemia or renal impairment. Avoid IM administration due to erratic absorption and tissue necrosis. IV administration must be slow (≤50 mg/min in adults) to prevent hypotension and bradycardia; incompatible with dextrose solutions. Gingival hyperplasia is common; ensure good oral hygiene. Co-administration with valproate displaces phenytoin from protein binding, increasing free fraction. Fosphenytoin is a prodrug with better tolerability for IV/IM use. |
| Patient Advice | Take Dilantin exactly as prescribed; do not change dose or stop without consulting your doctor. · Swallow capsules whole; do not crush or chew. Shake oral suspension well before each dose. · Avoid alcohol; it can decrease seizure control and increase side effects. · Practice good oral hygiene to reduce gum swelling; brush gently and see dentist regularly. · Report any skin rash, fever, severe drowsiness, or unusual bleeding/bruising immediately. · Dilantin may cause dizziness or blurred vision; avoid driving until you know how it affects you. · Use effective birth control, as Dilantin can reduce hormonal contraceptive efficacy. · Do not switch between brands or formulations without doctor approval. |