PHENYTEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PHENYTEX (PHENYTEX).
Stabilizes neuronal membranes by promoting sodium efflux and inhibiting calcium influx, thereby reducing repetitive firing of action potentials. Also enhances GABA-mediated inhibition.
| Metabolism | Primarily hepatic via CYP2C9 and CYP2C19 enzymes; exhibits saturation (nonlinear) pharmacokinetics at therapeutic concentrations. |
| Excretion | Renal (hepatic metabolism to inactive metabolites; <5% excreted unchanged in urine; biliary/fecal excretion minimal) |
| Half-life | 22 hours (range 7-42 hours; prolonged in hepatic impairment; clinical context: steady-state achieved in 5-7 days) |
| Protein binding | 90% (primarily albumin; decreased in uremia, hypoalbuminemia; free fraction increased) |
| Volume of Distribution | 0.6 L/kg (clinical meaning: moderate distribution, indicating tissue binding; Vd increases in pregnancy and hepatic disease) |
| Bioavailability | Oral (tablet): 85-95%; Intramuscular: 70-80% (erratic absorption, not recommended); Intravenous: 100% (as fosphenytoin prodrug) |
| Onset of Action | Oral: 30-60 minutes (tablet); Intravenous: 10-15 minutes (with fosphenytoin conversion) |
| Duration of Action | 12-24 hours (therapeutic serum levels maintained for 12-24 hours after single dose; clinical notes: once-daily dosing often sufficient for epilepsy) |
| Molecular Weight | 252.27 |
300-400 mg/day orally in divided doses, typically 100 mg three times daily or 200 mg twice daily; loading dose 1 g orally divided into three doses (400 mg, 300 mg, 300 mg) at 2-hour intervals, or 10-15 mg/kg IV at a rate not exceeding 50 mg/min.
| Dosage form | CAPSULE |
| Renal impairment | GFR 10-50 mL/min: administer 75% of usual dose; GFR <10 mL/min: administer 50% of usual dose; hemodialysis: supplement 50% of usual dose post-dialysis. |
| Liver impairment | Child-Pugh Class A: no adjustment needed; Child-Pugh Class B: reduce dose by 25-50%; Child-Pugh Class C: reduce dose by 50-75% or consider alternative; monitor serum concentrations. |
| Pediatric use | Loading dose: 15-20 mg/kg IV/PO; maintenance: 5-10 mg/kg/day in 2-3 divided doses; start at 5 mg/kg/day in 2 divided doses, maximum 300 mg/day; therapeutic drug monitoring recommended. |
| Geriatric use | Start at lower end of dosing range (100 mg once or twice daily); consider reduced clearance; monitor serum albumin and phenytoin levels (free phenytoin preferred); adjust based on clinical response and toxicity. |
| 1st trimester | Associated with major congenital malformations including neural tube defects, cleft palate, and congenital heart disease. Risk of fetal hydantoin syndrome. Avoid if possible. |
| 2nd trimester | May cause fetal growth restriction and neurodevelopmental deficits. Use only if clearly needed and no alternative. |
| 3rd trimester | Risk of neonatal hemorrhage (vitamin K deficiency), withdrawal symptoms, and coagulopathy. Monitor INR in mother and administer vitamin K to newborn. |
Clinical note
Comprehensive clinical and safety monograph for PHENYTEX (PHENYTEX).
| Placental transfer | Phenytoin crosses the placenta readily; fetal serum concentrations may approximate maternal levels. Binding to fetal plasma proteins is lower, leading to higher free fraction in fetus. |
| Breastfeeding | Phenytoin is excreted into breast milk in low concentrations (5-10% of maternal serum). Reported infant serum levels are subtherapeutic. Monitor infant for drowsiness, poor feeding, and rash. Consider risk of idiosyncratic reactions. Generally considered compatible with breastfeeding, but use with caution in premature or ill infants. |
■ FDA Black Box Warning
Intravenous phenytoin is contraindicated in patients with sinus bradycardia, sinoatrial block, second- and third-degree AV block, or Adams-Stokes syndrome due to risk of severe bradycardia and hypotension.
| Serious Effects |
Hypersensitivity to phenytoin or hydantoinsSinus bradycardiaSinoatrial blockSecond- and third-degree AV blockAdams-Stokes syndrome
| Precautions | Cardiovascular risks (hypotension, bradycardia, arrhythmias) with IV administration; hepatotoxicity; hematologic reactions (agranulocytosis, thrombocytopenia); hypersensitivity reactions (DRESS syndrome); teratogenicity (fetal hydantoin syndrome); metabolic effects (hyperglycemia, osteomalacia); gum hyperplasia; CNS effects (nystagmus, ataxia, sedation); interactions with warfarin, oral contraceptives, and antiretrovirals. |
| Food/Dietary | Avoid alcohol; may increase CNS depression. Enteral tube feeding may reduce phenytoin absorption; hold tube feeding 2 hours before and after dose. Calcium supplements, antacids, and dairy products may decrease absorption; space 2-3 hours apart. Folic acid supplementation may be needed due to phenytoin-induced folate deficiency. Grapefruit juice may increase phenytoin levels; avoid concurrent use. |
Loading safety data…
| Lactation Rating | L2 (Limited Data - Compatible) |
| Teratogenic Risk | First trimester: Increased risk of major congenital malformations, including orofacial clefts, cardiac defects, and neural tube defects (fetal hydantoin syndrome). Second trimester: Continued risk of growth restriction and neurodevelopmental effects. Third trimester: Risk of neonatal hemorrhage due to vitamin K deficiency; withdrawal symptoms in neonates. |
| Fetal Monitoring | Maternal: Serum phenytoin concentrations (total and free), liver function tests, complete blood count, folate levels. Fetal: Ultrasound for anatomy (18-20 weeks), fetal echocardiography; consider amniocentesis for high-risk cases. Neonatal: Observe for withdrawal, hemorrhage, and sedation. |
| Fertility Effects | Phenytoin may reduce efficacy of oral contraceptives via enzyme induction, leading to contraceptive failure. No direct fertility impairment in males or females reported, but hormonal changes may affect menstrual regularity. |
| Clinical Pearls | Phenytoin (PHENYTEX) is a narrow therapeutic index drug; monitor free phenytoin levels in hypoalbuminemia or renal impairment. Fosphenytoin is preferred for IV loading due to lower risk of infusion-site reactions. Avoid IM administration due to erratic absorption. Phenytoin induces CYP3A4 and CYP2C9; adjust doses of warfarin, oral contraceptives, and antiretrovirals. Gingival hyperplasia is common; emphasize oral hygiene. Use with caution in porphyria. |
| Patient Advice | Take phenytoin exactly as prescribed; do not change dose or stop without consulting your doctor. · Swallow tablets whole; do not crush or chew. Suspension must be shaken well before each use. · Notify your doctor if you develop rash, fever, swollen lymph nodes, or jaundice (signs of severe hypersensitivity). · Avoid sudden discontinuation to prevent rebound seizures. · Maintain good oral hygiene and visit dentist regularly to prevent gum overgrowth. · Use reliable contraception as phenytoin reduces efficacy of hormonal birth control. · Report any unusual bleeding or bruising (risk of vitamin K deficiency). · Do not drive or operate heavy machinery until you know how phenytoin affects you; may cause dizziness or drowsiness. |