PHENYTEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHENYTEX (PHENYTEX).

How it works

Stabilizes neuronal membranes by promoting sodium efflux and inhibiting calcium influx, thereby reducing repetitive firing of action potentials. Also enhances GABA-mediated inhibition.

What the body does with it

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)

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PHENYTEX (PHENYTEX).

Breastfeeding	Phenytoin is excreted in breast milk with an M/P ratio of approximately 0.18-0.45. Infant serum levels are low, but cases of sedation and poor sucking have been reported. Benefits generally outweigh risks, but monitor infant for drowsiness and adequate weight gain.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to hydantoins; history of prior acute hepatotoxicity attributable to phenytoin; sinus bradycardia, sinoatrial block, second- or third-degree AV block, or Adams-Stokes syndrome (for intravenous administration); coadministration with delavirdine.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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PHENYTEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHENYTEX (PHENYTEX).

How it works

Stabilizes neuronal membranes by promoting sodium efflux and inhibiting calcium influx, thereby reducing repetitive firing of action potentials. Also enhances GABA-mediated inhibition.

What the body does with it

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)

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PHENYTEX (PHENYTEX).

Breastfeeding	Phenytoin is excreted in breast milk with an M/P ratio of approximately 0.18-0.45. Infant serum levels are low, but cases of sedation and poor sucking have been reported. Benefits generally outweigh risks, but monitor infant for drowsiness and adequate weight gain.
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.