DILANTIN-30

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DILANTIN-30 (DILANTIN-30).

How it works

Stabilizes neuronal membranes by promoting sodium channel inactivation, thereby inhibiting repetitive firing of action potentials.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DILANTIN-30 (DILANTIN-30).

Breastfeeding	Phenytoin excreted into breast milk in small amounts; M/P ratio approximately 0.18-0.45. Generally considered compatible with breastfeeding, but monitor infant for drowsiness, poor feeding, and possible allergic reactions.
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.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of suicidal thoughts or behavior; monitor for changes in mood or behavior.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to phenytoin or hydantoins; sinus bradycardia, sinoatrial block, second- or third-degree AV block, or Adams-Stokes syndrome; use with delavirdine.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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DILANTIN-30

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DILANTIN-30 (DILANTIN-30).

How it works

Stabilizes neuronal membranes by promoting sodium channel inactivation, thereby inhibiting repetitive firing of action potentials.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DILANTIN-30 (DILANTIN-30).

Breastfeeding	Phenytoin excreted into breast milk in small amounts; M/P ratio approximately 0.18-0.45. Generally considered compatible with breastfeeding, but monitor infant for drowsiness, poor feeding, and possible allergic reactions.
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.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of suicidal thoughts or behavior; monitor for changes in mood or behavior.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to phenytoin or hydantoins; sinus bradycardia, sinoatrial block, second- or third-degree AV block, or Adams-Stokes syndrome; use with delavirdine.