DIPHENYLAN SODIUM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DIPHENYLAN SODIUM (DIPHENYLAN SODIUM).

How it works

Phenytoin, the active component, stabilizes neuronal membranes by promoting sodium efflux and inhibiting sodium influx, thereby limiting the spread of seizure activity. It also reduces voltage-gated sodium channel activity.

What the body does with it

Metabolism	Primarily hepatic metabolism via CYP2C9 and CYP2C19 isoenzymes, with saturation kinetics at therapeutic concentrations. Major metabolite: 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH).
Excretion	Primarily hepatic metabolism via CYP450; <5% excreted unchanged in urine. Biliary/fecal excretion accounts for approximately 20-30% of metabolites.
Half-life	22 hours (range 10-34 hours); prolonged in hepatic impairment or with CYP inhibitors; correlates with time to steady state (~5 days).
Protein binding	90-95% mainly to albumin; displaces and is displaced by other highly protein-bound drugs.
Volume of Distribution	0.6-0.8 L/kg; larger in neonates (up to 1.2 L/kg); indicates extensive tissue binding, particularly in brain and adipose.
Bioavailability	Oral: 85-95% (capsules and tablets); intramuscular: 70-80% due to precipitation at injection site.
Onset of Action	Oral: 20-60 minutes; intravenous: 3-5 minutes; intramuscular: 30-120 minutes (slow and erratic absorption).
Duration of Action	Oral: 6-24 hours (dose-dependent); IV: 1-3 hours for antiarrhythmic effect; prolonged with loading dose due to tissue redistribution.

Classification & Brands

Dosing & administration

100 mg orally every 8 hours

Dosage form	CAPSULE
Renal impairment	No adjustment required for GFR >30 mL/min; for GFR 10-30 mL/min, administer every 12-24 hours; for GFR <10 mL/min, administer every 24 hours with monitoring of serum levels
Liver impairment	Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 25-50%; Child-Pugh Class C: avoid use or reduce dose by 50-75% with close monitoring
Pediatric use	5-7 mg/kg/day orally divided every 8-12 hours, not to exceed 300 mg/day
Geriatric use	Initial dose of 50 mg orally every 8 hours, titrate slowly based on response and tolerability; monitor renal function and serum levels

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DIPHENYLAN SODIUM (DIPHENYLAN SODIUM).

Breastfeeding	Diphenhydramine is excreted into breast milk in small amounts; reported M/P ratio is approximately 0.5 to 1.0. In infants, risks of drowsiness, irritability, and paradoxical excitation. Generally considered compatible with breastfeeding, but monitor infant for adverse effects.
Teratogenic Risk	First trimester: Increased risk of major congenital malformations including neural tube defects, cleft palate, and congenital heart defects. Second and third trimesters: Risks of bleeding disorders in the newborn due to vitamin K deficiency, and potential for neonatal withdrawal and growth restriction.

Warnings & precautions

■ FDA Black Box Warning

Intravenous administration: Risk of serious cardiovascular reactions including hypotension and cardiac arrest, especially in elderly patients and those with underlying cardiac disease. Rate of infusion should not exceed 50 mg/min in adults.

Side Effect Profile

Serious Effects

Absolute Contraindications

Absolute: Hypersensitivity to phenytoin, hydantoins, or any component; sinus bradycardia, sinoatrial block, second- or third-degree AV block, or Stokes-Adams syndrome (IV formulation); concurrent use with delavirdine. Relative: Pregnancy (especially first trimester; weigh risk vs benefit), hepatic impairment, alcoholism, porphyria.

Clinical Precautions

Precautions

1. Cardiovascular risk with IV administration. 2. Suicide risk and behavioral changes. 3. Hepatotoxicity (monitor LFTs). 4. Hematologic effects (agranulocytosis, thrombocytopenia). 5. Lymphadenopathy. 6. Teratogenicity (fetal hydantoin syndrome). 7. Hyperglycemia. 8. Withdrawal seizures. 9. Dermatologic reactions (Stevens-Johnson syndrome). 10. Osteoporosis with chronic use.

Clinical Tips & Counseling

Drug interactions

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DIPHENYLAN SODIUM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DIPHENYLAN SODIUM (DIPHENYLAN SODIUM).

How it works

What the body does with it

Metabolism	Primarily hepatic metabolism via CYP2C9 and CYP2C19 isoenzymes, with saturation kinetics at therapeutic concentrations. Major metabolite: 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH).
Excretion	Primarily hepatic metabolism via CYP450; <5% excreted unchanged in urine. Biliary/fecal excretion accounts for approximately 20-30% of metabolites.
Half-life	22 hours (range 10-34 hours); prolonged in hepatic impairment or with CYP inhibitors; correlates with time to steady state (~5 days).
Protein binding	90-95% mainly to albumin; displaces and is displaced by other highly protein-bound drugs.
Volume of Distribution	0.6-0.8 L/kg; larger in neonates (up to 1.2 L/kg); indicates extensive tissue binding, particularly in brain and adipose.
Bioavailability	Oral: 85-95% (capsules and tablets); intramuscular: 70-80% due to precipitation at injection site.
Onset of Action	Oral: 20-60 minutes; intravenous: 3-5 minutes; intramuscular: 30-120 minutes (slow and erratic absorption).
Duration of Action	Oral: 6-24 hours (dose-dependent); IV: 1-3 hours for antiarrhythmic effect; prolonged with loading dose due to tissue redistribution.

Classification & Brands

Dosing & administration

100 mg orally every 8 hours

Dosage form	CAPSULE
Renal impairment	No adjustment required for GFR >30 mL/min; for GFR 10-30 mL/min, administer every 12-24 hours; for GFR <10 mL/min, administer every 24 hours with monitoring of serum levels
Liver impairment	Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 25-50%; Child-Pugh Class C: avoid use or reduce dose by 50-75% with close monitoring
Pediatric use	5-7 mg/kg/day orally divided every 8-12 hours, not to exceed 300 mg/day
Geriatric use	Initial dose of 50 mg orally every 8 hours, titrate slowly based on response and tolerability; monitor renal function and serum levels

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DIPHENYLAN SODIUM (DIPHENYLAN SODIUM).

Breastfeeding	Diphenhydramine is excreted into breast milk in small amounts; reported M/P ratio is approximately 0.5 to 1.0. In infants, risks of drowsiness, irritability, and paradoxical excitation. Generally considered compatible with breastfeeding, but monitor infant for adverse effects.
Teratogenic Risk	First trimester: Increased risk of major congenital malformations including neural tube defects, cleft palate, and congenital heart defects. Second and third trimesters: Risks of bleeding disorders in the newborn due to vitamin K deficiency, and potential for neonatal withdrawal and growth restriction.