TEGRETOL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TEGRETOL (TEGRETOL).

How it works

Voltage-gated sodium channel blocker; stabilizes neuronal membranes and inhibits repetitive firing. Also inhibits glutamate release and enhances GABA activity.

What the body does with it

Metabolism	Hepatic via CYP3A4; induces CYP3A4, CYP2C8, CYP2C9, CYP1A2, and CYP2C19. Undergoes autoinduction.
Excretion	Primarily hepatic metabolism; ~72% excreted in urine (as metabolites, <2% unchanged), ~28% excreted in feces via bile.
Half-life	Single dose: 25–65 hours (mean ~35 h); chronic therapy: 12–17 hours due to autoinduction; clinical context: requires 3–4 weeks to reach steady-state after dose adjustment.
Protein binding	76% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8–1.4 L/kg; indicates extensive tissue distribution and penetration into CSF.
Bioavailability	Oral immediate-release: ~89%; extended-release: 85–90% (relative to immediate-release); no parenteral formulation available.
Onset of Action	Oral: 0.5–1 hour (immediate-release), 4–8 hours (extended-release); intravenous: not available; rectal: 15–30 minutes (suppository).
Duration of Action	Oral immediate-release: 6–12 hours; extended-release: 12–24 hours; clinical note: dose frequency based on half-life and formulation.

Classification & Brands

Action Class	Sodium channel modulators (AED)
Brand Substitutes	Antilep 100mg Tablet, Mezocar LA 100mg Tablet, Zigma 100mg Tablet, Mezaril Kid 100mg Tablet, Carbazep 100mg Tablet, Mezocar LA 300mg Tablet, Carbacontin 300mg Tablet, Arilep 300mg Tablet, Carbasafe 300mg Tablet, Seizurone OX 300mg Tablet

Dosing & administration

Initial: 200 mg orally twice daily; increase by 200 mg/day at weekly intervals. Maintenance: 800-1200 mg/day in 2-4 divided doses. Maximum dose: 1600 mg/day. Extended-release: 200-400 mg twice daily.

Dosage form	TABLET, CHEWABLE
Renal impairment	GFR >30 mL/min: No adjustment. GFR 10-30 mL/min: Reduce dose by 25-50%. GFR <10 mL/min: Avoid or reduce by 50%.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Contraindicated.
Pediatric use	6-12 years: Initial 100 mg orally twice daily or 10-20 mg/kg/day in 2-3 divided doses; increase weekly by 100 mg/day. Maintenance: 15-30 mg/kg/day. Maximum: 1000 mg/day.
Geriatric use	Start at low end of dosing range (200-400 mg/day in 2 divided doses). Titrate slowly due to increased risk of hyponatremia and adverse effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TEGRETOL (TEGRETOL).

Breastfeeding	Limited data; carbamazepine is excreted into breast milk. M/P ratio approximately 0.4-0.6. Infant plasma levels are low but monitor for sedation, poor suckling, and rash. Benefits generally outweigh risks.
Teratogenic Risk	First trimester: Increased risk of neural tube defects, craniofacial anomalies, and hypospadias. Second and third trimesters: Risk of developmental delay, microcephaly, and coagulation disorders due to Vitamin K deficiency.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Aplastic anemia and agranulocytosis (rare but fatal); monitor CBC before and during therapy. Also contraindicated with MAOIs and certain conditions.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of bone marrow suppression, hypersensitivity to carbamazepine or tricyclic antidepressants (cross-sensitivity), concomitant use of MAOIs (within 14 days), and concomitant use of nefazodone or delayirdine.

Clinical Precautions

Precautions

Stevens-Johnson syndrome/toxic epidermal necrolysis (associated with HLA-B*1502 in Asian populations), hyponatremia, SIADH, hepatic porphyria, decreased thyroid function, drowsiness, dizziness, ataxia, and teratogenicity (increased risk of neural tube defects).

Clinical Tips & Counseling

Drug interactions

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TEGRETOL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TEGRETOL (TEGRETOL).

How it works

Voltage-gated sodium channel blocker; stabilizes neuronal membranes and inhibits repetitive firing. Also inhibits glutamate release and enhances GABA activity.

What the body does with it

Metabolism	Hepatic via CYP3A4; induces CYP3A4, CYP2C8, CYP2C9, CYP1A2, and CYP2C19. Undergoes autoinduction.
Excretion	Primarily hepatic metabolism; ~72% excreted in urine (as metabolites, <2% unchanged), ~28% excreted in feces via bile.
Half-life	Single dose: 25–65 hours (mean ~35 h); chronic therapy: 12–17 hours due to autoinduction; clinical context: requires 3–4 weeks to reach steady-state after dose adjustment.
Protein binding	76% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8–1.4 L/kg; indicates extensive tissue distribution and penetration into CSF.
Bioavailability	Oral immediate-release: ~89%; extended-release: 85–90% (relative to immediate-release); no parenteral formulation available.
Onset of Action	Oral: 0.5–1 hour (immediate-release), 4–8 hours (extended-release); intravenous: not available; rectal: 15–30 minutes (suppository).
Duration of Action	Oral immediate-release: 6–12 hours; extended-release: 12–24 hours; clinical note: dose frequency based on half-life and formulation.

Classification & Brands

Action Class	Sodium channel modulators (AED)
Brand Substitutes	Antilep 100mg Tablet, Mezocar LA 100mg Tablet, Zigma 100mg Tablet, Mezaril Kid 100mg Tablet, Carbazep 100mg Tablet, Mezocar LA 300mg Tablet, Carbacontin 300mg Tablet, Arilep 300mg Tablet, Carbasafe 300mg Tablet, Seizurone OX 300mg Tablet

Dosing & administration

Initial: 200 mg orally twice daily; increase by 200 mg/day at weekly intervals. Maintenance: 800-1200 mg/day in 2-4 divided doses. Maximum dose: 1600 mg/day. Extended-release: 200-400 mg twice daily.

Dosage form	TABLET, CHEWABLE
Renal impairment	GFR >30 mL/min: No adjustment. GFR 10-30 mL/min: Reduce dose by 25-50%. GFR <10 mL/min: Avoid or reduce by 50%.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Contraindicated.
Pediatric use	6-12 years: Initial 100 mg orally twice daily or 10-20 mg/kg/day in 2-3 divided doses; increase weekly by 100 mg/day. Maintenance: 15-30 mg/kg/day. Maximum: 1000 mg/day.
Geriatric use	Start at low end of dosing range (200-400 mg/day in 2 divided doses). Titrate slowly due to increased risk of hyponatremia and adverse effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TEGRETOL (TEGRETOL).

Breastfeeding	Limited data; carbamazepine is excreted into breast milk. M/P ratio approximately 0.4-0.6. Infant plasma levels are low but monitor for sedation, poor suckling, and rash. Benefits generally outweigh risks.
Teratogenic Risk	First trimester: Increased risk of neural tube defects, craniofacial anomalies, and hypospadias. Second and third trimesters: Risk of developmental delay, microcephaly, and coagulation disorders due to Vitamin K deficiency.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Aplastic anemia and agranulocytosis (rare but fatal); monitor CBC before and during therapy. Also contraindicated with MAOIs and certain conditions.