TEGRETOL-XR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TEGRETOL-XR (TEGRETOL-XR).

How it works

Carbamazepine stabilizes inactivated state of voltage-gated sodium channels, thereby inhibiting repetitive neuronal firing and reducing synaptic transmission.

What the body does with it

Metabolism	Hepatic via CYP3A4; also metabolized by CYP2C8. Carbamazepine induces its own metabolism and that of other drugs via CYP3A4.
Excretion	Renal: ~72% as unchanged drug and metabolites (primarily glucuronides). Fecal: ~28% via bile (enterohepatic recirculation possible).
Half-life	Initial: 25-65 hours; chronic dosing: 12-17 hours due to autoinduction. Steady-state reached in 2-4 weeks.
Protein binding	75-90% primarily to albumin; binding is concentration-dependent and saturable at high doses.
Volume of Distribution	0.8-1.4 L/kg; approximately 0.8 L/kg in adults. Signifies distribution into total body water and tissues.
Bioavailability	Extended-release tablets: ~89% relative to immediate-release; food does not affect extent but may delay absorption (Cmax reduced by ~30%).
Onset of Action	Oral extended-release: 1-2 weeks for therapeutic anticonvulsant effect; acute analgesic effect for trigeminal neuralgia: 24-48 hours.
Duration of Action	Extended-release formulation maintains therapeutic levels for 12-24 hours with twice-daily dosing. Autoinduction may reduce duration over time.

Classification & Brands

Dosing & administration

200-400 mg orally twice daily; maximum 1200 mg/day for monotherapy, 1600 mg/day for combination therapy.

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	CrCl <10 mL/min: avoid use. CrCl 10-50 mL/min: reduce dose by 25-50% and monitor levels.
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 twice daily, increase by 100 mg/day weekly; maintenance 15-30 mg/kg/day in 2 divided doses. <6 years: 10-20 mg/kg/day in 2-3 divided doses; maximum 35 mg/kg/day.
Geriatric use	Start at lower end of dosing range (200 mg/day) due to increased sensitivity; monitor for hyponatremia and ataxia.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TEGRETOL-XR (TEGRETOL-XR).

Breastfeeding	Carbamazepine is excreted in breast milk with an M/P ratio of 0.24-0.69. Infant serum levels are 6-65% of maternal levels. Monitor infant for drowsiness, poor suckling, and rash. Benefits generally outweigh risks; however, consider alternative if infant develops adverse effects.
Teratogenic Risk	Pregnancy Category D. First trimester exposure increases risk of neural tube defects (spina bifida, 1%), craniofacial anomalies, and congenital heart defects. Second and third trimester exposure may cause fetal anticonvulsant syndrome (growth retardation, developmental delay) and neonatal hemorrhage due to vitamin K deficiency. Risk of major malformations is 2-3 times baseline.

Warnings & precautions

■ FDA Black Box Warning

Aplastic anemia and agranulocytosis have been reported in association with carbamazepine therapy. Patients should be informed of the early signs and symptoms of hematologic disorders.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of bone marrow depression","Hypersensitivity to carbamazepine or tricyclic antidepressants","Use of MAOIs within 14 days","Concomitant use of linezolid or methylene blue","Acute intermittent porphyria","HLA-B*1502 allele in patients of Asian ancestry at higher risk for SJS/TEN"]

Clinical Precautions

Precautions

["Hematologic toxicity: monitor CBC at baseline and periodically","Severe dermatologic reactions (e.g., SJS, TEN, DRESS) especially in HLA-B*1502-positive patients","Hyponatremia, SIADH","Hepatic effects: monitor LFTs","Cardiovascular effects: AV block, bradycardia","Suicidal ideation/behavior","Central nervous system effects: dizziness, drowsiness, ataxia","Increased intraocular pressure","Potential for fetal harm (pregnancy category D)","Drug interactions: induces CYP3A4, inhibits CYP2C9/2C19"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

TEGRETOL-XR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TEGRETOL-XR (TEGRETOL-XR).

How it works

Carbamazepine stabilizes inactivated state of voltage-gated sodium channels, thereby inhibiting repetitive neuronal firing and reducing synaptic transmission.

What the body does with it

Metabolism	Hepatic via CYP3A4; also metabolized by CYP2C8. Carbamazepine induces its own metabolism and that of other drugs via CYP3A4.
Excretion	Renal: ~72% as unchanged drug and metabolites (primarily glucuronides). Fecal: ~28% via bile (enterohepatic recirculation possible).
Half-life	Initial: 25-65 hours; chronic dosing: 12-17 hours due to autoinduction. Steady-state reached in 2-4 weeks.
Protein binding	75-90% primarily to albumin; binding is concentration-dependent and saturable at high doses.
Volume of Distribution	0.8-1.4 L/kg; approximately 0.8 L/kg in adults. Signifies distribution into total body water and tissues.
Bioavailability	Extended-release tablets: ~89% relative to immediate-release; food does not affect extent but may delay absorption (Cmax reduced by ~30%).
Onset of Action	Oral extended-release: 1-2 weeks for therapeutic anticonvulsant effect; acute analgesic effect for trigeminal neuralgia: 24-48 hours.
Duration of Action	Extended-release formulation maintains therapeutic levels for 12-24 hours with twice-daily dosing. Autoinduction may reduce duration over time.

Classification & Brands

Dosing & administration

200-400 mg orally twice daily; maximum 1200 mg/day for monotherapy, 1600 mg/day for combination therapy.

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	CrCl <10 mL/min: avoid use. CrCl 10-50 mL/min: reduce dose by 25-50% and monitor levels.
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 twice daily, increase by 100 mg/day weekly; maintenance 15-30 mg/kg/day in 2 divided doses. <6 years: 10-20 mg/kg/day in 2-3 divided doses; maximum 35 mg/kg/day.
Geriatric use	Start at lower end of dosing range (200 mg/day) due to increased sensitivity; monitor for hyponatremia and ataxia.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TEGRETOL-XR (TEGRETOL-XR).

Breastfeeding	Carbamazepine is excreted in breast milk with an M/P ratio of 0.24-0.69. Infant serum levels are 6-65% of maternal levels. Monitor infant for drowsiness, poor suckling, and rash. Benefits generally outweigh risks; however, consider alternative if infant develops adverse effects.
Teratogenic Risk	Pregnancy Category D. First trimester exposure increases risk of neural tube defects (spina bifida, 1%), craniofacial anomalies, and congenital heart defects. Second and third trimester exposure may cause fetal anticonvulsant syndrome (growth retardation, developmental delay) and neonatal hemorrhage due to vitamin K deficiency. Risk of major malformations is 2-3 times baseline.

Warnings & precautions

■ FDA Black Box Warning

Aplastic anemia and agranulocytosis have been reported in association with carbamazepine therapy. Patients should be informed of the early signs and symptoms of hematologic disorders.