TEGRETOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TEGRETOL (TEGRETOL).
Voltage-gated sodium channel blocker; stabilizes neuronal membranes and inhibits repetitive firing. Also inhibits glutamate release and enhances GABA activity.
| 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. |
| Molecular Weight | 236.27 |
| 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 |
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. |
| 1st trimester | Associated with increased risk of neural tube defects (e.g., spina bifida) and other congenital malformations including craniofacial defects, cardiovascular anomalies, and hypospadias. Use only if benefit outweighs risk; consider folic acid supplementation. |
| 2nd trimester | Increased risk for developmental delay, microcephaly, and growth restriction. Monitor for fetal anomalies and adjust dose to lowest effective level. |
| 3rd trimester | Risk of neonatal hemorrhage due to vitamin K deficiency, coagulopathy, and withdrawal symptoms (including seizures). Administer vitamin K to neonate and monitor for bleeding. |
Clinical note
Comprehensive clinical and safety monograph for TEGRETOL (TEGRETOL).
| Placental transfer | Carbamazepine freely crosses the placenta, with cord blood concentrations approximately 50-80% of maternal serum levels. |
| Breastfeeding | Carbamazepine is excreted into breast milk at low concentrations (2-5% of maternal weight-adjusted dose). The American Academy of Pediatrics considers it compatible with breastfeeding, but monitor infant for drowsiness, poor sucking, and possible hepatic effects. High doses may require infant monitoring for adverse effects. |
■ FDA Black Box Warning
Aplastic anemia and agranulocytosis (rare but fatal); monitor CBC before and during therapy. Also contraindicated with MAOIs and certain conditions.
| Serious Effects |
Known hypersensitivity to carbamazepine or tricyclic antidepressants (e.g., amitriptyline)History of bone marrow depression (e.g., agranulocytosis, aplastic anemia)Concomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuationAcute intermittent porphyriaSevere hepatic impairment or active liver diseaseAV heart blockCoadministration with nefazodone or delavirdine
| 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). |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase carbamazepine levels. Take with food to reduce gastrointestinal irritation. High-fat meals may increase rate of absorption but not extent; consistency is key. No other significant food restrictions, but a consistent dietary pattern is advised to maintain stable drug levels. |
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| Lactation Rating | L2 (Safer) |
| 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 | Serum carbamazepine levels, complete blood count, liver function tests, and electrolytes. Fetal ultrasound for neural tube defects and anatomical survey. Vitamin K supplementation in third trimester for neonatal prophylaxis. |
| Fertility Effects | Carbamazepine may induce cytochrome P450 enzymes, potentially affecting sex hormone metabolism. Reported menstrual irregularities, reduced fertility, and possible decreased efficacy of oral contraceptives. No definite adverse effect on male fertility. |
| Clinical Pearls | Tegretol (carbamazepine) is an antiepileptic drug that also has mood-stabilizing properties. It induces its own metabolism via CYP3A4, requiring dose adjustments over the first few weeks. Therapeutic drug monitoring is recommended: target total carbamazepine trough levels are 4-12 mcg/mL. CBC and LFTs should be monitored at baseline and periodically due to risk of aplastic anemia and agranulocytosis. Caution in patients with HLA-B*1502 allele (Asian descent) due to increased risk of Stevens-Johnson syndrome. Avoid use with MAOIs. May reduce efficacy of oral contraceptives, warfarin, and many other drugs due to CYP induction. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly as seizure breakthrough or status epilepticus may occur. · Report any fever, sore throat, rash, mouth ulcers, easy bruising, or bleeding immediately – these could be signs of blood disorders. · May cause dizziness and drowsiness; avoid driving or operating machinery until effects are known. · Avoid alcohol; it may increase side effects like drowsiness and dizziness. · If you are of Asian ancestry, your doctor may test for a specific gene (HLA-B*1502) before starting this medication. · Do not crush or chew extended-release tablets; swallow whole. · If you use oral contraceptives, consult your doctor; Tegretol may make them less effective. · Store at room temperature, away from moisture and heat. · Do not take old medication; discard unused tablets properly. · Regular blood tests are needed to monitor drug levels and check for side effects. |