Carbamazepine

# Carbamazepine ## Overview - **Classification**: Anticonvulsant, Mood Stabilizer, Neuropathic Pain Agent. - **Mechanism**: Stabilizes neuronal membranes by blocking voltage-gated sodium channels, reducing repetitive neuronal firing. Also affects calcium channels and neurotransmitter release. ## Primary Indications 1. **Epilepsy**: Partial seizures (simple and complex), generalized tonic-clonic seizures. 2. **Trigeminal Neuralgia**: Symptomatic treatment of severe pain. 3. **Bipolar Disorder**: Treatment of acute manic and mixed episodes, maintenance treatment. ## Adult Dosing ### Standard Dosing **Epilepsy & Trigeminal Neuralgia (Immediate Release - IR)** - **Initial Dose**: **200 mg** twice daily or **100 mg** 4 times daily. - **Titration**: Increase by **200 mg/day** weekly until optimal response. - **Maintenance Dose**: **800-1200 mg/day** (typically in 2-4 divided doses). - **Frequency**: 2-4 times daily (IR) or twice daily (Extended Release - XR). - **Route**: Oral. - **Maximum Dose**: **1600 mg/day** (rarely **2000 mg/day** under strict monitoring). **Bipolar Disorder (Acute Mania - IR)** - **Initial Dose**: **200 mg** twice daily. - **Titration**: Gradually increase to **400-1600 mg/day**. - **Frequency**: Twice daily (XR) or 2-4 times daily (IR). - **Route**: Oral. - **Maximum Dose**: **1600 mg/day**. ### Dose Adjustments - **Renal Impairment**: No specific dose adjustment guidelines. Use with caution. Monitor for adverse effects. - **Hepatic Impairment**: Use with caution. Monitor LFTs. Consider lower initial doses and slower titration. - **Elderly Patients**: Start with lower doses (e.g., **100 mg** twice daily). Titrate slowly due to increased sensitivity and potential for adverse effects. ## Pediatric Dosing (Immediate Release - IR) ### Neonates (0-28 days) - **Dose**: Generally avoided due to immature hepatic metabolism and toxicity risk. - **Special Notes**: If used, monitor serum levels closely due to unpredictable pharmacokinetics. ### Infants (1-12 months) - **Initial Dose**: **5 mg/kg/day** in 2-4 divided doses. - **Frequency**: 2-4 times daily. - **Titration**: Increase by **5 mg/kg/day** weekly. - **Maximum**: **20 mg/kg/day**. - **Special Notes**: Target serum levels **4-12 mcg/mL**. ### Children (1-12 years) - **Initial Dose**: **10-20 mg/kg/day** in 2-4 divided doses. - **Frequency**: 2-4 times daily. - **Titration**: Increase weekly to achieve optimal response. - **Typical Range**: **20-30 mg/kg/day**. - **Maximum**: **1000 mg/day** for children 1-5 years, **1200 mg/day** for 6-12 years. - **Special Notes**: For children <6 years, start with **100 mg** twice daily (IR) or **10 mg/kg/day**. ### Adolescents (13-18 years) - **Dose**: Approach adult dosing, starting with **200 mg** twice daily (IR). - **Titration**: Increase gradually by **200 mg/day** weekly. - **Maximum**: **1600 mg/day**. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to carbamazepine or tricyclic antidepressants. - **Absolute**: History of bone marrow depression (e.g., aplastic anemia, agranulocytosis). - **Absolute**: Concomitant use with MAOIs (within 14 days). - **Absolute**: Concomitant use with nefazodone. - **Absolute**: History of porphyria. ### Common Adverse Effects - **Very Common (>10%)**: Dizziness, somnolence, ataxia, nausea, vomiting, blurred vision. - **Common (1-10%)**: Diplopia, headache, dry mouth, rash, hyponatremia, fatigue. - **Serious but Rare**: Aplastic anemia, agranulocytosis, SJS/TEN, DRESS syndrome, hepatic failure, cardiac conduction abnormalities (e.g., AV block). ### Key Drug Interactions - **Strong CYP3A4 Inducers (e.g., rifampin, phenobarbital)**: Decrease carbamazepine levels; may require dose increase. - **Strong CYP3A4 Inhibitors (e.g., ketoconazole, fluconazole, grapefruit juice)**: Increase carbamazepine levels; risk of toxicity. - **Other Anticonvulsants (e.g., phenytoin, valproate)**: Bidirectional interactions; monitor levels of both drugs. - **Oral Contraceptives**: Decreased efficacy; advise alternative contraception. - **Warfarin**: Decreased anticoagulant effect; monitor INR closely. ## Monitoring & Follow-up - **Before Treatment**: CBC with differential, LFTs, renal function, electrolytes (Na+), ophthalmic exam. HLA-B*1502 testing (Asian descent). - **During Treatment**: CBC, LFTs, renal function, Na+ (initially monthly, then quarterly/annually). Carbamazepine serum levels. - **Clinical Signs**: Rash, fever, sore throat, mouth ulcers, easy bruising/bleeding, yellow skin/eyes, confusion, ataxia, vision changes. ## Clinical Pearls - 💡 **Autoinduction**: Carbamazepine induces its own metabolism (CYP3A4) over 2-4 weeks; dose may need to be adjusted after initial titration. - 💡 **Take with food**: To improve absorption and reduce GI upset. - 💡 **HLA-B*1502 testing**: Screen patients of Asian descent prior to initiation to identify increased risk of SJS/TEN. - 💡 **Suicidality**: Monitor for suicidal thoughts/behavior, as with all antiepileptic drugs. - 💡 **Formulations**: Do not crush or chew extended-release tablets. Suspension available for pediatric use or those unable to swallow tablets. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.