Tegretol
Tegretol
Generic Name
Tegretol
Brand Names
for Carbamazepine*
Mechanism
- Voltage‑gated sodium channel blockade: Suppresses the high‑frequency firing of neurons by prolonging the inactivated state of Na⁺ channels, thereby stabilizing hyper‑excitable neuronal membranes.
- Reduction in glutamate release: Inhibits presynaptic voltage‑sensitive Ca²⁺ currents, decreasing excitatory neurotransmission.
- Partial dentin‑spike suppression: Contributes to pain control in neuropathic conditions (e.g., trigeminal neuralgia).
These actions collectively reduce the propensity for seizure activity and neuropathic pain.
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Pharmacokinetics
| Parameter | Details |
| Absorption | Oral bioavailability 70–90 % with linear kinetics up to ~400 mg; self‑induction of metabolism begins after 3–4 days. |
| Distribution | Protein‑binding ~90 % (predominantly albumin, α‑1‑acid glycoprotein); steady‑state volume of distribution 0.5–0.8 L/kg. |
| Metabolism | Hepatic CYP3A4/2C8 mediated oxidation (humoral x‑en route). Cycle‑dependent induction leads to non‑linear clearance. |
| Excretion | Renal (70 % as metabolites); elimination half‑life 12–27 h (shorter in younger patients). |
| Drug Interactions |
• Inducers (rifampin, phenytoin, carbamazepine itself): ↑ clearance → ↓ levels. • Inhibitors (ketoconazole, fluconazole, cimetidine): ↓ clearance → ↑ toxicity. • Warfarin, oral contraceptives, clopidogrel: ↑ risk of bleeding due to CYP3A4 induction. |
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Indications
- Epilepsy: partial‑onset seizures (with or without secondary generalization); tonic‑clonic seizures (monotherapy or adjunct).
- Neuro‑pain: idiopathic trigeminal neuralgia; post‑herpetic neuralgia (limited evidence).
- Mood disorders: adjunctive therapy for bipolar disorder (maintenance phase).
- Interventional: as a short‑term anti‑arrhythmic in certain supraventricular tachycardias (rare).
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Contraindications
- Absolute Contraindications:
- Known hypersensitivity to carbamazepine or phenobarbital.
- Sepsis, blood dyscrasias (e.g., aplastic anemia, leukopenia), or severe hepatic disease.
- Absolute Warnings:
- Use pregnancy category X – teratogenic (e.g., neural tube defects).
- Carcinoma of the lip or mucosa – risk of carcinogenic potential.
- Caution:
- Pulmonary fibrosis, interstitial lung disease.
- QT prolongation if combined with other QT‑extending agents.
- Renal insufficiency → dose adjustment.
- Children: dose titration slower; watch for developmental disturbances (e.g., growth retardation).
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Dosing
| Population | Starting Dose | Maintenance Dose | Titration | Peak Trough Range (µg/mL) |
| Adults | 100 mg PO BID (or 200 mg QHS) | 400–800 mg/day (split BID) | +50 mg Q2–3 days; may up to 1200 mg/day | 10–20 |
| Children (≥12 y) | 5 mg/kg/day (max 200 mg/day) | 290–420 mg/day | +50–100 mg Q2–3 days | 10–20 |
| Elderly | Start 100 mg PO BID; reduce by 25–50 % if renal/hepatic impairment | |||
| Pregnancy (category X) | Avoid unless benefits outweigh risks | |||
| Administration | *Take with food or milk to reduce GI upset.* | *Avoid abrupt discontinuation – risk of breakthrough seizures or withdrawal euphoria.* | *Use liquid formulation or compounding for children or swallowing difficulties.* |
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Adverse Effects
| Common | Serious |
| • Dizziness, ataxia, blurred vision | • Severe hypersensitivity (drug reaction with eosinophilia and systemic symptoms – DRESS). |
| • Nausea, vomiting, rash | • Hematologic disorders (aplastic anemia, agranulocytosis). |
| • Somnolence, constipation | • Thromboembolic events (from increased platelet aggregation). |
| • Weight loss, loss of taste | • Severe skin reactions (Stevens–Johnson syndrome, toxic epidermal necrolysis). |
| • GI upset, headaches | • Hepatotoxicity (ALP/ALT/AST rise). |
| • Interaction‑related enzyme induction (e.g., warfarin warrier)** | • Liver failure (rare). |
Key point: Monitor CBC and liver enzymes early in therapy and periodically thereafter.
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Monitoring
- Serum drug levels: 10–20 µg/mL for seizure control; 15–20 µg/mL for neuropathic pain.
- CBC: baseline, then monthly for the first 3 months, then every 3–6 months.
- Liver function tests (LFTs): baseline, then at 4 weeks, 3 months, then yearly.
- Renal function: baseline, then every 6–12 months.
- Pregnancy test (women of childbearing age).
- Coagulation profile (INR) when on warfarin or other anticoagulants.
- ECG while on QT‑extending combination therapy.
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Clinical Pearls
1. Auto‑induction: Carbamazepine’s metabolism becomes more efficient after 3–4 days; thus maintain the same dose for 7–10 days before checking trough.
2. Liquid vs tablet: Liquid preparations provide better titration for kids and patients who cannot swallow tablets; keep them refrigerated.
3. Avoid sudden taper: Withdrawal can precipitate hyperexcitability and bradycardia; taper over ≥4 weeks in adolescents.
4. Drug–drug synergy: When combined with valproate, avoid high dose valproate (>400 mg/day) because of increased pancreatic irritation risk.
5. Patch test before therapy: A simple ~2–3‑day skin patch test for carbamazepine reduces the risk of severe hypersensitivity, especially in epilepsy patients with previous sulfonamide allergies.
6. Stunting risk: Children on long‑term carbamazepine may experience growth retardation—annual height/weight monitoring.
7. Teratogenicity: Inform patients that carbamazepine is category X; adequate folic acid and pregnancy planning is essential.
8. AM/PM split: For adult dosing, clinicians often prescribe 100 mg BID rather than a single high QHS dose to blunt morning flushing and improve compliance.
9. Rifampin interaction: When concurrently prescribed rifampin, carbamazepine may be ineffective; consider anticonvulsant switches (e.g., levetiracetam).
10. Serum level target for neuropathic pain: 15–20 µg/mL yields optimal benefit with acceptable toxicity?
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