Cazep CR

• Epilepsy:
  Treatment of partial seizures with complex symptomatology, generalized tonic-clonic seizures, and mixed seizure patterns.
• Trigeminal Neuralgia:
  Management of pain associated with trigeminal neuralgia.
• Bipolar Disorder:
  Used for acute manic and mixed episodes, and maintenance treatment to prevent mood swings.
• Off-label Uses:
  Neuropathic pain syndromes, glossopharyngeal neuralgia, and alcohol withdrawal syndrome.

• Adults (Epilepsy):
  Initial dose: 100 mg twice daily.
  Maintenance dose: 800–1200 mg daily divided into 2–4 doses. Maximum dose may reach 1600 mg/day in divided doses.
• Pediatrics:
  Initial dose: 10–20 mg/kg/day in divided doses.
  Maintenance: Adjust based on clinical response and serum levels.
• Trigeminal Neuralgia:
  Start with 100 mg twice daily, titrate to effective dose, usually 200–1200 mg/day in divided doses.
• Bipolar Disorder:
  Typical dose range: 400–1200 mg/day in divided doses.
• Dose Adjustments:
  Reduce dose in hepatic impairment.
  In renal impairment, monitor plasma levels closely.
• Administration:
  Oral tablets or suspension, taken with food to reduce GI irritation.

Carbamazepine stabilizes the inactivated state of voltage-gated sodium channels in neuronal membranes, inhibiting repetitive neuronal firing and reducing synaptic propagation of excitatory impulses. This suppression of high-frequency neuronal discharge diminishes seizure activity and reduces neuropathic pain transmission. Additionally, carbamazepine modulates glutamate release and may affect central neurotransmitter systems involved in mood regulation.

• Absorption:
  Well absorbed orally with peak plasma levels reached in 4–8 hours.
• Bioavailability:
  Approximately 70–85%.
• Distribution:
  Widely distributed; plasma protein binding around 75%.
• Metabolism:
  Extensively metabolized in the liver primarily by CYP3A4 to active metabolite carbamazepine-10,11-epoxide.
• Half-life:
  Initially 25–65 hours; with chronic dosing 12–17 hours due to autoinduction.
• Elimination:
  Excreted in urine mainly as metabolites.

• Pregnancy:
  FDA Category D. Associated with risk of congenital malformations including neural tube defects; use only if benefits outweigh risks.
• Lactation:
  Excreted in breast milk; potential for adverse effects in nursing infants. Caution advised.

• Primary: Antiepileptic
• Subclass: Sodium channel blocker

• Known hypersensitivity to carbamazepine or tricyclic antidepressants.
• History of bone marrow depression.
• Use in patients with atrioventricular block or concurrent use of monoamine oxidase inhibitors (MAOIs).
• Severe hepatic impairment.

• Risk of serious dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), particularly in patients with HLA-B*1502 allele.
• Blood dyscrasias: monitor for aplastic anemia and agranulocytosis.
• Hyponatremia risk due to SIADH.
• Hepatotoxicity; monitor liver function tests.
• Risk of dizziness, drowsiness affecting ability to drive or operate machinery.
• Monitor serum levels for toxicity and therapeutic range.
• Potential for drug dependence and withdrawal seizures upon abrupt discontinuation.

Common:

• Dizziness, drowsiness, ataxia
• Nausea, vomiting
• Diplopia, blurred vision
• Hyponatremia
• Rash

Serious/Rare:

• Stevens-Johnson syndrome, toxic epidermal necrolysis
• Aplastic anemia, agranulocytosis
• Hepatitis
• Cardiac conduction abnormalities
• Suicidal ideation

• CYP3A4 Inducer:
  Carbamazepine induces its own metabolism and metabolism of other drugs (e.g., warfarin, oral contraceptives, phenytoin).
• CYP3A4 Inhibitors:
  May increase carbamazepine levels, risking toxicity.
• Other CNS depressants:
  Additive sedation and respiratory depression risk.
• MAO inhibitors:
  Contraindicated due to risk of hypertensive crisis.
• Grapefruit juice:
  May increase carbamazepine plasma concentration.

• Genetic testing for HLA-B*1502 allele recommended in patients of Asian descent before initiation to reduce risk of severe cutaneous adverse reactions.
• Updated recommendations emphasize slow titration to minimize CNS adverse effects.
• Monitoring guidelines stress regular CBC and liver function tests during therapy.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Keep out of reach of children.