Oxcarbazepine

Approved Indications:

• Partial-Onset Seizures (with or without secondary generalization):
• Monotherapy in adults and children ≥4 years
• Adjunctive therapy in adults and children ≥2 years

Clinically Accepted Off-Label Uses:

• Bipolar Disorder (Acute mania and maintenance):
• Used as a mood stabilizer in patients intolerant to lithium or valproate
• Trigeminal Neuralgia:
• As an alternative to carbamazepine for neuropathic facial pain
• Peripheral Neuropathy and Neuropathic Pain:
• Off-label use in chronic pain syndromes when first-line agents are ineffective or not tolerated

Route: Oral
Administration: May be taken with or without food. Shake suspension well before each use.

Adults:

• Monotherapy:
• Start with 600 mg/day (300 mg twice daily)
• Titrate by 300 mg/day every 3 days to a typical dose of 1200 mg/day
• Maximum: 2400 mg/day, based on clinical response
• Adjunctive Therapy:
• Start with 600 mg/day in two divided doses
• Usual maintenance dose: 1200 mg/day
• Max: 2400 mg/day if tolerated

Pediatrics:

• Adjunctive Therapy (≥2 years):
• Starting dose: 8–10 mg/kg/day in two divided doses
• Usual maintenance: 30–46 mg/kg/day, not to exceed 60 mg/kg/day or 2400 mg/day
• Monotherapy (≥4 years):
• Start at 8–10 mg/kg/day, titrate as tolerated
• Maximum: 60 mg/kg/day or 2400 mg/day

Elderly:

• Begin with lower initial doses (e.g., 300 mg twice daily)
• Monitor renal function and serum sodium closely

Renal Impairment (CrCl <30 mL/min):

• Reduce starting dose to 300 mg/day, titrate cautiously
• Monitor for accumulation and adverse effects

Hepatic Impairment:

• No dose adjustment required for mild to moderate liver impairment
• Use with caution in severe hepatic dysfunction

Oxcarbazepine is a voltage-gated sodium channel blocker that stabilizes hyperexcitable neuronal membranes and inhibits repetitive neuronal firing. It is rapidly converted to its active metabolite, 10-monohydroxy derivative (MHD), which exerts the main therapeutic effects. By inhibiting sodium influx, it reduces neuronal excitability and seizure propagation. It may also affect calcium and potassium currents, contributing to its anticonvulsant and mood-stabilizing actions.

• Absorption: Rapid and complete oral absorption
• Bioavailability: ~95% (as MHD)
• Time to Peak (MHD): 4–6 hours
• Protein Binding: ~40% (MHD)
• Metabolism:
• Rapid hepatic conversion to MHD (active metabolite)
• Further metabolized via glucuronidation (not CYP-dependent)
• Half-life:
• Oxcarbazepine: 1–5 hours
• MHD: 9–11 hours
• Elimination:
• ~95% excreted in urine (as MHD and its conjugates)
• <1% excreted unchanged in feces

• Pregnancy:
• FDA Category C
• May cause fetal harm. Potential risk of neural tube defects, cleft lip/palate, and developmental delays.
• Use only if clearly needed. Recommend folic acid supplementation before and during pregnancy.
• Lactation:
• Excreted into breast milk in low concentrations
• Generally considered compatible with breastfeeding, but monitor infant for sedation, feeding issues, or rash

• Primary Class: Antiepileptic (AED)
• Subclass: Dibenzazepine derivative
• Generation: Second-generation AED (structurally related to carbamazepine)

• Hypersensitivity to oxcarbazepine or any component of the formulation
• History of hypersensitivity reaction to carbamazepine or other aromatic anticonvulsants
• Known hereditary galactose intolerance (with certain tablet excipients)
• Severe hyponatremia (<125 mmol/L), unless corrected
• Concurrent use with MAO inhibitors is not recommended

• Hyponatremia:
• Occurs in 2–30% of patients; may be asymptomatic or cause fatigue, confusion, or seizures. Monitor sodium regularly, especially in the elderly or when combined with diuretics.
• Serious Skin Reactions:
• Risk of Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN), especially in patients with HLA-B*1502 allele (prevalent in Asian populations). Genetic testing recommended before initiation in at-risk populations.
• DRESS Syndrome (Multiorgan Hypersensitivity):
• Includes fever, rash, eosinophilia, liver and kidney dysfunction. Discontinue immediately if suspected.
• CNS Effects:
• Drowsiness, dizziness, and ataxia are dose-related. Caution with driving and machinery.
• Suicidal Ideation:
• Monitor mood and behavior. Antiepileptics may increase suicide risk in some patients.
• Withdrawal Seizures:
• Do not discontinue abruptly. Taper gradually to reduce the risk of increased seizure frequency.

Common (≥1%):

• CNS: Dizziness, somnolence, fatigue, headache, ataxia, vertigo
• GI: Nausea, vomiting, abdominal pain
• Skin: Rash, pruritus
• Metabolic: Hyponatremia

Less Common:

• Diplopia, tremor, visual disturbances
• Mood swings, irritability, depression
• Weight gain

Serious (Rare):

• Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN)
• DRESS syndrome
• Aplastic anemia, leukopenia
• Hepatotoxicity
• Anaphylaxis, angioedema
• Suicidal ideation

• Oral Contraceptives:
• Oxcarbazepine induces CYP3A4, reducing contraceptive efficacy → Use alternative contraception
• CNS Depressants:
• Additive sedation with alcohol, benzodiazepines, opioids
• Phenytoin & Phenobarbital:
• May increase serum levels of these drugs → Monitor for toxicity
• Carbamazepine:
• Increased risk of cross-reactive hypersensitivity
• Valproate & Lamotrigine:
• May reduce plasma levels of these drugs
• CYP Involvement:
• Mild CYP3A4/5 induction
• Inhibits CYP2C19 (may increase phenytoin levels)

• HLA-B*1502 Testing:
• Strongly recommended in Asian populations before initiating oxcarbazepine to reduce SJS/TEN risk
• Updated Seizure Guidelines (ILAE, 2022–2023):
• Oxcarbazepine is included as a first-line or alternative AED for focal seizures in adults and children
• Suicidality Warning (FDA & EMA):
• Class-wide warning added to all antiepileptic drugs
• Therapeutic Drug Monitoring:
• Serum MHD level monitoring may be considered in specific clinical scenarios (e.g., toxicity, non-compliance)

• Tablets:
• Store at 20°C to 25°C (68°F to 77°F)
• Protect from light and moisture
• Keep in tightly closed containers
• Oral Suspension:
• Store at room temperature (15°C to 30°C)
• Do not refrigerate or freeze
• After opening, use within 7 weeks
• Shake well before each use