Trileptal - Drug Monograph

Introduction

Trileptal (oxcarbazepine) is an antiepileptic drug (AED) structurally derived from carbamazepine. It is approved by the FDA for use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults and children with epilepsy. First approved in the United States in 2000, Trileptal offers a favorable side effect profile compared to older antiepileptic medications and has become a widely used therapeutic option in neurology practice.

Mechanism of Action

Oxcarbazepine exerts its antiepileptic effects primarily through blockade of voltage-sensitive sodium channels, stabilizing hyperexcited neuronal membranes, inhibiting repetitive neuronal firing, and diminishing synaptic impulse propagation. The drug's main active metabolite, 10-monohydroxy derivative (MHD), is largely responsible for its pharmacological activity. Unlike carbamazepine, oxcarbazepine does not form reactive epoxide metabolites, which contributes to its improved safety profile.

Indications

• FDA-approved indications:

- Monotherapy or adjunctive therapy for partial seizures in adults - Monotherapy or adjunctive therapy for partial seizures in children aged 4-16 years - Adjunctive therapy for partial seizures in children aged 2-4 years

• Off-label uses:

- Bipolar disorder maintenance therapy - Neuropathic pain conditions (trigeminal neuralgia, diabetic neuropathy) - Borderline personality disorder (mood stabilization)

Dosage and Administration

• Initial: 300 mg twice daily
• May increase by 300 mg/day every third day to a dose of 1200 mg/day
• Target maintenance dose: 1200-2400 mg/day

• Initial: 300 mg twice daily
• May increase by 600 mg/day at weekly intervals
• Recommended dose: 600-2400 mg/day

• Children 2-4 years: Initial 8-10 mg/kg/day divided twice daily, not to exceed 600 mg/day
• Children 4-16 years: Based on weight:

- 20-29 kg: 900 mg/day - 29.1-39 kg: 1200 mg/day - >39 kg: 1800 mg/day

• Renal impairment: Dose adjustment required for CrCl <30 mL/min
• Hepatic impairment: No dosage adjustment needed for mild to moderate impairment; use with caution in severe impairment
• Elderly: Initiate at lower doses due to possible decreased renal function
• Pregnancy: Category C; use only if potential benefit justifies potential risk

Pharmacokinetics

• Absorption: Completely absorbed after oral administration; bioavailability approximately 100%
• Distribution: Volume of distribution: 49 L for MHD; 40% protein binding
• Metabolism: Rapidly reduced to active metabolite MHD; extensive hepatic metabolism via cytosolic enzymes
• Elimination: Renal excretion (95% as MHD glucuronide conjugates); half-life of MHD: 8-10 hours
• Time to peak concentration: 4.5 hours for MHD

Contraindications

• Hypersensitivity to oxcarbazepine, eslicarbazepine, or any component of the formulation
• History of hypersensitivity reaction to carbamazepine (cross-reactivity approximately 25-30%)

Warnings and Precautions

• Hyponatremia: May occur in up to 25% of patients; monitor sodium levels, especially during initiation and dose titration
• Serious dermatological reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis (monitor for skin reactions)
• Suicidal behavior and ideation: Antiepileptic drugs increase risk of suicidal thoughts or behavior
• Withdrawal seizures: Abrupt discontinuation may increase seizure frequency; taper gradually
• Cognitive effects: May cause dizziness, somnolence, ataxia, and visual disturbances
• Multi-organ hypersensitivity reactions: Monitor for fever, rash, and organ involvement
• Hematologic effects: Reports of leukopenia, thrombocytopenia, and agranulocytosis

Drug Interactions

• Strong CYP3A4 inducers: Phenytoin, phenobarbital, rifampin (may decrease MHD concentrations)
• Oral contraceptives: May reduce efficacy of hormonal contraceptives (recommend additional non-hormonal contraception)
• Calcium channel blockers: Felodipine concentrations may be reduced
• Other CNS depressants: Enhanced sedative effects with alcohol, benzodiazepines, opioids
• Carbamazepine: May decrease MHD concentrations by 40%

Adverse Effects

• Dizziness (22-49%)
• Somnolence (20-36%)
• Diplopia (5-15%)
• Fatigue (15%)
• Nausea (14-29%)
• Headache (13-32%)
• Ataxia (5-31%)
• Vomiting (7-36%)

• Hyponatremia (SIADH)
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Anaphylactic reactions
• Hepatitis
• Pancreatitis
• Blood dyscrasias
• Suicidal ideation

Monitoring Parameters

• Baseline:

- Serum sodium levels - Liver function tests - Complete blood count - Pregnancy test (if applicable)

• During therapy:

- Serum sodium levels (at baseline, after 2-4 weeks, then every 3 months) - Seizure frequency and characteristics - Signs of hypersensitivity reactions - Mood changes and suicidal ideation - Cognitive and neurological effects - Adherence assessment

• Therapeutic drug monitoring:

- Not routinely required - MHD therapeutic range: 12-30 mg/L (trough levels)

Patient Education

• Take medication exactly as prescribed; do not stop abruptly
• May cause dizziness or drowsiness—avoid driving or operating machinery until effects are known
• Report any skin rash, fever, or unusual symptoms immediately
• Maintain adequate fluid intake unless contraindicated
• Use additional non-hormonal contraception if taking oral contraceptives
• Regular blood tests are necessary to monitor sodium levels
• Avoid alcohol consumption during therapy
• Keep all scheduled medical appointments
• Wear medical alert identification indicating epilepsy diagnosis and medication use
• Report mood changes, depression, or suicidal thoughts to healthcare provider

References

1. FDA Prescribing Information: Trileptal (oxcarbazepine) tablets. Revised 2022. 2. Glauser T, Ben-Menachem E, Bourgeois B, et al. ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2013;54(3):551-563. 3. French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy. Neurology. 2004;62(8):1261-1273. 4. Schmidt D, Elger CE. Practical clinical management of oxcarbazepine in epilepsy. Expert Opin Pharmacother. 2004;5(7):1597-1605. 5. Bialer M, Johannessen SI, Levy RH, et al. Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI). Epilepsy Res. 2013;103(1):2-30. 6. Patsalos PN, Berry DJ, Bourgeois BF, et al. Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008;49(7):1239-1276. 7. Mintzer S, Boppana P, Toguri J, et al. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine. Epilepsia. 2006;47(3):510-515.