What is the starting dose and titration regimen of zonisamide (Zonegran) for a 14-year-old male with Juvenile Myoclonic Epilepsy (JME), weighing 49kg, who is currently taking Keppra (Levetiracetam) 1250mg twice daily (bid) and Lamotrigine 100mg bid?

Zonisamide Dosing for a 14-Year-Old Male with JME

For a 14-year-old male with JME weighing 49kg who is already on Keppra 1250mg bid and Lamotrigine 100mg bid, the recommended starting dose of zonisamide is 100mg daily with titration by 100mg every 2 weeks to a goal dosage of 200-400mg daily. 1

Starting Dose and Titration Schedule

1. Initial dose: 100mg once daily
2. Titration: Increase by 100mg every 2 weeks
3. Target maintenance dose: 200-400mg daily (can be given as a single daily dose)

This titration schedule allows for monitoring of tolerability while gradually achieving therapeutic levels.

Rationale for Dosing

The recommended dosing is based on established guidelines for anticonvulsant therapy in adolescents. According to the FDA drug label, zonisamide is typically initiated at lower doses and gradually increased to minimize side effects 2. The American Academy of Neurology guidelines support this approach for adjunctive therapy in epilepsy management.

Considerations for This Patient

• Age and weight: At 14 years old and 49kg, this patient should follow the adult dosing schedule as he is above the pediatric threshold
• Current medications: The patient is already on two antiepileptic drugs (Keppra and Lamotrigine), making drug interactions an important consideration
• Type of epilepsy: JME typically responds well to broad-spectrum antiepileptic drugs, and zonisamide has shown efficacy in this syndrome 3

Monitoring Recommendations

• Monitor serum electrolytes and renal function twice annually
• Watch for potential side effects including:
  • Irritability
  • Confusion
  • Depression
  • Weight loss

Drug Interactions and Special Considerations

• Enzyme induction: Levetiracetam (Keppra) is not a significant enzyme inducer, but lamotrigine may have some effect on zonisamide metabolism
• Carbonic anhydrase inhibition: Zonisamide acts as a carbonic anhydrase inhibitor, which increases the risk of kidney stones 1
• Titration speed: While some studies suggest the possibility of more rapid loading doses 4, the standard titration is recommended for this adolescent patient to minimize adverse effects

Evidence for Efficacy in JME

Zonisamide has demonstrated effectiveness in JME with studies showing:

• 80% of patients on zonisamide monotherapy achieving good seizure control (≥50% reduction) 3
• 62% of patients becoming free of myoclonic seizures 3
• Higher retention rates for patients with generalized seizures compared to those with partial seizures 5

Common Pitfalls to Avoid

1. Rapid titration: Increasing the dose too quickly can lead to increased side effects without improved efficacy
2. Inadequate hydration: Due to the risk of kidney stones, adequate hydration should be emphasized
3. Overlooking drug interactions: While zonisamide has fewer interactions than some antiepileptic drugs, its metabolism can be affected by enzyme-inducing medications
4. Ignoring weight loss: Zonisamide can cause weight loss, which should be monitored in adolescents

By following this dosing regimen and monitoring plan, zonisamide can be safely added to this patient's current antiepileptic regimen with the goal of improved seizure control for his JME.