Keppra

# Keppra ## Overview - **Classification**: Anticonvulsant, pyrrolidine derivative. - **Mechanism**: Binds to synaptic vesicle protein 2A (SV2A) in the brain, modulating neurotransmitter release. ## Primary Indications 1. **Partial-Onset Seizures (POS)** - Adjunctive therapy in patients ≥1 month, monotherapy in patients ≥4 years. 2. **Myoclonic Seizures** - Adjunctive therapy in patients ≥12 years with Juvenile Myoclonic Epilepsy (JME). 3. **Primary Generalized Tonic-Clonic Seizures (PGTCS)** - Adjunctive therapy in patients ≥6 years with Idiopathic Generalized Epilepsy. ## Adult Dosing ### Standard Dosing **Partial-Onset Seizures (POS)** - **Dose**: Initial **500 mg PO BID** - **Frequency**: Twice daily - **Route**: Oral (immediate-release or extended-release) or IV - **Titration**: Increase by **500 mg/day** every 2 weeks. - **Maintenance**: **1000 mg** to **3000 mg/day** in 2 divided doses. - **Maximum**: **3000 mg/day** **Myoclonic Seizures (JME) & Primary Generalized Tonic-Clonic Seizures (PGTCS)** - **Dose**: Initial **500 mg PO BID** - **Frequency**: Twice daily - **Route**: Oral (immediate-release) - **Titration**: Increase by **1000 mg/day** every 2 weeks. - **Maintenance**: **1000 mg** to **3000 mg/day** in 2 divided doses. - **Maximum**: **3000 mg/day** **IV Administration** (for POS, Myoclonic, PGTCS) - **Dose**: Equivalent to oral dose (e.g., initial **500 mg IV BID**) - **Frequency**: Twice daily - **Route**: Intravenous infusion over **15 minutes** ### Dose Adjustments - **Renal Impairment**: Requires significant dose adjustment. - CrCl 50-79 mL/min: **500-1500 mg PO BID** - CrCl 30-49 mL/min: **250-750 mg PO BID** - CrCl <30 mL/min (non-dialysis): **250-500 mg PO BID** - ESRD on dialysis: **500-1000 mg PO QD** plus a **250-500 mg supplemental dose** post-dialysis. - **Hepatic Impairment**: No specific dose adjustment for mild-to-moderate. Severe impairment (Child-Pugh C) may require reduction if CrCl is also low. - **Elderly Patients**: Start at the lower end of the dosing range and titrate slowly due to potential age-related decline in renal function. ## Pediatric Dosing ### Neonates (0-28 days) - Off-label use for neonatal seizures - **Dose**: Initial **10 mg/kg IV/PO Q12H** - **Frequency**: Every 12 hours - **Maximum**: Up to **60 mg/kg/day** (in divided doses). - **Special Notes**: Monitor closely for sedation. Oral solution preferred. ### Infants (1-12 months) - Partial-onset seizures - **Dose**: Initial **10 mg/kg PO BID** - **Frequency**: Twice daily - **Titration**: Increase by **20 mg/kg/day** every 2 weeks. - **Maximum**: **50 mg/kg/day** in 2 divided doses. ### Children (1-12 years) **Partial-Onset Seizures** - **Dose**: Initial **10 mg/kg PO BID** - **Frequency**: Twice daily - **Titration**: Increase by **20 mg/kg/day** every 2 weeks. - **Maximum**: **60 mg/kg/day** (not to exceed **3000 mg/day**). **Myoclonic Seizures (12+ years only) & PGTCS (6+ years only)** - **Dose**: Initial **10 mg/kg PO BID** - **Frequency**: Twice daily - **Titration**: Increase by **20 mg/kg/day** every 2 weeks. - **Maximum**: **60 mg/kg/day** (not to exceed **3000 mg/day**). ### Adolescents (13-18 years) - **Dose**: Approach adult dosing. Initial **250-500 mg PO BID**. - **Frequency**: Twice daily - **Maximum**: **3000 mg/day**. ## Safety Information ### Contraindications - **Absolute**: Known hypersensitivity to levetiracetam or any component. ### Common Adverse Effects - **Very Common (>10%)**: Somnolence, asthenia, dizziness, infection (e.g., nasopharyngitis), headache. - **Common (1-10%)**: Anorexia, ataxia, depression, aggression, irritability, anxiety, nausea, diarrhea, vomiting. - **Serious but Rare**: Suicidal ideation, psychosis, Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), DRESS syndrome, angioedema, blood dyscrasias (e.g., neutropenia, agranulocytosis). ### Key Drug Interactions - **No significant CYP450 interactions**: Levetiracetam has minimal drug interactions. - **Methotrexate**: May decrease clearance of methotrexate. Monitor methotrexate levels. - **Oral Contraceptives**: No known interaction. - **Other AEDs**: Does not significantly affect levels of other anti-epileptic drugs. ## Monitoring & Follow-up - **Before Treatment**: Baseline renal function (CrCl). No other routine labs needed. - **During Treatment**: - Monitor for seizure control and adverse effects, especially neuropsychiatric changes (irritability, aggression, depression, suicidal thoughts). - Assess renal function periodically, particularly in the elderly or those with changing clinical status. - Consider CBC with differential if patient develops signs of infection or unexplained weakness. - **Clinical Signs**: Watch for behavioral changes (agitation, hostility), mood disturbances, severe skin reactions, signs of infection. ## Clinical Pearls - 💡 **Titration**: Gradual titration over weeks helps minimize initial CNS side effects like somnolence and dizziness. - 💡 **Renal Adjustment**: Dose adjustment based on CrCl is crucial due to primary renal elimination. - 💡 **Behavioral AEs**: Counsel patients and caregivers on potential for irritability, aggression, depression, or psychosis; report immediately. - 💡 **Formulations**: Available as immediate-release tablets, extended-release tablets (once daily), oral solution, and IV formulation. IV is bioequivalent to oral. - 💡 **Withdrawal**: Do not abruptly discontinue; taper slowly over at least 2-4 weeks to minimize risk of increased seizure frequency. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.