Keppra
Keppra
Generic Name
Keppra
Mechanism
- Binding to synaptic vesicle protein 2A (SV2A) – modulates neurotransmitter release, reducing hyperexcitability.
- Stabilizes neuronal membranes – limits rapid depolarization, preventing seizure propagation.
- Minimal interactions with GABA, glutamate, or voltage‑gated ion channels, accounting for its favorable side‑effect profile.
Pharmacokinetics
| Parameter | Value | Notes |
| Absorption | Rapid, >99 % oral bioavailability | Peak plasma 1–2 h |
| Distribution | ~30 % protein‑bound | Despite modest binding, CNS penetration is adequate. |
| Metabolism | Primarily renal excretion unchanged | Limited hepatic metabolism → low drug‑drug interactions. |
| Half‑life | 7–12 h (depends on renal function) | Dose adjustment required for severe CKD. |
| Special Populations |
• CKD: extend dosing interval or lower dose. • Pregnancy: animal data show no teratogenicity, but human data limited. |
Indications
- Adjunctive therapy for partial‑onset seizures in adults and children ≥1 yr.
- Myoclonic seizures in juvenile myoclonic epilepsy.
- Primary generalized tonic‑clonic seizures (off‑label, limited data).
- Acutely for status epilepticus after first‑line agents fail (US FDA “rescue” label).
Contraindications
- Absolute Contraindication: Hypersensitivity to levetiracetam or any excipient.
- Warnings: Use cautiously in severe renal impairment; monitor serum creatinine.
- Medication interactions:
- Strong inhibitors of CYP3A4 may indirectly alter levetiracetam exposure via drug‑interaction with other co‑administered AEDs (e.g., valproate).
- Cimetidine reduces plasma levels in a dose‑dependent manner.
- Psychiatric risk: Mood instability, irritability, and suicidal ideation reported in ~2 % of patients; monitor closely.
Dosing
- Adult (≥18 yr)
- *Focal seizures*: 1000 mg BID; titrate 500 mg BID every 2–4 weeks up to 3000 mg/day.
- *Myoclonic seizures*: 1000 mg BID; titrate to 2000–3000 mg/day.
- Pediatric (1–17 yr)
- 20 mg/kg/day divided BID ➜ titrate 10 mg/kg/day every 2–4 weeks.
- Renal dosing (CrCl < 50 mL/min): Cut dose by 50 % and halve dosing interval.
- Formulations: Oral tablets, oral solution, and IV 100 mg/mL (pre‑filled syringe).
- Tapering: Must be performed slowly (≥2 weeks) to avoid seizure rebound.
Adverse Effects
| Adverse Effect | Incidence | Notes |
| Somnolence, dizziness | 5–15 % | Often dose‑related; adjust schedule. |
| Mood changes (irritability, aggression) | ~2 % | Intensive monitoring; consider psychiatric assessment if persistent. |
| Weight loss | <5 % | Rare; usually transient. |
| Lead poisoning | – | One case of lead‑induced neurological sequelae in a malnourished child; ensure proper handling of IV formulation. |
| Non‑serious GI symptoms (nausea, vomiting) | <5 % | Bypass by taking with food. |
| Serious: Rare anaphylaxis, severe rash, and rare cases of seizures due to dose withdrawal. |
Monitoring
- Renal function: Creatinine, eGFR at baseline, every 3 months, or when dose is titrated.
- Serum levetiracetam (optional): Only in special scenarios (renal impairment, suspected non‑adherence).
- Psychiatric evaluation: Baseline and every 6 months, or if mood changes.
- Pregnancy: Routine obstetric monitoring; no mandatory cessation.
Clinical Pearls
- Rapid onset: Levetiracetam peaks within 1–2 h; ideal for patients needing urgent seizure control (e.g., status epilepticus).
- Minimal CYP interactions → safe to co‑administer with polytherapy AEDs (valproate, carbamazepine, phenytoin).
- “Quiet” side‑effect profile makes it a first‐line adjunct in patients who are sensitive to sedation.
- Renal dose adjustment guidelines are exact**: if CrCl < 30 mL/min, 500 mg BID; 50 % in a single step; a 2‑week taper may prevent withdrawal seizures.
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• *Reference Advisory:* Use reputable pharmaco‑resources such as *Current Medical Pharmacology* or the *UpToDate* levetiracetam review for the latest clinical guidance.