Keppra XR
Keppra XR
Generic Name
Keppra XR
Mechanism
- Selective modulation of synaptic vesicle protein‑2A (SV2A), altering neurotransmitter release and reducing neuronal excitability.
- Inhibits high‑frequency action‑potential firing without affecting voltage‑dependent ion channels or the GABA system.
- Lacks significant affinity for GABA_A, GABA_B, or benzodiazepine receptors, explaining its low sedative profile.
Pharmacokinetics
| Parameter | Typical value (single dose) | Notes |
| Absorption | ~97 % oral bioavailability | Peak plasma (T_max) 1–2 h; XR provides steady rise over 4–6 h. |
| Distribution | Volume of distribution ≈0.1 L/kg | Protein binding <10 % (minimal displacement). |
| Metabolism | Non‑CYP mediated; ~90 % excreted unchanged | Minimal drug‑drug interaction potential. |
| Elimination | Renal clearance ≈72 % of dose | Clearance reduced in severe renal impairment; dose adjustment required. |
| Half‑life | 7 h (XR) vs 4 h (IR) | XR formulation supports BID dosing. |
Indications
- Adjunctive therapy for partial‑onset seizures in adults and children ≥2 years.
- Maintenance therapy for myoclonic seizures (e.g., juvenile myoclonic epilepsy).
- Not approved for the treatment of status epilepticus or tonic‑clonic seizures alone.
Contraindications
- Contraindicated in patients with known hypersensitivity to levetiracetam or any formulation component.
- Caution in severe renal impairment (CrCl < 30 mL/min); dose adjustment or discontinuation may be necessary.
- Behavioral/psychiatric warning: increased risk of agitation, irritability, aggression, depression, and suicidal thoughts; psychiatric evaluation recommended for patients with mood disorder history.
Dosing
| Population | Starting Dose | Titration | Maintenance | Formulation |
| Adults – partial seizures | 750 mg BID | Increase 250–500 mg BID every 2–4 weeks | 1 – 3 g BID (max 4 g/day) | Keppra XR 375 mg capsules (two capsules = 750 mg) |
| Children (≥2 yrs) – partial/myoclonic | 7.5 mg/kg BID | Increase 2.5 mg/kg BID weekly | 5 – 15 mg/kg BID | Same as adults, weight‑adjusted |
• Co‑administration: No dose adjustment needed with other AEDs (e.g., carbamazepine, valproate).
• Food: No interaction; take with or without food.
Adverse Effects
- Common (≥10 %): somnolence, headache, dizziness, fatigue, irritability, asthenia.
- Serious (≤1 %):
- Psychiatric: depression, suicidal ideation, aggression.
- Hallucinations, psychosis.
- Severe cutaneous reactions (rare).
*Note:* A small subset may develop acute kidney injury; monitor serum creatinine if baseline abnormal.
Monitoring
- Renal function: Serum creatinine or CrCl at baseline, then every 3–6 months.
- Psychiatric assessment: baseline mood evaluation; monitor for new or worsening symptoms.
- Serum electrolytes: optional if clinically indicated (e.g., fluid/electrolyte disorders).
- Seizure frequency and seizure diary: assess therapeutic response after 4–8 weeks.
Clinical Pearls
- Extended‑release timing: Take Keppra XR doses with a consistent meal schedule to minimize fluctuations in brain concentration and maintain quality of life.
- Drug‑interaction edge: Levetiracetam’s minimal CYP450 involvement means it can be paired safely with multiple AEDs and non‑AED medications (e.g., SSRIs, warfarin).
- Re‑titration strategy: If a patient experiences breakthrough seizures, increase by 500 mg BID at a 2‑week interval rather than a single jump to avoid withdrawal‑type psychosis.
- Renal dosing algorithm: For CrCl 30–49 mL/min, reduce starting dose to 500 mg BID; for CrCl <30 mL/min, start 250 mg BID and titrate slowly.
- Patient education: Emphasize that levetiracetam does not impair vision; avoid driving until seizure control is achieved, not due to drug effect.
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• *Key pharmacology terms: anticonvulsant, levetiracetam, SV2A, partial‑onset seizures, extended‑release, renal clearance, psychiatric adverse events.*