Generic Name

Levetiracetam

Mechanism

• Primary target: Binds with high affinity to the synaptic vesicle protein 2A (SV2A) located on presynaptic membranes.
• Effect on neurotransmission: Modulates calcium‑dependent synaptic vesicle release, thereby reducing excessive excitatory glutamate transmission and stabilizing neuronal firing without affecting ion channels or GABA receptors.
• Additional actions: May inhibit postsynaptic D‑serine receptors and modulate NMDA receptor activity, contributing to its anticonvulsant effect.

Pharmacokinetics

• Route & absorption: Oral; 100 % bioavailability; rapid, independent of food intake.
• Distribution: Low protein binding (~10 %); crosses the blood‑brain barrier and the placenta; detectable in breast milk.
• Metabolism: Minimal—primarily hydrolysis to an inactive glucuronide conjugate in liver and kidney.
• Elimination: Renal excretion (≈66 % unchanged; 30 % as glucuronide).
• Half‑life: ~5–7 h (adult), ~7–10 h (pediatric < 2 y).
• Drug interactions: Minimal CYP450 involvement; weak interaction with valproic acid (increases serum levels of both).
• Special populations:
• Renal impairment: Dose reduction proportional to CrCl.
• Pregnancy: Category C; crosses placenta—use when benefits outweigh risks.
• Breastfeeding: Small amounts transferred; generally considered safe.

Indications

• Partial‑onset seizures (as adjunctive therapy).
• Secondary generalized tonic‑clonic seizures in partial‑onset epilepsy.
• Juvenile myoclonic epilepsy (monotherapy or add‑on).
• Generalized tonic‑clonic seizures (often combined with other AEDs).

Contraindications

• Contraindications:
• Known hypersensitivity to levetiracetam or other analogs.
• Warnings:
• Mood/behavioral changes: Depression, irritability, aggression, and, rarely, suicidal ideation.
• Drug–drug interactions: Co‑administration with potent CYP inhibitors or valproic acid may elevate levels.
• Renal impairment: Requires dose adjustment; severe renal failure (CrCl < 30 mL/min) contraindicated unless therapeutic necessity.
• Pregnancy: Potential teratogenicity—consult obstetrician before initiation.

Dosing

• Administration: Oral capsules or liquid formulation (5 mg/mL).
• Missed dose: Take the next dose as scheduled; do not double dose.
• Co‑administration: Can be given with food or on empty stomach; no food‑based absorption delay.

Adverse Effects

• Common (≥5 %):
• Somnolence, dizziness, fatigue.
• Headache, irritability, constipation.
• Gastrointestinal upset: nausea, vomiting.
• Mood alterations: depression, anxiety.
• Serious (≤1 %):
• Aggression or violent behavior.
• Suicidal ideation (screening recommended).
• Severe skin reactions (Steven–Johnson syndrome).
• Ocular issues: cataracts (rare, long‑term exposure).
• Laboratory abnormalities: Normal serum electrolytes; monitor liver function if combined with hepatotoxic AEDs.

Monitoring

• Renal function: Serum creatinine, BUN, CrCl at baseline, then quarterly or after dose changes.
• Serum drug levels: Not routinely required; useful in therapeutic drug monitoring (TDM) when interpatient variability or interactions suspected.
• Mental status: Baseline questionnaire (PHQ‑9, GAD‑7); repeat after 4–6 weeks, especially if mood changes arise.
• Pregnancy testing (women of childbearing potential).
• Breastfeeding mothers: Monitor infant for sedation or irritability if on high doses.
• Seizure frequency and adverse events: Document in patient chart for dose adjustment.

Clinical Pearls

• Rapid onset & short half‑life make levetiracetam ideal for acute seizure clusters and for use in ICU settings.
• Renal clearance dependence: A dose‑adjustment algorithm based on creatinine clearance ensures toxicity avoidance while maintaining efficacy.
• Low pregnancy risk vs. other AEDs: Compared to valproate, better safety profile in pregnancy; still counsel about teratogenic risk.
• High CNS availability means mood side effects can occur even at low doses—screen patients with a history of psychiatric disorders.
• Drug interactions: Co‑administration with valproic acid or high‑dose CYP3A4 inhibitors can raise plasma levetiracetam levels—monitor for sedation or behavioral changes.
• Economical choice: Generic availability reduces cost, making it a good first‑line add‑on in resource‑limited settings.
• No need for serum level monitoring in most cases—reliance on clinical response and side‑effect profile simplifies outpatient management.

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• *This drug card provides evidence‑based, concise information for medical students and clinicians. For detailed prescribing information, refer to the FDA label and local guidelines.*