Epicet XR

Approved Indications:

• Partial-Onset Seizures:
  Monotherapy for adults and adolescents (≥16 years) with newly diagnosed epilepsy; adjunctive therapy in patients ≥1 month old.
• Myoclonic Seizures:
  Adjunctive therapy for myoclonic seizures in adolescents (≥12 years) with juvenile myoclonic epilepsy (JME).
• Primary Generalized Tonic-Clonic Seizures (PGTCS):
  Adjunctive therapy in patients ≥6 years with idiopathic generalized epilepsy.

Clinically Accepted (Off-Label) Uses:

• Status Epilepticus (Refractory):
  Intravenous use in treatment-resistant cases.
• Seizure Prophylaxis:
  After neurosurgery or traumatic brain injury due to favorable safety profile.
• Bipolar Disorder (Adjunct):
  Investigated in mood stabilization when conventional therapies are inadequate.

Route: Oral (tablets, solution), Intravenous (IV)

Adults and Adolescents (≥16 years):

• Initial dose (monotherapy): 500 mg twice daily
• Titration: Increase by 500 mg twice daily every 2 weeks
• Maximum dose: 1500 mg twice daily (3000 mg/day)

Adjunctive Therapy:

• Adults & Children ≥12 years:
  500 mg twice daily → up to 1500 mg twice daily
• Children 4–11 years:
  10 mg/kg twice daily → up to 30 mg/kg twice daily (max 3000 mg/day)
• Children 6 months–<4 years:
  10 mg/kg twice daily → up to 25 mg/kg twice daily
• Infants 1 month–<6 months:
  7 mg/kg twice daily → up to 21 mg/kg twice daily

Renal Impairment (adjust according to creatinine clearance):

• CrCl 50–80 mL/min: 500–1000 mg twice daily
• CrCl 30–49 mL/min: 250–750 mg twice daily
• CrCl <30 mL/min: 250–500 mg twice daily
• ESRD (on dialysis): 500–1000 mg every 24 hours + 250–500 mg post-dialysis

Hepatic Impairment:

• Mild to moderate: No dose adjustment
• Severe with renal impairment: Adjust dose according to renal function

Levetiracetam binds selectively to the synaptic vesicle protein 2A (SV2A) in the brain, which plays a critical role in vesicle exocytosis and neurotransmitter release. This binding modulates synaptic transmission and inhibits hypersynchronous neuronal firing associated with seizures. Unlike other antiepileptics, Levetiracetam does not affect sodium or calcium channels or GABAergic mechanisms, contributing to its favorable interaction and side effect profile.

• Absorption: Rapid and complete; not affected by food
• Bioavailability: ~100%
• Time to Peak Plasma Level: 1–2 hours
• Plasma Protein Binding: <10%
• Volume of Distribution: 0.5–0.7 L/kg
• Metabolism: Minimal (24% hydrolyzed to inactive metabolite); not via CYP enzymes
• Half-life: 6–8 hours (prolonged in renal impairment)
• Excretion: ~66% unchanged in urine; ~24% as inactive metabolites
• Steady-State: Achieved within 2 days

• Pregnancy: Category C
  Animal studies show adverse fetal effects; no controlled human data. Crosses the placenta. Use only if clearly needed.
• Lactation: Excreted into breast milk. Limited data suggest safety, but monitor infants for sedation, poor feeding, or irritability.
• Recommendation: Use only when benefits outweigh risks; lowest effective dose advised.

• Primary Class: Antiepileptic
• Subclass: Pyrrolidone derivative
• Generation: Second-generation broad-spectrum antiepileptic

• Known hypersensitivity to Levetiracetam or any of its components
• Prior serious allergic reactions (e.g., Stevens-Johnson syndrome)
• Use of oral solution in patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption

• Neuropsychiatric effects: Risk of depression, aggression, psychosis, suicidal thoughts—monitor patients closely.
• Somnolence and dizziness: Caution during activities requiring alertness
• Abrupt discontinuation: May trigger increased seizure frequency—taper gradually
• Renal impairment: Requires dose adjustment
• Blood dyscrasias (rare): Monitor complete blood counts if long-term use
• Serious skin reactions (rare): Discontinue immediately if rash or mucosal lesions appear

Common:

• CNS: Somnolence, dizziness, headache, fatigue
• Psychiatric: Irritability, agitation, mood swings, aggression
• GI: Nausea, vomiting, decreased appetite

Less Common:

• Insomnia, tremor, blurred vision
• Rash, pruritus

Serious (Rare):

• Stevens-Johnson syndrome
• Suicidal ideation
• Psychosis or hallucinations
• Pancytopenia
• Anaphylaxis or angioedema

Onset & Dose-Dependence:

• Most CNS side effects occur during the first few weeks; often dose-related and resolve on their own or with dose adjustment.

• Enzyme systems: Does not induce or inhibit CYP450 enzymes → minimal interaction risk
• Methotrexate: May reduce methotrexate clearance—monitor toxicity
• Sedatives/CNS depressants (e.g., alcohol, benzodiazepines): Additive drowsiness
• Other antiepileptics (e.g., valproate, carbamazepine): No significant interaction
• Oral contraceptives: No effect

• ILAE Guidelines (2023–2024): Reaffirm Levetiracetam as first-line for focal epilepsy due to safety and tolerability
• Status Epilepticus Use: Increasing role in acute management protocols, including pediatric and adult status epilepticus
• Surgical Prophylaxis: Recommended post-craniotomy seizure prevention in updated neurosurgical guidelines
• Pediatric Epilepsy: Widely accepted for infants ≥1 month as adjunctive therapy

• Temperature: Store at 20°C to 25°C (68°F to 77°F); allowable range: 15°C–30°C
• Humidity: Store in a dry area
• Light Protection: No special requirements
• Oral solution: Shake well before use; follow discard instructions after opening (usually within 7–8 weeks)
• IV form: Store and prepare as per manufacturer guidelines; use promptly after dilution
• Handling: Keep out of reach of children; do not use damaged or discolored tablets