Introduction
Keppra XR (levetiracetam extended-release) is an antiepileptic drug (AED) indicated for the adjunctive treatment of partial-onset seizures in patients 12 years of age and older. As an extended-release formulation, it offers the advantage of once-daily dosing, potentially improving medication adherence while maintaining therapeutic efficacy.
Mechanism of Action
Levetiracetam's exact mechanism of action remains incompletely understood. Unlike traditional AEDs, it does not appear to act primarily through sodium channel modulation or GABAergic pathways. The drug binds selectively to synaptic vesicle protein 2A (SV2A) in the brain, which is involved in synaptic vesicle exocytosis. This interaction is thought to modulate neurotransmitter release and stabilize neuronal membranes, thereby reducing seizure activity.
Indications
- Adjunctive therapy for partial-onset seizures with or without secondary generalization in patients ≥12 years with epilepsy
- Not indicated for monotherapy or for primary generalized seizures
Dosage and Administration
Initial Dose: 1000 mg once daily Titration: May increase by 1000 mg every 2 weeks Maximum Dose: 3000 mg once daily Administration: Swallow tablets whole with liquid; do not crush, chew, or split Timing: Administer at approximately the same time each day Special Populations:- Renal impairment: Dose adjustment required based on creatinine clearance
- Hepatic impairment: No dosage adjustment needed for mild to moderate impairment; use with caution in severe impairment
- Geriatric patients: Adjust based on renal function
- Pediatrics: Not approved for patients <12 years
Pharmacokinetics
Absorption: Extended-release formulation provides gradual absorption with peak concentrations at approximately 4 hours Bioavailability: Similar to immediate-release formulation Distribution: Volume of distribution ~0.5-0.7 L/kg; minimal protein binding (<10%) Metabolism: Primarily hydrolyzed by enzymatic processes (not CYP450 dependent) Elimination: Renal excretion (66% unchanged); half-life ~7-8 hours Steady State: Achieved within 2 days of initiationContraindications
- Hypersensitivity to levetiracetam, other pyrrolidine derivatives, or any component of the formulation
Warnings and Precautions
Psychiatric Effects: May cause psychiatric symptoms including psychosis, hallucinations, anger, aggression, and depression Suicidal Behavior: Antiepileptic drugs increase risk of suicidal thoughts or behavior Somnolence and Fatigue: May impair mental and physical abilities required for hazardous tasks Withdrawal: Abrupt discontinuation may increase seizure frequency; taper gradually Hematologic Effects: Rare cases of pancytopenia and agranulocytosis reportedDrug Interactions
Minimal CYP450 Interactions: Unlike many AEDs, Keppra XR has negligible effects on cytochrome P450 enzymes Potential Interactions:- Methotrexate: May decrease methotrexate concentrations
- Oral contraceptives: No significant interaction demonstrated
- Other CNS depressants: Additive sedative effects with alcohol, benzodiazepines, barbiturates
Adverse Effects
Most Common (≥5%):- Somnolence (15%)
- Dizziness (10%)
- Fatigue (8%)
- Irritability (5%)
- Psychiatric symptoms (psychosis, aggression)
- Suicidal ideation
- Hematologic abnormalities
- Severe dermatologic reactions
- Coordination difficulties
Monitoring Parameters
Baseline:- Seizure frequency and characteristics
- Renal function (creatinine clearance)
- Psychiatric history assessment
- Seizure frequency diary
- Mental status and behavioral changes
- Signs of hematologic abnormalities
- Renal function in patients with compromised renal function
- Adherence assessment
Patient Education
- Take medication at the same time each day with or without food
- Do not crush, chew, or break tablets
- Report any mood changes, depression, or suicidal thoughts immediately
- Avoid alcohol and other CNS depressants
- Do not stop abruptly; consult provider before discontinuing
- Use caution when operating machinery or driving until effects are known
- Inform all healthcare providers about Keppra XR use
- Keep regular follow-up appointments with neurologist
References
1. FDA Prescribing Information: Keppra XR (levetiracetam extended-release tablets) 2. Epilepsia. 2010;51(6):1069-1077. "Efficacy and safety of levetiracetam extended-release formulation" 3. Neurology. 2007;69(22):2047-2052. "Once-daily extended-release levetiracetam for partial-onset seizures" 4. CNS Drugs. 2008;22(3):265-274. "Clinical pharmacokinetics of levetiracetam extended-release" 5. Epilepsy Research. 2009;85(1):112-116. "Long-term safety and efficacy of levetiracetam extended-release" 6. Clinical Therapeutics. 2011;33(12):1943-1950. "Dose-response relationship of levetiracetam extended-release"
Note: This information is for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.