Keppra (levetiracetam) is an antiepileptic drug (AED) indicated for the adjunctive treatment of partial onset seizures, myoclonic seizures, and primary generalized tonic-clonic seizures in adults and children with epilepsy. As a second-generation medication, it offers a distinct mechanism of action, targeting synaptic vesicle protein 2A (SV2A), which is involved in neurotransmitter release. Its favorable pharmacokinetic profile, including minimal protein binding and lack of hepatic metabolism, reduces the potential for drug interactions and makes it a versatile option in complex treatment regimens. Keppra is available in multiple formulations—tablets, oral solution, and injectable—providing flexibility for various patient needs and clinical scenarios.

Features

• Active pharmaceutical ingredient: Levetiracetam.
• Available in immediate-release tablets (250 mg, 500 mg, 750 mg, 1000 mg), extended-release tablets (500 mg, 750 mg), an oral solution (100 mg/mL), and an intravenous injection (100 mg/mL).
• Mechanism of Action: Binds to synaptic vesicle protein 2A (SV2A) in the brain, believed to modulate synaptic neurotransmitter release and inhibit neuronal hypersynchronization.
• Pharmacokinetics: Rapidly and almost completely absorbed after oral administration; bioavailability is nearly 100%. Not significantly bound to plasma proteins (<10%).
• Metabolism: Not hepatically metabolized via the cytochrome P450 system. The major metabolic pathway is enzymatic hydrolysis of the acetamide group.
• Elimination: Primarily excreted renally as unchanged drug (66%) and an inactive metabolite (24%). Elimination half-life is approximately 6-8 hours in adults with normal renal function.

Benefits

• Provides effective adjunctive therapy for multiple seizure types, contributing to a significant reduction in seizure frequency.
• Exhibits a linear and predictable pharmacokinetic profile, allowing for straightforward dose titration and management.
• Lacks complex hepatic metabolism, minimizing the risk of pharmacokinetic interactions with other commonly co-prescribed medications.
• Generally well-tolerated profile with a lower incidence of certain side effects common to older antiepileptic drugs, such as significant weight change or cosmetic effects.
• Availability of an intravenous formulation allows for seamless transition from oral therapy in patients who are temporarily unable to take medication by mouth.
• Rapid titration schedules are often possible, allowing for quicker achievement of therapeutic efficacy compared to some other AEDs.

Common use

Keppra is primarily used for the adjunctive treatment of partial onset seizures with or without secondary generalization in adults and children 1 month of age and older with epilepsy. It is also approved as adjunctive therapy for myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy, and for primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy. Its use is established in both newly diagnosed and treatment-resistant epilepsy populations.

Dosage and direction

Dosing must be individualized based on clinical response and tolerability. For adjunctive therapy of partial onset seizures in adults and adolescents (16+ years), the initial dose is 500 mg twice daily. This can be increased by 500 mg twice daily every 2 weeks to a recommended maximum dose of 1500 mg twice daily. For the oral solution, dosing is equivalent and should be measured with a calibrated dosing syringe. For intravenous use, it is administered as a 15-minute infusion and is bioequivalent to the oral forms. Dosage adjustments are mandatory in patients with renal impairment, calculated based on creatinine clearance. For pediatric patients, dosing is based on body weight. The extended-release tablets are taken once daily and are not interchangeable mg-per-mg with the immediate-release formulation.

Precautions

Patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and unusual changes in mood or behavior. Caution is advised in patients with a history of psychiatric disorders. As with other AEDs, Keppra may cause dizziness and somnolence, which could impair physical or mental abilities required for potentially hazardous tasks like driving or operating machinery. Patients should be advised not to drive or operate complex machinery until they are familiar with the drug’s effects. Gradual withdrawal is recommended to minimize the potential for increased seizure frequency. Hematological parameters have been monitored in clinical studies; although abnormalities were rare, caution is warranted.

Contraindications

Keppra is contraindicated in patients with a known hypersensitivity to levetiracetam, any of the inactive ingredients, or other pyrrolidine derivatives. There are no other absolute contraindications.

Possible side effect

The most common adverse reactions observed in placebo-controlled adult studies (incidence ≥5% and greater than placebo) are:

• Somnolence (15% vs 8% placebo)
• Asthenia (15% vs 9% placebo)
• Dizziness (9% vs 4% placebo)
• Infection (13% vs 8% placebo) Other reported side effects include:
• Behavioral effects: agitation, aggression, anxiety, apathy, emotional lability, anger, depression, hostility, irritability, and psychotic symptoms.
• Neurological effects: coordination difficulties, headache.
• Gastrointestinal effects: anorexia, diarrhea, nausea, vomiting.
• General: fatigue.

Drug interaction

Formal interaction studies have shown no clinically significant pharmacokinetic interactions with digoxin, warfarin, oral contraceptives (ethinylestradiol/levonorgestrel), or probenecid. Due to its lack of significant cytochrome P450 metabolism, it is less likely to be involved in pharmacokinetic interactions. However, potential pharmacodynamic interactions (additive CNS depressant effects) can occur with alcohol and other central nervous system depressants (e.g., benzodiazepines, barbiturates, opioids, sedating antihistamines).

Missed dose

If a dose is missed, the patient should take it as soon as they remember. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should not take a double dose to make up for the missed one. Maintaining a consistent dosing schedule is critical for stable plasma concentrations and optimal seizure control.

Overdose

Symptoms of overdose are primarily an extension of its adverse effect profile and may include severe drowsiness, agitation, aggression, respiratory depression, and coma. In cases of overdose, general supportive measures should be initiated, including monitoring of vital signs. Hemodialysis significantly enhances the clearance of levetiracetam (approximately 50% removed in a 4-hour session) and should be considered in the management of a severe overdose.

Storage

Keppra tablets and oral solution should be stored at room temperature, 15°C to 30°C (59°F to 86°F). The oral solution should be protected from light and stored in its original container. The intravenous solution should be stored at room temperature and protected from light. All formulations must be kept out of reach of children. Do not use any medication beyond its expiration date.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content has been compiled from available scientific literature but may not encompass all available data or the most recent labeling changes.

Reviews

Clinical trials and extensive post-marketing surveillance have established Keppra as a well-regarded antiepileptic drug. It is frequently cited in neurology for its efficacy across a broad spectrum of seizure types and its favorable drug interaction profile. Many clinicians value its rapid titration schedule and the utility of its intravenous formulation. Patient-reported outcomes often highlight its effectiveness in reducing seizure burden. However, reviews also consistently note the potential for neuropsychiatric adverse events, particularly in pediatric and adolescent populations, underscoring the necessity for careful patient selection and monitoring. Its role in the treatment algorithm for epilepsy remains significant and well-supported by evidence.