Keppra: Effective Seizure Control with Proven Tolerability
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Synonyms | |||
Keppra (levetiracetam) is an antiepileptic drug (AED) indicated for the treatment of partial onset, myoclonic, and primary generalized tonic-clonic seizures in adults and children. 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 well-established efficacy profile, coupled with a generally favorable side effect and pharmacokinetic profile, makes it a cornerstone in modern epilepsy management protocols. Keppra is available in multiple formulations, including 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), oral solution (100 mg/mL), and intravenous injection (100 mg/mL)
- Mechanism of action: Binds to synaptic vesicle protein 2A (SV2A) in the brain
- Rapid and nearly complete absorption after oral administration; bioavailability is greater than 95%
- Linear pharmacokinetics; not extensively metabolized in the liver (hydrolysis of the acetamide group; not cytochrome P450 dependent)
- Primarily excreted renally (66% of dose unchanged in urine)
- Half-life is approximately 6–8 hours in adults with normal renal function
- Minimal plasma protein binding (<10%)
Benefits
- Demonstrated high efficacy in reducing seizure frequency across multiple seizure types in both monotherapy and adjunctive therapy settings.
- Generally favorable tolerability profile with a low incidence of severe adverse reactions compared to many older antiepileptic drugs.
- Lack of significant pharmacokinetic drug interactions, making it easier to combine with other medications.
- Flexible dosing regimens and multiple formulations allow for individualized treatment plans tailored to patient age, renal function, and clinical status.
- Rapid titration possible in many patients, allowing for quicker achievement of therapeutic doses.
- Well-studied in both adult and pediatric populations, providing a robust evidence base for its use.
Common use
Keppra is primarily used for the management of epilepsy. Its approved indications include adjunctive therapy in the treatment of partial onset seizures with or without secondary generalization in adults and children 1 month of age and older with epilepsy; adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy; and adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy. It is also approved as monotherapy for the treatment of partial onset seizures with or without secondary generalization in adults and children 4 years of age and older with epilepsy. Off-label, it is sometimes used in the management of neuropathic pain, migraine prophylaxis, and certain psychiatric conditions, though evidence supporting these uses is less robust.
Dosage and direction
Dosage must be individualized according to the patient’s clinical response, tolerability, renal function, and age. For adjunctive therapy in adults and adolescents (16 years and older) with partial onset seizures: Initiate with 500 mg twice daily. May increase by 500 mg twice daily every 2 weeks to a maximum recommended daily dose of 3000 mg. For adjunctive therapy in adults and adolescents (12 years and older) with myoclonic seizures: Initiate with 500 mg twice daily. May increase by 500 mg twice daily every 2 weeks to a maximum recommended daily dose of 3000 mg. For adjunctive therapy in adults and children (6 years and older) with primary generalized tonic-clonic seizures: Initiate with 500 mg twice daily. May increase by 500 mg twice daily every 2 weeks to a maximum recommended daily dose of 3000 mg. For monotherapy in adults and children (4 years and older) with partial onset seizures: Initiate with 500 mg twice daily. May increase by 500 mg twice daily every 2 weeks to a maximum recommended daily dose of 1500 mg twice daily. Dosage adjustment is required in patients with renal impairment. The oral solution and tablets may be taken with or without food. The intravenous formulation is bioequivalent to the oral forms and is used when oral administration is temporarily not feasible.
Precautions
Patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or unusual changes in mood or behavior. Neuropsychiatric adverse reactions, including psychosis, hallucinations, and aggression, have been reported. Caution is advised when treating patients with a history of psychiatric conditions. Patients should be warned about the potential for dizziness and somnolence, which could impair their ability to perform potentially hazardous activities such as driving or operating machinery. Abrupt withdrawal may lead to increased seizure frequency; therefore, Keppra should be withdrawn gradually. Hematological parameters have been rarely affected; full blood counts are recommended if clinical signs of infection emerge. Use in patients with renal impairment requires dosage adjustment based on creatinine clearance. The safety and efficacy of Keppra in pregnant women have not been established; use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Contraindications
Keppra is contraindicated in patients with a known hypersensitivity to levetiracetam, any of the inactive ingredients, or other pyrrolidine derivatives.
Possible side effect
The most common adverse reactions observed in controlled clinical trials (incidence greater than placebo) include:
- Somnolence
- Asthenia
- Dizziness
- Infection
- Nasopharyngitis Less common but potentially serious adverse reactions can include:
- Psychiatric symptoms: agitation, aggression, anxiety, apathy, emotional lability, anger, depression, hostility, irritability, personality disorders, psychotic disorder, suicidal ideation
- Neurological effects: amnesia, anxiety, ataxia, convulsion, paresthesia, vertigo
- Hematological effects: leukopenia, neutropenia, pancytopenia (rare)
- Other: hepatitis, pancreatitis (rare), Stevens-Johnson syndrome (rare), toxic epidermal necrolysis (rare)
Drug interaction
Keppra has no known clinically significant pharmacokinetic interactions with other antiepileptic drugs (e.g., carbamazepine, gabapentin, lamotrigine, phenobarbital, phenytoin, primidone, valproic acid) or with other commonly co-administered drugs such as oral contraceptives, warfarin, or digoxin. This is due to its minimal metabolism via the cytochrome P450 system and low protein binding. However, pharmacodynamic interactions (e.g., additive CNS depressant effects with alcohol or other sedatives) are possible.
Missed dose
If a dose is missed, it should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped and the regular dosing schedule resumed. Doubling the dose to make up for a missed dose is not recommended.
Overdose
Symptoms of overdose are primarily related to CNS depression and may include somnolence, agitation, aggression, respiratory depression, and coma. There is no specific antidote. In the event of overdose, general supportive measures should be instituted, including monitoring of vital signs and observation of the clinical status of the patient. Hemodialysis is effective, removing approximately 50% of the drug in 4 hours, and should be considered in cases of severe overdose.
Storage
Store at room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Keep the oral solution in the original container and protect from light. Keep all medications out of the reach of children and pets.
Disclaimer
This information is for educational purposes 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.
Reviews
(Note: Simulated expert commentary based on clinical trial data and post-marketing surveillance) “Keppra has become a first-line choice for many neurologists due to its predictable pharmacokinetics and favorable interaction profile. Its efficacy in a broad range of seizure types is well-documented in numerous randomized controlled trials. The main challenges in clinical practice remain the management of behavioral side effects in a subset of patients, particularly children and adolescents. Overall, it represents a significant advancement in antiepileptic therapy.” – Clinical Neurologist “From a pharmacokinetic standpoint, Keppra is an ideal agent. Its renal excretion and lack of hepatic metabolism minimize concerns in polypharmacy patients, especially the elderly. The availability of an IV formulation is invaluable in perioperative and ICU settings.” – Clinical Pharmacologist “While generally well-tolerated, clinicians must remain vigilant for neuropsychiatric adverse events, which can sometimes be severe. Patient and caregiver education is paramount. The ability to titrate quickly is a distinct advantage in achieving rapid seizure control.” – Epileptologist