Keppra

Keppra (levetiracetam) is an antiepileptic drug (AED) indicated for the treatment of partial onset seizures, myoclonic seizures, and primary generalized tonic-clonic seizures in adults and children. As a second-generation medication, it offers a distinct mechanism of action, favorable pharmacokinetic profile, and a well-established safety record, making it a cornerstone in modern epilepsy management protocols. Its use extends to monotherapy and adjunctive therapy, providing neurologists with a versatile tool for tailored treatment plans aimed at achieving and maintaining seizure freedom.

Features

• Active pharmaceutical ingredient: Levetiracetam
• Available in multiple formulations: 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)
• Rapid and nearly complete absorption following oral administration, with bioavailability exceeding 95%
• Minimal protein binding (<10%) and primarily renal excretion, with 66% of the dose excreted unchanged in urine
• Linear pharmacokinetics with dose-proportional increases in plasma concentrations
• Not extensively metabolized by the hepatic cytochrome P450 system, reducing potential for complex metabolic interactions

Benefits

• Effective Seizure Reduction: Demonstrated significant reduction in seizure frequency across multiple epilepsy types in controlled clinical trials.
• Rapid Therapeutic Onset: Achieves steady-state concentrations within 2 days with twice-daily dosing, allowing for quicker titration and efficacy assessment.
• Favorable Safety Profile: Generally well-tolerated with a lower incidence of severe adverse effects compared to older antiepileptic drugs.
• Minimal Drug Interactions: Lack of hepatic enzyme induction or inhibition simplifies co-administration with other medications, including oral contraceptives and anticoagulants.
• Pediatric and Adult Formulations: Availability of oral solution and appropriate dosing guidelines supports use across age groups, including infants as young as 1 month.
• Flexible Dosing Options: Multiple strengths and formulations (including IV for when oral administration is not feasible) facilitate individualized treatment regimens.

Common use

Keppra is primarily prescribed for the management of epilepsy. It is approved as:

• Adjunctive therapy in the treatment of partial onset seizures in patients 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.
• 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.
• Monotherapy for the treatment of partial onset seizures in patients 16 years of age and older.

Off-label uses may include the treatment of neuropathic pain, migraine prophylaxis, and certain psychiatric conditions, though these applications require careful specialist evaluation and are not FDA-approved indications.

Dosage and direction

Dosage must be individualized according to the patient’s clinical response, renal function, and tolerability. The following represents general guidance; always follow prescribing physician’s instructions.

Adults and Adolescents (16 years and older):

• Adjunctive Therapy for Partial Onset Seizures: Initiate with 500 mg twice daily. May increase by 500 mg twice daily every 2 weeks. Maximum recommended daily dose is 3000 mg.
• Adjunctive Therapy for Myoclonic Seizures: Initiate with 500 mg twice daily. May increase by 500 mg twice daily every 2 weeks. Maximum recommended daily dose is 3000 mg.
• Adjunctive Therapy for Primary Generalized Tonic-Clonic Seizures: Initiate with 500 mg twice daily. May increase by 500 mg twice daily every 2 weeks. Maximum recommended daily dose is 3000 mg.
• Monotherapy for Partial Onset Seizures: Initiate with 500 mg twice daily. May increase by 500 mg twice daily every 2 weeks. Maximum recommended daily dose is 3000 mg.

Children (1 month to <16 years): Dosing is based on body weight. Please consult specific pediatric dosing tables and a neurologist. Oral solution is often used for accurate weight-based dosing in younger children.

Patients with Renal Impairment: Dosage adjustment is necessary. For creatinine clearance (CrCl):

• 50-80 mL/min: 500 to 1000 mg every 12 hours
• 30-50 mL/min: 250 to 750 mg every 12 hours
• <30 mL/min: 250 to 500 mg every 12 hours
• End-stage renal disease patients on dialysis: 500 to 1000 mg every 24 hours, with a supplemental dose following dialysis.

Administration:

• Tablets should be swallowed whole with a sufficient amount of liquid. They can be taken with or without food.
• Oral solution should be measured with the provided dosing syringe. It may be diluted in a glass of water.
• IV injection is for use when oral administration is temporarily not feasible. It should be administered as a 15-minute intravenous infusion.

Precautions

• Neuropsychiatric Effects: Monitor patients for the emergence or worsening of depression, suicidal thoughts or behavior, and unusual changes in mood or behavior. Reactions including psychosis, hallucinations, anger, and aggression have been reported.
• Somnolence and Fatigue: May impair mental and/or physical abilities required for performing hazardous tasks, such as driving or operating machinery. Patients should be cautioned until they gain experience with the drug.
• Coordination Difficulties: Some patients may experience dizziness and disturbances in coordination. Dose reduction or discontinuation may be necessary.
• Withdrawal Seizures: As with all antiepileptic drugs, Keppra should be withdrawn gradually to minimize the potential of increased seizure frequency.
• Hematological Monitoring: Although rare, there have been reports of decreases in red blood cell count, white blood cell count, and platelet count. Consider hematological testing if signs of infection, anemia, or bleeding occur.
• Renal Function: Dose adjustment is required in patients with renal impairment. Assess creatinine clearance before initiation and periodically during treatment.

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 (occurring in >10% of patients and greater than placebo) are somnolence, asthenia, infection, and dizziness. Other observed side effects include:

• Very common (>1/10): Headache, somnolence, fatigue.
• Common (≥1/100 to <1/10): Anorexia, depression, emotional lability, aggression, anxiety, insomnia, nervousness, irritability, convulsion, balance disorder, dizziness, lethargy, tremor, vertigo, amblyopia, diplopia, cough, diarrhea, nausea, vomiting, abdominal pain, rash, accidental injury.
• Uncommon (≥1/1,000 to <1/100): Suicidal ideation, panic attack, personality disorder, thinking abnormal, amnesia, ataxia, paresthesia, confusion, hallucinations, eczema, pruritus, leukopenia, neutropenia, thrombocytopenia.
• Rare (<1/1,000): Pancreatitis, hepatic failure, Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, pancytopenia.

Drug interaction

Formal pharmacokinetic interaction studies show Keppra has low interaction potential:

• Does not inhibit major CYP isoforms (CYP1A2, 2C9, 2C19, 2D6, 3A4) or UGT1A1.
• Does not induce CYP3A4.
• Probenecid, a renal tubular secretion inhibitor, increased the renal clearance of the primary metabolite, but not of levetiracetam itself. No dose adjustment is recommended.
• No clinically significant interactions have been observed with digoxin, warfarin, or oral contraceptives (containing ethinylestradiol and levonorgestrel).
• Co-administration with other CNS depressants (e.g., alcohol, benzodiazepines, barbiturates, other AEDs) may potentiate sedative effects.

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. Do not take a double dose to make up for a missed one.

Overdose

Symptoms of overdose are primarily related to the known adverse effects of the drug and may include somnolence, agitation, aggression, depressed level of consciousness, 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 has been shown to enhance the clearance of levetiracetam (approximately 50% of the drug is removed in a 4-hour session) 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 bottle and protect from light. Use within 3 months of first opening the bottle.
• Keep all medications out of the reach of children and pets.

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.

Reviews

Clinical and patient-reported outcomes consistently highlight Keppra’s role as a effective and generally well-tolerated antiepileptic agent. In numerous randomized controlled trials, it demonstrated statistically significant superiority over placebo in reducing seizure frequency. Many neurologists appreciate its predictable pharmacokinetics and low interaction profile, which simplifies polypharmacy management. Patient feedback often notes the advantage of rapid titration and the availability of multiple formulations. Commonly cited drawbacks include the potential for behavioral side effects like irritability, which appears to be more prevalent in the pediatric population. Overall, it remains a first-line choice for many specialists managing a broad spectrum of seizure disorders.