Should the dosage of Levetiracetam (Keppra) be increased for a patient with a subtherapeutic level of 2.0, currently taking 1000 milligrams (mg) twice daily (bid)?

From the Guidelines

I would not recommend increasing the Keppra (levetiracetam) dose at this time. A Keppra level of 2.0 mg/L is considered subtherapeutic, but the current dosage of 1000 mg twice daily may still be effective for some patients. However, according to the study 1, a loading dose of 1,500 mg oral load is safe and well-tolerated, and may be considered to rapidly achieve therapeutic levels.

Key Considerations

• The therapeutic range of Keppra is not explicitly stated in the provided study, but it is generally considered to be between 6-20 mg/L, although this can vary depending on the patient and the specific clinical context.
• Increasing the dose unnecessarily could lead to more side effects such as dizziness, fatigue, or behavioral changes without additional therapeutic benefit, as seen with other antiepileptic medications in the study 1.
• Clinical response should always take precedence over laboratory values - if the patient is still experiencing breakthrough seizures despite this level, then a dose increase might be warranted regardless of the therapeutic level.
• The study 1 provides information on loading doses and routes of administration for various antiepileptic medications, but does not specifically address the issue of subtherapeutic levels or dose adjustments.

Potential Next Steps

• Monitor the patient's seizure activity and adjust the dose as needed to achieve optimal seizure control.
• Consider consulting with a neurologist or other specialist to determine the best course of treatment for the patient.
• Review the patient's medication regimen and medical history to identify any potential interactions or underlying conditions that may be contributing to the subtherapeutic Keppra level.

From the FDA Drug Label

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID) Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. The patient is currently taking 1000 mg twice daily (bid), which is 2000 mg per day.

• The dosage can be increased by 1000 mg/day every 2 weeks to a maximum recommended daily dose of 3000 mg.
• Since the patient has a subtherapeutic level, the dosage can be increased.
• The next dosage increase would be to 3000 mg per day, given as 1500 mg bid 2.

From the Research

Levetiracetam Dosage Considerations

• The patient is currently taking 1000 milligrams (mg) of Levetiracetam twice daily (bid) and has a subtherapeutic level of 2.0, indicating that the dosage may need to be increased 3, 4.
• Studies have shown that Levetiracetam is effective in reducing seizure frequency in a dose-dependent manner, with higher doses resulting in greater reductions in seizure frequency 4, 5.
• The therapeutic range of Levetiracetam is wide, and the dosage may need to be individualized based on the patient's response to treatment and serum concentration levels 3, 5.

Factors Influencing Levetiracetam Dosage

• Age and enzyme-inducing drugs (EIDs) can influence the pharmacokinetics of Levetiracetam, and dosage adjustments may be necessary in certain patient populations 3.
• Higher dosages of Levetiracetam may be necessary in patients taking EIDs, while lower dosages may be necessary in elderly patients (> 65 years of age) 3.
• The dosage of Levetiracetam may also need to be adjusted in patients with renal or hepatic impairment, although specific guidance on dosage adjustments in these patient populations is limited 5.

Clinical Evidence for Levetiracetam Dosage

• A study of adult patients with partial epilepsy found that Levetiracetam 1000 mg/day and 2000 mg/day were effective in reducing seizure frequency, with the higher dose resulting in a greater reduction in seizure frequency 4.
• Another study found that Levetiracetam 3000 mg/day was effective in reducing seizure frequency and increasing the number of seizure-free patients, although the effects of lower doses on these outcomes were unclear 5.
• A review of the literature on Levetiracetam found that the drug is generally well-tolerated, with a low potential for drug interactions and a favorable tolerability profile 5.