What is the recommended dosage adjustment for a patient taking Keppra (levetiracetam) 750 mg bid with a subtherapeutic level?

From the Guidelines

For a patient taking Keppra (levetiracetam) 750 mg bid with a subtherapeutic level, the recommended dosage adjustment would be to increase the dose, considering a loading dose of 1500 mg oral load as suggested by 1. Given the patient's current dose of 750 mg bid, a potential adjustment could be to increase the dose to 1000 mg bid, with the option to further titrate as needed and tolerated, up to the maximum dose. It's crucial to monitor for adverse effects such as fatigue, dizziness, and rarely, pain at the infusion site, as noted in the study 1. When adjusting Keppra dosage, it's essential to consider the patient's renal function, as Keppra is primarily eliminated through the kidneys, and dosage adjustments may be necessary for patients with renal impairment. After dosage adjustment, a follow-up level should be checked after reaching steady state (approximately 2-3 days) to ensure therapeutic levels have been achieved. Key considerations include:

• Monitoring for adverse effects
• Assessing renal function before increasing the dose
• Potential for further titration based on patient response and tolerance
• The importance of achieving and maintaining therapeutic levels to prevent seizure recurrence, as guided by the principles outlined in 1.

From the FDA Drug Label

Although in some studies there was a tendency toward greater response with higher dose, a consistent increase in response with increased dose has not been shown. 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 1500 mg/day (750 mg bid) which is below the maximum recommended daily dose of 3000 mg. Considering the patient has a subtherapeutic level, the dosage can be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The recommended dosage adjustment for this patient would be to increase the dose to 2500 mg/day (1250 mg bid) and monitor the patient's response before further adjustments. 2

From the Research

Dosage Adjustment for Subtherapeutic Keppra Level

The patient is currently taking Keppra 750 mg bid, with a subtherapeutic level of < 2. To determine the recommended dosage adjustment, we can look at the following evidence:

• A study published in 2000 3 found that levetiracetam was effective in reducing seizure frequency at doses ranging from 1000 to 4000 mg per day.
• A review of randomized controlled trials published in 2001 4 found that levetiracetam reduced seizure frequency when used as an add-on treatment for patients with drug-resistant localization-related epilepsy, with an increase in efficacy with increasing dose.
• A pharmacokinetic study published in 2004 5 found that levetiracetam is rapidly absorbed and has a bioavailability of >95%, with plasma concentrations increasing in proportion to dose over the clinically relevant dose range.
• A retrospective cohort study published in 2023 6 found that patients receiving a total daily dose of levetiracetam >1000 mg had a lower seizure incidence than those receiving 1000 mg per day.
• A prospective observational study published in 2024 7 found that higher doses of levetiracetam (750-1000 mg bid) were more likely to lead to optimal drug levels and reduced the odds of seizure compared to low-dose regimens (500 mg bid).

Recommended Dosage Adjustment

Based on the evidence, it is recommended to increase the dosage of Keppra to achieve a therapeutic level. The exact dosage adjustment will depend on the patient's individual needs and response to treatment. Some possible options include:

• Increasing the dose to 1000 mg bid, as studied in 6 and 7
• Increasing the dose to 1500 mg bid, as this is within the effective dose range found in 3 and 4
• Monitoring the patient's serum levels and adjusting the dose accordingly, as recommended in 7

Key Points to Consider

• The patient's current dose of 750 mg bid is not achieving a therapeutic level, and an increase in dose is likely necessary.
• The evidence suggests that higher doses of levetiracetam are more effective in reducing seizure frequency and achieving optimal drug levels.
• The patient's individual needs and response to treatment should be taken into account when determining the optimal dosage adjustment.