About This Dosing Guide

This guide provides supplementary clinical information for the Keppra Loading Dose Calculator. It details the principles behind intravenous (IV) levetiracetam dosing for conditions like status epilepticus and seizure prophylaxis, explains the calculator’s outputs, and offers context on administration, safety, and dose adjustments. Always use this information in conjunction with institutional protocols and clinical judgment.

Understanding the Calculator’s Outputs

After entering the required patient data, the calculator provides a comprehensive dosing recommendation that includes:

• Calculated Dose: The initial dose in mg, calculated directly from the patient’s weight and the selected mg/kg regimen.
• Final Recommended Loading Dose: The dose to be administered, capped at a maximum of 4500 mg for safety as per common clinical practice.
• Volume to Draw: The precise volume of levetiracetam solution (in mL) to withdraw from the vial based on the selected IV concentration.
• Recommended Starting Maintenance Dose: A suggested dose range for subsequent administrations, adjusted based on the patient’s calculated or known creatinine clearance (CrCl).
• Renal Adjustment Tier: The category of renal function (e.g., Normal, Mild Impairment) that determines the appropriate maintenance dosing schedule.

How to Use the Calculator

To ensure accurate dose calculation, follow these steps:

1. Enter Patient Weight: Input the patient’s actual body weight in either kilograms (kg) or pounds (lbs). The tool will automatically convert between units.
2. Select Indication: Choose the clinical reason for the loading dose. Options typically include status epilepticus (60 mg/kg) or seizure prophylaxis at high (40 mg/kg) or standard (20 mg/kg) doses. A custom mg/kg value can also be entered.
3. Determine Renal Function: You can either have the tool calculate the Creatinine Clearance (CrCl) using the Cockcroft-Gault formula (requiring age, sex, and serum creatinine) or enter a known CrCl value directly.
4. Select IV Concentration: Choose the concentration of the levetiracetam IV product available at your institution (e.g., 100 mg/mL).

Dosing and Administration Overview

A levetiracetam loading dose is a large, initial dose given to rapidly achieve therapeutic drug concentrations in the body, which is critical in emergencies like status epilepticus. This is followed by smaller, regular maintenance doses to maintain that level.

• Maximum Dose: The loading dose is typically capped at 4500 mg, even if the weight-based calculation exceeds this amount.
• Administration: The calculated dose must be diluted in 100 mL of a compatible solution (e.g., Normal Saline, Lactated Ringer’s, D5W).
• Infusion Rate: The diluted solution should be administered as an intravenous infusion over 15 minutes. Rapid IV push is not recommended.
• Renal Impairment: The initial loading dose is generally not adjusted for renal dysfunction. However, all subsequent maintenance doses must be adjusted based on creatinine clearance to prevent drug accumulation and toxicity.

Switching Between IV and Oral

When a patient is stable and can tolerate oral medications, switching from intravenous to oral levetiracetam is straightforward. The conversion is 1:1. For example, a patient receiving 1000 mg of IV levetiracetam every 12 hours can be switched to a 1000 mg oral tablet every 12 hours.

Missed Dose Protocol

For a missed maintenance dose, the patient should take it as soon as they remember. If it is almost time for the next scheduled dose, they should skip the missed dose and resume their normal dosing schedule. Patients should not take a double dose to make up for a missed one. Consult a pharmacist or physician for specific guidance.

Safety Alerts and Considerations

• Behavioral Reactions: Levetiracetam can cause psychiatric symptoms, including psychotic symptoms, suicidal ideation, irritability, and depression. Monitor all patients for behavioral changes.
• Somnolence and Dizziness: Drowsiness and asthenia are common side effects, particularly at the beginning of treatment. Patients should be cautioned against operating heavy machinery.
• Hematologic Abnormalities: Minor decreases in red blood cell counts and neutrophil counts have been observed. Monitor complete blood counts if clinically warranted.
• Renal Dose Adjustment: Failure to adjust maintenance doses in patients with renal impairment can lead to toxic drug levels. Always assess renal function before starting a maintenance regimen.

Frequently Asked Questions (FAQ)

Why is the loading dose capped at 4500 mg?

The 4500 mg cap is a widely accepted practice based on clinical trials and package inserts for safety and tolerability. Doses beyond this level have not been sufficiently studied and may increase the risk of adverse effects without providing additional efficacy.

Is the loading dose adjusted for poor renal function?

No. The purpose of a loading dose is to quickly achieve a therapeutic level. Since it is a single dose, it is generally not adjusted for renal function. However, all subsequent maintenance doses are critically dependent on renal function and must be adjusted accordingly.

How does the calculator determine Creatinine Clearance (CrCl)?

The tool uses the Cockcroft-Gault formula: CrCl = [(140 – Age) × Weight (kg)] / [72 × Serum Creatinine (mg/dL)]. For female patients, the result is multiplied by 0.85.

What are the compatible diluents for IV levetiracetam?

Levetiracetam injection is compatible with 0.9% Sodium Chloride (Normal Saline), Lactated Ringer’s solution, and 5% Dextrose in Water (D5W).

What weight should I use for obese patients?

Most guidelines recommend using actual body weight for calculating levetiracetam doses, even in obese patients, as the drug distributes widely. However, some institutions may cap the weight used for calculation (e.g., at 120 kg). Always follow local institutional protocols.

Can the loading dose be given faster than 15 minutes?

No, the recommended infusion time is 15 minutes. Faster administration may increase the risk of adverse effects like dizziness or local irritation without improving onset of action.

Does this calculator work for pediatric patients?

Yes, the principles of weight-based loading for status epilepticus (60 mg/kg) also apply to pediatric patients, as supported by the AES guidelines. The maximum dose cap of 4500 mg also generally applies.

Why is a supplemental dose needed for dialysis patients?

Levetiracetam is significantly removed by hemodialysis. A supplemental dose after a dialysis session may be required to maintain therapeutic drug levels. The exact dose and timing should be determined by institutional protocol or a clinical pharmacist.

References

1. UCB, Inc. KEPPRA® (levetiracetam) injection prescribing information. Smyrna, GA; 2018.
2. Glauser T, Shinnar S, et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48-61.
3. Leppik IE. The place of levetiracetam in the treatment of epilepsy. Epilepsia. 2001;42 Suppl 4:44-5.
4. UCB S.A. Keppra Professional Site. Accessed on the current date.