Levetiracetam (Keppra®)

Levetiracetam (Keppra®) is characterized by a half-life of 2 to 4 hrs in dogs (regular release) and 4 to 7 hrs in cats; variability among animals is likely to be marked. For extended release, the half-live may be 1-2 hrs longer. As such, if the dosing interval is 8 hr most, if not all of each dose will be eliminated during a dosing interval in dogs and 50% to 75% of the dose will be eliminated in cats. For extended release, with a 12 hr dosing interval, the same may be true. “Steady-state” never truly occurs for levetiracetam in dogs (and may not in cats) because the drug does not accumulate with each dose.

The therapeutic range recommended in dogs or cats currently is that recommended in humans which is a trough concentration of that is 5 to 45 mcg/ml, depending on the resource.

When: Because minimal accumulation occurs, concentrations can be measured within days to 1 week of initiating a new dosing regimen.

Sampling times:

We suggest that dosing regimens be designed based on both a peak and trough as drug therapy is initiated. A single sample collected before trough cannot predict drug concentrations throughout the dosing interval. For example, assuming a peak concentration of 50 mcg/ml is achieved, and a 2 hr half-life, this means that three elimination half-lives will lapse before the next dose. Concentrations will be subtherapeutic before the next dose: 50 to 25 to 12.5 to 6.125 mcg/ml. It is important to know your patient’s half-life. This will allow you as clinician to assess how short the half-life is and in turn, warn the client about the magnitude of fluctuation in drug concentrations during the dosing interval and the risk of drug concentrations dropping below the therapeutic range. Once a half-life has been calculated for your patient, an appropriate dosing interval can be designed. The peak sample should be taken at 2 to 3 hrs and the trough just before the next dose unless otherwise directed based on previous monitoring that indicated the half-life was too short for drug to be detected at 8 or 12 hrs.

If only a single sample can be collected, it should be a trough sample. Note that if you collect a sample at 12 hrs, with an 8 hr dosing interval, the trough measurement may markedly underestimate the true trough concentration. For recommendations, it is critical that the timing of sample collection be provided on the submission form.

In the case of therapeutic failure, we do not suggest that the sample only be collected at the same time during a dosing interval that the seizure occurred, but that a trough sample be collected as well such that half-life can be calculated.

Other considerations:

A slow release levetiracetam (Keppra®) product is available for use in humans; our preliminary data suggests the half-life will be longer in dogs, allowing (potentially) a 12 dosing interval. However, monitoring both a peak and trough will be important to establishing the correct dosing interval in dogs or cats when using the slow release product. Note that the compounded slow release product that is designed for humans is not likely to demonstrate slow release kinetics in the dog (or cat). Monitoring should be done to demonstrate its efficacy.

Phenobarbital may decrease levetiracetam half-life.

Levetiracetam is metabolized largely by plasma enzymes. Metabolism will continue in situ in plasma. As such, serum samples should be collected to avoid falsely lower than actual concentrations.