Diagnostic Use
This test is primarily used to confirm adherence to prescribed levetiracetam, in the management of overdose or in managing patients with altered clearance (e.g. children, pubertal, pregnant/post-partum patients, elderly).
Under most circumstances, plasma levels can be predicted from dosing Levetiracetam as mg per kg body weight and creatinine clearance, thus no need for therapeutic drug monitoring. Levetiracetam has a high availability (dose dependent) with peak plasma concentration occurring about 1 hour after oral administration. Its pharmacokinetic profile is linear with low intra- and inter- subject variability. There is negligible protein binding. Plasma half-life in healthy adults is around 6-8 hours. Steady state is achieved after two days of a twice daily administration schedule. Levetiracetam does not interact with CYP nor UGT isoenzyme systems. No dose adjustment is needed in mild to moderate hepatic impairment. There is no pharmacokinetic interaction with other anticonvulsants while a pharmacodynamics interaction has been reported between Levetiracetam and carbamazepine, with increased incidence of CNS side effects.
About 66% of the drug is excreted unchanged in urine while about 24% is hydrolysed as inactive metabolites. Compared with non-pregnant adults, there is increased plasma clearance in 0-12 year old children (by about 40%) and in pregnancy (especially 3rd trimester, by around 50-60%), and decreased clearance in the elderly (by around 40%). This phenomenon is mostly related to physiological variations in renal clearance of Levetiracetam. In moderate to severe renal impairment, there is a need for dose reduction. Dosage schedule adjustment table relating to creatinine clearance can be found from New Zealand Medsafe data sheet.
Interpretation
There are no well validated controlled trials of use of plasma trough Levetiracetam therapeutic intervals, thus it can only be used as a crude guide to the likelihood of efficacy and risk of toxicity. A therapeutic interval of 12- 6 mg/L is recommended by International League Epilepsy (ILAE, Patsalos 2008).
Toxicities associated with Levetiracetam include somnolence, asthaenia, a slight in increase in incidence of community acquired common cold and upper respiratory tract infections, and a statistically significant but clinical minor reduction in haematocrit, RBC count and mostly transient reduction in WBC or neutrophil count. Toxicities may be associated with blood concentration even within the therapeutic range. Toxic level has not been well established.
Reference Intervals
Units: mg/L
Therapeutic interval: 12 – 46