levetiracetam and Kidney-Failure--Chronic

A subset of the 27 safety and pharmacokinetic studies of levetiracetam has been conducted in selected special populations: children, the elderly, and people with renal or hepatic impairment. The results of these studies indicate that higher doses need to be used for children (on a per-weight basis), and individuals with renal dysfunction require dosage modifications related to creatinine clearance. Individuals with hepatic impairment do not require modifications from standard doses. Little information is available on the effect of levetiracetam on the developing fetus, so cautious use during pregnancy is recommended until more information is available. Additional studies will refine the recommendations for use of levetiracetam in these special populations.

Topics: Adult; Age Factors; Aged; Anticonvulsants; Child; Comorbidity; Contraceptives, Oral; Drug Approval; Drug Interactions; Epilepsy; Female; Humans; Kidney Failure, Chronic; Levetiracetam; Liver Diseases; Male; Middle Aged; Piracetam; Sex Factors

The anti-epileptic drug levetiracetam is excreted renally. The objective of this trial was to evaluate the pharmacokinetics of levetiracetam in Japanese patients with renal impairment including end-stage renal disease (ESRD) to confirm that existing dosing instructions-based on data from European patients-are appropriate in a Japanese population.. This was a nonrandomised, open-label trial. Six participants were allocated to each of five groups (normal renal function, mild, moderate and severe renal impairment and ESRD); 30 participants in total. Participants received a single dose of levetiracetam 500 mg (normal or mild), 250 mg (moderate or severe), or 500 mg followed by 250 mg post-haemodialysis (ESRD). Blood and urine samples were obtained serially for levetiracetam and metabolite determinations. Noncompartmental pharmacokinetic parameters were calculated and steady-state profiles were simulated using the superposition method.. In this trial, levetiracetam total clearance decreased proportionally with creatinine clearance: 52, 31, 25, 20 and 11 mL/min/1.73 m(2) in healthy controls and in patients with mild, moderate, severe renal impairment, and ESRD, respectively. Simulated levetiracetam plasma profiles using the recommended dose adjustments were within the range for normal renal function. Overall, results from this trial were consistent with historical European data.. These findings confirm that the dosing instructions are appropriate for Japanese patients with renal impairment including ESRD.

Topics: Adult; Aged; Animals; Case-Control Studies; Dose-Response Relationship, Drug; Humans; Japan; Kidney Failure, Chronic; Levetiracetam; Male; Middle Aged; Piracetam; Renal Insufficiency; Young Adult

Levetiracetam (LEV) is primarily renally eliminated. In end-stage renal disease (ESRD) patients on hemodialysis (HD), pharmacokinetic studies recommend daily dosing with 50% supplemental doses after 4-hour HD sessions. However, poor medication adherence after HD could result in fluctuating plasma drug levels.. To compare two LEV dosing regimens, daily versus twice-daily (BID), in ESRD patients undergoing HD.. Consecutive ESRD patients (April 2013 to May 2014) receiving maintenance inpatient HD and prescribed LEV prior to admission to our academic tertiary hospital were prospectively analyzed. Demographics, initial lab values, adverse reactions, seizures, and LEV regimens were recorded. LEV levels were obtained pre-HD and post-HD along with levels after receiving post-HD doses. Recovery of plasma levels after HD was assessed by comparison of levels predialysis versus postdialysis and post-HD doses.. We identified 22 patients who met inclusion criteria; 14 BID and 8 daily dosing. Mean predialysis, postdialysis, and post-HD dose plasma levels were higher in patients receiving LEV BID compared with daily (43.1 ± 6.3, 19.4 ± 5.2, 34.9 ± 4.3 vs 21.1 ± 3.9, 6.9 ± 1.5, 11.9 ± 1.7 µg/mL; P < 0.05). BID post-HD levels were 41.9 ± 4.6% of predialysis levels versus 36.9 ± 7.3% with daily dosing ( P = 0.275). Post-HD dose levels were 81.4±4.3% of predialysis on LEV BID versus 65.7 ± 8.8% on LEV daily ( P = 0.045). No seizures were reported during hospital admission in either group.. Compared to LEV daily, BID dosing achieved significantly higher levels and a better recovery to predialysis levels. Although limited by small numbers, a similar relationship between postdialysis levels was not detected.

Topics: Adult; Aged; Anticonvulsants; Clinical Protocols; Drug Administration Schedule; Female; Humans; Kidney Failure, Chronic; Levetiracetam; Male; Middle Aged; Piracetam; Renal Dialysis; Seizures