levetiracetam and Renal-Insufficiency

A good balance between safety and tolerability is necessary for an antiepileptic drug (AED) to be successful in the management of patients with epilepsy. Levetiracetam is one of the new generation of AEDs licensed as an add-on therapy for the treatment of patients with partial-onset seizures. Leveti-racetam's mechanisms of action are not fully understood. Controlled clinical trials, open-label studies, and postmarketing surveillance indicate that leveti-racetam has a favorable safety profile characterized by little effect on vital signs or clinical laboratory values, reported adverse events that are mild to moderate, and no known drug-drug interactions. The tolerability of levetiracetam may extend to both pediatric and elderly patients based on analyses of small numbers of patients. Tolerability is maintained over the long term. Levetirac-etam does not appear to have a different safety profile in learning-disabled patients. Levetiracetam appears to have a good balance between tolerability and efficacy in the treatment of a wide variety of patients with partial epilepsy.

Topics: Age Factors; Anticonvulsants; Drug Interactions; Epilepsy; Humans; Levetiracetam; Persons with Mental Disabilities; Piracetam; Renal Insufficiency; Seizures

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

Granulomatous interstitial nephritis (GIN) is a type of tubulointerstitial nephritis characterised by tubulointerstitial infiltration of mononuclear cells and eosinophils. It accounts for about 6% of all tubulointerstitial nephritis and is detected in ∼0.5%-0.9% of all renal biopsies. GIN has been linked to several antibiotics, non steroidal anti-inflammatory drugs (NSAIDs), and granulomatous disorders like tuberculosis and sarcoidosis but is rarely reported with anti-epileptic medications like phenytoin and levetiracetam. We present a case report of a man in his early 20's with previously normal renal function who developed GIN following levetiracetam and phenytoin consumption for 7 years. After withdrawal of the causative drug and starting steroid therapy, his kidney function gradually improved. In cases of GIN, medication history is important in the evaluation of aetiology.

Topics: Anticonvulsants; Granuloma; Humans; Levetiracetam; Male; Nephritis, Interstitial; Phenytoin; Renal Insufficiency

Levetiracetam (LEV) is an anti-epileptic drug approved for use in various populations. The pharmacokinetic (PK) behavior of LEV may be altered in the elderly and patients with renal and hepatic impairment. Thus, dosage adjustment is required. This study was conducted to investigate how the physiologically-based PK (PBPK) model describes the PKs of LEV in adult and elderly populations, as well as to predict the PKs of LEV in patients with renal and hepatic impairment in both populations. The whole-body PBPK models were developed using the reported physicochemical properties of LEV and clinical data. The models were validated using data from clinical studies with different dose ranges and different routes and intervals of administration. The fit performance of the models was assessed by comparing predicted and observed blood concentration data and PK parameters. It is recommended that the doses be reduced to ~70%, 60%, and 45% of the adult dose for the mild, moderate, and severe renal impairment populations and ~95%, 80%, and 57% of the adult dose for the Child Pugh-A (CP-A), Child Pugh-B (CP-B), and Child Pugh-C (CP-C) hepatic impairment populations, respectively. No dose adjustment is required for the healthy elderly population, but dose reduction is required for the elderly with organ dysfunction accordingly, on a scale similar to that of adults. A PBPK model of LEV was successfully developed to optimize dosing regimens for special populations.

Topics: Adult; Aged; Humans; Kidney; Levetiracetam; Liver Diseases; Models, Biological; Renal Insufficiency

In patients requiring hemodialysis, the extracorporeal circuit is expected to remove the majority of serum levetiracetam. The preferred levetiracetam dosing regimen in critically ill patients exhibiting complex pharmacokinetic profiles undergoing hemodialysis is unknown. The objective of this case is to describe levetiracetam pharmacokinetics in a critically ill anephric patient receiving intermittent hemodialysis.. This is a case report of a single patient.. A 43-year-old anephric female was admitted to the intensive care unit for concerns of new onset seizure activity. She was loaded with 2000 mg levetiracetam followed by a 750 mg daily maintenance dose. The levetiracetam volume of distribution was 0.48 L/kg, and the interdialytic elimination half-life was 31 h. Hemodialysis removed nearly 85% of serum levetiracetam, and the patient exhibited slightly higher than expected non-renal elimination. Pharmacokinetic simulations identified 500 mg daily with 750 mg post-dialysis supplements as the regimen most likely to reduce variability in serum levetiracetam concentrations and achieve levels in the therapeutic range.. Substantial elimination of levetiracetam by hemodialysis occurred in this case, and non-renal clearance was slightly higher than in previous reports. Insufficient intradialytic or post-dialysis levetiracetam concentrations may place patients at risk of breakthrough seizures. This case indicates that dialysis patients on levetiracetam may require higher post-dialysis supplemental doses than currently recommended and tailored therapy supported by therapeutic drug monitoring.

Topics: Adult; Anticonvulsants; Critical Illness; Female; Humans; Levetiracetam; Renal Dialysis; Renal Insufficiency; Seizures

Levetiracetam clearance is dependent on renal (major) and hepatic (minor) elimination pathways. In the setting of organ dysfunction, dose reductions are recommended to prevent accumulation. Continuous venovenous hemofiltration (CVVH) has been shown to eliminate levetiracetam, but the preferred dosing regimen when a patient is on CVVH and has concomitant acute liver dysfunction is unknown. The objective of this case is to describe levetiracetam dosing and pharmacokinetics in the setting of CVVH and acute liver dysfunction.. This is a case report of a single patient.. A 59-year-old male was admitted to the intensive care unit for acute onset multiorgan dysfunction associated with a hematologic disorder. His hospital course was complicated by persistent liver dysfunction with a model for end-stage liver disease score of 47 and renal failure which necessitated initiation of CVVH. On hospital day two, the patient developed new-onset focal seizures secondary to metabolic abnormalities that resulted in the initiation of levetiracetam 1000 mg intravenously twice daily. The peak concentration at steady state was 32.2 mcg/mL, and the trough concentration was 16.1 mcg/mL (goal 12-46 mcg/mL). The volume of distribution was 0.65 L/kg, and the elimination half-life was 11.4 h.. Levetiracetam pharmacokinetics observed in this case approximated those seen in a normal healthy patient and a regimen of 1000 mg twice daily achieved serum trough concentrations at the lower limit of the target range. This case indicates that in a patient with acute liver dysfunction on CVVH, 1000 mg twice daily may be considered as an empiric levetiracetam regimen.

Topics: Anticonvulsants; Hemofiltration; Humans; Levetiracetam; Liver Failure, Acute; Male; Middle Aged; Piracetam; Renal Insufficiency

Anticonvulsant hypersensitivity syndrome is an adverse drug reaction usually occurring from 1 to 8 weeks after exposure to antiepileptic drugs. It can threaten life by affecting the liver, kidneys, central nervous system or lungs. We present a 47-year-old patient treated with phenytoin, lamotrigine and clobazam for 7 years. He presented with hepatic and renal failure in relation to this syndrome demonstrated by renal biopsy. Prognosis was excellent due to an early diagnosis leading to cessation of the causative agents. Levetiracetam was started with a good response.

Topics: Anticonvulsants; Drug Hypersensitivity Syndrome; Epilepsy; Humans; Levetiracetam; Liver Failure; Male; Middle Aged; Piracetam; Renal Insufficiency

Triphasic waves are seen in the electro-encephalogram of adult patients with toxic-metabolic encephalopathies of various origins. Levetiracetam is a broad spectrum anti-epileptic drug with renal elimination and no hepatic metabolism. We describe the case of encephalopathy with triphasic waves concomitant with levetiracetam accumulation in a patient with chronic renal failure. The condition was reversible after down-titration of levetiracetam with no change of the renal function. Other causes of metabolic encephalopathy were excluded. Moreover, this patient suffered from a probable cortical myoclonus that relapsed after cessation of the drug but was well controlled by a low dosage adapted to the renal failure. In cases of metabolic encephalopathy with triphasic waves in a patient with renal failure taking levetiracetam, it is important to exclude toxic accumulation of levetiracetam among other causes.

Topics: Aged, 80 and over; Anticonvulsants; Electroencephalography; Epilepsies, Myoclonic; Female; Humans; Levetiracetam; Piracetam; Renal Insufficiency

A 17-year-old girl who had started on levetiracetam because of new onset partial complex seizures developed acute renal failure and biopsy-confirmed interstitial nephritis 10 days after starting the drug. She made a complete and rapid recovery after discontinuation of levetiracetam and administration of oral corticosteroids. Levetiracetam, known to be predominantly excreted by the kidneys, has not previously been reported to cause significant renal complications in children. Children taking levetiracetam who present with abdominal pain, malaise, vomiting, oliguria, rash, or urticaria may require screening laboratory evaluation for potential renal adverse effects.

Topics: Adolescent; Adrenal Cortex Hormones; Anticonvulsants; Contraindications; Female; Humans; Kidney; Levetiracetam; Nephritis, Interstitial; Piracetam; Renal Insufficiency; Seizures