levetiracetam and Acute-Kidney-Injury

The aim of this review was to evaluate current literature for dosing recommendations for the use of antiepileptic medications in patients receiving renal replacement therapy (RRT).. With the assistance of an experienced medical librarian specialized in pharmacy and toxicology, we searched MEDLINE, EMBASE, CINAHL, Web of Science, WorldCat, and Scopus through May 2016.. Four hundred three articles were screened for inclusion, of which 130 were identified as potentially relevant. Micromedex® DRUGDEX as well as package inserts were used to obtain known pharmacokinetic properties and dosage adjustment recommendations in RRT if known.. Data regarding antiepileptic drug use in RRT are limited and mostly consist of case reports limiting our proposed dosing recommendations. Known pharmacokinetic parameters should guide dosing, and recommendations are provided where possible.. Additional studies are necessary before specific dosing recommendations can be made for most antiepileptic drugs in critically ill patients receiving RRT, specifically with newer agents.

Topics: Acetamides; Acute Kidney Injury; Amines; Anticonvulsants; Carbamates; Critical Illness; Cyclohexanecarboxylic Acids; Dibenzazepines; Dose-Response Relationship, Drug; Ethosuximide; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lacosamide; Lamotrigine; Levetiracetam; Phenobarbital; Phenylcarbamates; Phenylenediamines; Phenytoin; Piracetam; Propylene Glycols; Renal Dialysis; Renal Replacement Therapy; Seizures; Topiramate; Triazines; Valproic Acid; Zonisamide

Limited data exist on the effect of continuous renal replacement therapy (CRRT) methods on anti-epileptic drug pharmacokinetics (PK). This prospective practice-based PK study aims to assess the impact of continuous venovenous hemofiltration (CVVH), a modality of CRRT, on levetiracetam PK in critically ill patients and to derive individualized dosing recommendations. Eleven patients receiving oral or intravenous levetiracetam and CVVH in various intensive care units at a large academic medical center were enrolled to investigate the need for dosing adjustments. Prefilter, postfilter, and ultrafiltrate samples were obtained before dosing, after the completion of the infusion or 1-hour postoral dose, and up to 6 additional time points postinfusion or postoral administration. Patient-specific blood and ultrafiltrate flow rates and laboratory values were also collected at the time of sampling. The average sieving coefficient (SC) for levetiracetam was 0.89 ± 0.1, indicating high filter efficiency. Six of the 11 patients experienced concentrations outside the reported therapeutic range (12-46 mg/L). The average volume of distribution was 0.73 L/kg. CVVH clearance contributes a major fraction of the total levetiracetam clearance (36-73%) in neurocritically ill patients. The average bias and precision of the estimated vs. observed total clearance value was ~ 10.6% and 21.5%. Major dose determinants were identified to be SC and effluent flow rate. Patients with higher ultrafiltrate rates will have increased drug clearance and, therefore, will require higher doses in order to match exposures seen in patients with normal renal function.

Topics: Academic Medical Centers; Acute Kidney Injury; Administration, Intravenous; Administration, Oral; Aged; Anticonvulsants; Area Under Curve; Continuous Renal Replacement Therapy; Critical Illness; Dose-Response Relationship, Drug; Female; Glomerular Filtration Rate; Humans; Intensive Care Units; Levetiracetam; Male; Middle Aged; Prospective Studies; Renal Elimination; Seizures

Acute kidney injury is an expected adverse drug reaction listed in the European Union (EU) Summary of Product Characteristics (SmPC) for levetiracetam, one of the most widely used modern antiseizure medications (ASMs).. We conducted a voluntary post-authorization safety study to characterize the rate of acute renal failure (ARF) in patients exposed to levetiracetam versus other ASMs.. New users of ASMs without prior renal dysfunction were identified and followed for 30 days in the IBM. Overall, 110,336 patients were eligible for the monotherapy cohort and 96,215 were eligible for the polytherapy cohort. The overall crude rate of ARF following a new ASM was 6.0 and 6.5 per 10,000 patients for the 'monotherapy' and 'polytherapy' cohorts, respectively, in the first 30 days after the index date. In the monotherapy cohort, the IRR for ARF was 1.37 (95% confidence interval [CI] 0.80-2.34) and the corresponding IRD was 2.0 (95% CI - 1.12 to 5.12) additional ARFs per 10,000 patient-months. In the polytherapy cohort, the adjusted IRR for ARF was 0.94 (95% CI 0.51-1.74) and the corresponding IRD was - 0.42 cases per 10,000 patient-months (95% CI - 4.01 to 3.17).. The rate of ARFs in ASM new users was very low. In patients without prior ASMs, the estimated difference in risk of ARF associated with initiation of levetiracetam versus initiation of other ASMs was small, with 95% CIs compatible with small protective or harmful effects. In patients receiving polytherapy, the difference was compatible with the null and the 95% CI with small protective or harmful effects.

Topics: Acute Kidney Injury; Anticonvulsants; Cohort Studies; Humans; Incidence; Levetiracetam

Levetiracetam is a newer second-generation anticonvulsant for the treatment of generalized and partial seizure disorders. Common adverse effects are rhabdomyolysis and neuropsychiatric problems, such as somnolence, dizziness, and mood changes. The present report describes the first case, to our knowledge, of levetiracetam overdose resulting in acute kidney injury for which hemodialysis was required.. A 51-year-old man presented with hypotension and disturbance of consciousness with subsequent development of oliguria and elevated creatinine. Based on his history of ingesting a large dose of levetiracetam and the course of the disease, he was considered to have been poisoned by levetiracetam.. Acute kidney injury induced by levetiracetam poisoning.. Dialysis was performed for the rapidly progressing renal failure. His renal function improved, and he was weaned from dialysis and discharged home on the 19th day.. We should be aware of the possibility that severe renal function deterioration may occur in some patients with levetiracetam overdose. It is possible that clinicians underestimate the occurrence of this problem. In cases of acute renal failure in levetiracetam poisoning, induction of dialysis is beneficial.

Topics: Acute Kidney Injury; Anticonvulsants; Creatinine; Drug Overdose; Humans; Levetiracetam; Male; Middle Aged; Renal Dialysis

Symptoms of COVID-19, as reported during the SARS-CoV-2 pandemic in 2019-2020, are primarily respiratory and gastrointestinal, with sparse reports on neurological manifestations. We describe the case of a 17-year old female with Cornelia de Lange syndrome and well controlled epilepsy, who sustained significant cortical injury during a COVID-19 associated multi-inflammatory syndrome.

Topics: Acute Kidney Injury; Adolescent; Airway Extubation; Anticonvulsants; Blood Coagulation Disorders; Bone Marrow Failure Disorders; Brain Diseases; Brain Edema; C-Reactive Protein; COVID-19; De Lange Syndrome; Disease Progression; Electroencephalography; Epilepsy; Female; Ferritins; Humans; Influenza B virus; Influenza, Human; Levetiracetam; Magnetic Resonance Imaging; Midazolam; Necrosis; Phenobarbital; Pseudomonas Infections; Respiration, Artificial; Rhabdomyolysis; SARS-CoV-2; Seizures; Sepsis; Systemic Inflammatory Response Syndrome; Tachycardia, Ventricular

BACKGROUND Cefepime-induced neurotoxicity has been described in intensive care units (ICUs) and neuro ICU settings, occurring in patients started on cefepime for management of severe infections and sepsis. Most cases occur within 1 to 10 days after starting the drug. We publish a case that occurred on the general medical ward of a patient who had been on cefepime therapy for 4 weeks prior to admission. The aim of this study was to improve the knowledge of this serious condition to general internists as our patient was being managed on the general medical ward. CASE REPORT A 72-year-old female on prolonged intravenous antibiotics for sacral and pelvic osteomyelitis presented with acute encephalopathy and aphasia in the setting of an acute kidney injury. Due to the acute focal neurologic deficit, she was initially admitted as a stroke alert. After a negative magnetic resonance imaging (MRI) of the brain, an electroencephalogram (EEG) was pursued and showed nonconvulsive status epilepticus (NCSE). NCSE was likely a result of cefepime therapy in the setting of an acute kidney injury. CONCLUSIONS Cefepime-induced neurotoxicity should be suspected in any patient on cefepime therapy who develops acute changes in mental status, myoclonus, or evidence of seizures. Risk factors for the disease include older age, renal dysfunction, critical illness, and inappropriate dosing based upon renal function. A high index of suspicion is required and delays in diagnosis are common as there are frequently multiple possible causes for altered mental status in systemically ill patients requiring treatment with broad-spectrum antibiotics.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Anticonvulsants; Aphasia; Brain Diseases; Cefepime; Female; Humans; Levetiracetam; Lorazepam; Osteomyelitis; Status Epilepticus

Regulatory agencies warn about the risk of AKI with levetiracetam use on the basis of information from case reports. We conducted this study to determine whether new levetiracetam use versus nonuse is associated with a higher risk of AKI.. This was a population-based retrospective cohort study of adults with epilepsy in Ontario, Canada. Patients who received a new outpatient prescription for levetiracetam between January 1, 2004 and March 1, 2017 were matched to two nonusers on stage of CKD, recorded seizure in the prior 90 days, and logit of a propensity score for levetiracetam use. The primary outcome was a hospital encounter (emergency department visit or hospitalization) with AKI within 30 days of cohort entry. Secondary outcomes were AKI within 180 days and change in the concentration of serum creatinine. We assessed the primary outcome using health care diagnosis codes. We evaluated the change in the concentration of serum creatinine in a subpopulation with laboratory measurements.. We matched 3980 levetiracetam users to 7960 nonusers (mean age 55 years, 51% women). Levetiracetam use was not significantly associated with a higher risk of AKI within 30 days (13 [0.33%] events in levetiracetam users and 21 [0.26%] events in nonusers [odds ratio, 1.24; 95% confidence interval, 0.62 to 2.47]). Similarly, there was no significant association with AKI within 180 days (odds ratio, 0.70; 95% confidence interval, 0.43 to 1.13). The change in the concentration of serum creatinine did not significantly differ between levetiracetam users and nonusers.. In this population-based study levetiracetam use was not associated with a higher risk of AKI.. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_12_11_Yau_Podcast.mp3.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anticonvulsants; Creatinine; Emergency Service, Hospital; Female; Humans; Levetiracetam; Membrane Glycoproteins; Middle Aged; Nephritis, Interstitial; Nephrology; Patient Admission; Receptors, Interleukin-1; Referral and Consultation; Retrospective Studies; Rhabdomyolysis; Risk Factors; Time Factors

A 75-year-old man was admitted with abdominal pain and fresh rectal bleeding. Significantly, he had no risk factors for

Topics: Abdominal Pain; Acute Kidney Injury; Aged; Anti-Bacterial Agents; Anticonvulsants; Critical Care; Enterocolitis, Pseudomembranous; Escherichia coli Infections; Escherichia coli O157; Gastrointestinal Hemorrhage; Hemolytic-Uremic Syndrome; Humans; Levetiracetam; Male; Piracetam; Renal Replacement Therapy; Sigmoidoscopy; Treatment Outcome; Valproic Acid

Levetiracetam is an antiepileptic medication that has been reported to be both well-tolerated and effective in treating generalized tonic-clonic, myoclonic, and partial-onset seizures. The adverse effects most commonly reported in tolerability trials include somnolence, fatigue/asthenia, headaches, dizziness, and nausea. However, there have been a few reports suggesting possible detrimental effects of levetiracetam on renal function.. Here we describe the case of a previously healthy 23-year-old female patient who developed acute kidney injury 1 day after the initiation of levetiracetam therapy for new-onset seizures.. Based on the time course of the patient's rise in serum creatinine and the exclusion of other causes, this case suggests that levetiracetam use contributed to the acute kidney injury.. Levetiracetam is a widely used drug that has been reported to be generally tolerable and effective; however, it has the potential to negatively affect renal function. This potential consequence of therapy should be considered when deciding whether or not to prescribe this medication, and renal function should be monitored during treatment.

Topics: Acute Kidney Injury; Anticonvulsants; Female; Humans; Levetiracetam; Piracetam; Seizures; Young Adult

A 45-year-old man with a new diagnosis of low grade glioma was started on an escalating dose of levetiracetam (Lev) for seizure management. He gradually developed intractable nausea/vomiting and a high creatinine concentration due to acute renal failure which was attributed to Lev-induced interstitial nephritis. The medication was changed and his renal function rapidly improved to his baseline.

Topics: Acute Kidney Injury; Anticonvulsants; Astrocytoma; Brain Neoplasms; Humans; Levetiracetam; Male; Middle Aged; Nephritis, Interstitial; Piracetam; Seizures