levetiracetam and Drug-Overdose

Levetiracetam is an anticonvulsant agent that was first approved for use in the United States in 1999 and has a maximum recommended adult dose of 3000 mg daily. It has been noted to have a relatively mild adverse effect profile, with the most common side effects being somnolence, asthenia, infection, and dizziness. Although it has been widely prescribed, there have been few reports on the safety of this agent in overdose.. We present the case of a 49-year-old man who ingested over 22 500 mg of levetiracetam in a suicide attempt. The patient arrived at the Emergency Department 6·5 h after the ingestion and was noted to have no significant sequelae from the ingestion. Based on the patient's weight, he ingested 358 mg/kg of levetiracetam.. The few cases of levetiracetam overdose reported in the literature were associated with relatively mild, if any, symptoms. However, one patient who overdosed on levetiracetam became obtunded and developed significant respiratory distress that required intubation and ventilatory support. Therefore, clinical vigilance is still required in the cases of levetiracetam overdose.

Topics: Anticonvulsants; Drug Overdose; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Suicide, Attempted

Multiple new anticonvulsants have been introduced recently and they are supplanting the older medications. Whereas the older drugs have well-recognized side effects, both in typical therapeutic doses and in overdosage, the properties of the newer ones are unique and largely unknown to all but sub-specialists.. This article gives a concise overview of the potential complications of these new medications in both therapeutic use and overdose.. Clinically significant side effects of the new anticonvulsants, such as metabolic acidosis from topiramate, autoimmune reactions from lamotrigine, hyponatremia from oxcarbazepine, or psychosis from levitiracetam can cause serious morbidity and mortality if unrecognized. The effects of these medications in overdose are also largely unknown to most emergency physicians.. This article reviews the major potential side effects of the new seizure medications and the treatment of their overdoses for the practicing emergency physician.

Topics: Acidosis; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Overdose; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Psychoses, Substance-Induced; Seizures; Tiagabine; Topiramate; Triazines

Levetiracetam was approved in November 1999 as add-on therapy for the treatment of partial-onset seizures in adults (age 16 years and older). This review focuses on recently published data from four well-controlled studies in patients with partial-onset seizures with or without secondary generalization. When levetiracetam was given along with other antiepileptic drugs (AEDs), the most frequently reported adverse events were central nervous system related. Adverse events were usually mild to moderate in intensity, with the most frequently reported events occurring predominantly during the first 4 weeks of treatment. No relationship was apparent between the dose of levetiracetam and the most commonly reported adverse events in well-controlled clinical trials within the recommended dose range of 1,000-3,000 mg/day. Levetiracetam is a Pregnancy Category C drug. Overall, when used in combination with other AEDs, levetiracetam was generally well tolerated as add-on treatment for partial-onset seizures.

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Central Nervous System Diseases; Controlled Clinical Trials as Topic; Death, Sudden; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Approval; Drug Overdose; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Female; Humans; Incidence; Infant, Newborn; Levetiracetam; Male; Piracetam; Placebos; Pregnancy

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

Topics: Adolescent; Anticonvulsants; Antidepressive Agents, Second-Generation; Bupropion; Depressive Disorder; Drug Overdose; Electrocardiography; Female; Follow-Up Studies; Humans; Levetiracetam; Myoclonus; Suicide, Attempted; Tachycardia

Levetiracetam and topiramate are newer anticonvulsants, which is why international data on overdoses of these drugs are lacking. Only a few mild adverse reactions have been noted. These anticonvulsants have been the drug of choice for neurologists. Despite their wide usage, there is a dearth of literature on symptoms and signs of their toxicity. Presented here is the case of a 21-year-old female who overdosed twice on levetiracetam and topiramate. The woman was admitted and discharged after the first overdose. Ten days later, she took multiple tablets of both drugs and was seen again. Amazingly, the woman went home after the incident with no complications at all.

Topics: Anticonvulsants; Antidotes; Charcoal; Drug Overdose; Female; Fructose; Humans; Levetiracetam; Piracetam; Topiramate; Young Adult

Topics: Administration, Oral; Anticonvulsants; Drug Overdose; Drug Packaging; Epilepsy; Humans; Levetiracetam; Medication Errors; Solutions

Levetiracetam is an anti-epileptic drug commonly used in intensive care when seizure is suspected as a possible cause of coma. We propose to question the cofounding effect of Levetiracetam during the prognostication process in a case of anoxic coma. We report the story of a young woman presenting a comatose state following a hypoxic cardiac arrest. After a first EEG presenting an intermediate EEG pattern, a seizure suspicion led to prescribe Levetiracetam. The EEG showed then the appearance of burst suppression, which was compatible with a very severe pattern of post-anoxic coma. This aggravation was in fact related to an overdose of Levetiracetam (the only medication introduced recently) and was reversible after Levetiracetam cessation. The increased plasmatic dosages of Levetiracetam confirming this overdose could have been favoured by a moderate reduction of renal clearance, previously underestimated because of a low body-weight. This EEG dynamic was unexpected under Levetiracetam and could sign a functional instability after anoxia. Burst suppression is classically observed with high doses of anaesthetics, but is not expected after a minor anti-epileptic drug. This report proposes that Levetiracetam tolerance might not be straightforward after brain lesions and engages us to avoid confounding factors during the awakening prognostication, which is mainly based on the severity of the EEG. Hence, prognosis should not be decided on an isolated parameter, especially if the dynamic is atypical after a new prescription, even for well-known drugs. For any suspicion, the drug's dosage and replacement should be managed before any premature care's withdrawal.

Topics: Adult; Anticonvulsants; Coma; Drug Overdose; Electroencephalography; Female; Heart Arrest; Humans; Hypoxia; Levetiracetam; Piracetam

The 42-year-old woman who had been taking 300 mg phenytoin and 2,000 mg levetiracetam daily took 28.6 g of phenytoin and was transferred to our critical care center. The blood phenytoin concentration was 67.9 μg/mL on admission and decreased to 53.4 μg/mL on hospital day 2. Tonic seizures occurred several times on hospital day 2; thus, we resumed levetiracetam via a nasogastric tube. Thereafter, no further seizures were observed. We thought the seizure to have been caused by temporary withdrawal of levetiracetam because it did not occur on the day when the blood phenytoin concentration peaked and stopped altogether after resumption of levetiracetam. We considered that to treat the convulsion attack resulting from an overdose of the other antiepileptic drug with a different action mechanism, it was necessary to promptly restart the administration of the antiepileptic drug, which the patient was usually administered.

Topics: Acute Disease; Adult; Anticonvulsants; Drug Combinations; Drug Overdose; Female; Humans; Levetiracetam; Phenytoin; Seizures

To describe the cardiovascular toxicity and pharmacokinetics of levetiracetam in overdose.. A 43-year-old female presented 8 h post ingestion of 60-80 g of levetiracetam with mild central nervous system depression, bradycardia, hypotension and oliguria. Her cardiovascular toxicity transiently responded to atropine and intravenous fluids. A bedside echocardiogram demonstrated normal left and right ventricular contractility. Despite her cardiovascular toxicity and oliguria, she had normal serial venous lactates and renal function; and made a complete recovery over 48 h. Her levetiracetam concentration was 463 mcg/ml 8 h post ingestion (therapeutic range 10-40 mcg/ml) and her concentration-time data best fitted a one-compartment model with first-order input and an elimination half-life of 10.4 h.. Levetiracetam in large ingestions appears to cause bradycardia and hypotension that is potentially responsive to atropine and intravenous fluids. Based on a normal echocardiogram, the mechanism for this effect may be levetiracetam acting at muscarinic receptors at high concentration. The pharmacokinetics of levetiracetam in overdose appeared to be similar to therapeutic levetiracetam dosing.

Topics: Adult; Atropine; Bradycardia; Cardiovascular System; Drug Overdose; Female; Humans; Hypotension; Levetiracetam; Oliguria; Piracetam

Lacosamide treats partial seizures by enhancing slow inactivation of voltage-gated sodium channels. The described cardiac toxicity of lacosamide in the literature to date includes atrioventricular blockade (PR prolongation), atrial flutter, atrial fibrillation, sinus pauses, ventricular tachycardia and a single cardiac arrest. We report a second case of cardiac arrest following an intentional lacosamide overdose.. A 16 year-old female with a seizure disorder was found unresponsive in pulseless ventricular tachycardia after intentionally ingesting 4.5 g (76 mg/kg) lacosamide, 120 mg (2 mg/kg) cyclobenzaprine and an unknown amount of levetiracetam. Exact time of ingestion was unknown. Her initial electrocardiogram (ECG) demonstrated sinus tachycardia at 139 beats per minute, QRS duration 112 ms, and terminal R-wave in lead aVR > 3 mm. Despite treatment with 150 mEq of sodium bicarbonate, she had persistent EKG findings eight hours after presentation. Her serum lacosamide concentration nine hours after presentation was elevated at 22.8 μg/mL, while serum cyclobenzaprine concentration was 16 ng/mL (therapeutic: 10-30 ng/mL), and serum levetiracetam concentration was 22.7 μg/mL (therapeutic: 12-46 μg/mL). On hospital day three, ECG demonstrated resolution of the terminal R-wave with QRS of 78 ms. The patient recovered without physical or neurologic sequelae.. The patient's lacosamide, cyclobenzaprine and levetiracetam overdose was associated with QRS prolongation and terminal right axis deviation--suggesting sodium channel blockade as a likely etiology for her cardiac arrest. Cyclobenzaprine has potential for sodium channel blockade and ventricular dysrhythmias although cardiac toxicity due to cyclobenzaprine alone is rare. The combination of cyclobenzaprine with lacosamide may have resulted in cardiovascular collapse. In conclusion, overdose of lacosamide combined with therapeutic concentrations of sodium channel blocking xenobiotics may cause cardiac conduction delays and cardiac arrest.

Topics: Acetamides; Adolescent; Amitriptyline; Anticonvulsants; Drug Interactions; Drug Overdose; Electrocardiography; Epilepsy; Female; Heart Arrest; Humans; Lacosamide; Levetiracetam; Piracetam; Risk Factors; Sodium Bicarbonate; Sodium Channel Blockers; Sodium Channels; Suicide, Attempted; Tachycardia, Ventricular; Treatment Outcome

Levetiracetam (Keppra®) is one of the newer anticonvulsant drugs used to treat seizures. Since 2003, the North Carolina Office of the Chief Medical Examiner Toxicology Laboratory has collected quantitative levetiracetam data in samples for 56 postmortem cases. The data presented herein will provide the forensic community with concentrations to assist in the interpretation of levetiracetam in postmortem blood. Decedents were divided into two groups according to manner of death as determined by the medical examiner for the purposes of studying levetiracetam concentrations. There were equal numbers of natural (N = 28) and non-natural deaths (N = 28). These data were subsequently divided into subgroups for further study to explore the therapeutic range of levetiracetam and how it relates to postmortem data. The cases not certified as natural were investigated to study levetiracetam concentrations in cases where it was determined to contribute to the cause of death (attributed) and those where it was not (unattributed). Until now, the literature has only reported levetiracetam overdoses in which the individuals have recovered with respiratory support. Discussed are two suicidal drug deaths from 2010 that are noted to have elevated levels of levetiracetam, 190 and 35 mg/L. Also included in the complete data set are postmortem concentrations for five patients under the age of 10 with levetiracetam ranging from 1.4 to 50 mg/L. This paper will also address the adverse effects of the drug and explore its potential risk for suicide.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Cause of Death; Child; Child, Preschool; Drug Overdose; Female; Humans; Levetiracetam; Male; Middle Aged; North Carolina; Piracetam; Suicide; Young Adult

Very limited data is available regarding the safety of levetiracetam in cases of unintentional or intentional ingestions.. All cases of single agent ingestions of levetiracetam, excluding adverse drug reactions (ADRs), reported to 61 American poison control centers during 2000-2009 were identified. Demographics, dose, symptoms, and medical outcome were abstracted from each case record.. A total of 222 cases of single agent levetiracetam ingestions were reported during the study period. Median age was 14.0 years (IQR: 2.0 years, 39.0 years) and 51.8% were female. In 207 of 222 cases (93.2%) medical outcome was known. No deaths were reported and only 1 (0.5%) case resulted in a major outcome and 3 (1.4%) cases resulted in moderate outcomes. Minor, minimal, or no effects were reported in 198 (89.2%) cases. In 27 (12.2%) cases, ingestion was intentional and in 192 (86.5%) unintentional. There were no major outcomes and only one case (1.4%) of moderate outcome in 74 children aged 6 years or less. All ingestions in these children were unintentional.. In this study with a limited number of cases, intentional and unintentional ingestions of levetiracetam were safe in the majority of cases.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Child, Preschool; Databases, Factual; Drug Overdose; Female; Humans; Infant; Levetiracetam; Male; Middle Aged; Piracetam; Poison Control Centers; Retrospective Studies; Young Adult

Topics: Anticonvulsants; Child, Preschool; Drug Overdose; Female; Humans; Levetiracetam; Piracetam; Seizures

Levetiracetam (Keppra) is a new anticonvulsant used to treat partial complex seizures that is also being investigated for its mood-stabilizing properties. Although its precise mechanism of action is unknown, levetiracetam does not appear to directly interact with the GABA system. We report the first intentional overdose with levetiracetam including clinical effects and serial serum concentrations.. A 38-year-old woman reportedly ingested 60 (500 mg) tablets of levetiracetam that she used as a mood-stabilizing medication for bipolar disorder. She had no other prescription medications available and no other medical history. She vomited 4 hours after ingestion and presented to the ED 2 hours later. In the ED, the patient was obtunded and was intubated secondary to respiratory depression. Her only other significant clinical finding was diminished deep tendon reflexes. Serum ethanol, lithium, carbamazepine, phenytoin, and valproic acid levels were all negative as was a subsequent urine screen for drugs of abuse. Her levetiracetam serum concentration was 400 microg/mL at 6 hours, 72 microg/mL at 18 hours, and 60 microg/mL at 20.5 hours (therapeutic serum concentration is 10-37 microg/mL). The elimination half-life was calculated to be 5.14 hours. She was extubated the next hospital day and recovered without sequelae.. In overdose, levetiracetam is sedating and causes respiratory depression, however, recovery is rapid with supportive care. This is the first reported case of levetiracetam overdose; serial serum concentrations suggest first-order elimination even at concentrations 10-40 fold higher than therapeutic.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Drug Overdose; Female; Half-Life; Humans; Levetiracetam; Neurologic Examination; Piracetam; Poisoning; Respiration, Artificial; Respiratory Insufficiency; Suicide, Attempted