Levetiracetam and topiramate poisoning: Two overdoses on those drugs with no lasting effects.

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.

Cardiovascular toxicity with levetiracetam overdose.

OBJECTIVE: To describe the cardiovascular toxicity and pharmacokinetics of levetiracetam in overdose. CASE REPORT: 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. DISCUSSION: 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.

Cardiac sodium channel blockade after an intentional ingestion of lacosamide, cyclobenzaprine, and levetiracetam: Case report.

CONTEXT: 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. CASE DETAILS: 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. DISCUSSION: 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.

An 11-year review of levetiracetam ingestions in children less than 6 years of age.

BACKGROUND: Levetiracetam is a new anticonvulsant, which works to block high-voltage-activated Ca(++) channels in children, for partial-onset seizures. Reports of clinical experience with pediatric ingestions are minimal. The purpose of this study was to characterize the toxicity of accidental levetiracetam exposures in children less than 6 years of age. METHODS: This was an 11-year retrospective observational case series of pediatric (< 6 years old) levetiracetam ingestions reported to a Poison Control System from 2002 to 2013. Case narratives were individually reviewed to collect desired information on exposure and clinical course. Inclusion criteria were levetiracetam as a single ingested medication, age less than 6 years, treatment in a health care facility, and followed to a known outcome. RESULTS: Eighty-two cases met inclusion criteria with 55% female patients and overall median age of 2.0 years (range: 1-60 months). The levetiracetam dose ingested was reported in 69 (84.1%) cases, with exact dose (median dose, 45.0 mg/kg; range, 10.5-1429 mg/kg) reported in 33 cases (40.2%). Of these, twenty-nine cases (88%) involved the oral solution formulation and 28 cases (85%) had unintentional therapeutic error as the cause of the exposure. No dose-response relationship was demonstrated; however, the odds of a levetiracetam-naive patient, (median dose, 26.9 mg/kg; N = 15) with an unintentional exposure, developing drowsiness or ataxia was 6 times that of a patient who was not naïve to levetiracetam (median dose, 70.1 mg/kg; N = 20) (Odds ratio [OR], 6.0; 95% confidence interval [CI], 1.03-35.91).Of the 82 cases, 17 (20.7%) developed untoward clinical effects of drowsiness and/or ataxia. Eighty patients (97.6%) were treated and discharged from the emergency department, and two patients (2.4%) were admitted. The two patients admitted included a two-month old who was accidentally given a dose 10 times that of her usual dose and a 3-year old who was lethargic on arrival to the hospital after ingestion of an unknown dose. Of all patients, 66 patients (80.5%) had no effect from the drug exposure. The medical outcome was considered to be minor in 15 cases (18.3%), and moderate in 1 case (1.2%). There were no cases with major outcomes and no deaths. CONCLUSIONS: Pediatric levetiracetam exposures were associated with few transient clinical effects. Poison Control Centers may wish to consider acuity of ingestion when developing send-in protocols.

Overdose with levetiracetam: a case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: 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. CASE SUMMARY: 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. WHAT IS NEW AND CONCLUSION: 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.

Postmortem levetiracetam (Keppra®) data from North Carolina.

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.

Safety of non-therapeutic levetiracetam ingestions--a poison center based study.

BACKGROUND: Very limited data is available regarding the safety of levetiracetam in cases of unintentional or intentional ingestions. METHODS: 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. RESULTS: 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. CONCLUSIONS: In this study with a limited number of cases, intentional and unintentional ingestions of levetiracetam were safe in the majority of cases.

Acute levetiracetam overdose presented with mild adverse events.

PURPOSE: Overdose of levetiracetam may produce neurotoxicity. CASE REPORT: We reported a patient with epilepsy who took an overdose of 63 grams of levetiracetam with mild adverse events. The patient presented mild blurred vision and mild ataxia that rapidly subsided within one day with supportive care. The laboratory tests showed mild leucopenia and mild thrombocytopenia that gradually returned to normal within 2 months. CONCLUSION: The pharmacokinetics, tolerability and adaptation of levetiracetam might play a role in the mild adverse events of levetiracetam overdose in our patient.

A case of levetiracetam (Keppra) poisoning with clinical and toxicokinetic data.

BACKGROUND: 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. CASE REPORT: 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. CONCLUSION: 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.

Safety profile of levetiracetam.

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.