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.

A fatal intoxication case involving topiramate.

Topiramate belongs to a new group of anticonvulsive drugs primarily applied in treatment of epilepsy and in preventive therapy of migraines. Topiramate is structurally unrelated to other antiepileptic drugs and acts by multiple neurostabilizing mechanisms. However, the pharmacology of topiramate appears to be complex and some of its pharmacodynamic actions still remain to be elucidated. This case report documents a fatal intoxication involving topiramate. A 41-year old woman with a known history of psychiatric disorder was found unresponsive by her husband. Resuscitation efforts did not succeed and the woman was pronounced dead at the intensive care unit four hours later. At the scene, drug packages of topiramate, citalopram and flunitrazepam were found. Autopsy including histological examination revealed morphological signs of an acute intoxication and shock. A comprehensive toxicological analysis with GC-MS was performed on the deceased's autopsy samples (femoral blood, bile, kidney, gastric content). The results revealed the presence of topiramate at a concentration of 49mg/L in the femoral blood sample, thus clearly exceeding the therapeutic range. Additionally, citalopram (0.85mg/L) and flunitrazepam in traces (<2µg/L) were detected in peripheral blood. Based on the autopsy findings and toxicological results, the cause of death was primarily attributed to an intoxication with topiramate in combination with citalopram.

Clinical effects and toxicokinetic evaluation following massive topiramate ingestion.

Topiramate is used to treat a variety of neurologic and psychiatric diseases due to its benign safety profile. Data regarding the toxicity and toxicokinetics of topiramate in acute overdose are limited. A case of massive, acute ingestion resulting in the highest reported topiramate level is presented, including toxicokinetic evaluation. A 37-year-old woman presented with coma unresponsive to naloxone following topiramate ingestion. She had normal vital signs without respiratory depression. She was intubated for airway protection, given 3.5 mg lorazepam IV for facial and neck muscle twitching, and transferred to our facility. No additional sedation was required for 18 h on the ventilator. Following mental status improvement, the patient was extubated. Confusion, dysarthria, and imbalance resolved over the next 2 days. Nonanion gap metabolic acidosis persisted for 3 days. Peak serum topiramate level was 356.6 microg/ml (reference range, 5-20 microg/ml). Massive topiramate ingestion led to prolonged coma with normal vital signs and nonanion gap metabolic acidosis. Coma of this severity has not been previously reported. Serum half-life, which has not been studied after overdose, was 16 h. Despite the large ingestion and significant presenting symptoms, the patient recovered fully with supportive intensive care alone. Massive acute topiramate ingestion may lead to nonanion gap metabolic acidosis and prolonged coma which resolves with intensive supportive care. Toxicokinetic data following large, suicidal ingestion of topiramate were similar to previously published pharmacokinetic information.

Topiramate overdose: a case report of a patient with extremely high topiramate serum concentrations and nonconvulsive status epilepticus.

We report the case of a 21-year-old man with idiopathic generalized epilepsy who ingested about 8,000 mg of topiramate (TPM) in a suicide attempt. On admission to the hospital he had a nonconvulsive status epilepticus and received 4 mg lorazepam i.v. He recovered rapidly despite an initial TPM concentration of 144.6 microg/ml. To our knowledge, this is the first report of a patient who survived such a high TPM concentration. The case indicates that nonconvulsive status epilepticus could be a manifestation of TPM intoxication.

Acute topiramate overdose--clinical manifestations.

INTRODUCTION: The clinical manifestations of acute topiramate toxicity are described. METHODS: Seven cases of acute and acute-on-chronic topiramate toxicity observed in two clinical units of Polish Poison Control Centers in 2004-2005 were analyzed. RESULTS: The patients were 4 women and 2 men aged between 16 and 38 (mean 21.0 +/- 8.4) years. The doses of topiramate ranged from 10.7 to 218 mg/kg. The most frequent symptom was somnolence (66.7%) and, vertigo, agitation, and mydriasis were less common (33.4%). One patient who was not previously treated with topiramate experienced three secondarily generalized tonic-clonic seizures. Metabolic acidosis, lasting for 3-7 days, was observed in four cases, and did not influence the outcome. CONCLUSIONS: The clinical manifestations of acute poisonings with topiramate ranged from asymptomatic to severe, but no distant sequelae or fatalities were observed. The course of acute poisoning seems to be more severe in patients who were not previously treated with topiramate.

Topiramate-positive death-investigation and impaired-driving cases in Washington State.

Topiramate (Topamax), an effective seizure disorder treatment, received additional FDA approval for prevention of migraine headaches in August 2004 and has gained attention for its off-label uses, including psychiatric and eating disorders, neuropathic pain, and alcohol and drug dependency. Side effects of sedation, dizziness, ataxia, speech difficulty, nystagmus, paresthesia, and metabolic acidosis are described. The manufacturer reports that tolerance to the antiseizure properties does not develop. With its established efficacy for epilepsy treatment and its increased use for other disorders, topiramate-positive findings are more common in death-investigation and human-performance casework. To evaluate the role of topiramate, we reviewed all topiramate-positive cases from our laboratory between 1998 and 2004, which constituted 132 cases (63 death investigations, 68 suspected impaired drivers, and 1 sexual assault case). The subjects were predominantly female (69%) with a mean and median age of 42. Blood topiramate concentrations ranged from 1 to 180 mg/L (median 6.4 mg/L, mean 8.4 mg/L), and 94% were positive for at least one additional drug. There was evidence of psychomotor impairment in some drivers with blood concentrations within the normal therapeutic range, and deaths attributed to topiramate alone occurred at concentrations as low as 50 mg/L.

Pediatric case report of topiramate toxicity.

BACKGROUND: Topiramate is an FDA-approved second generation antiepileptic drug with actions on voltage-dependent sodium and calcium channels and GABA and excitatory amino acid receptors. There has only been one prior pediatric case report of topiramate toxicity. We report a 33-month-old girl with persisting neurologic symptoms after acute ingestion of topiramate. CASE REPORT: A 33-month-old girl was found at her sitter'shouse with a bottle of topiramate (100-mg tablets). She presented to the emergency department 3 days post-ingestion. The child appeared confused and was only able to crawl. At one point, she looked directly at mother and asked, "Where is my mommy?" She had visual hallucinations and screamed while pointing to objects on the wall. Neurologic exam was notable for the slurred speech and severe ataxia. All laboratory testing, urine chemical dependency screen, CSF, chest X-ray, head CT, and EEG showed no abnormalities. Topiramate level on the third day post-ingestion was 9.4 mcg/mL, and 4.2 mcg/mL on the fourth day. Patient became oriented to family and regained normal gait on the fourth day. Her slurred speech persisted until the sixth day after ingestion. CONCLUSION: Topiramate is an anti-epileptic drug with multifactorial mechanisms of action not entirely understood. We report here a 33-month-old girl with prolonged neurologic symptoms including hallucination, slurred speech, and severe ataxia after acute topiramate ingestion. This is the first pediatric case report of hallucination and prolonged neurologic symptoms with acute topiramate ingestion.

Evaluation of toxicity of topiramate exposures reported to poison centers.

Published literature on the toxicity of a topiramate overdose is limited to case reports. This retrospective study of poison center data was performed to examine the severity of topiramate overdoses. Data on single substance exposures to topiramate reported to the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS) in 2000 and 2001 were retrospectively analysed. A total of 567 cases met the inclusion criteria, of which 39% occurred in adults over 19 years of age and 30.2% in children < or = 4 years old. The majority of patients (62.1%) experienced no toxicity. The most common clinical effects reported were drowsiness/lethargy (15.5%), dizziness/vertigo (4.9%), agitation (4.9%), confusion (3.9%), nausea (2.6%) and vomiting (2.5%). Symptomatic patients were older than asymptomatic patients and adults were more likely to be managed in a healthcare facility (P <0.0001). Patients who received gastrointestinal decontamination experienced less serious outcomes than those without decontamination (P <0.02). It is concluded that clinicians should expect relatively mild mental status changes in adults or children with toxicity from topiramate overdose. Serious toxic effects, such as CNS depression with respiratory depression or persistent non-anion gap metabolic acidosis, are infrequent.

Acute suicidal intoxication with topiramate.

According to the best of our knowledge this is the first case of intoxication with topiramate in Polish medical literature. A case of a 15-year-old female who tried to commit suicide with 450 mg of Topamax was described. There were no significant changes in the medical examination as well as biochemical results. An agitation which transformed into bradykinesia and bradyphasia and lasted for about 24 hours were the only complaints of the patient.

Intentional topiramate ingestion in an adolescent female.

OBJECTIVE: To describe an intentional topiramate ingestion by an adolescent and warn of the potential for topiramate abuse. CASE SUMMARY: A 17-year-old female intentionally ingested approximately eight 100-mg topiramate tablets for the purpose of "getting high." Soon after ingestion, she was found at school obtunded and nonresponsive. Upon transfer to the emergency department, she became combative and aggressive with evolving neurologic abnormalities including incoherence, confusion, disorientation, and significant speech impairments including echolalia. Approximately 24 hours after ingestion, the patient had completely recovered without requiring specific treatment or experiencing sequelae. DISCUSSION: The clinical effects following acute topiramate intoxication appear consistent with the drug's known pharmacologic properties. There are few other reports of topiramate ingestions and most cases have had mild outcomes. CONCLUSIONS: Due to the multifactorial effects topiramate may have upon the central nervous system and its anorectic effect, abuse of this drug by adolescents should be considered upon presentation of an adolescent with mental status changes.

Fatal acute topiramate toxicity.

A 44-year-old Caucasian female was found dead in bed. Qualitative screening detected ethanol, phenobarbital, and methotrimeprazine. However, none were sufficient to attribute as the cause of death. Additionally, high concentrations of topiramate, an antiepilieptic agent, were found. Analysis of available biological fluids and tissues was carried out with the following results: blood (central) 170 mg/L, liver 140 mg/kg, stomach contents greater than 300 mg, and vitreous fluid 65 mg/L. The cause of death was ascribed to topiramate overdose.

Acute topiramate toxicity.

Topiramate (Topamax) is an anti-epileptic medication for which acute toxicity is infrequently reported. A 5-yr-old girl, not previously taking topiramate, developed neurological symptoms after acute ingestion of this medication. She was intermittently agitated, complained of "not being able to feel anything," demonstrated arching movements of the back, and perseverated upon questioning. Computerized tomography of the head and electroencephalography were both normal, and urine toxicology testing for drugs of abuse was negative. A serum topiramate level was 10.5 mcg/mL, confirming the ingestion. The patient was observed for 24 h, over which time her symptoms completely resolved.

Chronic fructose intoxication after infancy in children with hereditary fructose intolerance. A cause of growth retardation.

In two unrelated boys, 5.3 and 3.8 years of age with hereditary fructose intolerance, apparently isolated growth retardation (-2.71 S.D. and -2.40 S.D.) occurred after infancy, even though acute symptomatic fructose intoxication was prevented by restriction of dietary fructose. When more stringent restriction of dietary fructose was instituted (approximately 40 mg per kilogram of body weight per day), growth velocity increased from the 25th to the 97th percentile in one child and from well below the 3d to above the 75th percentile in the other. When restriction of dietary fructose was experimentally relaxed (from 10 to 250 mg per kilogram per day), neither boy had symptoms, hypoglycemia, or evidence of hepatic or renal dysfunction, but both had sustained hyperuricemia and hyperuricosuria and increases in the plasma concentration and urinary excretion of magnesium. We conclude that in patients with hereditary fructose intolerance, clinically important chronic fructose intoxication can occur after infancy without causing symptoms of acute fructose intoxication and can be expressed as an apparently isolated, reversible retardation of somatic growth with a continuing disorder of adenine nucleotide metabolism, characterized in part by recurrently increased rates of degradation of adenine nucleotides.