Levetirasetam (Keppra, Epixx)

Clinical Effects:

PYRROLIDINONE DERIVATIVES
  • USES: These drugs are classified as “nootropics”, or cognitive-enhancing agents. With the exception of levetiracetam, they are used for therapy of cognitive disorders, such as Alzheimer’s disease, organic brain syndrome, dementia, and dyslexia. Levetiracetam, an antiepileptic agent, is approved for adjunctive treatment of partial complex seizures in epileptic adults. PHARMACOLOGY: The pyrrolidinone nootropics (agents which are believed to enhance learning and memory) are cyclic derivatives of gamma-butyric acid (GABA), although they have no significant affinity for GABA or benzodiazepine receptors. Levetiracetam is a soluble ethyl analogue of piracetam, and it possesses antiepileptic, anxiolytic, and cognitive enhancing properties. Only the S-enantiomer of levetiracetam has anticonvulsant activity. Piracetam appears to have anti-myoclonic properties. EPIDEMIOLOGY: Overdoses are rare. MILD TO MODERATE TOXICITY: Overdose data are limited. Vomiting and drowsiness have been reported. SEVERE TOXICITY: Coma and respiratory depression have been reported. ADVERSE EFFECTS: COMMON: During clinical trials, the most common adverse effects reported were somnolence, dizziness, ataxia, asthenia, nervousness, headache, coordination difficulties and behavioral abnormalities. Generalized rash or ecchymosis, abdominal pain, constipation, diarrhea, dyspepsia, gastroenteritis, nausea, vomiting, anemia, leukopenia, elevations of liver enzymes, and increased respiratory infections (e.g. coughing, pharyngitis, rhinitis, and sinusitis) have also been reported in clinical trials.

Range of Toxicity:

PYRROLIDINONE DERIVATIVES
  • TOXICITY: The highest dose of levetiracetam given in clinical development was 6000 mg/day. Based on limited levetiracetam overdoses, drowsiness was the only reported clinical effect. An adult developed CNS depression, but recovered completely following a 30 g ingestion of levetiracetam. Two children who accidentally received high doses (4 and 10 times the recommended daily doses) of levetiracetam did not experience any major side effects. Piracetam doses of up to 32 grams/day have been given, with drowsiness as the dose-limiting factor. THERAPEUTIC DOSE: ANIRACETAM: 500 mg orally twice daily. LEVETIRACETAM: Initial oral dosage is 500 mg twice daily; may be increased by 1000 mg/day every 2 weeks. Maximum recommended daily dose is 3000 mg. PIRACETAM: Oral doses of 2 to 4 g 3 times daily, increasing to 18 to 24 g daily, for myoclonus. PRAMIRACETAM: Oral doses of 600 mg twice daily or up to 4000 mg/day have been used.

Treatment:

PYRROLIDINONE DERIVATIVES
  • Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. Closely monitor neurologic function; treat seizures with benzodiazepines.
  • Decontamination: PREHOSPITAL: Prehospital emesis and activated charcoal are not recommended because of the potential for somnolence and rarely, seizures. HOSPITAL: Consider activated charcoal in a patient with a potentially toxic ingestion who is able to maintain their airway or if airway is protected.
  • Airway management: Endotracheal intubation may be necessary if significant CNS depression develops.
  • Antidote: None.
  • Seizure: Administer IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.
  • Enhanced elimination procedure: Hemodialysis has been reported to result in significant clearance of levetiracetam. During a 4-hour hemodialysis procedure, 50% of levetiracetam is removed from the body.
  • Monitoring of patient: Monitor vital signs and mental status following significant overdose. Monitor CBC with differential, liver enzymes, and fluid/electrolyte status in symptomatic patients. Monitor serum sodium and urine electrolytes if SIADH is suspected.
  • Patient disposition: HOME CRITERIA: Asymptomatic children (other than mild drowsiness) with a minor inadvertent ingestion may be monitored at home. OBSERVATION CRITERIA: All patients with deliberate self-harm ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with unintentional ingestions who are symptomatic should be observed in a healthcare facility. ADMISSION CRITERIA: Patients with a deliberate ingestions demonstrating seizure activity or other persistent neurotoxicity should be admitted. CONSULT CRITERIA: Call a Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
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