Levetiracetam

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Levetiracetam (Keppra) is an anticonvulsant drug used to treat epilepsy. Levetiracetam is effective in the treatment of partial seizures as adjuvant as well as monotherapy

Contents

[edit] BRAND NAMES

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[edit] STRUCTURE

Levetiracetam.jpg

[edit] MECHANISM OF ACTION

Levetiracetam has been shown in in vitro studies to bind to a specific site in rodent brain tissue. This binding site is the synaptic vesicle protein (SV2A), believed to be involved in vesicle fusion and neurotransmitter exocytosis. Levetiracetam and related analogues show a rank order of affinity for binding to SV2A which correlates with the potency of their anti-seizure protection in the mouse audiogenic model of epilepsy. This finding suggests that the interaction between levetiracetam and SV2A seems to contribute to the antiepileptic mechanism of action of this drug.

[edit] INDICATIONS

Levetiracetam Tablets and Oral solution:

  • Monotherapy in the treatment of partial onset seizures with or without secondary generalisation in patients from 16 years of age with newly diagnosed epilepsy (Europe)
  • Adjunctive therapy for partial onset seizures with or without secondary generalisation in adults, adolescents, children and infants from 1 month of age with epilepsy (Europe and USA)
  • Adjunctive therapy for myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic Epilepsy (JME) (Europe and USA)
  • Adjunctive therapy for the treatment of Primary Generalised Tonic-Clonic (PGTC) seizures in adults and adolescents from 12 years of age with Idiopathic Generalised Epilepsy (IGE). (Europe)
  • Adjunctive therapy for the treatment of Primary Generalised Tonic-Clonic (PGTC) seizures in adults and adolescents from 6 years of age with Idiopathic Generalised Epilepsy (IGE). (USA)

[edit] DOSAGE

  • Monotherapy for adults and adolescents from 16 years of age (Europe): The recommended starting dose is 250 mg twice daily which should be increased to an initial therapeutic dose of 500 mg twice daily after two weeks. The dose can be further increased by 250 mg twice daily every two weeks depending upon the clinical response. The maximum dose is 1500 mg twice daily. (Europe)


  • Partial Onset Seizures:
    • 1 Month to < 6 Months: 7 mg/kg twice daily, increase in increments of 7 mg/kg twice daily every 2 weeks to recommended dose of 21 mg/kg twice daily (USA)
    • 1 Month to < 6 Months: 10 mg/kg twice daily, increase in increments of 10 mg/kg twice daily every 2 weeks to a maximum dose of 30 mg/kg twice daily (Europe)
    • 6 Months to < 4 Years: 10 mg/kg twice daily, increase in increments of 10 mg/kg twice daily every 2 weeks to recommended dose of 25 mg/kg twice daily (Europe and USA)
    • 4 Years to < 16 Years: 10 mg/kg twice daily, increase in increments of 10 mg/kg twice daily every 2 weeks to recommended dose of 30 mg/kg twice daily (Europe and USA)
    • Adults 16 Years and Older: 500 mg twice daily, increase as needed and tolerated in increments of 500 mg twice daily every 2 weeks to a maximum recommended dose of 1500 mg twice daily (Europe and USA)


  • Myoclonic Seizures in Adults and Pediatric Patients 12 Years and Older: 500 mg twice daily, increase by 500 mg twice daily every 2 weeks to recommended dose of 1500 mg twice daily (Europe and USA)


  • Primary Generalized Tonic-Clonic Seizures
    • 6 Years to < 16 Years: 10 mg/kg twice daily, increase in increments of 10 mg/kg twice daily every 2 weeks to recommended dose of 30 mg/kg twice daily (USA)
    • Adults 16 Years and Older: 500 mg twice daily, increase by 500 mg twice daily every 2 weeks to recommended dose of 1500 mg twice daily (USA)
    • Adults 12 Years and Older: 500 mg twice daily, increase by 500 mg twice daily every 2 weeks to recommended dose of 1500 mg twice daily (Europe)


Adult Patients with Impaired Renal Function: Dose adjustment is recommended, based on the patient’s estimated creatinine clearance

[edit] CONTRAINDICATIONS

  • Hypersensitivity to Levetiracetam

[edit] WARNINGS AND PRECAUTIONS

  • Psychiatric Symptoms: Behavioral abnormalities including psychotic symptoms, suicidal ideation, irritability, and aggressive behavior have been observed. Monitor patients for psychiatric signs and symptoms.
  • Suicidal Behavior and Ideation: A meta-analysis of randomized placebo-controlled trials of anti-epileptic medicinal products (including levetiracetam) has shown a small increased risk of suicidal thoughts and behaviour. Monitor patients for new or worsening depression, suicidal thoughts/behavior, and/or unusual changes in mood or behavior.
  • Somnolence and Fatigue: Monitor patients for these symptoms and advise patients not to drive or operate machinery until they have gained sufficient experience on Levetiracetam
  • Withdrawal Seizures: Levetiracetam must be gradually withdrawn
  • Renal impairment: The administration of Levetiracetam to patients with renal impairment may require dose adjustment.
  • Dermatological reactions: Although rare, serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in both children and adults treated with levetiracetam. Levetiracetam should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related.

[edit] INTERACTIONS

Levetiracetam and its major metabolite, are neither inhibitors of, nor high affinity substrates for, human liver CYPP450 isoforms, epoxide hydrolase or UDP-glucuronidation enzymes; Levetiracetam is unlikely to produce, or be subject to pharmacokinetic interactions.

  • Levetiracetam does not affect the in vitro glucuronidation of valproic acid.

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US). Levetiracetam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Nursing Mothers: Levetiracetam is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from Levetiracetam, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother

[edit] SIDE EFFECTS

Most common adverse reactions include:

  • Adult patients: Somnolence, asthenia (Weakness), nasopharyngitis, headache, dizziness, aggression, irritability, anxiety, insomnia, decreased appetite, ataxia (lack of voluntary coordination of muscle movements), tremor (involuntary trembling), cough, abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea and depression.

[edit] RELATED LINKS

What Is Keppra?
Pharmacology of Antiepileptic Drugs

[edit] BIBLIOGRAPHY

[edit] REFERENCES