Levetiracetam is an antiepileptic agent that modulates neurotransmission and potentiates the GABAergic neurons.

It is used to treat the following conditions:

• As an adjunctive treatment of focal or partial-onset seizures in adults and children with epilepsy.

• As adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents with juvenile myoclonic epilepsy.

• As adjunctive therapy in patients with generalized tonic-clonic seizures in adults and children older than 6 years of age with idiopathic generalized epilepsy.

Off Label Uses of Levetiracetam in Adults include:

• • For seizure prophylaxis in patients with craniotomy

  • Status epilepticus

  • For short-term prophylaxis of seizures in subarachnoid hemorrhage

  • For short-term seizure prophylaxis in severe acute traumatic brain injury.

Levetiracetam Dose in Adults

Dose in the treatment of Craniotomy for seizure prophylaxis as an alternative agent for phenytoin (off-label):

• 1,000 mg/day intravenous or orally in 2 divided doses.
• Adjust the dose based on tolerability and efficacy.

Dose in the treatment of Focal (partial) onset seizures and generalized onset seizures:

(It is FDA approved for juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures and may be used as an off-label treatment for other seizure types)

• Immediate-release:
  • 500 mg orally two times a day.
  • The dose may be increased every 2 weeks by 500 mg/dose to the maximum recommended dose of 1,500 mg two times a day.
• Extended-release (FDA approved only for focal or partial-onset seizures):
  • 1,000 mg orally once a day.
  • The dose may be increased every 2 weeks by 1,000 mg/day to a maximum of 3,000 mg once a day.

Dose as off-label use in the treatment of Status epilepticus:

• 1,000 - 3,000 mg intravenous administered at a rate of 2 - 5 mg/kg/minute or
• 40 - 60 mg/kg intravenous as a single dose infused over 15 minutes in combination with a parenteral benzodiazepine to the maximum dose of 4,500 mg.

Dose in the treatment of Subarachnoid hemorrhage for short-term seizure prophylaxis as off-label use: 

• Loading dose:
  • 20 mg/kg intravenous over one hour.
• Maintenance dose:
  • 1,000 mg intravenous over 15 minutes twice daily for 7 days.
  • The dose may be increased to a maximum dose of 1,500 mg twice daily if necessary.

Dose in the treatment of Severe Acute Traumatic brain injury for short-term seizure prophylaxis (off-label use):

• Loading dose:
  • 20 mg/kg intravenous over one hour.
• Maintenance dose:
  • 1,000 mg intravenous over 15 minutes twice daily for 7 days.
  • The dose may be increased to a maximum dose of 1,500 mg twice daily if necessary.

Levetiracetam Dose in Children

Dose in the treatment of Myoclonic seizures with juvenile myoclonic epilepsy:

• Children older than 12 years and Adolescents:
  • 500 mg two times a day initially.
  • The dose may be increased every 2 weeks by 500 mg/dose two times a day to the recommended dose of 1,500 mg two times a day.
  • Efficacy of doses less than 3,000 mg/day has not been studied.

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Partial onset seizures:​​​​​​​

• Infants 1 to 6 months of age:
  • 7 mg/kg/dose two times a day initially
  • The dose may be increased every 2 weeks by 7 mg/kg/dose two times a day to the recommended dose of 21 mg/kg/dose two times a day.
• Infants older than 6 months and Children less than years:
  • 10 mg/kg/dose two times a day.
  • The dose may be increased every 2 weeks by 10 mg/kg/dose two times a day to the recommended dose of 25 mg/kg/dose two times a day.
• Children older than 4 years and Adolescents less than 16 years:
  • 10 mg/kg/dose intravenous initially two times a day.
  • The dose may be increased every 2 weeks by 10 mg/kg/dose two times a day to a maximum of 30 mg/kg/dose two times a day.
  • The maximum daily dose is 3,000 mg/day.

• Immediate release:
  • Weight-directed dosing:
    • 10 mg/kg/dose two times a day.
    • The dose may be increased dosage every 2 weeks by 10 mg/kg/dose two times a day to a maximum of 30 mg/kg/dose two times a day (the maximum daily dose is 3,000 mg/day)
  • Fixed dosing (immediate-release):
    • • 20 - 40 kg:
        • 250 mg two times a day.
        • Increase the dose every 2 weeks by 250 mg two times a day to the maximum recommended dose of 750 mg two times a day.
      • More than 40 kgs:
        • 500 mg two times a day.
        • Increase the dose every 2 weeks by 500 mg two times a day to the maximum recommended dose of 1,500 mg two times a day.
• Extended-release:
  • Children older than 12 years and Adolescents:
    • 1,000 mg once a day.
    • The dose may be increased every 2 weeks by 1,000 mg/day to a maximum of 3,000 mg once a day.
  • Adolescents 16 years of age and older:
    • 500 mg intravenous two times a day.
    • Increase the dose every 2 weeks by 500 mg/dose two times a day to a maximum dose of 1,500 mg two times a day.
    • Efficacy of doses greater than 3,000 mg/day has not been established.
  • Immediate-release:
    • 500 mg orally two times a day.
    • The dose may be increased every 2 weeks by 500 mg two times a day to the maximum recommended dose of 1,500 mg two times a day.
  • Extended-release:
    • 1,000 mg orally once a day.
    • Increase the dose every 2 weeks by 1,000 mg/day to a maximum of 3,000 mg once a day.

Dose in patients with refractory Status epilepticus:

• Infants, Children, and Adolescents:
  • 20 - 60 mg/kg intravenous as a single dose

Note: The maximum dose in adults is 3,000 mg/dose.

• Children and Adolescents:
  • 60 mg/kg intravenous as a single dose to a maximum dose of 4,500 mg/dose.

Dose in the treatment of primary generalized Tonic-clonic seizures:

• Children older than 6 years and Adolescents less than 16 years:
  • 10 mg/kg/dose intravenous two times a day.
  • Increase the dose every 2 weeks by 10 mg/kg/dose two times a day to the recommended dose of 30 mg/kg/dose two times a day.
  • Efficacy of doses less than 60 mg/kg/day has not been established.
• Immediate-release:
  • Weight-directed:
    • 10 mg/kg/dose two times a day.
    • Increase the dose every 2 weeks by 10 mg/kg/dose two times a day to the recommended dose of 30 mg/kg/dose two times a day.
    • Efficacy of doses less than 60 mg/kg/day has not been established.
• Fixed-dosing: Orally disintegrating tablets:
  • 20 - 40 kg:
    • 250 mg orally two times a day.
    • Increase the dose every 2 weeks by 250 mg two times a day to the maximum recommended dose of 750 mg two times a day.
  • More than 40 kg:
    • 500 mg orally two times a day.
    • Increase the dose every 2 weeks by 500 mg two times a day to the maximum recommended dose of 1,500 mg two times a day.
    • Efficacy of doses less than 3,000 mg/day has not been established.
• Adolescents 16 years of age or older:
  • 500 mg two times a day.
  • Increase the dose every 2 weeks by 500 mg/dose two times a day to the recommended dose of 1,500 mg two times a day.
  • Efficacy of doses less than 3,000 mg/day has not been established.

Pregnancy Risk Factor C

• Levetiracetam passes the placental barrier.
• Animal studies have shown adverse effects.
• Although there have been no major congenital malformations, it is recommended to take the lowest possible dose.

Use of levetiracetam while breastfeeding

• Breast milk contains levetiracetam. Breastfeeding is compatible with the excreted amount
• Hypotonia, vomiting, weight loss and poor suckling are some of the possible side effects.
• Manufacturer recommends that you avoid breastfeeding.

Levetiracetam Dose in Renal Disease:

Notice:You can estimate the CrCl using the Cockcroft–Gault formula, adjusted for body surface area as follows:

CrCl (1.73 m2/min) = CrCl(mL/minute/BSA (m2a) x 1.73

• Intravenous and immediate-release formulations
  • CrCl greater than 80 mL/minute/1.73m2
    • 500-1,500 mg twice daily
  • CrCl 50 - 80 mg/minute/1.73m2:
    • 500-1000 mg twice daily
  • CrCl 30-50 mL/minute/1.73m2
    • 250-750 mg twice daily
  • CrCl 30mL/minute/1.73m2
    • 250-500 mg twice daily
  • End-stage renal disease that requires hemodialysis
    • 50% of the drug can be dialyzed
    • 500-1000 mg daily
    • After hemodialysis, a supplement of 250-500 mg is recommended.
  • Peritoneal dialysis
    • 500-1000 mg daily
  • Continuous renal replacement therapy
    • 250-750 mg twice daily
• Extended-release tablets
  • CrCl greater than 80 mL/minute/1.73m 2
    • 1000 - 3,000 mg daily
  • CrCl 50 – 80 mL/minute/1.73m 2
    • 1000 - 2,000 mg daily
  • CrCl 30-50 mL/minute/1.73 2
    • 500 to 1,500 mg daily.
  • CrCl less than 30mL/minute/1.73m 2
    • 500-1000 mg daily
  • ESRD requires hemodialysis
    • Use immediate-release formulations

Levetiracetam Dose in Liver Disease:

Adjustment in the dose is not necessary

Common Side Effects of Levetiracetam Include:

• Cardiovascular:
  • Increased Blood Pressure
• Central Nervous System:
  • Behavioral Problems
  • Headache
  • Psychotic Symptoms
  • Drowsiness
  • Irritability
  • Fatigue
• Gastrointestinal:
  • Vomiting
• Infection:
  • Infection
• Neuromuscular & Skeletal:
  • Weakness
• Respiratory:
  • Nasopharyngitis

Less Common Side Effects of Levetiracetam Include:

• Central Nervous System:
  • Aggressive Behavior
  • Dizziness
  • Pain
  • Lethargy
  • Insomnia
  • Depression
  • Vertigo
  • Emotional Lability
  • Agitation
  • Nervousness
  • Ataxia
  • Falling
  • Mood Changes
  • Confusion
  • Amnesia
  • Anxiety
  • Hostility
  • Paranoia
  • Paresthesia
  • Sedation
• Gastrointestinal:
  • Upper Abdominal Pain
  • Decreased Appetite
  • Diarrhea
  • Nausea
  • Anorexia
  • Constipation
  • Gastroenteritis
• Hematologic & Oncologic:
  • Eosinophilia
  • Bruise
  • Decreased White Blood Cell Count
  • Decreased Neutrophils
• Infection:
  • Influenza
• Neuromuscular & Skeletal:
  • Neck Pain
  • Arthralgia
  • Joint Sprain
• Ophthalmic:
  • Conjunctivitis
  • Diplopia
• Otic:
  • Otalgia
• Respiratory:
  • Nasal Congestion
  • Cough
  • Pharyngolaryngeal Pain
  • Pharyngitis
  • Rhinitis
  • Sinusitis
• Miscellaneous:
  • Head Trauma

Contraindication to Levetiracetam Include:​​​​​​​

• Severe allergic reactions such as anaphylaxis and angioedema due to levetiracetam, or any component of it.

Warnings and Precautions​​​​​​​

• Depression in the CNS:
  • CNS depression may result from impaired coordination, ataxia or abnormal gait, fatigue and weakness.
  • These symptoms are most common in the first month of therapy.
  • Before initiating therapy, patients who use heavy machinery or have higher mental abilities should be screened.
• Dermatologic reactions
  • It has been linked to severe reactions such as Stevens Johnson syndrome or toxic epidermal necropsy.
  • Allergies can occur in as little as 2 weeks or up to 4 months.
  • It is important to stop all treatment and look into alternative treatments.
• Hematologic effects
  • It is possible to develop cytopenias from its use. This could manifest as anemia or leukopenia and neutropenia. Its use may cause an increase in eosinophils.
  • There have been cases of agranulocytosis and pancytopenia as well as thrombocytopenia.
• Hypersensitivity reactions
  • Hypotension, angioedema and hypotension may all occur, which can be potentially life-threatening.
  • It is important to stop all treatment immediately and start the appropriate therapy.
• Hypertension
  • Children younger than 4 years old have had diastolic blood pressure elevations.
• Psychiatric symptoms
  • Psychosis, hallucinations and paranoia can occur. These symptoms may need to be reduced or discontinued therapy.
• Suicidal thoughts:
  • Suicidal ideation should be checked for by the patient if they show changes in behavior, suicidal thoughts or depression.
• Renal impairment
  • Patients with impaired renal function should not use it. These patients may require dose adjustment.
  • Patients on hemodialysis need to be informed that the immediate-release formulation is better than the extended-release formulation.

Monitoring Parameters:

• Depression in the CNS:
  • It can manifest as impaired coordination, ataxia and weakness, dizziness, dizziness, dizziness, weakness, somnolence, impaired coordination, impaired gait, ataxia, and abnormal gait.
• Psychiatric symptoms and behavioral symptoms
  • Aggression, agitation and anxiety, anger, apathy. confusion, depersonalization.
• Blood pressure dialystolicChildren under 4 years old are considered to be infants.
• Blood CP or CBCPatients who are febrile or have recurrent infections or coagulation disorders may be at risk.

How to administer Levetiracetam?

• Intravenous:
  • It should not be intramuscularly administered. It should be administered intravenously over a period of 15 minutes.
• Oral:
  • You can administer it without regard to your meals.
  • Use a calibrated measuring instrument (not a teaspoon or household tablespoon) to give the oral solution.
  • Tablets should not be broken, chewed, or crushed.
  • You can either mix the suspension tablets with water in a cup, and then ingest them immediately or place the tablet on your tongue and drink water. 
  • It may take between 2 and 27 seconds for the tablet to dissolve in your mouth before it can be swallowed.

Mechanism of action of Levetiracetam:

It is believed that it inhibits voltage-dependent N type calcium channels, facilitates GABAergic inhibitory transmittance, and binds with the synaptic proteins that regulate neurotransmitter release.

It's fast and complete.Intake. The absorption of food is delayed by between 1 and 2 hours.

DistributionIt is very similar to body fluid. The drug contains less than 10%.

Protein-bound The majority of the drug isMetabolizedIn the blood (but not by the enzyme Cytochrome p450). The drug's bioavailability is nearly 100%.

Elimination of Half-LifePatients with kidney failure experience an increase in their renal function. It has a half life elimination of 5.3 +/– 1.3 hours for infants and children younger than 4 hours, 6 +/– 1.1 hours for children aged 4-12 years, and 6 – 8 hours for adults.

It is nowPeak plasma concentrationIt takes between 1 and 2 hours (shorter in a fasting state, but longer in the fed-state).

It isExcretedIn the urine, 66% of it is unchanged drug. 27% are inactive metabolites. It is partially absorbed after it has undergone glomerular filtrations.

International Brands of Levetiracetam:

• Abbott-Levetiracetam
• ACT Levetiracetam
• APO-Levetiracetam
• Auro-Levetiracetam
• BIO-Levetiracetam
• DOM-Levetiracetam
• JAMP-Levetiracetam
• Keppra
• NAT-Levetiracetam
• PHL-Levetiracetam
• PMS-Levetiracetam
• Priva-Levetiracetam
• PRO-Levetiracetam-250
• PRO-Levetiracetam-500
• PRO-Levetiracetam-750
• RAN-Levetiracetam
• SANDOZ Levetiracetam
• VAN-Levetiracetam
• Azacetam
• Callexe
• Callexe XR
• Ceumid
• Citazar
• Desitrend
• Dretacen
• E Keppra
• Eletam
• Epictal
• Epilen
• Epiletam
• Epilev
• Epsytam
• Erata
• Eterlox
• Focale
• Iracet
• Ivetra
• Kepcet
• Kepcitam
• Kepdin
• Keplidon
• Keppra
• Keppra I.V.
• Keppra XR
• Kevesy
• Kevtam
• Kopodex
• Laurak
• Lecetam
• Lethira
• Letram
• Lev Desitin
• Levepex
• Levetacis
• Levetam
• Levetrim
• Levetstad
• Levicitam
• Levim
• Levipil
• Levit
• Levitam
• Levron
• Malomibe
• Matever
• Nobelin
• Normeg
• Prepalepan
• Repitend
• Rivoleve
• Tietari
• Torleva
• Trund
• Vexlev
• Zitera

Levetiracetam Brands in Pakistan: