Levetiracetam


Generic Medicine Info
Indications and Dosage
Intravenous
Partial seizures with or without secondary generalisation
Adult: As alternative when oral use is temporarily not feasible: Monotherapy in newly diagnosed patients: Initially, 250 mg bid, increased to the initial therapeutic dose of 500 mg bid after 2 weeks. Dose may be further increased by 250 mg bid every 2 weeks according to response. Max: 1,500 mg bid. Adjunctive therapy: Initially, 500 mg bid on the 1st day of treatment. Dose may be adjusted in 500 mg bid increases or decreases every 2-4 weeks according to response and tolerability. Max: 1,500 mg bid. All doses are given via infusion over 15 minutes. Max treatment duration: 4 days. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).
Child: Monotherapy in newly diagnosed patients: ≥16 years Same as adult dose. Adjunctive therapy: 4-11 years and 12-17 years weighing <50 kg: Initially, 10 mg/kg bid; may be adjusted in increases or decreases of up to 10 mg/kg bid every 2 weeks according to response and tolerability. Max: 30 mg/kg bid. Use the lowest effective dose and most appropriate pharmaceutical form based on age, weight and dose; 12-17 years weighing ≥50 kg: Same as adult dose. All doses are given via infusion over 15 minutes. Max treatment duration: 4 days. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).

Intravenous
Myoclonic seizures
Adult: As alternative when oral use is temporarily not feasible: Adjunctive therapy in patients with juvenile myoclonic epilepsy: Initially, 500 mg bid on the 1st day of treatment. Dose may be adjusted in 500 mg bid increases or decreases every 2-4 weeks according to response and tolerability. Doses to be given via infusion over 15 minutes. Max: 1,500 mg bid. Max treatment duration: 4 days. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).
Child: Adjunctive therapy in patients with juvenile myoclonic epilepsy: 12-17 years weighing <50 kg: Initially, 10 mg/kg bid; may be adjusted in increases or decreases of up to 10 mg/kg bid every 2 weeks according to response and tolerability. Max: 30 mg/kg bid; ≥50 kg: Same as adult dose. All doses are given via infusion over 15 minutes. Max treatment duration: 4 days. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).

Intravenous
Primary generalised tonic-clonic seizures
Adult: As alternative when oral use is temporarily not feasible: Adjunctive therapy in patients with idiopathic generalised epilepsy: Initially, 500 mg bid on the 1st day of treatment. Dose may be adjusted in 500 mg bid increases or decreases every 2-4 weeks according to response and tolerability. Doses to be given via infusion over 15 minutes. Max: 1,500 mg bid. Max treatment duration: 4 days. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).
Child: Adjunctive therapy in patients with idiopathic generalised epilepsy: 12-17 years weighing <50 kg: Initially, 10 mg/kg bid; may be adjusted in increases or decreases of up to 10 mg/kg bid every 2 weeks according to response and tolerability. Max: 30 mg/kg bid; ≥50 kg: Same as adult dose. All doses are given via infusion over 15 minutes. Max treatment duration: 4 days. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).

Oral
Primary generalised tonic-clonic seizures
Adult: Adjunctive therapy in patients with idiopathic generalised epilepsy: As immediate release: Initially, 500 mg bid on the 1st day of treatment. Dose may be adjusted in 500 mg bid increases or decreases every 2-4 weeks according to response and tolerability. Max: 1,500 mg bid. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).
Child: Adjunctive therapy in patients with idiopathic generalised epilepsy: As immediate release: 12-17 years weighing <50 kg: Initially, 10 mg/kg bid; may be adjusted in increases or decreases of up to 10 mg/kg bid every 2 weeks according to response and tolerability. Max: 30 mg/kg bid; ≥50 kg: Same as adult dose. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).

Oral
Myoclonic seizures
Adult: Adjunctive therapy in patients with juvenile myoclonic epilepsy: As immediate release: Initially, 500 mg bid on the 1st day of treatment. Dose may be adjusted in 500 mg bid increases or decreases every 2-4 weeks according to response and tolerability. Max: 1,500 mg bid. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).
Child: Adjunctive therapy in patients with juvenile myoclonic epilepsy: As immediate release: 12-17 years weighing <50 kg: Initially, 10 mg/kg bid; may be adjusted in increases or decreases of up to 10 mg/kg bid every 2 weeks according to response and tolerability. Max: 30 mg/kg bid; ≥50 kg: Same as adult dose. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).

Oral
Partial seizures with or without secondary generalisation
Adult: As immediate-release: Monotherapy in newly diagnosed patients: Initially, 250 mg bid, increased to the initial therapeutic dose of 500 mg bid after 2 weeks. Dose may be further increased by 250 mg bid every 2 weeks according to response. Max: 1,500 mg bid. Adjunctive therapy: Initially, 500 mg bid on the 1st day of treatment. Dose may be adjusted in 500 mg bid increases or decreases every 2-4 weeks according to response and tolerability. Max: 1,500 mg bid. As extended-release: Monotherapy or adjunctive therapy: Initially, 1,000 mg once daily, may be increased in increments of 1,000 mg every 2 weeks according to response and tolerability. Max: 3,000 mg once daily. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).
Child: As immediate-release: Monotherapy in newly diagnosed patients: ≥16 years Same as adult dose. Adjunctive therapy: 1 to <6 months Initially, 7 mg/kg bid; may be adjusted in increases or decreases of up to 7 mg/kg bid every 2 weeks according to response and tolerability. Max: 21 mg/kg bid; 6-23 months, 2-11 years, and 12-17 years weighing <50 kg: Initially, 10 mg/kg bid; may be adjusted in increases or decreases of up to 10 mg/kg bid every 2 weeks according to response and tolerability. Max: 30 mg/kg bid. Oral solution is preferred in infants <6 months and children <6 years, weighing <25 kg, those unable to swallow tab, or for doses <250 mg. Use the lowest effective dose and most appropriate pharmaceutical form based on age, weight and dose; 12-17 years weighing ≥50 kg: Same as adult dose. As extended-release: Monotherapy or adjunctive therapy: ≥12 years weighing ≥50 kg: Same as adult dose. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).
Renal Impairment
Oral (immediate- and extended-release):
Partial seizures with or without secondary generalisation:
As immediate-release: Adults: ESRD patients undergoing dialysis: 750 mg loading dose on 1st day of treatment, followed by 500-1,000 mg once daily; supplemental dose of 250-500 mg is recommended after dialysis. CrCl <30 mL/min/1.73 m2: 250-500 mg bid. CrCl 30-49 mL/min/1.73 m2: 250-750 mg bid. CrCl 50-79 mL/min/1.73 m2: 500-1,000 mg bid. Refer to specific product guidelines for dosage adjustments in adolescents and children. As extended-release: Adults: CrCl <30 mL/min/1.73 m2: 500-1,000 mg 24 hourly. CrCl 30-50 mL/min/1.73 m2: 500-1,500 mg 24 hourly. CrCl 50-80 mL/min/1.73 m2: 1,000-2,000 mg 24 hourly.

IV:
Partial seizures with or without secondary generalisation:
Adults: ESRD patients undergoing dialysis: 750 mg loading dose on 1st day of treatment, followed by 500-1,000 mg once daily; supplemental dose of 250-500 mg is recommended after dialysis. CrCl <30 mL/min/1.73 m2: 250-500 mg bid. CrCl 30-49 mL/min/1.73 m2: 250-750 mg bid. CrCl 50-79 mL/min/1.73 m2: 500-1,000 mg bid. Refer to specific product guidelines for dosage adjustments in adolescents and children.

Oral (immediate-release) and IV:
Myoclonic seizures; Primary generalised tonic-clonic seizures:
Adults: ESRD patients undergoing dialysis: 750 mg loading dose on 1st day of treatment, followed by 500-1,000 mg once daily; supplemental dose of 250-500 mg is recommended after dialysis. CrCl <30 mL/min/1.73 m2: 250-500 mg bid. CrCl 30-49 mL/min/1.73 m2: 250-750 mg bid. CrCl 50-79 mL/min/1.73 m2: 500-1,000 mg bid. Refer to specific product guidelines for dosage adjustments in adolescents and children.
Hepatic Impairment
Oral (immediate-release) and IV:
Severe: Reduce the daily maintenance dose by 50% in patients with CrCl <60 mL/min/1.73 m2. Assess renal function prior to dose selection.
Administration
May be taken with or without food. Oral soln may be taken directly or diluted in a glass of water.
Reconstitution
Oral solution: May be diluted in a glass of water. IV infusion: Dilute required dose in 100 mL of 0.9% NaCl solution, Lactated Ringer's solution or dextrose 5% solution.
Contraindications
Hypersensitivity.
Special Precautions
Patient with QTc-interval prolongation, pre-existing cardiac disease, electrolyte disturbances. The total daily dose and administration frequency should be the same or maintained when switching between oral and IV form. Avoid abrupt withdrawal. Renal and severe hepatic impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Suicidal ideation and behaviour; psychotic symptoms and behavioural abnormalities (e.g. irritability, aggressiveness); somnolence, fatigue, coordination difficulties; serious skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis); increased blood pressure (in patients 1 month to <4 years). Rarely, acute kidney injury, decreased blood cell counts (e.g. agranulocytosis, leucopenia, neutropenia, thrombocytopenia, pancytopenia); exacerbated seizure frequency or severity; prolonged QT interval.
Ear and labyrinth disorders: Vertigo.
Gastrointestinal disorders: Abdominal pain, nausea, vomiting, diarrhoea, dyspepsia.
General disorders and administration site conditions: Lethargy, asthenia.
Infections and infestations: Influenza.
Metabolism and nutrition disorders: Anorexia.
Musculoskeletal and connective tissue disorders: Neck pain.
Nervous system disorders: Headache, dizziness, balance disorder, tremor.
Psychiatric disorders: Anxiety, depression, hostility, insomnia, nervousness.
Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, cough, pharyngitis, nasal congestion, pharyngolaryngeal pain.
Skin and subcutaneous tissue disorders: Rash.
Potentially Fatal: Anaphylaxis or angioedema.
IV/Parenteral/PO: C
Patient Counseling Information
This drug may cause somnolence, fatigue or coordination difficulties; if affected, do not drive or operate machinery.
Monitoring Parameters
Assess renal function before starting treatment especially in patients with severely impaired hepatic function. Monitor therapeutic response (e.g. seizure activity, type, duration) at the start and throughout the treatment; diastolic blood pressure (in children 1 month to <4 years); signs and symptoms of CNS depression or hypersensitivity reaction. Observe for emergence or worsening of depression, suicidal thoughts, and unusual changes in mood or behaviour.
Overdosage
Symptoms: Agitation, aggression, depressed level of consciousness, somnolence, respiratory depression, and coma. Management: Symptomatic and supportive treatment. May perform gastric lavage or induce emesis. May perform haemodialysis.
Drug Interactions
Increased serum concentration of methotrexate. May decreased the efficacy of oral levetiracetam when taken with osmotic laxative macrogol. May increase risk of QT interval prolongation with drugs affecting QTc-interval.
Food Interaction
May increase CNS depressant effects of alcohol.
Action
Description: Levetiracetam is a pyrrolidine derivative anticonvulsant agent. The exact mechanism of action is unknown; however, studies suggest that it is involved in the central pharmacologic effects such as partial inhibition of N-type Ca currents, facilitation of GABA-ergic inhibitory transmission by displacing negative modulators, and reduction of delayed rectifier K current. Furthermore, it appears to bind to a synaptic protein that is believed to be involved in vesicle fusion and neurotransmitter exocytosis.
Pharmacokinetics:
Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract (oral). Bioavailability: Approx 100%. Time to peak plasma concentration: IV: 5-30 minutes; Oral: Approx 1.3 hours (immediate-release); approx 4 hours (extended-release).
Distribution: Crosses placenta and enters breast milk. Volume of distribution: Approx 0.5-0.7 L/kg. Plasma protein binding: <10%.
Metabolism: Not extensively metabolised. 24% of the dose undergoes enzymatic hydrolysis of acetamide group (major metabolic pathway) into inactive metabolites.
Excretion: Mainly via urine (66% as unchanged drug; 27% as inactive metabolites); faeces (0.3%). Plasma elimination half-life: Approx 7 hours.
Chemical Structure

Chemical Structure Image
Levetiracetam

Source: National Center for Biotechnology Information. PubChem Database. Levetiracetam, CID=5284583, https://pubchem.ncbi.nlm.nih.gov/compound/Levetiracetam (accessed on Jan. 22, 2020)

Storage
Store between 15-30°C.
MIMS Class
Anticonvulsants
ATC Classification
N03AX14 - levetiracetam ; Belongs to the class of other antiepileptics.
References
AFT Pharmaceuticals Ltd. Levetiracetam-AFT Oral Solution 100 mg/mL and Concentrate Solution for IV Infusion 500 mg/5 mL data sheet 17 March 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 10/06/2021.

Anon. Levetiracetam. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/07/2021.

Buckingham R (ed). Levetiracetam. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/06/2021.

Desitrend 500 mg Coated Granules in Sachet (Desitin Arzneimittel GMBH). MHRA. https://products.mhra.gov.uk. Accessed 10/06/2021.

Joint Formulary Committee. Levetiracetam. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/06/2021.

Keppra 250 mg, 500 mg, 1000 mg Film-Coated Tablet, 100 mg/mL Oral Solution, and 100 mg/mL Concentrate for Solution for Infusion (GlaxoSmithKline Pharmaceutical Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 10/06/2021.

Keppra Film-Coated Tablets, 100 mg/mL Oral Solution, and 100 mg/mL Concentrate for Solution for Infusion (UCB Pharma SA). European Medicines Agency [online]. Accessed 10/06/2021.

Keppra Injection, Solution, Concentrate (UCB, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/06/2021.

Keppra Tablet, Film Coated and Solution (UCB, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/06/2021.

Keppra XR Tablet, Film Coated, Extended Release (UCB, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/06/2021.

Levet 250 mg and 500 mg Film-Coated Tablet (Novartis Corporation [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 10/06/2021.

Levetiracetam 100 mg/mL Concentrate for Solution for Infusion (Altan Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 10/06/2021.

Levetiracetam Milpharm 100 mg/mL Oral Solution (Milpharm Limited). MHRA. https://products.mhra.gov.uk. Accessed 10/06/2021.

Levetiracetam-Lupin 1000 mg Film-Coated Tablets (Lupin Healthcare [UK] Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 10/06/2021.

Levetiracetam. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 14/09/2021.

REX Medical Limited. Everet 250 mg, 500 mg, 750 mg, 100 mg Film-Coated Tablets, and 100 mg/mL Oral Solution data sheet 14 August 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 10/06/2021.

Spritam Tablet, For Suspension (Aprecia Pharmaceuticals, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/06/2021.

Disclaimer: This information is independently developed by MIMS based on Levetiracetam from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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