Levetiracetam oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of levetiracetam.
Drugs List
Therapeutic Indications
Uses
Epilepsy (idiopathic generalised) - tonic-clonic seizures: adjunctive
Epilepsy (newly diagnosed) - partial seizures: monotherapy
Epilepsy-partial seizures with/without secondary generalisation-adjunctive
Myoclonic seizures in Juvenile Myoclonic Epilepsy: adjunctive treatment
Adjunctive therapy in the treatment of partial onset seizures with or without secondary generalisation in patients with epilepsy aged 1 month and over. Adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents with Juvenile Myoclonic Epilepsy aged 12 years and over. Adjunctive therapy in the treatment of primary generalised tonic-clonic seizures in adults and adolescents aged 12 years and over with Idiopathic Generalised Epilepsy. Monotherapy in the treatment of partial onset seizures with or without secondary generalisation in patients with newly diagnosed epilepsy aged 16 years and over.
Dosage
Adults
The maximum dose is 1500mg twice a day.
Monotherapy
Initial dose: 250mg twice a day, for 2 weeks.
Maintenance dose: 500mg twice a day. Dose may be increased every 2 weeks, in steps of 250mg twice a day, based on individual patient response.
The following alternate dosing schedule may also be suitable:
Initial dose: 250mg once a day, for 1 week.
Maintenance dose: 250mg twice a day. Doses may be increased every 2 weeks in steps of 250mg twice a day, based on individual patient response.
Adjunctive Therapy
500mg twice a day. Doses may be increased every 2 to 4 weeks in steps of 500mg twice a day, based on individual patient response.
The following alternate dosing schedule may also be suitable:
Initial dose: 250mg twice a day. Doses may be increased every 2 to 4 weeks in steps of 500mg twice a day, based on individual patient response.
Children
Levetiracetam granules are unsuitable for children under 6 years.
Monotherapy
Children aged 16 to 18 years
(See Dosage; Adult)
Children under 16 years
Not recommended.
Adjunctive Therapy
Children weighing over 50kg
(See Dosage; Adult)
Children aged 6 months to 18 years weighing less than 50kg
Initial dose: 10mg/kg twice a day.
Dose may be increased every 2 weeks, in steps of 10mg/kg twice a day, based on individual patient response. Maximum dose should not exceed 30mg/kg twice a day.
Alternative sources suggest an initial dose of 10mg/kg once daily with further increases as above.
Children aged 1 to 6 months
Initial dose: 7mg/kg twice a day.
Dose may be increased every 2 weeks, in steps of 7mg/kg twice a day, based on individual patient response. Maximum dose should not exceed 21mg/kg twice a day.
Alternative sources suggest an initial dose of 7mg/kg once daily with further increases as above.
Patients with Renal Impairment
Adults
Creatinine clearance greater than or equal to 80 ml/minute/1.73 metre squared: 500mg to 1500mg twice daily
Creatinine clearance 50 to 79 ml/minute/1.73 metre squared: 500mg to 1000mg twice daily
Creatinine clearance 30 to 49 ml/minute/1.73 metre squared: 250mg to 750mg twice daily
Creatinine clearance less than 30 ml/minute/1.73 metre squared: 250mg to 500mg twice daily
End stage renal disease undergoing dialysis: 500mg to 1000mg once daily. A 750mg loading dose is recommended on the first day of treatment with levetiracetam. Following dialysis, a 250mg to 500mg supplemental dose is recommended.
Children
Infants aged 1 month to less than 6 months
Creatinine clearance greater than or equal to 80 ml/minute/1.73 metre squared: 7mg/kg to 21mg/kg twice daily
Creatinine clearance 50 to 79 ml/minute/1.73 metre squared: 7mg/kg to 14mg/kg twice daily
Creatinine clearance 30 to 49 ml/minute/1.73 metre squared: 3.5mg/kg to 10.5mg/kg twice daily
Creatinine clearance less than 30 ml/minute/1.73 metre squared: 3.5mg/kg to 7mg/kg twice daily
End-stage renal disease patients undergoing dialysis: 7mg/kg to 14mg/kg once daily. A 10.5mg/kg loading dose is recommended on the first day of treatment with levetiracetam. Following dialysis, a 3.5mg/kg to 7mg/kg supplemental dose is recommended.
Infants aged 6 to 23 months, children and adolescents weighing less than 50kg
Creatinine clearance greater than or equal to 80 ml/minute/1.73 metre squared: 10mg/kg to 30mg/kg twice daily
Creatinine clearance 50 to 79 ml/minute/1.73 metre squared: 10mg/kg to 20mg/kg twice daily
Creatinine clearance 30 to 49 ml/minute/1.73 metre squared: 5mg/kg to 15mg/kg twice daily
Creatinine clearance less than 30 ml/minute/1.73 metre squared: 5mg/kg to 10mg/kg twice daily
End-stage renal disease patients undergoing dialysis: 10mg/kg to 20mg/kg once daily. A 15mg/kg loading dose is recommended on the first day of treatment with levetiracetam. Following dialysis, a 5mg/kg to 10mg/kg supplemental dose is recommended.
Patients with Hepatic Impairment
Severe hepatic impairment
Creatinine clearance below 60 ml/min/1.73m squared: 50% reduction of the daily maintenance is recommended.
Additional Dosage Information
Discontinuation
Adults and adolescents weighing more than 50kg: 500mg decreases twice daily every two to four weeks.
Infants older than 6 months, children and adolescents weighing less than 50kg: dose decrease should not exceed 10mg/kg twice daily every two weeks.
In infants (less than 6 months): dose decrease should not exceed 7mg/kg twice daily every two weeks.
Contraindications
Neonates under 1 month
Long QT syndrome
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
Females of childbearing potential
Suicidal ideation
Breastfeeding
Electrolyte imbalance
Hereditary fructose intolerance
History of torsade de pointes
Pregnancy
Renal impairment
Severe hepatic impairment
Correct electrolyte disorders before treatment
Dose adjustment may be necessary in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Folic acid 5mg daily required pre-conception to end of 1st trimester
Not all available products are recommended for all age groups/body weights
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Some formulations contain hydroxybenzoate
Some formulations contain sunset yellow (E110); may cause allergic reaction
Tablet formulation not suitable for children under 6 years
Assess renal function prior to initiating therapy in hepatic impairment
Consider monitoring ECG in patients at risk of QT prolongation
May increase seizure frequency
Monitor for mental changes, suicidal depression and antisocial behaviour
Monitor patient for signs and symptoms of depression
Monitor patients for signs of psychosis, mania or aggressive behaviour
Monitor serum electrolytes
Refer women considering pregnancy for specialist advice and monitoring
Advise patient to report any aggravated convulsions immediately
Advise patients/carers to seek medical advice if suicidal intent develops
Consider discontinuation if psychotic or manic symptoms occur
Do not withdraw this drug suddenly
Advise patient to seek advice at first indications of pregnancy
Maintain treatment at the lowest effective dose
Not licensed for all indications in all age groups
Female: Ensure adequate contraception during treatment
Rare cases of decreased blood cell counts have been associated with levetiracetam. Complete blood cell counts are advised in patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders.
Long term effects on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children remain unknown.
Levetiracetam may rarely exacerbate seizure frequency or severity. This paradoxical effect has been mostly reported within the first month after initiation of levetiracetam or increase of the dose. This was reversible after drug discontinuation or dose decrease.
In case of patients with signs suggesting important mood and/or personality changes, treatment adaptation or gradual discontinuation should be considered.
Pregnancy and Lactation
Pregnancy
Use levetiracetam with caution in pregnancy.
The manufacturers do not recommend using levetiracetam during pregnancy unless clinically necessary.
Postmarketing data do not suggest a substantial increase in the risk for major congenital malformations, although a teratogenic risk cannot be completely excluded. Animal studies have shown reproductive toxicity. Therapy with multiple antiepileptic medicinal products is associated with a higher risk of congenital malformations than monotherapy and, therefore monotherapy should be considered. Limited epidemiological studies do not suggest an increased risk of neurodevelopmental disorders or delays. A decrease in plasma concentrations have been observed during pregnancy due to physiological changes, the decrease is more pronounced during the third trimester. The lowest effective dose is recommended and appropriate clinical management of pregnant women treated with levetiracetam should be ensured. Abrupt discontinuation of antiepileptic treatments may exacerbate the disease which could be harmful to both mother and the foetus.
Schaefer (2015) concludes medication with levetiracetam may continue if the current residual uncertainty about its teratogenic risk is acceptable. Severe growth restriction has been observed, although confirmation is needed.
Lactation
Use levetiracetam with caution in breastfeeding.
Levetiracetam is excreted in human breast milk.
The manufacturers only recommend using levetiracetam during breastfeeding when the benefits outweigh the risks.
LactMed (2018) states that maternal doses of levetiracetam up to 3500mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. If levetiracetam is required by the mother, it is not a reason to discontinue breastfeeding. The infant should be monitored for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsants.
Side Effects
Abdominal pain
Abnormal liver function tests
Abnormal thinking
Accidental injury
Aggression
Agitation
Agranulocytosis
Alopecia
Amnesia
Anger
Anorexia
Anxiety
Asthenia
Ataxia
Athetosis
Attention disturbances
Behavioural disturbances
Blurred vision
Bone marrow depression
Confusion
Convulsions
Cough increased
Delirium
Depression
Diarrhoea
Diplopia
Dizziness
Drowsiness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dyskinesia
Dyspepsia
Eczema
Emotional lability
Encephalopathy
Erythema multiforme
Fatigue
Gait abnormality
Hallucinations
Headache
Hepatic failure
Hepatitis
Hepatobiliary disorders
Hostility
Hyperkinesia
Hyponatraemia
Impaired co-ordination
Impaired memory
Infections
Insomnia
Irritability
Lethargy
Leucopenia
Loss of balance
Malaise
Mood changes
Muscle weakness
Myalgia
Nasopharyngitis
Nausea
Nervousness
Neutropenia
Pancreatitis
Pancytopenia
Panic attack
Paraesthesia
Personality disorder
Postural dizziness
Prolongation of QT interval
Pruritus
Psychomotor hyperactivity
Psychotic symptoms
Rash
Seizures
Somnolence
Stevens-Johnson syndrome
Suicidal tendencies
Thrombocytopenia
Toxic epidermal necrolysis
Tremor
Vertigo
Vomiting
Weakness
Weight gain
Weight loss
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: July 2018
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Summary of Product Characteristics: Desitrend 250mg, 500mg and 1000mg granules. Desitin Pharma. Revised November 2018.
Summary of Product Characteristics: Keppra 250mg, 500mg, 750mg & 1000mg film coated Tablets, 100mg/ml oral solution. UCB Pharma S.A. Revised October 2020.
HPRA 10th September 2018
Available at: https://www.hpra.ie/homepage/medicines/safety-notices
Last accessed: 07 November 2018
MHRA Drug Safety Update January 2021
Available at: https://www.mhra.gov.uk
Last accessed: 12 May 2021
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 23 July 2018
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Levetiracetam Last revised: 02 July 2018
Last accessed 23 July 2018
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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