Levetiracetam parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral 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 4 years and over. Adjunctive therapy in the treatment of myoclonic seizures in patients with Juvenile Myoclonic Epilepsy aged 12 years and over. Adjunctive therapy in the treatment of primary generalised tonic-clonic seizures in patients with Idiopathic Generalised Epilepsy aged 12 years and over. 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
Levetiracetam injection is an alternative for patients when administration of oral levetiracetam is temporarily not possible. Conversion to or from oral to intravenous administration can be done directly without titration. The total daily dose and frequency of administration should remain the same.
There is no experience with intravenous administration of levetiracetam for longer than 4 days.
Adults
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.
Maximum dose 1500mg twice a day.
The following alternate dosing schedule may also be suitable:
Initial dose: 250mg once a day, for 1 to 2 weeks.
Maintenance dose: 250mg twice a day. Dose may be increased every 2 weeks in steps of 250mg twice a day, based on individual patient response.
Maximum dose 1500mg twice a day.
Adjunctive Therapy
Initial dose: 500mg twice a day.
Maintenance dose: may be increased every 2 to 4 weeks in steps of 500mg twice a day, based on individual patient response.
Maximum dose 1500mg twice a day.
The following alternate dosing schedule may also be suitable:
Initial dose: 250mg twice a day.
Maintenance dose: may be increased every 2 to 4 weeks in steps of 500mg twice a day, based on individual patient response.
Maximum dose 1500mg twice a day.
Children
Monotherapy
Children aged 16 to 18 years
(See Dosage; Adult)
Children under 16 years
Not recommended.
Adjunctive Therapy
Children weighing 50kg or more
(See Dosage; Adult)
Children aged 4 to 18 years weighing less than 50kg
Initial dose: 10mg/kg twice a day.
Maintenance dose: may be increased every 2 weeks, in steps of 10mg/kg twice a day, based on individual patient response.
Maximum dose 30mg/kg twice a day.
The following alternate dosing schedule may also be suitable:
Initial dose: 10mg/kg once a day.
Maintenance dose: may be increased every 2 weeks, in steps of 10mg/kg twice a day, based on individual patient response.
Maximum dose 30mg/kg twice a day.
Patients with Renal Impairment
Daily dose must be individualised according to renal function.
Adults and adolescents weighing 50kg or more
Normal renal function (eGFR greater than or equal to 80 ml/minute/1.73 metre squared): 500mg to 1500mg twice daily.
Mild renal impairment (eGFR 50 to 79 ml/minute/1.73 metre squared): 500mg to 1000mg twice daily.
Moderate renal impairment (eGFR 30 to 49 ml/minute/1.73 metre squared): 250mg to 750mg twice daily.
Severe renal impairment (eGFR less than 30 ml/minute/1.73 metre squared): 250mg to 500mg twice daily.
End-stage renal disease patients 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 aged 4 years and over and adolescents weighing less than 50kg
Normal renal function (eGFR greater than or equal to 80 ml/minute/1.73 metre squared): 10mg/kg to 30mg/kg twice daily.
Mild renal impairment (eGFR 50 to 79 ml/minute/1.73 metre squared):10mg/kg to 20mg/kg twice daily.
Moderate renal impairment (eGFR 30 to 49 ml/minute/1.73 metre squared): 5mg/kg to 15mg/kg twice daily.
Severe renal impairment (eGFR 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
Assess renal function prior to treatment initiation. Reduce the dose by 50% in patients with both severe hepatic impairment and an eGFR less than 60ml/min/1.73 metre squared.
Administration
For intravenous infusion only.
Some products require dilution prior to administration.
Contraindications
Children under 4 years
Long QT syndrome
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
Females of childbearing potential
Restricted sodium intake
Suicidal ideation
Breastfeeding
Electrolyte imbalance
History of torsade de pointes
Pregnancy
Renal impairment - eGFR below 80ml/minute/1.73m sq
Severe hepatic impairment
Correct electrolyte disorders before treatment
Dose adjustment may be necessary in patients with hepatic impairment
Reduce dose in patients with eGFR below 80ml/minute/1.73m sq
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Patient should be converted to oral therapy as soon as possible
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 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
Withdraw treatment gradually under supervision of a specialist
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
Only recommended for short term use
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment
Rare cases of decreased blood cell counts have been described in association with levetiracetam administration. Complete blood cell counts are advised in patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders.
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.
Data does not suggest a substantial increase in the risk for major congenital malformations during the first trimester of pregnancy, although a teratogenic risk cannot be excluded. Therapy with multiple antiepileptic medicinal products is associated with a higher risk of congenital malformations than monotherapy and therefore monotherapy should be considered. Animal studies have shown reproductive toxicity.
Levetiracetam is not recommended during pregnancy by manufacturers unless clinically necessary.
A decrease in plasma concentrations have been observed during pregnancy due to physiological changes. Plasma decrease is more pronounced during the third trimester. Appropriate clinical management of pregnant women treated with levetiracetam should be ensured. 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 and is therefore not recommended by manufacturers. However, if levetiracetam treatment is needed during breastfeeding, the benefit and risk of the treatment should be weighed against the importance of breastfeeding. Exposed infants 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
Acute kidney injury
Aggression
Agitation
Agranulocytosis
Alopecia
Amnesia
Anaphylaxis
Anger
Angioedema
Anorexia
Anxiety
Asthenia
Ataxia
Athetosis
Attention disturbances
Behavioural disturbances
Blood dyscrasias
Blurred vision
Bone marrow depression
Chorea
Confusion
Convulsions
Cough increased
Creatine phosphokinase increased
Delirium
Depression
Diarrhoea
Diplopia
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dyskinesia
Dyspepsia
Eczema
Emotional lability
Encephalopathy
Erythema multiforme
Fatigue
Gait abnormality
Hallucinations
Headache
Hepatic failure
Hepatitis
Hostility
Hyperkinesia
Hypersensitivity reactions
Hyponatraemia
Impaired co-ordination
Impaired memory
Infections
Insomnia
Irritability
Lethargy
Leucopenia
Loss of balance
Mood changes
Muscle weakness
Myalgia
Nasopharyngitis
Nausea
Nervousness
Neutropenia
Pancreatitis
Pancytopenia
Panic attack
Paraesthesia
Personality disorder
Prolongation of QT interval
Pruritus
Psychotic symptoms
Rash
Rhabdomyolysis
Somnolence
Stevens-Johnson syndrome
Suicidal tendencies
Thrombocytopenia
Toxic epidermal necrolysis
Tremor
Vertigo
Vomiting
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: February 2019
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. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Keppra 100mg/ml concentrate for solution for infusion. UCB Pharma S.A. Revised October 2020.
Summary of Product Characteristics: Kevesy 10mg/ml solution for infusion. Stragen UK Ltd. Revised December 2016.
Summary of Product Characteristics: Kevesy 15mg/ml solution for infusion. Stragen UK Ltd. Revised December 2016.
Summary of Product Characteristics: Kevesy 5mg/ml solution for infusion. Stragen UK Ltd. Revised December 2016.
Summary of Product Characteristics: Desitrend 100mg/ml concentrate for solution for infusion. Desitin Arzneimittel GmbH. Revised January 2017.
Summary of Product Characteristics: Levetiracetam 100mg/ml concentrate for solution for infusion. Sun Pharmaceuticals. Revised October 2018.
Summary of Product Characteristics: Levetiracetam 100mg/ml concentrate for solution for infusion. Wockhardt UK Ltd. Revised July 2017.
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: 06 February 2019
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: 31 October 18
Last accessed: 06 February 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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