Levetiracetam (subcutaneous infusion)

• Injection 500mg/5ml, ampoules

• Generic preparations are available as well as Keppra

Licensed

• Levetiracetam solution for infusion is licensed for intravenous use only.
• Mono or adjunctive treatment of partial onset seizures, adjunctive treatment of myoclonic and generalised tonic-clonic seizures.

†Unlicensed

• Unlicensed use when administered by CSCI.
• Monotherapy of generalised seizures. Refer to seizures guideline.
• In palliative care CSCI Levetiracetam may be considered by specialist palliative care practitioners as an alternative for patients when oral administration of Levetiracetam is not feasible or when a benzodiazepine (midazolam/clonazepam) is inappropriate, for example if sedation proves troublesome.

• Contra-indicated in people with hypersensitivity to other pyrrolidine derivatives, for example procyclidine
• Use with caution in patients with renal or hepatic impairment or with a psychiatric disorder. See below for dose adjustments according to renal function.
• Avoid abrupt withdrawal.

Important drug interactions

None.

Side effects

• Very common: somnolence, headache, nasopharyngitis.
• Common: depression, hostility/aggression, anxiety, insomnia, nervousness/irritability, convulsion, dizziness, balance disorders, vertigo, lethargy, tremor, anorexia, cough, abdominal pain, diarrhoea, dyspepsia, vomiting, nausea, rash, asthenia/fatigue. Less common but serious reactions include depression, psychosis, suicidality, leukopenia, neutropenia, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, hyponatremia.
• May rarely exacerbate seizure frequency or severity
• Refer to full Summaries of Product Characteristics (SPCs) for complete tabulated list of adverse effects.

The initial starting dose for monotherapy is 500mg/24 hours, and titrated/increased if needed at fortnightly intervals. If the patient has been taking oral levetiracetam use a PO:SC dose ratio of 1:1.

The subcutaneous (SC) administration of levetiracetam is unlicensed, but published reports and case studies suggest administration by either SC or continuous subcutaneous infusion (CSCI) at concentrations of up to 100mg/ml is well tolerated.

• Given over 24 hours via a syringe pump (CSCI) using water for injection as diluent. Maximal dilution with WFI is recommended in order to preserve the infusion site.
• Two syringe pumps may be required for doses above 2g/day or the use of a 50ml syringe.

In situations where the patient has not previously received levetiracetam there is limited information on how to proceed. The licensed dose titration can take at least 2 weeks to reach a therapeutic dose. Off-label approach is to start at 1g by CSCI over 24 hours and increase as necessary over 2 to 4 days to 3g by CSCI over 24 hours.

Use in impaired renal function

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• Unlike other anti-epileptics, levetiracetam has a low potential for pharmacokinetic drug interactions.
• Consider administering levetiracetam using two syringe pumps if daily doses are above 2g/day or with the appearance of skin reactions.

Dickman A, Schneider J. The Syringe Driver. 4th ed: Oxford University Press; 2016.

Lopez-Saca JM, Vaquero J, Larumbe A, Urdiroz J, Centeno C. Repeated use of subcutaneous levetiracetam in a palliative care patient. J Pain Symptom Manage. 2013;45(5):e7-8.

Remi C, Lorenzl S, Vyhnalek B, Rastorfer K, Feddersen B. Continuous subcutaneous use of levetiracetam: a retrospective review of tolerability and clinical effects. J Pain Palliat Care Pharmacother. 2014;28(4):371-7.

Levetiracetam Monographs. Summary of Product Characteristics (SPC) http://www.medicines.org.uk/emc/

Twycross R, Wilcock A, Howard P. Palliative Care Formulary PCF6. 6th ed. England: Pharmaceutical Press; 2017.