Levetiracetam management

Guideline statements

Subcutaneous levetiracetam has a potential role in the treatment of epileptic seizures in palliative care patients who are unable to take their medications orally and when IV access is not an appropriate intervention to maintain good seizure control.

Use of subcutaneous levetiracetam is ‘off licence’ and this should be discussed with the patient as with any other off licence medication.

Oral bioavailability of levetiracetam is 95-100% therefore it is recommended that subcutaneous dosing should mirror standard oral dose.

For a patient already receiving oral levetiracetam the ratio for conversion from oral to subcutaneous use is 1:1 (level D evidence).

The usual starting dose, in a patient not previously using oral levetiracetam, is 500-1000mg over 24 hours via continuous subcutaneous infusion (CSCI).

The oral formulation states a dose increase of 500mg at two week intervals is advised.
Patient condition should be considered when deciding on a titration schedule in this patient group.

The maximum licensed dose is 3000mg over 24 hours. Higher doses (up to 4000mg) have been stated in the literature (level D evidence).

Both 0.9% saline and water for injection have been used as a diluent (level D evidence).

Levetiracetam is available as a 100mg/ml IV formulation (5ml ampoules). Its use subcutaneously is off licence and when used via CSCI the recommended dilution for IV use cannot be achieved. The osmolarity of levetiracetam has been reported as high and this may add to the risk of inflammatory site reactions. To reduce the likelihood of site reactions as with all syringe drivers, it is recommended to use the highest dilution possible (level D evidence).

Levetiracetam can be infused in a 30ml syringe over 24 hours, however there may be limitations to the dose that can delivered due to volume capacity (i.e. typically the maximum dose of levetiracetam that can be delivered through a BD T34 syringe driver using a 30ml syringe will be 2grams due to the volume – please refer local policies on delivery of CSCI).

When higher doses are required the volumes can be problematic to administer.
Alternative options (depending on local policies on delivery of CSCI) may include running the levetiracetam in either a 50ml syringe or to use two 12 hourly 30ml syringe drivers (level D evidence). There is also a T60 syringe driver pump available which some hospice in-patient units keep for this purpose.

There is limited evidence available regarding the compatibility of subcutaneous levetiracetam with other medications and no data on drug stability when mixed with other agents. It is advisable to run levetiracetam in a separate syringe driver where possible. 

It has been combined successfully in individual case reports with (level D evidence):

  • morphine sulfate
  • oxycodone
  • midazolam
  • metoclopramide
  • haloperidol
  • hyoscine butylbromide
  • levomepromazine
  • dexamethasone
  • methadone
  • rantidine
  • diamorphine

Please contact pharmacy for further advice.
Generally sodium chloride 0.9% is used as the diluent for combincations and local skin reactions occur in 5% of patients (PCF7)

Other issues

There have been cases of mild erythema to the infusion site (level D evidence). For information regarding the general side effects of levetiracetam please consult the manufacturer’s Summary of Product Characteristics (SPC).

Dose adjustment is required in renal failure (see table below). Dose reduction is not required in mild to moderate hepatic impairment.

Group: Normal
Creatinine clearance (ml/min/1.73m2): >80
Dose and frequency: 500 to 1500mg twice daily

Group: Mild
Creatinine clearance (ml/min/1.73m2): 50-79
Dose and frequency: 500 to 1000mg twice daily

Group: Moderate
Creatinine clearance (ml/min/1.73m2): 30-49
Dose and frequency: 250 to 750mg twice daily

Group: Severe
Creatinine clearance (ml/min/1.73m2): <30
Dose and frequency: 250 to 500mg twice daily

Group: Dialysis
Creatinine clearance (ml/min/1.73m2): n/a
Dose and frequency: 500 to 1000mg once daily

Benzodiazepines remain the first line treatment for a prolonged seizure or status epilepticus.

Disclaimer (SPAGG - Rewrite)

This Guide is intended for use by healthcare professionals and the expectation is that they will use clinical judgement, medical, and nursing knowledge in applying the general principles and recommendations contained within. They are not meant to replace the many available texts on the subject of palliative care.

Some of the management strategies describe the use of drugs outside their licensed indications. They are, however, established and accepted good practice. Please refer to the current BNF for further guidance.

While WMPCPS takes every care to compile accurate information , we cannot guarantee its correctness and completeness and it is subject to change. We do not accept responsibility for any loss, damage or expense resulting from the use of this information.