Guideline for the use of Anticonvulsant Medications when the Oral Route is Unavailable
Introduction
Children on anti-epileptic drugs (AEDs) may be unable to take regular medications due to multiple reasons. These could include acute illness such as severe gastro-enteritis or electively being nil-by-mouth for surgery.
 
This guidance has been developed to assist in prescribing for children who are nil by mouth while on AEDs.

Scope
This is general guidance to assist prescribers. We advise prescribers to evaluate each case carefully. Pharmacy and the treating clinical team should be consulted in anticipation of administration difficulties or if any questions or concerns about this guidance.
 
Where possible, antiepileptic drugs should be given before and after surgery, in consultation with the anaesthetic team. Sometimes it may be possible to administer the pre-surgical dose but not the post-operative doses. Agreement may need to be sought between an anaesthetist and a surgeon. The PEJ route may need to be considered.
 
Please note this is not an exhaustive list e.g. – Zonisamide, Brivaracetam, Stiripentol. Your local pharmacy team and the paediatric neurology team at University Hospital can be contacted in such cases.
 
Purpose
To optimise giving of anti-convulsant medications, and thus seizure control, when usual route/drug not possible due to surgery or illness.

Definitions
  • AED – Anti-epileptic drug 
  • NBM – Nil by mouth 
Definitions​
Carbamazepine
Alternative Route/Drug
Dose Adjustment
Notes
PR Carbamazepine
Increase dose by 25%

​(125mg PR can be considered approx. equivalent to 100mg of tabs, final dose adjustment dependent on clinical response)
For PR dosing: NB: unlicensed use
increase total daily dose by 25%, then round dose to nearest suppository size. Suppositories available in 125mg & 250mg sizes [1]. [Max dose by rectum 250mg qds].
​
Please note that max duration use of carbamazepine suppositories is 7 days, as suppositories may cause rectal irritation. [1,2,3,4]

Note: oral liquid has been used rectally(off label), this should only beconsidered if suppositories are not tolerated. The oral liquid will need to be diluted, should be retained for at least 2 hours but may have a laxative effect [5]
Clobazam
Alternative Route/Drug
Dose Adjustment
IV Clonazepam

10mg clobazam = 0.75mg clonazepam IV
PR Diazepam
10mg clobazam = 7.5mg diazepam rectal solution or suppositories
IV Diazepam
10mg clobazam = 7.5mg diazepam IV
Clonazepam
Alternative Route/Drug
Dose Adjustment
Notes
PR Diazepam
0.5mg clonazepam = 5mg diazepam PR
Speak to paediatric neurology for advice
IV Diazepam
0.5mg clonazepam = 5mg diazepam IV
 
Ethosuxamide
Alternative Route/Drug
Dose Adjustment
Notes
PR Ethosuxamide
Give capsule rectally at the same dose
Unlicensed use
Gabapentin
Alternative Route/Drug
Speak to paediatric neurology for advice. Poor absorption rectally [8]
Lacosamide
Alternative Route/Drug
Dose Adjustment
Notes
Lacosamide IV Infusion
Same as oral [9, 10]
 
Lamotrigine
Alternative Route/Drug
Dose Adjustment
Notes
Lacosamide IV Infusion
Same as oral
Speak to neurology for advice.
NB unlicensed use: 100mg dispersible tablet dissolved in 6ml room temperature water and given rectally [11].
Use enema prior to administration, using a catheter, administer in lateral decubitus position and patient should maintain a supine position for 60 minutes, monitor for expulsion​ 
Levetiracetam
Alternative Route/Drug
Dose Adjustment
Notes
IV Levetiracetam Infusion
Same as oral [12]
  
Nitrazepam
Alternative Route/Drug
Speak to paediatric neurology for advice. Switch to alternative
Oxcarbazepine
Alternative Route/Drug
Dose Adjustment
Notes
Consider switch to PR Carbamazepine
300mg oxcarbazepine = 250mg carbamazepine supps. 
​[Max dose by rectum 250mg qds].
 Check for any contra-indications to carbamazepine e.g. rash. Speak to paediatric neurology.
Please note that the conversion of oxcarbazepine to carbamazepine has not been researched thoroughly and as a Category 1 and Category 2 antiepileptic, the MHRA advised that switching should only be conducted by a neurologist with appropriate monitoring.​
Perampanel
Alternative Route/Drug
Speak to paediatric neurology for advice on alternative 
Phenobarbitone
Alternative Route/Drug
Dose Adjustment
Notes
IV infusion
Same as oral dose
 
Phenytoin (Sodium)
Alternative Route/Drug
Dose Adjustment
Notes
Give as IV
Same as oral dose of phenytoin sodium capsules
Infatabs and suspension are in the form of phenytoin and the injection is the sodium salt. To convert the dose and multiply the oral phenytoin dose by 1.1 to calculate equivalent IV dose.
In practice would recommend using the same dose and adjusting as required.
Plasma phenytoin concentration monitoring is recommended [15].
Rufinamide
Alternative Route/Drug
Speak to paediatric neurology for advice on alternative 
Sodium Valproate
Alternative Route/Drug
Dose Adjustment
Notes
IV infusion
Same as oral dose
 
Topiramate
Alternative Route/Drug
Dose Adjustment
Notes
Can be given PR
Same as oral dose
Speak to paediatric neurology for advice, usually switch to an alternative.
​
NB: unlicensed use
tablets dissolved in 5-10ml water and given rectally [17]
Vigabatrin
Alternative Route/Drug
Dose Adjustment
Notes
Can be given PR
Same as oral dose
NB: unlicensed use

​Dissolve the contents of sachet in 5- 10ml water and administer rectally [18]. Speak to paediatric neurology for advice.
Zonisamide
Alternative Route/Drug
Speak to paediatric neurology for advice on alternative 
Alternatives – Consult Paediatric Neurology team

Dependent upon type of epilepsy, contraindications to drugs, length of expected change of route ofadministration – it may be appropriate to consider short term alternatives which can be tolerated at therapeutic doses with ease such as IV Levetiracetam (Keppra), IV Lacosamide, IV Sodium Valproate, IV Diazepam. These can be discussed with the paediatric neurology team at University Hospital Southampton.
 
Unlicensed medication

​To ensure safe use of unlicensed medication, an unlicensed form needs to be filled out as per your individual organisation policy
Implementation
This guideline will be made available regionally on the PIER Website. Local leads for children with epilepsy will disseminate guideline and raise awareness locally.
 
Process for Monitoring Compliance

​Process for Monitoring EffectivenessReduced variation in practice has been shown to improve outcomes. Please detail how the impact of this guideline will be measured to demonstrate its effectiveness and identify areas for further development. Where possible this should include patient reported outcomes.
References​

  1. UKMi Pharmacists. Why is there a limit on the dose and duration of use for carbamazepine suppositories?', UKMi Medicines Q&As. undefined: 1-2.
  2. Arvidsson J, Nilsson H et al. Replacing carbamazepine slow-release tablets with carbamazepine suppositories: apharmacokinetic and clinical study in children with epilepsy. J Child Neurol 1995; 10: 114 – 117.
  3. Summary of Product Characteristics. Tegretol Suppositories 125mg, 250mg, Novartis Pharmaceuticals UK Ltd. Date last updated 06/06/14
  4. Neuvonen, PJ. Tokola, O. . Bioavailability of rectally administered carbamazepine mixture. British Journal of Clinical Pharmacology 1987; 24: 839-841
  5. Evelina London. Carbamazepine. http://cms.ubqo.com/public/d2595446-ce3c-47ff-9dcc-63167d9f4b80/content/fa97afa3-fb50-47fc-9012-cf8c89baf204 (accessed 16/08/2019).
  6. Klosterskov , JP. Abild, K. Nohr,PM. Serum concentration of clonazepam after rectal administration.. Acta Neurologica Scandavia 1983; 68(6): 417-720
  7. Evelina London. Clonazepam. http://cms.ubqo.com/public/d2595446-ce3c-47ff-9dcc-63167d9f4b80/content/af5eeff3-624c-4dd2-bebd-db3073410e9e (accessed 16/08/2019).
  8. Evelina London. Gabapentin. http://cms.ubqo.com/public/d2595446-ce3c-47ff-9dcc-63167d9f4b80/content/a26eeea9-1d8b-4eb1-a808-73279cfe868b (accessed 16/08/2019).
  9. Cawello, W. Bonn, R. Boekens, H.. Bioequivalence of intravenous and oral formulations of the antiepileptic drug lacosamide. Pharmacology 2012; 90(1): 40-46
  10. BNF. British National Formulary (Lacosamide Monograph). https://bnfc.nice.org.uk/drug/lacosamide.html#indicationsAndDoses (accessed 16/08/2019).
  11. Evelina London. Lamotrigine. http://cms.ubqo.com/public/d2595446-ce3c-47ff-9dcc-63167d9f4b80/content/3280ae3e-6e6e-4b5d-a277-1f15e80d28be (accessed 16/08/2019).
  12. BNF. . British National Formulary: Levetiracetam https://bnf.nice.org.uk/drug/levetiracetam.html (accessed 14/8/19).
  13. Beydoun, A. Kultuay, E. Oxcarbazepine. Expert Opinion Pharmacotherapy 2002; 3(1): 59-71
  14. Evelina London. Phenobarbitone. http://cms.ubqo.com/public/d2595446-ce3c-47ff-9dcc-63167d9f4b80/content/86faa472-a4fe-4329-a3b0-d6703c882fec (accessed 16/08/2019).
  15. Evelina London. Phenytoin. http://cms.ubqo.com/public/d2595446-ce3c-47ff-9dcc- 63167d9f4b80/content/99e5ed1f-8143-453e-a8ea-45984597e32a (accessed 16/08/2019).
  16. Evelina London. Sodium Valproate. http://cms.ubqo.com/public/d2595446-ce3c-47ff-9dcc-63167d9f4b80/content/61c9e83a-d789-4960-823d-b8e3920f07e3 (accessed 16/08/2019).
  17. Conway, JM. Birnbaum, AK. Kiel, RL. Cloyd, JC. . Relative bioavailability of topiramate administered rectally. Epilepsy Research 2003; 54(2): 91-96.
  18. Evelina London. Vigabatrin. http://cms.ubqo.com/public/d2595446-ce3c-47ff-9dcc-63167d9f4b80/content/22ff4713-e25b-4350-ba5b-9b6f47d37b82 (accessed 16/08/2019).
  19. Wichards, WSW. Schobben AFAM. Leijten FSS. Perioperative substitution of anti-epileptic drugs. J Neurol (2013) 260:2865-2875.

Acknowledgements
​
This guideline has been adapted from Oxford University Hospital NHS Trust and The University Hospitals BristolNHS Foundation Trust Clinical Guideline ‘Anti-epileptics for nil by mouth (NBM) patients”
Document Version: 
1.0

Lead Authors: 
Kate Pryde, Consultant Paediatrician, UHS
Jaspal Singh, Consultant Paediatric Neurologist, UHS
Rosemary Dempsey, Lead Pharmacist Women & Child Health, UHS
Approving Network:
Wessex Neuroscience Network

Date of Approval: 
November 2022

Review Due:
November 2025