If you are not a HCP, please click here

Intended for UK Healthcare Professionals.

The prescribing information link and adverse event reporting statement are found at the bottom of this page.

Midazolam Protocol Resources
If you are not a HCP, please click here

Intended for UK Healthcare Professionals.
The prescribing information link and adverse event reporting statement are found at the bottom of this page.

Midazolam Protocol Resources
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Epistatus® in Paediatric Care

About Epistatus®

What is Epistatus®?

Posology and indication

The active ingredient in Epistatus® is oromucosal midazolam (as maleate).1-4 Epistatus® is indicated for the treatment of prolonged, acute, convulsive seizures in adults, infants, children and adolescents aged 3 months and above*. Epistatus® must only be used by parents / caregivers where the patient has been diagnosed to have epilepsy.1-4

*For infants between 3-6 months of age treatment should be in a hospital setting where monitoring is possible and resuscitation equipment is available.

Mechanism of action

  • Midazolam is a rapid-acting member of the benzodiazepine class of drugs, which exerts its anti-convulsant effect via the potentiation of inhibitory γ-aminobutyric acid (GABA) signalling5
 
  • The GABA receptor is a ligand-gated chloride channel. In the presence of its natural ligand GABA, the GABA receptor channel opens, allowing chloride ions to pass across the neural membrane into the cell.5,6 This induces hyperpolarisation of the membrane potential and therefore the creation of an action potential in response to excitatory stimuli is less likely5,6
 
 
  • Benzodiazepines bind via the α-subunit of the receptor (GABA-A), stabilising the open state of the chloride channel, and enhancing the effect of GABA5,6
 
  • GABA binding consequently results in a greater influx of chloride ions, which further stabilises the neurone against excitatory signals5,6 (see figure below)

Formulation and presentation

Epistatus® is a sweetened, sugar-free, slightly viscous midazolam formulation designed for oromucosal administration.1-4 Epistatus® is presented in a single-unit pack for prescribing flexibility, which can be tailored to prolonged, acute, convulsive seizure frequency for individualised patient treatment.7

References:

  1. Epistatus® 2.5 mg Oromucosal Solution Summary of Product Characteristics (SmPC).
  2. Epistatus® 5 mg Oromucosal Solution SmPC.
  3. Epistatus® 7.5 mg Oromucosal Solution SmPC.
  4. Epistatus® 10 mg Oromucosal Solution SmPC.
  5. Blumer, J.L. (1998) ‘Clinical Pharmacology of Midazolam in Infants and Children,’ Clinical Pharmacokinetics, 35, pp. 37-47.
  6. Griffin, C.E. III, Kaye, A.M., Bueno, F.R. et al. (2013) ‘Benzodiazepine pharmacology and central nervous system mediated effects’, Ochsner J, Summer, 13(2), pp. 214-223.
  7. Fisher, L. and Ludwig, C. (2020) ‘Buccal Midazolam Solution for the Management of Prolonged Acute Convulsive Seizures: A Cost Analysis’, PharmacoEconomics – Open, 4(1), pp. 171-179.

UK-EPI-2400074

Date of Preparation: November 2024

Key features of Epistatus®

Epistatus® is a sweetened, sugar-free, slightly viscous midazolam formulation. It is a pre-filled syringe with a smooth, rounded tip to protect the delicate oral mucosa, and a bite-resistant plastic polymer.1-4 Epistatus® is licensed in 4-age specific doses:1-4

Epistatus® 2.5 mg dose1

  • For children aged 3-6 months (in a hospital setting) and >6 months to <1 year of age, the standard dose is 2.5 mg contained in a volume of 0.25 mL1

Epistatus® 5 mg dose2

  • For children aged 1 year to less than 5 years of age, the standard dose is 5 mg contained in a volume of 0.5 mL2

Epistatus® 7.5 mg dose3

  • For children aged 5 years to less than 10 years of age, the standard dose is 7.5 mg contained in a volume of 0.75 mL3

Epistatus® 10 mg dose4

  • For children, adults and adolescents aged 10 years and above, the standard dose is 10 mg contained in a volume of 1 mL4

Portable design1-4

The device is housed within a tough yet lightweight outer casing that is both protective and tamper-evident1-4

  • Epistatus® should not be stored in a fridge1-4

 

  • Epistatus® can be carried with your patient at all times1-4

 

  • The amber sheath protects from ultra-violet light to maintain midazolam stability1-4

 

  • The outer plastic casing is recyclable1-4

Prescribing flexibility5

Single-unit pack can be tailored to prolonged, acute, convulsive seizure frequency for individualised patient treatment5

  • The syringe has a transparent barrel with black-tipped plunger so carers can see the dose delivered1-4

UK-EPI-2400074

Date of Preparation: November 2024

How to administer Epistatus®

Epistatus® should be used exactly as directed by the doctor or epilepsy nurse. If the instructions on this page are different from what is written in the care plan, always follow the care plan instructions. Epistatus® is for oromucosal (“buccal”) use only, and must only be used in the mouth. It should be administered directly from the pre-filled buccal syringe into the patient’s buccal cavity (the space between the inner cheek and the gums):1-4

As soon as the person’s seizure starts, make a note of the time.

Place something soft under the head for protection and support. Locate the person’s Epistatus® and continue timing the seizure. If it goes on for 5 minutes or more, Epistatus® should be administered.

Check the medication for the expiry date, and do not use if the solution is not clear (e.g. cloudy or white particles present).

Unscrew the amber cap/sheath.

Pull back the cheek and insert into the space between the cheek and teeth (buccal cavity). Do not put in between teeth.

Administer medicine slowly, 2-3 seconds in each cheek, or just into one over 4-5 seconds if difficulty in accessing one buccal cavity.

Dispose of the syringe and cap safely.
Put the person into the recovery
position once the seizure has finished.

Note the time. If the person’s seizure doesn’t stop within 5 minutes of giving Epistatus®, call an ambulance.

Record what happened in the person’s care plan.

How to administer

After receiving Epistatus®, patients should be kept under supervision by a carer. If the seizure does not stop shortly after administration or the condition improves but the seizure starts again, call an ambulance, taking into account instructions from the care plan and their doctor.

A second dose of Epistatus® should not be given without medical advice.

This video is also available for patients and carers to access directly via the Epistatus® patient website, accessible here. This website has been produced by SERB Pharmaceuticals as an educational resource for patients / carers who have been prescribed Epistatus. To email your patient a copy of the Patient Website’s URL and, please click here.

To download the video, please contact SERB Pharmaceuticals via Epistatus@serb.com

References:

  1. Epistatus® 2.5 mg Oromucosal Solution Summary of Product Characteristics (SmPC).
  2. Epistatus® 5 mg Oromucosal Solution SmPC. 
  3. Epistatus® 7.5 mg Oromucosal Solution SmPC. 
  4. Epistatus® 10 mg Oromucosal Solution SmPC. 

UK-EPI-2400074

Date of Preparation: November 2024

Resources for Patients

If you would like a hard-copy supply of Epistatus® patient support materials, please contact your SERB Pharmaceuticals representative by clicking here.

Epistatus® patient website

The Epistatus® patient website contains useful patient resources, including general information about epilepsy along with reference information and training materials that are specific to Epistatus®. There is also a special section for children with a younger reading age. Please note that due to the presence of product-specific information, this website is only suitable for patients, and their parents or carers, who currently have a prescription for Epistatus®.

This website is produced and provided as an educational resource for patients and carers by SERB Pharmaceuticals, and is accessible here. To email your patient a copy of the Patient Website’s URL please click here.

UK-EPI-2400074

Date of Preparation: November 2024

Efficacy and Safety Profile

Established efficacy in treatment of prolonged, acute, convulsive seizures (PACS) in paediatric patients1-4

Data supporting the efficacy of Epistatus® oromucosal solution in the treatment of acute seizures is derived from bibliographic sources.1-4 The efficacy of oromucosal midazolam is comparable to diazepam1-4

  • Seven key trials compared oromucosal midazolam (n=981) vs intravenous or rectal diazepam*

 

  • Cessation of visible signs of seizures within 10 minutes was observed in 65% – 100% of patients who received oromucosal midazolam (n=435)1-3
 
  • Additionally, in 3 of the studies, cessation of visible signs of seizures within 10 minutes without reccurence within 1 hour was observed in 56% – 100% of patients (n=323)4
 
*Data from five controlled studies vs rectal diazepam and two studies vs intravenous diazepam

Clinical safety profile information

The safety profile of midazolam was comparable to rectal diazepam in published clinical trials. Respiratory depression occurs at a rate of up to 5% although this is a known complication of convulsive seizures as well as being related to benzodiazepine use.1-4

Adverse Events

Please consult the SmPC for the full list of adverse drug reactions before prescribing.

References:

  1. Epistatus® 2.5 mg Oromucosal Solution Summary of Product Characteristics (SmPC). 
  2. Epistatus® 5 mg Oromucosal Solution SmPC.
  3. Epistatus® 7.5 mg Oromucosal Solution SmPC.
  4. Epistatus® 10 mg Oromucosal Solution SmPC.

UK-EPI-2400074

Date of Preparation: November 2024

Seizures:
The Facts

Epistatus® in Adult Care

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Resources

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