Intended for UK Healthcare Professionals.

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

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

Epistatus® in adults

Epistatus® in Adult Care

Epistatus® in Adult Care

What is Epistatus®?

Posology and indication

The active ingredient in Epistatus® is oromucosal midazolam (as maleate).1 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

*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) signalling2
 
  • 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.2,3 This induces hyperpolarisation of the membrane potential and therefore the creation of an action potential in response to excitatory stimuli is less likely2,3
 
 
  • Benzodiazepines bind via the α-subunit of the receptor (GABA-A), stabilising the open state of the chloride channel, and enhancing the effect of GABA2,3
 
  • GABA binding consequently results in a greater influx of chloride ions, which further stabilises the neurone against excitatory signals2,3 (see figure below)

Formulation and presentation

Epistatus® is a sweetened, sugar-free, slightly viscous midazolam formulation designed for oromucosal administration.1 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.4

References:

  1. Epistatus® 10 mg Oromucosal Solution SmPC.
  2. Blumer, J.L. (1998) ‘Clinical Pharmacology of Midazolam in Infants and Children,’ Clinical Pharmacokinetics, 35, pp. 37-47.
  3. 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.
  4. 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-2400075

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

Epistatus® 10 mg dose1

  • For children, adults and adolescents aged 10 years and above, the standard dose is 10 mg contained in a volume of 1 mL1

Portable design1

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

  • Epistatus® should not be stored in a fridge1

 

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

 

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

 

  • The outer plastic casing is recyclable1

Prescribing flexibility1,2

Single-unit pack can be tailored to prolonged, acute, convulsive seizure frequency for individualised patient treatment2

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

References:

  1. Epistatus® 10 mg Oromucosal Solution SmPC.
  2. 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-2400075

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

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 here.

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

References:

  1. Epistatus® 10 mg Oromucosal Solution SmPC. 

UK-EPI-2400075

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 their parents or carers, 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-2400075

Date of Preparation: November 2024

Efficacy and Safety Profile

Established efficacy in treatment of prolonged, acute, convulsive seizures (PACS) in adult patients1,2

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

 

  • The efficacy of Epistatus® oromucosal midazolam maleate solution in adults has been demonstrated in three trials that together included 58 adults with epilepsy1

 

In a retrospective observational study of adults from four UK secondary-care outpatient clinics who needed emergency treatment of an epileptic seizure (mainly generalised tonic/clonic [72.6%] or focal [13.0%]):

 

  • 82.9% (124/146) of patients achieved seizure cessation with 10 mg of oromucosal midazolam maleate2

 

  • The mean length of time to seizure cessation following a 10 mg dose of oromucosal midazolam maleate was 5.5 minutes (n=38, SD 4.5, median 5.0, IQR 2.1-5.0)2

 

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

Adverse Events

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

References:

  1. Epistatus® 10 mg Oromucosal Solution SmPC.
  2. Shankar, R. et al. (2021) ‘Oro-mucosal midazolam maleate: Use and effectiveness in adults with epilepsy in the UK’, Epilepsy Behavior, 123, p. 108242.

UK-EPI-2400075

Date of Preparation: November 2024

Seizures:
The Facts

Epistatus® in Paediatric Care

Access

Resources