ABOUT BUCCOLAM (MIDAZOLAM)
Indication And Posology

Therapeutic Indications1

Treatment of prolonged, acute, convulsive seizures in infants, toddlers, children and adolescents (from 3 months to <18 years). BUCCOLAM must only be used by parents/carers where the patient has been diagnosed to have epilepsy.

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

Yellow

2.5MG

AGE RANGE

3 to 6 months hospital setting*
> 6 months to <1 year

MIDAZOLAM DOSE

2.5 mg in 0.5 ml

Blue

5MG

AGE RANGE

1 to < 5 years

MIDAZOLAM DOSE

5 mg in 1 ml

Purple

7.5MG

AGE RANGE

5 to <10 years

MIDAZOLAM DOSE

7.5 mg in 1.5 ml

Orange

10MG

AGE RANGE

10 to <18 years

MIDAZOLAM DOSE

10 mg in 2 ml

Posology1

BUCCOLAM is available in four unit-dose, age-specific, colour-coded, pre-filled oral syringes.

The appropriate dose for an individual patient should be prescribed by the patient’s clinician/epilepsy specialist nurse. BUCCOLAM must only be administered by parents/carers to a patient who has been diagnosed to have epilepsy.

*IMPORTANT: Treatment should be in a hospital setting where monitoring is possible and resuscitation equipment is available

Carers should only administer a single dose of midazolam. If the seizure has not stopped within 10 minutes after administration of midazolam, emergency medical assistance must be sought and the empty syringe given to the healthcare professional to provide information on the dose received by the patient.

A second or repeat dose when seizures re-occur after an initial response should not be given without prior medical advice.

Mechanism Of Action

Midazolam is a derivative of the imidazobenzodiazepine group. The free base is a lipophilic substance with low solubility in water. The basic nitrogen in position 2 of the imidazobenzodiazepine ring system enables midazolam to form the hydrochloride salt with acids. These produce a stable solution suitable for oromucosal administration.1

Benzodiazepines work effectively by binding to GABA (g-aminobutyric acid) receptors2 of post-synaptic cells.3 This hyperpolarises the post-synaptic neuron, inhibiting cell excitation and enhancing inhibitory neurotransmission, stopping the seizure.4
Cl–, chloride; GABA, g-aminobutyric acid; GT, GABA transporter Image adapted from Bialer M, et al. 2010.4

Formulation1

BUCCOLAM consists of the active ingredient, midazolam hydrochloride, and the following excipients sodium chloride, water for injections, hydrochloric acid and sodium hydroxide.

Contains no sugar, sweeteners, preservatives, flavourings, colorants or ethanol. Target pH is 2.9 to 3.7.

The shelf life for BUCCOLAM 2.5 mg is 18 months and BUCCOLAM 5 mg, 7.5 mg and 10 mg is 2 years.

Presentation1

Pre-filled syringes, which allow for specific dosing. Appearance: Unit-dose, age-specific, colour-coded, pre-filled oral syringes, supplied in a clear plastic tube, packed in boxes with four tubes per carton, plus a patient information leaflet.

ABOUT BUCCOLAM (MIDAZOLAM)

Clinical Efficacy And Safety Information

Clinical Efficacy Information1

In 4 rectal diazepam-controlled studies and one study versus intravenous diazepam, in a total of 688 children, cessation of visible signs of seizures within 10 minutes was observed in 65% to 78% of children receiving oromucosal midazolam*. Additionally, in 2 of the studies, cessation of visible signs of seizures within 10 minutes without recurrence within 1 hour after administration was observed in 56% to 70% of children.

The frequency and severity of adverse drug reactions reported for oromucosal midazolam* during published clinical trials were similar to the adverse drug reactions reported in the comparative group using rectal diazepam.

*BUCCOLAM is licensed for oromucosal administration only

Clinical Safety Information1

Summary of the safety profile

Published clinical studies show thatoromucosal midazolam was administered to approximately 443 children with seizures. 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 midazolam use. One episode of pruritus was possibly attributed to the use of buccal midazolam.

Common adverse events

Nervous system disorders

Common: Sedation, somnolence, depressed levels of consciousness, respiratory depression

Gastrointestinal disorders

Common: Nausea and vomiting

Skin and subcutaneous tissue disorders

Uncommon: Pruritus, rash and urticaria

Common: ≥1/100 to <1/10,
Uncommon: ≥1/1,000 to <1/100

Adverse Events

For the full list of adverse events, please refer to the BUCCOLAM SmPC.

Reporting Of Adverse Events

Adverse events should be reported. Reporting forms and information can be found at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Shire Pharmaceuticals Ltd. at: pv-uk@neuraxpharm.com.

References:

  1. BUCCOLAM SmPC. Available from: https://www.medicines.org.uk/emc/product/7460 (accessed 03 Apr 2020)
  2. Campo‐Soria C, Chang Y, Weiss DS. Mechanism of action of benzodiazepines on GABAA receptors. British Journal of Pharmacology. 2006 Aug;148(7):984-90
  3. Knoflach F, Hernandez MC, Bertrand D. GABAA receptor-mediated neurotransmission: Not so simple after all. Biochemical Pharmacology. 2016 Sep 1;115:10-7
  4. Bialer M, White HS. Key factors in the discovery and development of new antiepileptic drugs. Nature reviews Drug discovery. 2010 Jan;9(1):68

This information is provided as a resource to HCP’s who prescribe or administer Buccolam.

Reporting of adverse events (Healthcare Professionals in the UK)

Adverse events should be reported. Reporting forms and information can be found at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Neuraxpharm. at: pv-uk@neuraxpharm.com