Regulatory Decision Summary for Buccolam

This New Drug Submission was filed by Neuraxpharm Pharmaceuticals, S.L., to obtain market authorization, pursuant to section C.08.004 of the Food and Drug Regulations, for Buccolam (midazolam oromucosal solution) 2.5 milligram (mg)/0.5 millilitre (mL), 5 mg/1 mL, 7.5 mg/1.5 mL, and 10 mg/2 mL, in a pre-filled syringe for buccal administration.

Upon review of the submitted data package, Health Canada authorized Buccolam in patients aged from 3 months to less than 18 years of age, for the treatment of prolonged (lasting more than 5 minutes), acute, convulsive seizures distinct from a patient’s usual seizure pattern in patients with epilepsy.

The submission was filed as a Submission Relying on Third-Party Data according to the Guidance Document: Drug Submissions Relying on Third-Party Data (Literature and Market Experience).

Buccolam was presented as a unit-dose, ready-to-use delivery system, that is (i.e.), pre-filled plastic, single-use, oral dosing syringes available in four different, age-specific, colour-coded doses for ease of use during an emergency. The pre-filled syringes and age-banded dosing paradigm reduce the risk of dosing error and allow for a faster administration.

As this new drug submission relied on third party data, the efficacy and safety assessments of Buccolam for the cessation of prolonged, acute, convulsive seizures in children diagnosed with epilepsy relied on eight selected different randomized clinical trials from clinical literature references, as well as the wealth of knowledge on midazolam. Health Canada considered that the literature provided evidence of equivalent efficacy of Buccolam compared to other drug products for the sought indication and/or other drug products approved internationally and recommended by the Canadian Pediatric Society and the World Health Organization for the treatment of prolonged, acute, convulsive seizures in children.

Buccolam was well tolerated and presented a safety profile consistent with the known safety profile of midazolam drug products that have been used for more than forty years. The adverse events commonly reported with the use of Buccolam include coughing, nausea, drowsiness and somnolence, decreased respiratory rate, and blood pressure. Apnea and respiratory depression are the most frequent serious adverse events associated with this emergency medicine. Considering the potential severity of some adverse events in very vulnerable patients, when used for infants between 3-6 months of age, treatment with Buccolam was restricted to hospital setting where monitoring is possible and resuscitation equipment is available.

It must only be used by parents/caregivers when the patient has been diagnosed with epilepsy and is on stable regimens of anti-epileptic drugs.

The Buccolam New Drug Submission demonstrated a favorable benefit-harm-uncertainty profile for the treatment of prolonged, acute, convulsive seizures in children diagnosed with epilepsy on a stable regimen of antiepileptic drugs.

An updated Risk Management Plan for Buccolam was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Buccolam met Health Canada requirements.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for Buccolam for the treatment of prolonged, acute, convulsive seizures in children diagnosed with epilepsy on a stable regimen of antiepileptic drugs, when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance was recommended.

For further details about Buccolam, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.