Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of the safety profile
Published clinical studies show that oromucosal midazolam was administered to approx 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.

Tabulated list of adverse reactions
The table below lists the adverse reactions reported to occur when oromucosal midazolam was administered to children in clinical studies and post-marketing experience.

The frequency of adverse reactions is classified as follows:
Common: (≥ 1/100 to < 1/10)
Uncommon: (≥ 1/1,000 to < 1/100)
Very rare: (< 1/10,000),
Not known: cannot be estimated from the available data

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness: 
System Organ Class                              Frequency: Adverse Drug Reaction Psychiatric disorders                           Very rare:
Aggression**, agitation**, anger**, confusional state**,
euphoric mood**, hallucination**, hostility**, movement disorder**, physical assault**
Nervous system disorders                        Common:
Sedation, somnolence, depressed levels of consciousness,
Respiratory depression

Very rare:
Anterograde amnesia**, ataxia**, dizziness**, headache**,
seizure**, paradoxical reactions**
Cardiac disorders                               Very rare:
Bradycardia**, cardiac arrest**, hypotension**,
vasodilatation**
Respiratory, thoracic and mediastinal           Very rare: disorders                                       Apnoea**, dyspnoea**, laryngospasm**, respiratory arrest**
Gastrointestinal disorders                      Common:
Nausea and vomiting

Very rare:
Constipation**, dry mouth**
Skin and subcutaneous tissue disorders          Uncommon:
Pruritus, rash and urticarial

Not known:
Angioedema*
General disorders and administration site       Very rare: conditions                                      Fatigue**, hiccups**
Immune system disorders                         Not known:
Anaphylactic reaction*
**These adverse reactions have been reported to occur when midazolam is injected in children and/or adults, which may be of relevance to oromucosal administration.
* ADR identified from post-marketing experience.

Description of selected adverse reactions
An increased risk for falls and fractures has been recorded in elderly benzodiazepine users.

Life-threatening incidents are more likely to occur in those with pre-existing respiratory insufficiency or impaired cardiac function, particularly when a high dosage is administered (see section 4.4).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/ and emailed to the Registration Holder’s Patient Safety Unit at: drugsafety@neopharmgroup.com