Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Table 4 summarises the undesirable effects which have been reported (frequency not known, cannot be estimated from the available data) to occur when midazolam is injected.

Tabulated list of adverse reactions
Frequency categories are as follows:
Very common: ≥1/10
Common: ≥1/100 to <1/10
Uncommon: ≥1/1,000 to <1/100
Rare: ≥1/10,000 to <1/1,000
Very rare: <1/10,000
Not known (cannot be estimated from the available data)

Table 4: Summary of adverse reactions
Immune System Disorders frequency not known                            Hypersensitivity, angioedema, anaphylactic shock


Psychiatric Disorders frequency not known                            Confusional state, disorientation, emotional and mood disturbances,changes in libido

Physical drug dependence and withdrawal syndrome

Abuse
Paradoxical reactions* including;
restlessness, agitation, irritability,
nervousness, hostility, anger, aggressiveness,
anxiety, nightmares, abnormal dreams,
hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects, paroxysmal excitement
Nervous System Disorders frequency not known                            Involuntary movements (including tonic/clonic movements and muscle tremor)*, hyperactivity*

Sedation (prolonged and postoperative),
alertness decreased, somnolence, headache,
dizziness, ataxia, anterograde amnesia**, the duration of which is directly related to the administered dose

Convulsions have been reported in premature infants and neonates
Drug withdrawal convulsions
Cardiac Disorders frequency not known                            Cardiac arrest, bradycardia, Kounis syndrome****
Vascular Disorders frequency not known                            Hypotension, vasodilation, thrombophlebitis, thrombosis
Respiratory Disorders
frequency not known                              Respiratory depression, apnoea, respiratory arrest, dyspnea, laryngospasm, hiccups
Gastrointestinal Disorders frequency not known                              Nausea, vomiting, constipation, dry mouth
Skin and Subcutaneous Tissue Disorders frequency not known                              Rash, urticaria, pruritus General Disorders and Administration Site
Conditions frequency not known                              Fatigue, injection site erythema, injection site pain
Injury, Poisoning and Procedural
Complications frequency not known                              Falls, fractures***
Social Circumstances frequency not known                              Assault*

*Such paradoxical drug reactions have been reported, particularly among children and the elderly (see section 4.4).
**Anterograde amnesia may still be present at the end of the procedure and in few cases prolonged amnesia has been reported (see section 4.4).
***There have been reports of falls and fractures in benzodiazepine users. The risk of falls and fractures is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.
**** Particularly after parenteral administration

Renal impairment: There is a greater likelihood of adverse drug reactions in patients with severe renal impairment (see section 4.2).

Dependence: Use of midazolam - even in therapeutic doses - may lead to the development of physical dependence. After prolonged i.v. administration, discontinuation, especially abrupt discontinuation of the product, may be accompanied by withdrawal symptoms including withdrawal convulsions (seesection 4.4). Cases of abuse have been reported.

Severe cardio-respiratory adverse events have occurred. Life-threatening incidents are more likely to occur in adults over 60 years of age and those with pre-existing respiratory insufficiency or impaired cardiac function, particularly when the injection is given too rapidly or 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/