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 (see section 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 authorization 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/).