Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of the safety profile
The most commonly occurring adverse drug reactions include injection site pain/reaction, changes in vital signs and prolonged neuromuscular block. The most frequently reported serious adverse drug reactions during post-marketing surveillance is 'anaphylactic and anaphylactoid reactions' and associated symptoms. See also the explanations below the table.

Tabulated list of adverse reactions
MedDRA SOC              Preferred term1
Uncommon/rare2       Very rare (<1/10 000)    Not Known
(<1/100, >1/10000)

Immune system                                Hypersensitivity disorders                                    Anaphylactic reaction Anaphylactoid reaction
Anaphylactic shock
Anaphylactoid shock

Nervous system                               Flaccid paralysis disorders
Eye disorders                                                         Mydriasis2,3 Fixed pupils2,3
Cardiac disorders       Tachycardia                                   Kounis syndrome Vascular disorders      Hypotension          Circulatory collapse and shock

Flushing

Respiratory, thoracic                        Bronchospasm and mediastinal disorders
Skin and                                     Angioneurotic oedema subcutaneous tissue                          Urticaria disorders
Rash
Erythematous rash

Musculoskeletal and                          Muscular weakness4 connective tissue disorders                                    Steroid myopathy4 General disorders and   Drug ineffective          Face oedema administration site     Drug effect/ conditions              therapeutic response decreased
Drug effect/ therapeutic response increased

Injection site pain
Injection site reaction

Injury, poisoning and   Prolonged                 Airway complication of procedural              neuromuscular block       anaesthesia complications
Delayed recovery from anaesthesia
MedDRA version 8.1
1 Frequencies are estimates derived from post-marketing surveillance reports  and data from the general literature.
2 Post-marketing surveillance data cannot give precise incidence figures. For that
 reason, the reporting frequency was divided over three rather than five categories.
3 In the context of a potential increase of permeability or compromise of the integrity  of the Blood-Brain Barrier (BBB).
4 After long-term use in the ICU.

Anaphylaxis
Although very rare, severe anaphylactic reactions to neuromuscular blocking agents, including Rocurim, have been reported. Anaphylactic/anaphylactoid reactions are: bronchospasm, cardiovascular changes (e.g., hypotension, tachycardia, circulatory collapse – shock), and cutaneous changes (e.g., angioedema, urticaria). These reactions have, in some cases, been fatal. Due to the possible severity of these reactions, one should always assume they may occur and take the necessary precautions.
Since neuromuscular blocking agents are known to be capable of inducing histamine release both locally at the site of injection and systemically, the possible occurrence of itching and erythematous reaction at the site of injection and/or generalised histaminoid (anaphylactoid) reactions (see also under anaphylactic reactions above) should always be taken into consideration when administering these drugs.

In clinical studies, only a slight increase in mean plasma histamine levels has been observed following rapid bolus administration of 0.3-0.9 mg/kg rocuronium bromide.

Prolonged neuromuscular block
The most frequent adverse reaction to nondepolarising blocking agents as a class consists of an extension of the drug's pharmacological action beyond the time period needed. This may vary from skeletal muscle weakness to profound and prolonged skeletal muscle paralysis resulting in respiratory insufficiency or apnea.

Myopathy
Myopathy has been reported after the use of various neuromuscular blocking agents in the ICU in combination with corticosteroids (see section 4.4).

Local injection site reactions
During rapid sequence induction of anaesthesia, pain on injection has been reported, especially when the patient has not yet completely lost consciousness and particularly when propofol is used as the induction agent. In clinical studies, pain on injection has been noted in 16% of the patients who underwent rapid sequence induction of anaesthesia with propofol and in less than 0.5% of the patients who underwent rapid sequence induction of anaesthesia with fentanyl and thiopental.

Paediatric population
A meta-analysis of 11 clinical studies in paediatric patients (n=704) with rocuronium bromide (up to 1 mg/kg) showed that tachycardia was identified as adverse drug reaction with a frequency of 1.4%.

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: http://sideeffects.health.gov.il/
Additionally, you can report to Unipharm Ltd. via the following address: https://unipharm.co.il