Adverse reactions : תופעות לוואי

4.8) Undesirable effects:
Inhibitors of metabolism (e.g. cimetidine): Increased serum                a) Summary of the safety profile: Adverse reactions following administration levels of amide anaesthetics have been reported after concomitant          of the product are similar to those observed with other amide local administration of cimetidine.                                              anaesthetics combined with vasoconstrictors.
Halogenated volatile anaesthetics (e.g.: halothane): Reduced               These adverse reactions are, in general, dose-related and may result from doses of this product should be used due to sensitization of the           high plasma levels caused by overdose, rapid absorption or unintended heart to the arrhythmogenic effects of catecholamines: risk of severe      intravascular injection. They may also result from hypersensitivity, ventricular arrhythmia. The patient’s hemodynamic status should            idiosyncrasy, or diminished tolerance by the specific patient. Nervous be closely monitored.                                                      system disorders, cardiac disorders and vascular disorders are the most Non-selective beta-adrenergic blockers (e.g., propranolol,   frequently occurring adverse reactions.
nadolol): Reduced doses of this product should be            Serious adverse reactions are generally systemic. The presence of used due to possible increase in blood pressure. Close       epinephrine (adrenaline) increases the product’s safety profile due to cardiovascular monitoring is recommended.                    its sympathomimetic effects.
b) Tabulated list of adverse reactions:
(TCAs) Trycyclic antidepressants (e.g., amitriptyline,
The reported adverse reactions come from spontaneous reporting,
desipramine, imipramine, nortriptyline, maprotiline and clinical studies and literature.
protriptyline): Dose and rate of administration of this
By convention, frequency of initial signs of CNS or CVS toxicity is product should be reduced due to strengthening of considered as rare.
adrenaline activity. Close cardiovascular monitoring is
The frequencies classification follows the convention: Very common recommended.
(≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100), MAO inhibitors [both A-selective MAO inhibitors (e.g.,       Rare (≥ 1/10,000 to < 1/1,000), Very Rare (< 1/10,000) and “Not known brofaromine, moclobemide, toloxatone) and non-selective      (cannot be estimated from the available data)”.
MAO inhibitors (e.g., phenelzine, tranylcypromine,
linezolide)]: Use under strict medical supervision due to possible potentialization of the effects of adrenaline.
Rash (eruption)
MedDRA system                                                                          Uncommon Frequency   Adverse Reactions                                                      Pruritus (itching) Organ Class
Skin and                                Angioedema1 (oedema of
Infections and                                                 subcutaneous            Rare            face / tongue / lip / throat / Not known   Gingivitis infestations                                                   tissue disorders                        larynx / periorbital oedema) Urticaria
Immune system                   Hypersensitivity1
Rare                                                                               Hyperhidrosis disorders                       Anaphylactic /                                         Very rare Swelling face anaphylactoid reactions1
Musculoskeletal
Rare        Confusional state                                                      Myalgia and connective          Uncommon
Arthralgia
Psychiatric                     Euphoric mood                  tissue disorders disorders           Very rare   Anxiety / Nervousness /                                Common          Injection site reaction8 Agitation / Restlessness       General
Very rare       Injection site pain disorders and
Neuropathy peripheral2 : administration                          Injection site swelling
Neuralgia (neuropathic site conditions         Not known       Malaise pain)
Common      Headache                                                               Pyrexia Dizziness (light headedness)                   c) Description of selected adverse reactions: Nervous system
Tremor                        1.  Hypersensitivity (anaphylactic or anaphylactoid reactions) may disorders characteristically occur with various symptoms of rash (eruption),
Deep CNS depression:              urticarial, pruritus, bronchospasm/asthma, wheezing, and Loss of consciousness             angiodema. Angioedema include oedema of face / tongue / lip / Rare        Convulsion (including tonic       throat / larynx / periorbital oedema. Laryngo-pharyngeal oedema clonic seizure)                   may characteristically occur with hoarseness and / or dysphagia.
Somnolence                        Bronchospasm (bronchoconstriction) may characteristically occur with dyspnoea;
Visual impairment             2. These neural pathologies may occur with the various symptoms Eye disorders4      Rare        Vision blurred of abnormal sensations of the lips, tongue, and oral tissues.
Accommodation disorder        3. Respiratory depression may characteristically occur with various Ear and labyrinth                                                 symptoms such as apnoea (respiratory arrest); Very rare   Tinnitus disorders                                                     4. These neurally mediated effects are due to the presence of local Palpitations                      anaesthetic / vasoconstrictor at excessive concentrations regionally Common                                        or in the systemic circulation; Tachycardia
5. This mostly occurs in patients with underlying cardiac disease or Conduction disorders,             those receiving certain drugs (section 4.5) Cardiac                         atrioventricular block        6. Necrosis is due to excessive local effect of the vasoconstrictor disorders                       Bradyarrhythmia                   and mostly occurs in patients with underlying ischemic diseases; Cardiac arrest                7. This may be the sign of an injury to the lingual nerve Very rare
Tachyarrhytmia (including     8. Procedural pain, post procedural pain and contusion are symptoms ventricular                       that may be associated to injection site reaction extrasystoles and ventricular fibrillation)5    Because of the presence of adrenaline, precautions and monitoring should be enhanced in the following situations: patients stressed
Hypotension (with possible    prior dental procedure. Any previous knowledge of such underlying circulatory                   conditions in patients requiring dental anaesthesia should be minded collapse)                     and a minimal dose of local anaesthetic with vasoconstrictor used.
Common
Vascular                        Hypertension                  d) Paediatric population: The safety profile was similar in children disorders                       Pallor (local, regional,      and adolescents from 4 to 18 years old compared to adults.
general)
Reporting of suspected adverse reactions:
Vasodilatation                Reporting suspected adverse reactions after authorisation of the Very rare   Vasoconstriction              medicinal product is important. It allows continued monitoring of the Hot flush                     benefit / risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of
Common      Dyspnoea                      Health according to the National Regulation by using an online form: Respiratory,
Rare        Bronchospasm / asthma         https://sideeffects.health.gov.il / thoracic and