Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Adverse reactions, when they occur, are usually observed at the beginning of therapy and generally decrease in severity or disappear with continued use or upon decreasing the dose.

System Organ         Very Common          Common              Uncommon             Frequency Class                ≥ 1/10               ≥ 1/100 to <        ≥ 1/1,000 to         not known 1/10                < 1/100              (cannot be estimated from the available data)
Blood and                                                                          Thrombocytopenia, lymphatic                                                                          agranulocytosis, system disorders                                                                   pancytopenia Immune system                                                            Hypersensitivity disorders                                                                reactions, anaphylactic/oid reactions
Endocrine                                                                SIADH disorders
Metabolism and                                                           Hyponatremia nutrition disorders
Psychiatric                      Confusion,          Change in libido,   Disinhibition, euphoria, disorders                        depression,         decreased           suicidal unmasking of        orgasm              ideation/attempt,
depression                              paradoxical reactions,
including anxiety,
agitation, excitation,
hostility, aggression,
rage, sleep disturbances/insomnia,
sexual arousal,
hallucinations, drug abuse, drug dependence
Nervous system      Sedation,    Ataxia, dizziness                       Extrapyramidal disorders±          drowsiness                                           symptoms, tremor, dysarthria/slurred speech, headache,
convulsions/seizures,
amnesia, coma,
impaired attention/concentration,
balance disorder
Eye disorders                                                            Visual disturbances (including diplopia and blurred vision)
Ear and labyrinth                                                        Vertigo disorders
Vascular                                                                 Hypotension, lowering disorders                                                                in blood pressure Respiratory,                                                             Respiratory thoracic and                                                             depressionβ, apnea, mediastinal                                                              worsening of sleep disorders                                                                apnea, worsening of obstructive pulmonary disease
Gastrointestinal                                     Nausea              Constipation disorders
Hepatobiliary                                                            Jaundice disorders
Skin and                                                                 Angioedema, allergic subcutaneous                                                             skin reactions, alopecia tissue disorders
Musculoskeletal                  Muscle and                              weakness connective tissue disorders
Reproductive                                         Impotence system and breast disorders
General disorders   Fatigue      Asthenia                                Hypothermia, drug and                                                                      withdrawal syndrome administration site conditions
Investigations                                                           Increase in bilirubin, increase in liver transaminases,
increase in alkaline phosphatase
± Benzodiazepine effects on the CNS are dose-dependent, with more severe CNS depression occurring with high doses.
β The extent of respiratory depression with benzodiazepines is dose dependent, with more severe depression occurring with high doses.

Pre-existing depression may emerge during benzodiazepine use.

Transient anterograde amnesia or memory impairment may occur using therapeutic doses, the risk increasing at higher doses (see section 4.4)
Paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, delusion, rage, nightmares, hallucinations, psychoses, and inappropriate behaviour have been occasionally reported during benzodiazepine use. Such reactions may be more likely to occur in children and the elderly (see section 4.4).

Use (even at therapeutic doses) may lead to physical or psychological dependence and discontinuation of treatment may result in withdrawal reactions or rebound phenomena (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