Adverse reactions : תופעות לוואי

4.8. Undesirable effects
The most commonly reported adverse drug reactions (ADRs) are nausea, diarrhoea, vomiting, transient increase in transaminases, rash, and injection and infusion site reactions. ADRs derived from clinical studies and post-marketing surveillance with ciprofloxacin (oral, intravenous and sequential therapy) sorted by categories of frequency are listed below. The frequency analysis takes into account data from both oral and intravenous administration of ciprofloxacin.

System organ        Common          Uncommon           Rare ≥1/10,000 to       Very rare           Frequency class               ≥1/100 to <1/10 ≥1/1 000 to        <1/1,000                <1/10,000           unknown <1/100                                                         (cannot be estimated from the available data)
Infections and                       Mycotic           Antibiotic associated infestations                         superinfections   colitis (very rarely with possible fatal outcome) (see section 4.4)

Blood and                            Eosinophilia      Leukopenia,             Haemolytic lymphatic                                              Anaemia,                anaemia, system                                                 Neutropenia,            Agranulocytosis, disorders                                              Leukocytosis,           Pancytopenia Thrombocytopenia,       (life-
Thrombocytemia          threatening),
Bone marrow depression (life- threatening)
Immune system                         Allergic reaction,    Anaphylactic disorders                             Allergic oedema /     reaction, Angio-oedema          Anaphylactic shock (life- threatening),
(see section
4.4)
Serum sickness-like reaction

Endocrine                                                                       Syndrome of disorders                                                                       inappropriate secretion of antidiuretic hormone
(SIADH)



Metabolism and      Anorexia,         Hyperglycaemia,                           Hypoglycaemic nutrition           Decreased         Hypoglycaemia (see                        coma (see disorders           appetite          section 4.4)                              section 4.4) Psychiatric         Psychomotor       Confusion and         Psychotic             Mania, incl.
disorders (*)       hyperactivity /   disorientation,       reactions             hypomania agitation         Anxiety reaction,     (potentially
Abnormal dreams       culminating in
Depression            suicidal
(potentially          ideations/ culminating in        thoughts or suicidal              suicide ideations/thoughts    attempts and or suicide attempts   completed and completed         suicide) (see suicide) (see         section 4.4) section 4.4),
Hallucinations
Nervous system      Headache,         Par- and              Migraine,            Peripheral disorders (*)       Dizziness,        Dysaesthesia,         Disturbed            neuropathy Sleep             Hypoaesthesia,        coordination,        and disorders,        Tremor, Seizures      Gait disturbance,    polyneuropathy Taste disorders   (including status     Olfactory nerve      (see section epilepticus, see      disorders,           4.4) section 4.4),         Intracranial
Vertigo               hypertension and pseudotumor cerebri
Eye disorders (*)                     Visual                Visual colour disturbances          distortions
(e.g.diplopia)

Ear and labyrinth                     Tinnitus,
disorders (*)                         Hearing loss / hearing impaired
Cardiac disorders                                   Tachycardia                                Ventricular (**)                                                                                           arrhythmia and torsades de pointes
(reported predominantly in patients with risk factors for
QT prolongation),
ECG QT prolonged (see section 4.4 and
4.9).
Vascular                                            Vasodilation,        Vasculitis disorders (**)                                      Hypotension,
Syncope
Respiratory,                                        Dyspnoea thoracic and                                        (including asthmatic mediastinal                                         condition) disorders
Gastrointestinal    Nausea,     Vomiting,          Antibiotic-associated   Pancreatitis disorders           Diarrhoea   Gastrointestinal   colitis (very rarely and abdominal      with possible fatal pain,              outcome) (see
Dyspepsia,         section 4.4)
Flatulence
Hepato-biliary                  Increase in         Hepatic                Liver necrosis disorders                       transaminases,      impairment,            (very rarely Increased          Cholestatic icterus,   progressing to bilirubin           Hepatitis              life-threatening hepatic failure)
(see section 4.4)

Skin and                        Rash,               Photosensitivity       Petechiae,         Acute subcutaneous                    Pruritus,           reactions (see         Erythema           Generalised tissue disorders                Urticaria           section 4.4)           multiforme,        Exanthematous Erythema           Pustulosis nodosum,           (AGEP)
Stevens-           Drug Reaction
Johnson            with syndrome           Eosinophilia and
(potentially life-
Systemic threatening),
Toxic epidermal Symptoms necrolysis         (DRESS)
(potentially life- threatening)
Musculoskeletal                 Musculoskeletal     Myalgia                Muscular and connective                  pain (e.g.          Arthritis              weakness tissue disorders                extremity pain,     Increased muscle       Tendinitis back pain and       tone and cramping      Tendon ruptures chest pain),                               (predominantly
Arthralgia                                 Achilles tendon)
(see section 4.4),
Exacerbation of symptoms of myasthenia gravis (see section 4.4)

Renal and                       Renal               Renal failure,
urinary                         impairment          Haematuria,
disorders                                           Crystalluria (see section 4.4),
Tubulointerstitial nephritis
General             Injection and     Asthenia,         Oedema,
disorders and       infusion site     Fever             Sweating administration      reactions                           (hyperhidrosis) site               (only conditions (*)      intravenous
Investigations      administration)   Increase in       Prothrombin level                        International blood alkaline    abnormal, increased                      normalised phosphatase       amylase                                  ratio increased (in patients treated with
Vitamin K antagonists)


*Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious drug reactions affecting several, sometimes multiple, system organ classes and senses (including reactions such as tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and impairment of hearing, vision, taste and smell) have been reported in association with the use of quinolones and fluoroquinolones in some cases irrespective of preexisting risk factors (see section 4.4).
**Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.4).

The following undesirable effects have a higher frequency category in the subgroups of patients receiving intravenous or sequential (intravenous to oral) treatment:

Common                            Vomiting, transient increase in transaminases, rash Uncommon                          Thrombocytopenia, thrombocytaemia, confusion and disorientation, hallucinations, par- and dysaesthesia, seizures, vertigo, visual disturbances, hearing loss, tachycardia, vasodilatation,
hypotension, transient hepatic impairment, cholestatic icterus, renal failure, oedema
Rare                              Pancytopenia, bone marrow depression, anaphylactic shock, psychotic reactions, migraine, olfactory nerve disorders, hearing impaired, vasculitis, pancreatitis, liver necrosis, petechiae, tendon rupture


Paediatric population
The incidence of arthropathy (arthralgia, arthritis), mentioned above, is referring to data collected in studies with adults. In children, arthropathy is reported to occur commonly (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