Adverse reactions : תופעות לוואי

4.8 Undesirable effects
The overall frequency of adverse reactions from the clinical trial data base is about 7%. The commonest events involved the gastrointestinal system (about 5.0%) and the nervous system (about 2.0%).

The frequencies of adverse events are ranked according to the following: very common (> 1/10), common (> 1/100 to < 1/10), uncommon (> 1/1000 to < 1/100), rare (> 1/10 000 to < 1/1000), very rare (< 1/10,000), not known (cannot be estimated from the available data) including isolated reports.

The information given below is based on data from clinical studies and on extensive post marketing experience.

System organ       Common Uncommon            Rare            Very rare       Not known class              (> 1/100 to (> 1/1000 to < (>1/10,000 to < (<1/10,000)     (cannot be < 1/10)     1/100)         1/1000)                         estimated from the available data)

Infections and                 Fungal infestations                   infection,
Pathogen resistance

Blood and                                                     Anaemia,        Agranulocytosis, lymphatic system                                              Haemolytic      Bone marrow failure disorders                                                     anaemia,        Bone marrow failure Leucopenia,     may lead to
Eosinophilia,   pancytopenia
Thrombocyto- penia

Immune system                                 Anaphylactic    Anaphylactic disorders                                     reactiona,      Shocka, Anaphylactoid   Anaphylactoid reactiona,      shocka
Angioedemaa


System organ          Common Uncommon            Rare            Very rare            Not known class                 (> 1/100 to (> 1/1000 to < (>1/10,000 to < (<1/10,000)          (cannot be < 1/10)     1/100)         1/1000)                              estimated from the available data)

Metabolism and                                     Anorexia                           Hypoglycaemia in nutrition disorders                                                                   diabetics treated with hypoglycaemic agents (see section
4.4),
Hyperglycaemia,
Hypoglycaemic coma (see section
4.4)

Psychiatric                      Restlessness,     Psychotic         Abnormal         Psychotic disorders disorders*                       Sleep disorder,   disorder (for     dreams,          and depression with Agitation,        e.g.              Psychotic        self-endangering Insomnia          hallucination),   behaviour        behaviour including Anxiety,                           suicidal ideation
Confusional                        or suicide attempt state,                             (see section 4.4),
Nightmares,                        Nervousness
Depression,
Delirium
Nervous system                   Headache,         Somnolence,       Peripheral       Tremor, disorders*                       Dizziness         Paraesthesia,     sensory          Dyskinesia, Dysgeusia,        Neuropathya,     Ageusia,
Parosmia          peripheral       Syncope sensory motor neuropathya,
Convulsiona,
Extra- pyramidal symptoms or other disorders of muscular coordination

Eye disorders*                   Eye irritation    Visual            Allergic         Uveitis disturbances      conjunctivitis
(e.g. double vision, blurred vision)

Ear and                          Vertigo                             Tinnitus,        Hearing impaired labyrinth                                                            Hearing loss disorders*


System organ       Common Uncommon            Rare            Very rare       Not known class              (> 1/100 to (> 1/1000 to < (>1/10,000 to < (<1/10,000)     (cannot be < 1/10)     1/100)         1/1000)                         estimated from the available data)

Cardiac                                       Tachycardia                     Ventricular disorders**                                                                   Arrhythmias, torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), ECG
QT prolonged (see section 4.4 and 4.9)

Vascular                                      Hypotension     Circulatory disorders**                                                   collapse, Flushing

Respiratory,                  Cough,          Dyspnoea,                       Allergic pneumonitis, thoracic and                  Nasopharyn-     Bronchospasm                    Severe dyspnoea mediastinal                   gitis disorders
Gastrointestinal              Nausea,        Enterocolitis,   Pseudo-    Dyspepsia, disorders                     Vomiting,      sometimes        membranous Flatulence, Diarrhoea,     haemorrhagic     colitisa   Constipation,
abdominal pain                             Pancreatitis

Hepatobiliary                                 Hepatic         Jaundice        Hepatitis, which may disorders                                     enzymed         cholestatic     be severea, increased                       Severe liver injury,
(ALAT,                          including cases with
ASAT, LDH,                      acute liver failure,
gamma-GT                        sometimes fatal,
and/or alkaline                 have been reported phosphatas),                    with ofloxacin,
Blood bilirubin                 primarily in patients increased                       with underlying liver disorders (see section 4.4).


System organ        Common Uncommon            Rare            Very rare         Not known class               (> 1/100 to (> 1/1000 to < (>1/10,000 to < (<1/10,000)       (cannot be < 1/10)     1/100)         1/1000)                           estimated from the available data)

Skin and                       Rash,           Urticaria,       Toxic            Stevens-Johnson subcutaneous                   Pruritus        Hot flushes,     epidermal        syndrome, tissue disorders                               Hyperhidrosis,   necrolysis,      Acute generalised pustular rash    Photo-           exanthemous sensitivity      pustulosis,
reactiona,       Drug rash
Drug eruption,   Stomatitis,
vascular         Exfoliative dermatitis purpura,
Vasculitis,
which can lead in exceptional cases to skin necrosis,
Vesiculo- bullous rash,
Angioedema erythema multiforme
Musculoskeletal                                Tendonitis       Arthralgia,      Muscle weakness, and connective                                                  myalgia,         Rhabdomyolysis tissue disorders*                                               Tendon           and/or myopathy, rupture (e.g.    Muscle tear,
Achilles         Muscle rupture,
tendon) which    Ligament rupture,
may occur        Arthritis within 48 hours of treatment start and may be bilateral

Renal       and                                Serum            Renal            Acute interstitial urinary disorders                              creatinine       function         nephritis increased        disorder,
Acute renal failure
Congenital and                                                                   Attacks of familial/ genetic                                                                porphyria in patients disorders                                                                        with porphyria 

System organ         Common Uncommon            Rare            Very rare       Not known class                (> 1/100 to (> 1/1000 to < (>1/10,000 to < (<1/10,000)     (cannot be < 1/10)     1/100)         1/1000)                         estimated from the available data)

General disorders                                               Unsteady gait Asthenia, and administration                                                            Pyrexia, site conditions*                                                              Pain (including pain in back, chest, and extremities)

 a post-marketing experience

* 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 pre-existing risk factors (see section 4.4). A range of psychiatric symptoms may occur as part of these side effects, which may include, but are not necessarily limited to, sleep disorders, anxiety, panic attacks, confusion, or depression.

There are no pharmacological treatments established to be effective treatments of the symptoms of long lasting or disabling side effects associated with fluoroquinolones.
The frequency of these prolonged, disabling and potentially irreversible serious drug reactions cannot be estimated with precision using available data, but the reporting incidence from adverse drug reaction reports indicates the frequency is at minimum between 1/1,000 and 1/10,000 (corresponding to the Rare frequency category).

** 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).

Except in very rare instances (e.g. isolated cases of smell, taste and hearing disorders) the adverse effects observed subsided after discontinuation of ofloxacin.

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