Adverse reactions : תופעות לוואי

4.8    Undesirable effects

The following undesirable effects have been observed and reported during treatment with epirubicin with the following frequencies: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated form the available data).

More than 10% of treated patients can expect to develop undesirable effects. The most common undesirable effects are myelosuppression, gastrointestinal side effects, anorexia, alopecia, infection.

System Organ Class                 Frequency             Undesirable effects Infections and infestations        Common                Infection
Not Known             Septic shock, sepsis, pneumonia
Neoplasms benign,                  Rare                  Acute lymphocytic leukaemia, acute malignant and unspecified                                myelogenous leukaemia.
(incl. cysts and polyps)
Blood and lymphatic system         Very Common           Myelosuppression (leucopenia, disorders                                                granulocytopenia and neutropenia, anaemia and febrile neutropenia)
Uncommon              Thrombocytopenia
Not known             Haemorrhage and tissue hypoxia as result of myelosuppression.
Immune system disorders            Rare                  Anaphylaxis
(anaphylactic/anaphylactoid reactions with or without shock)

Metabolism and nutrition           Common                Anorexia, dehydration disorders                          Rare                  Hyperuricaemia (see section 4.4) 
Nervous system disorders           Rare                  Dizziness
Eye disorders                      Not known             Conjunctivitis, keratitis Cardiac disorders                  Rare                  Congestive heart failure, (dyspnoea; oedema, hepatomegaly, ascites,
pulmonary oedema, pleural effusions, gallop rhythm) cardiotoxicity (e.g. ECG abnormalities, arrhythmias,
cardiomyopathy), ventricular tachycardia, bradycardia, AV block,
bundle-branch block
Vascular disorders                 Common                Hot flashes
Uncommon              Phlebitis, thrombophlebitis
Not known             Shock, thromboembolism, including pulmonary emboli
Gastrointestinal disorders        Common                Mucositis, oesophagitis, stomatitis, characterised by pain, burning sensation, erosions, ulcerations,
bleeding; vomiting, diarrhoea,
nausea
Not known             Oral mucosa erosion, mouth ulceration, oral pain, mucosal burning sensation, mouth haemorrhage, and buccal pigmentation
Skin and subcutaneous             Very Common           Alopecia tissue disorders                  Rare                  Urticaria
Not Known             Local toxicity, rash, itch, skin changes, erythema, flushes, skin and nail hyperpigmentation,
photosensitivity, hypersensitivity to irradiated skin (radiation-recall reaction)
Renal and urinary disorders       Very common           Red coloration of urine for 1 to 2 days after administration
Reproductive system and           Rare                  Amenorrhoea, azoospermia breast disorders
General disorders and             Common                Infusion site erythema administration site conditions                        Rare                  Malaise, asthenia, fever, chills Not known             Phlebosclerosis, localpain, severe cellulitis, tissue necrosis after accidental paravenous injection
Investigations                    Rare                  Changes in transaminase levels Not Known             Asymptomatic drops in left ventricular ejection fraction

Neoplasms benign, malignant and unspecified (incl. cysts and polyps)
Secondary acute myeloid leukaemia with or without a pre-leukaemic phase, in patients treated with epirubicin in combination with DNA-damaging antineoplastic agents has been observed.
These leukaemias have a short (1-3 year) latency.

Blood and the lymphatic system disorders:
High doses of epirubicin have been safely administered in a large number of untreated patients having various solid tumours and have caused adverse events which are not different from those seen at conventional doses with the exception of reversible severe neutropenia (< 500 neutrophils/mm³ for < 7 days) which occurred in the majority of patients.
Only few patients required hospitalisation and supportive therapy for severe infectious complications at high doses.

Skin and subcutaneous tissue disorders:
Alopecia, normally reversible, appears in 60-90% of treated patients; it is accompanied by lack of beard growth in males.

General disorders and administration site conditions
Mucositis - may appear 5-10 days after the start of treatment, and usually involves stomatitis with areas of painful erosions, ulceration and bleeding, mainly along the side of the tongue and the sublingual mucosa.

Local pain and tissue necrosis (following accidental paravenous injection) may occur.

Undesirable effects after intravesical administration:
As only a small amount of active ingredient is reabsorbed after intravesical instillation, severe systemic adverse drug reactions are rare. Systemic side effects may occur in isolated cases during early start of instillation (within 24 hours after TUR), extensive tumour infestation of the bladder or bladder inflammation. Local side effects may if necessary be reduced by decreasing the concentration of the instillment (up to 1 mg/ml) within the given dosing recommendations or alternatively by prolonging the treatment interval.

Local undesirable effects after intravesical administration:
Common: Chemical cystitis (approx. 20%) in combination with dysuria, pain and uncommonly haematuria. Bacterial cystitis (approx. 17%) may occur, due to application, e.g.
unsterile catheters.
Rare: allergic reactions.

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