Adverse reactions : תופעות לוואי

4.8 Undesirable effects

For this product there is no modern clinical documentation which can be used as support for determining the frequency of undesirable effects. Undesirable effects may vary in their incidence depending on the indication and dose received and also when given in combination with other therapeutic agents.

The following convention has been utilised for the classification of frequency: Very common 1/10, common 1/100, <1/10, uncommon 1/1000 and <1/100, rare 1/10,000 and <1/1000, very rare <1/10,000, not known (cannot be estimated from the available data).


Body System                            Frequency         Side effects Neoplasms benign, malignant and        Not known         secondary acute myeloid leukaemia and unspecified (including cysts and                         myelodysplastic syndrome (see section 4.4).
polyps)
Blood and Lymphatic System             Very common bone marrow depression leading to leucopenia, Disorders                                          thrombocytopenia, neutropenia1 and anaemia.
Rare        haemolytic anaemia.
Immune System Disorders                Rare        hypersensitivity2 (see Skin and Subcutaneous Tissue Disorders).
Respiratory, Thoracic and              Rare        interstitial lung disease and pulmonary fibrosis Mediastinal Disorders                              (including fatal reports).
Gastrointestinal Disorders             Very common nausea3, vomiting3 and diarrhoea; stomatitis at high dose.
Rare        stomatitis at conventional dose.
Hepatobiliary Disorders                Rare        liver disorders ranging from abnormal liver function tests to clinical manifestations such as hepatitis and jaundice.
Skin and Subcutaneous Tissue           Very Common alopecia at high dose.
Disorders
Common            alopecia at conventional dose.
Rare              rash maculo-papular and pruritus (see Immune
System Disorders).
Renal and Urinary Disorders            Common            blood urea increased4 
Vascular Disorders5                    Not known         deep vein thrombosis and pulmonary embolism Reproductive system and breast         Not known         azoospermia, amenorrhoea.
disorders
General Disorders and                  Very common       pyrexia
Administration Site Conditions

1. Increased rate of haematological toxicities, particularly, neutropenia and thrombocytopenia, was observed in newly diagnosed elderly multiple myeloma in patients treated with melphalan in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone (see sections 4.4).
2. Allergic reactions to melphalan such as urticaria, oedema, skin rashes and anaphylactic shock have been reported uncommonly following initial or subsequent dosing, particularly after intravenous administration. Cardiac arrest has also been reported rarely in association with such events.
3. Gastrointestinal effects such as nausea and vomiting have been reported in up to 30% of patients receiving conventional oral doses of melphalan.
4. Temporary significant elevation of the blood urea has been commonly seen in the early stages of melphalan therapy in myeloma patients with renal damage.
5. The clinically important adverse reactions associated with the use of melphalan in combination with thalidomide and prednisone or dexamethasone and to a lesser extend melphalan with lenalidomide and prednisone include: deep vein thrombosis and pulmonary embolism (see sections 4.2 and 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
In addition, you can report to Padagis via the following address: Padagis.co.il