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 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 from the available data).
MedDRA system organ class               Frequency     Adverse reactions 
Neoplasms benign, malignant and                       Secondary acute myeloid leukaemia and unspecified (including cysts and        Not known     myelodysplastic syndrome (see section 4.4) polyps)

Blood and lymphatic system disorders Very common      Bone marrow depression, leading to leukopenia, thrombocytopenia, neutropenia1 and anaemia

Rare          Haemolytic anaemia



Immune system disorders                 Rare          Hypersensitivity2 (see skin and subcutaneous tissue disorders)



Respiratory, thoracic and mediastinal   Rare          Interstitial lung disease and pulmonary fibrosis disorders                                             (including fatal reports) 
Gastrointestinal disorders              Very common   At high dose: nausea, vomiting and diarrhoea; stomatitis 

Rare          Stomatitis at conventional dose

Hepato-biliary disorders                Rare          Hepatic disorders ranging from abnormal liver function tests to clinical manifestations such as hepatitis and jaundice; veno-occlusive disease following high-dose therapy
Skin and subcutaneous tissue            Very common   Alopecia at high dose disorders
Common        Alopecia at conventional dose

Rare          Maculopapular rashes and prurtitis (see also immune system disorders)

Musculoskeletal and connective tissue Very common     Muscular atrophy, muscle fibrosis, myalgia, increase in disorders3                                            creatinine phosphokinase in the blood 
Common        Compartment Syndrome

Not known     Muscle necrosis, rhabdomyolysis
Renal and urinary disorders             Common        Blood urea increased4 

Uncommon      Acute kidney injury


Reproductive system and breast          Common        Azoospermia and amenorrhoea disorders
Vascular disorders5                   Not known           Deep vein thrombosis and pulmonary embolism 
General disorders and administration Very common          Subjective and transient heat sensation of warmth and / site conditions                                           or tingling 

Common              Mucosal inflammation (mucositis)


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
Only with melphalan infusion after administration of regional perfusion in the limb.
4
Temporary significant elevation of the blood urea has been 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 section 4.4).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization 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.