Summary of the safety profile Cardioxane is administered together with anthracycline chemotherapy and, consequently, the relative contributions of anthracycline and Cardioxane to the adverse reaction profile may be unclear. The most common adverse reactions are haematological and gastroenterological reactions, primarily anaemia, leukopenia, nausea, vomiting and stomatitis, as well as asthenia and alopecia.
4). Tabulated list of adverse reactions The following table includes reactions from clinical trials and from post-marketing use. Due to the spontaneous nature of post-marketing reporting, such events are listed with frequency “not known” if they were not already identified as reactions from clinical trials.
Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: very common ( ≥ 1/10); common ( ≥ 1/100 to < 1/10); uncommon ( ≥ 1/1,000 to < 1/100); not known (cannot be estimated from the available data).
Table 1 Infections and infestations Uncommon Infection, sepsis Neoplasms benign, malignant and unspecified (including cysts and polyps) Uncommon Acute myeloid leukaemia Blood and lymphatic system disorders Very common Anaemia, leukopenia Common Neutropenia, thrombocytopenia, febrile neutropenia, granulocytopenia, febrile bone marrow aplasia, white blood cell count decreased Uncommon Eosinophil count increased, neutrophil count increased, platelet count increased, white blood cell count increased, lymphocyte count decreased, monocyte count decreased Immune system disorders Not known Anaphylactic reaction, hypersensitivity Metabolism and nutrition disorders Common Anorexia Nervous system disorders Common Paraesthesia, dizziness, headache, peripheral neuropathy Uncommon Syncope Ear and labyrinth disorders Uncommon Vertigo, ear infection Cardiac disorders Common Ejection fraction decreased, tachycardia Vascular disorders Common Phlebitis Uncommon Venous thrombosis, lymphoedema Not known Embolism Respiratory, thoracic and mediastinal disorders Common Dyspnoea, cough, pharyngitis, respiratory tract infections Not known Pulmonary embolism Gastrointestinal disorders Very common Nausea, vomiting, stomatitis Common Diarrhoea, constipation, abdominal pain, dyspepsia Uncommon Gingivitis, oral candidiasis Hepatobiliary disorders Common Transaminases increased Skin and subcutaneous tissue disorders Very common Alopecia Common Nail disorder, erythema Uncommon Cellulitis General disorders and administration site conditions Very common Asthenia Common Mucosal inflammation, pyrexia, fatigue, malaise, injection site reaction (including pain, swelling, burning sensation, erythema, pruritus, thrombosis), oedema Uncommon Thirst Clinical trial data The above table shows adverse reactions reported in clinical studies and having a reasonable possibility of a causal relationship with Cardioxane.
These data are derived from clinical trials in cancer patients where Cardioxane was used in combination with anthracycline-based chemotherapy, and where in some cases a control group of patients receiving chemotherapy alone can be referred to.
Patients receiving chemotherapy and Cardioxane (n=375): • Of these 76% were treated for breast cancer and 24% for a variety of advanced cancers. • Cardioxane treatment: a mean dose of 1010 mg/m² (median: 1000 mg/m²) in combination with doxorubicin, and a mean dose of 941 mg/m² (median: 997 mg/m²) in combination with epirubicin.
• Chemotherapy treatment received by patients treated for breast cancer: 45% combination therapy with doxorubicin 50 mg/m² (mainly with 5-fluorouracil and cyclophosphamide): 17% with epirubicin alone; 14% combination therapy with epirubicin 60 or 90 mg/m² (mainly with 5-fluorouracil and cyclophosphamide).
Patients receiving chemotherapy alone (n=157) • All were treated for breast cancer • Chemotherapy treatment received: 43% single agent epirubicin 120 mg/m²; 33% combination therapy with 50 mg/m² doxorubicin (mainly with 5-fluorouracil and cyclophosphamide); 24% combination therapy with epirubicin at 60 or 90 mg/m² (mainly with 5-fluorouracil and cyclophosphamide).
Description of selected adverse drug reactions Second primary malignancies AML has been reported uncommonly in adult breast cancer patients post-marketing. Safety profile at maximum tolerated dose Dexrazoxane's maximum tolerated dose (MTD) when given as monotherapy by short infusion every three weeks for cardioprotection has not been specifically studied.
In studies of dexrazoxane as a cytotoxic, its MTD is shown to be dependent on posology and dosing schedule, and varies from 3750 mg/m2 when short infusions are given in divided doses over 3 days to 7420 mg/m2 when given weekly for 4 weeks, with myelosuppression and abnormal liver function tests becoming dose-limiting.
g. AIDS). The following are adverse reactions reported when Cardioxane was given at doses around the MTD: neutropenia, thrombocytopenia, nausea, vomiting, and increase in hepatic parameters. Other toxic effects were malaise, low grade fever, increased urinary clearance of iron and zinc, anaemia, abnormal blood clotting, transient elevation of serum triglyceride and amylase levels, and a transient decrease in serum calcium level.
Paediatric population The safety experience in children is based primarily on literature reports of clinical trials in acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin’s disease and osteosarcoma, and post-marketing data.
In paediatric patients, second primary malignancies, including acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS), have been reported in clinical trials in both dexrazoxane and control groups. Although second primary malignancies were numerically higher in the dexrazoxane arms, there […]