HHE Sponsored handbook: Cardioprotection in clinical - Page 7

HHE 2019 7 References Intern Med 2010;152:409–17. 6 Tukenova M et al. Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer. J Clin Oncol 2010;28:1308–15. 7 Hershman DL, Shao T. Anthracycline cardiotoxicity after breast cancer treatment. Oncology (Williston Park) 2009;23:227–34. 8 Menna P et al. Anthracycline cardiotoxicity. Expert Opin Drug Saf 2012;11:S21–S36. 9 Felker GM et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med 2000;342: 1077–84. 10 Sun F, Shi J, Geng C. Dexrazoxane improves cardiac autonomic function in epirubicin-treated breast cancer patients with type 2 diabetes. Medicine (Baltimore) 2016;95:e5228. 11 Armstrong GT et al. Modifiable risk factors and major cardiac events among adult survivors of childhood cancer. J Clin Oncol 2013;31:3673–80. 12 Marty M et al. Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy. Ann Oncol 2006;17:614–22. 13 Gianni L et al. Anthracycline cardiotoxicity: from bench to bedside. J Clin Oncol 2008;26:3777–84. 14 Raj S, Franco VI, Lipshultz SE. Anthracycline-induced cardiotoxicity: a review of pathophysiology, diagnosis, and treatment. Curr Treat Options Cardiovasc Med 2014;16:315. 15 Zamorano JL et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J 2016;37:2768–801. 16 Armenian SH et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2017;35:893–911. 17 Asselin BL et al. Cardioprotection and safety of dexrazoxane in patients treated for newly diagnosed T-cell acute lymphoblastic leukemia or advanced-stage lymphoblastic non-Hodgkin lymphoma: a report of the Children’s Oncology Group randomized trial pediatric oncology group. J Clin Oncol 2016;34(8):854–62.​ 18 Geisberg CA, Sawyer DB. Mechanisms of anthracycline cardiotoxicity and strategies to decrease cardiac damage. Curr Hypertens Rep 2010;12:404–10. 19 Sawyer DB. Anthracyclines and heart failure. N Engl J Med 2013;368:1154–6. 20 Cvetkovic RS, Scott LJ. Dexrazoxane: a review of its use for cardioprotection during anthracycline chemotherapy. Drugs 2005;65:1005–24. 21 Lipshultz SE et al. Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin- treated childhood acute lymphoblastic leukemia survivors. Cancer 2016;122:946–53. PRESCRIBING INFORMATION CARDIOXANE 500 mg powder for solution for infusion Please refer to Summary of Product Characteristics (SmPC) before prescribing. myelosuppressive effects in addition to those caused by chemotherapy. Leucopenia and thrombocytopenia generally reverse quickly upon cessation of treatment. Haematological monitoring is therefore necessary. The combination of Cardioxane and chemotherapy may increase the risk of a second primary malignancy (SPM): Acute Myeloid Leukaemia (AML) has been reported uncommonly in adult breast cancer patients post- marketing; in paediatric patients, SPM, AML and myelodysplastic syndrome have been reported in clinical trials in both dexrazoxane and control groups. The long term effect of dexrazoxane on SPM is not known and cannot be estimated from the available data. The use of chemotherapy regimens including several cytotoxics (e.g. etoposide, doxorubicin, cyclophosphamide) has been associated with SPM, in particular AML and MOS, in paediatric patients with Hodgkin's disease and acute lymphoblastic leukaemia. It has been suggested that dexrazoxane may interfere with the anti-tumour efficacy of anthracyclines: in most adult studies no significant difference has been identified in response rate and overall survival between dexrazoxane and control groups; no paediatric study has reported a difference in oncological outcome between groups treated with dexrazoxane and those treated with anthracycline alone. Clearance of Cardioxane may be reduced in patients with renal impairment. Liver function tests are recommended in patients with known liver dysfunction during and after treatment. The use of Cardioxane and chemotherapy is associated with thromboembolism. Owing to the possibility of an anaphylactic reaction, a previous history of dexrazoxane allergy should be carefully assessed. febrile neutropenia, granulocytopenia, febrile bone marrow aplasia, anorexia, paraesthesia, dizziness, headache, peripheral neuropathy, decreased ejection fraction, tachycardia, phlebitis, dyspnoea, cough, pharyngitis, respiratory tract infections, nausea, vomiting, stomatitis, diarrhoea, constipation, abdominal pain, dyspepsia, increased transaminases, alopecia nail disorders, erythema, asthenia, mucosal inflammation, pyrexia, fatigue, malaise, injection site reaction and oedema. necessary. Breast-feeding is contraindicated. 1 Valcovici M et al. Cardiotoxicity of anthracycline therapy: current perspectives. Arch Med Sci 2016;12:428–35. 2 McGowan JV et al. Anthracycline chemotherapy and cardiotoxicity. Cardiovascular Drugs Ther 2017;31:63–75. 3 Smith LA et al. Cardiotoxicity of anthracycline agents for the treatment of cancer: Systematic review and meta-analysis of randomised controlled trials. BMC Cancer 2010;10:337. 4 Curigliano G et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23 Suppl 7: vii155–66. 5 Yeh JM et al. A model- based estimate of cumulative excess mortality in survivors of childhood cancer. Ann Active ingredient: 500 mg dexrazoxane. Indications: Cardioxane is indicated in adults for the prevention of chronic cumulative cardiotoxicity caused by anthracycline use in advanced and/or metastatic breast cancer patients who have received a prior cumulative dose of 300 mg/m 2 of doxorubicin or a prior cumulative dose of 540 mg/m 2 of epirubicin when further anthracycline treatment is required. Posology and Method of Administration: Cardioxane is administered by a short intravenous infusion (15 minutes), approximately 30 minutes prior to anthracycline administration at a doseequal to 10 times the anthracycline-equivalent dose. Renal impairment: The Cardioxane dose should be reduced by 50% in patients with moderate to severe renal impairment (creatinine clearance < 40 ml/min). Paediatric population: The safety and efficacy of Cardioxane in children aged 0 to 18 years have not been established. Warnings and Precautions: Cardioxane may cause Contraindications: Children aged 0 to 18 years who are planned to receive a cumulative dose of less than 300 mg/ m2 of doxorubicin or the equivalent cumulative dose of another anthracycline; hypersensitivity to active ingredient; concomitant vaccination with yellow fever vaccine; breastfeeding. Undesirable Effects: (Consult the SmPC for further details about adverse reactions). As Cardioxane is administered together with anthracyclines, the relative contributions of each treatment to the adverse reaction profile may be unclear. Potentially serious adverse reactions include infection, sepsis, acute myeloid leukaemia, anaphylactic reaction, venous thrombosis, pulmonary embolism and cellulitis. The most common adverse reactions are anaemia, leukopenia, neutropenia, thrombocytopenia, Interactions: Cardioxane does not affect the pharmacokinetics of doxorubicin, but may increase epirubicin clearance at high epirubicin doses. Concomitant use with live attenuated vaccines or phenytoin is not recommended. Concomitant use with ciclosporin or tacrolimus should be assessed carefully. During infusion, Cardioxane should not be mixed with any other medicinal products. Driving and Using Machines: Patients should be cautious if they experience fatigue during treatment. Basic NHS Price: £156.57. Legal Category: POM. Marketing Authorisation Number: PL 31644/0002. Marketing Authorisation Holder: Clinigen Healthcare Ltd., Pitcairn House, Crown Square, First Avenue, Burton- on-Trent, Staffordshire, DE14 2WW, United Kingdom. Date of Preparation: 18 September 2017. Version: Final 02.00 I 8 September 2017 Pregnancy and Lactation: Both sexually active men and women should use effective contraception during treatment. For men and women, the contraception should be continued for at least six months after treatment cessation. Cardioxane should not be used during pregnancy unless clearly Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse reactions should also be reported to Clinigen Healthcare Ltd. (address as above) Tel: +44 (0) 1283 494 340; email: PatientSafety@clinigengroup.com.