Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use
Myelosuppression
Myelosuppressive effects that may be additive to those of chemotherapy were reported with Cardioxane (see section 4.8). Cell counts at nadir may be lower in patients treated with dexrazoxane. Haematological monitoring is thus necessary. Leucopenia and thrombocytopenia generally reverse quickly upon cessation of treatment with Cardioxane.

At higher doses of chemotherapy, where the Cardioxane dose exceeds 1000 mg/m2, myelosuppression may increase significantly.

Second primary malignancies
Since dexrazoxane is a cytotoxic agent, with topoisomerase II inhibition activity, combination of dexrazoxane with chemotherapy may lead to an increased risk of second primary malignancy.

Oncology patients have an increased risk of second primary malignancies, regardless of treatment. Patients who have received cancer therapy also have an increased risk of second primary malignancy.

Acute Myeloid Leukaemia (AML) has been reported uncommonly in adult breast cancer patients post- marketing (see section 4.8).

Interference with chemotherapy
Since both dexrazoxane and anthracyclines are topoisomerase inhibitors, it has been suggested that dexrazoxane may interfere with the anti-tumour efficacy of anthracyclines based on mechanism of action.
However, in most adult studies no significant difference has been identified in response rate and overall survival between dexrazoxane and control groups. A significant decrease in tumour response rate was reported in one study of advanced breast cancer patients treated with doxorubicin and dexrazoxane compared to patients treated with doxorubicin and placebo. In this study placebo response rate was considered to be high (60.5%), which may be a contributing factor to the observed difference in response rate. Despite the difference in response rates, there was no significant difference in time to progression or overall survival between patients that had received either dexrazoxane or placebo in this study.

Patients with renal impairment
Clearance of dexrazoxane and its active metabolites may be reduced in patients with decreased creatinine clearance (see Section 4.2).

Liver disorders
Since liver dysfunction was occasionally observed in patients treated with Cardioxane (see section 4.8), it is recommended that routine liver function tests be performed before and during administration of dexrazoxane in patients with known liver function disorders.

Patients with cardiac disorders
Standard cardiac monitoring associated with doxorubicin or epirubicin treatment should be continued.

There are no data that support the use of dexrazoxane in patients with myocardial infarction within the past 12 months, pre-existing heart failure (including clinical heart failure secondary to anthracycline treatment), uncontrolled angina or symptomatic valvular heart disease.

Thromboembolism
Combination of dexrazoxane with chemotherapy may lead to an increased risk of thromboembolism (see section 4.8).
Women of child-bearing potential / Contraception in males and females Since dexrazoxane is a cytotoxic agent, sexually active men and women should use effective contraception during treatment. Women and men should continue using effective methods of contraception for at least 6 months after cessation of treatment with dexrazoxane (see section 4.6).

Geriatric patients (age 65 years or above)
There are no clinical trials comparing the efficacy or safety of dexrazoxane in geriatric patients to that in younger patients. However, in general, caution is required when treating elderly patients due to their greater use of other medicinal products, higher rates of concomitant diseases and possible reduced hepatic, renal or cardiac function.

Anaphylactic reaction
Anaphylactic reaction including angioedema, skin reactions, bronchospasm, respiratory distress, hypotension and loss of consciousness have been observed in patients treated with Cardioxane and anthracyclines (see section 4.8). Previous history of allergy to dexrazoxane should be carefully considered prior to administration (see section 4.3).

Effects on Driving

4.7   Effects on ability to drive and use machines
Cardioxane has moderate influence on the ability to drive and use machines. Patients should be advised to be cautious when driving or using machines if they experience fatigue during treatment with Cardioxane.