Daunoblastina Special Precautions





Zuellig Pharma


Full Prescribing Info
Special Precautions
General: Daunorubicin should be administered only under the supervision of physicians experienced in the use of cytotoxic therapy.
Patients should recover from acute toxicities of prior cytotoxic treatment (such as stomatitis, neutropenia, thrombocytopenia, and generalized infections) before beginning treatment with daunorubicin.
Hematologic Toxicity: Evaluation of response based on bone marrow status cellularity is necessary to guide daunorubicin treatment: myelosuppression will occur in all patients given therapeutic doses of the drug. Hematologic profiles should be assessed before and during each cycle of therapy with daunorubicin, including differential white blood cell (WBC) counts: marked cytopenia is expected and requires careful monitoring.
The nadir of leukocytes and platelets usually occurs between 10 and 14 days following drug administration, but cell counts generally return to the pre-treatment levels during the third week. Thrombocytopenia and anemia may also occur. Clinical consequences of severe myelosuppression include fever, infection, sepsis/septicemia, septic shock, hemorrhage, tissue hypoxia, or death. During a course of therapy special attention should be devoted to patients with severe neutropenia and fever (febrile neutropenia), a condition that can be possibly followed by septicemia and death.
Secondary Leukemia: Secondary leukemia, with or without a preleukemic phase, has been reported in patients treated with anthracyclines, including daunorubicin. Secondary leukemia is more common when such drugs are given in combination with DNA-damaging antineoplastic agents, in combination with radiotherapy, when patients have been heavily pre-treated with cytotoxic drugs, or when doses of the anthracyclines have been escalated. These leukemias can have a 1- to 3-year latency period.
Cardiac Function: Cardiotoxicity is a risk of anthracycline treatment that may be manifested by early (i.e., acute) or late (i.e., delayed) events.
Early (i.e., acute) Events: Early cardiotoxicity of daunorubicin consists mainly of sinus tachycardia and/or electrocardiogram (ECG) abnormalities such as non-specific ST-T wave changes. Tachyarrhythmias, including premature ventricular contractions, as well as heart block have also been reported. These effects do not usually predict subsequent development of delayed cardiotoxicity, are rarely of clinical importance, and are generally not a consideration for discontinuation of daunorubicin treatment.
Late (i.e., delayed) Events: Delayed cardiotoxicity usually develops late in the course of therapy with daunorubicin or within 2 to 3 months after treatment termination, but later events (several months to years after completion of treatment) have also been reported. Delayed cardiomyopathy is manifested by reduced left ventricular ejection fraction (LVEF) and/or signs and symptoms of congestive heart failure (CHF) such as dyspnea, pulmonary edema, dependent edema, cardiomegaly and hepatomegaly, oliguria, ascites, pleural effusion and gallop rhythm. Life-threatening CHF is the most severe form of anthracycline-induced cardiomyopathy and represents the cumulative dose-limiting toxicity of the drug.
Cardiac function should be assessed before patients undergo treatment with daunorubicin and must be monitored throughout therapy to minimize the risk of incurring severe cardiac impairment. The risk may be decreased through regular monitoring of LVEF during the course of treatment with prompt discontinuation of daunorubicin at the first sign of impaired function. The appropriate quantitative method for repeated assessment of cardiac function (evaluation of LVEF) includes multi-gated radionuclide angiography (MUGA) or echocardiography (ECHO). A baseline cardiac evaluation with an ECG and either a MUGA scan or an ECHO is recommended, especially in patients with risk factors for increased cardiotoxicity. Repeated MUGA or ECHO determinations of LVEF should be performed, particularly with higher, cumulative anthracycline doses. The technique used for assessment should be consistent throughout follow-up.
The risk of developing congestive heart failure (CHF) increases - in the absence of other cardiac risk factors - when the total cumulative dose of daunorubicin exceeds 500-600 mg/m2 in adults, 300 mg/m2 in children more than 2 years of age, or 10 mg/kg in children less than 2 years of age; these doses should only be exceeded with extreme caution.
Risk factors for cardiac toxicity include active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, and concomitant use of drugs with the ability to suppress cardiac contractility or cardiotoxic drugs (e.g., trastuzumab). Anthracyclines including daunorubicin should not be administered in combination with other cardiotoxic agents unless the patient's cardiac function is closely monitored. Patients receiving anthracyclines after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity. Under these conditions, a total cumulative dose of 400 mg/m2 in adults should be exceeded only with extreme caution.
Cardiac function must be carefully monitored in patients receiving high cumulative doses and in those with risk factors. However, cardiotoxicity with daunorubicin may occur at lower cumulative doses whether or not cardiac risk factors are present.
In infants and children there appears to be a greater susceptibility to anthracycline-induced cardiac toxicity, and a long-term periodic evaluation of cardiac function has to be performed.
It is probable that the toxicity of daunorubicin and other anthracyclines or anthracenediones is additive.
Gastrointestinal: Daunorubicin may cause nausea and vomiting. Severe nausea and vomiting may produce dehydration. Nausea and vomiting may be prevented or alleviated by the administration of appropriate antiemetic therapy.
Mucositis (mainly stomatitis, less often esophagitis) may occur in patients undergoing daunorubicin therapy. Mucositis/stomatitis generally appear early after drug administration and, if severe, may progress over a few days to mucosal ulcerations. Most patients recover from this adverse event by the third week of therapy.
Tumor Lysis Syndrome: Daunorubicin may induce hyperuricemia as a consequence of the extensive purine catabolism that accompanies rapid drug-induced lysis of neoplastic cells (tumor-lysis syndrome). Blood uric acid levels, potassium, calcium phosphate, and creatinine should be evaluated after initial treatment. Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor-lysis syndrome.
Effects at Site of Injection: Phlebosclerosis may result from an injection into a small vessel or from repeated injections into the same vein. Following the recommended administration procedures may minimize the risk of phlebitis/thrombophlebitis at the injection site (see Dosage & Administration).
Extravasation: Extravasation of daunorubicin during intravenous injection may produce local pain, severe tissue lesions (vesication, severe cellulitis) and necrosis. Should signs or symptoms of extravasation occur during intravenous administration of daunorubicin, the drug infusion should be immediately stopped.
Alopecia: Complete alopecia involving beard growth and the scalp, axillary and pubic hair occurs almost always with full doses of daunorubicin. This side-effect may cause distress to patients but is usually reversible, with regrowth of hair, which usually occurs within two to three months from the termination of therapy.
Immunosuppressant Effects/Increased Susceptibility to Infections: Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including daunorubicin may result in serious or fatal infections. Vaccination with a live vaccine should be avoided in patients receiving daunorubicin. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.
Effects on ability to drive and use machines: There have been no reports explicitly relating to effects of daunorubicin treatment on the ability to drive or use machines.
Hepatic Function:
The major route of elimination of daunorubicin is the hepatobiliary system. Serum total bilirubin should be evaluated before and during treatment with daunorubicin. Patients with elevated bilirubin may experience slower clearance of drug with an increase in overall toxicity. Lower doses are recommended in these patients (see Dosage & Administration). Patients with severe hepatic impairment must not receive daunorubicin (see Contraindications).
Renal Function: Renal impairment can also enhance the toxicity of the recommended doses of daunorubicin, and renal function should be evaluated before starting treatment with daunorubicin (see Dosage & Administration and Contraindications).
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