Epirubicin - Warnings and Precautions
The following warnings and precautions are taken directly from the US FDA-approved drug label for Epirubicin. This is the same information dispensing pharmacists read.
\u26a0\ufe0f Boxed Warning (Highest FDA Alert)
WARNING: CARDIAC TOXICITY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS, and SEVERE MYELOSUPPRESSION • Cardiac Toxicity: Myocardial damage, including acute left ventricular failure, can occur with ELLENCE. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 0.9% at a cumulative dose of 550 mg/m 2 , 1.6% at 700 mg/m 2 , and 3.3% at 900 mg/m 2 . The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess left ventricular ejection fraction (LVEF) before and regularly during and after treatment with ELLENCE [see Warnings and Precautions ] . • Secondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including ELLENCE [see Warnings and Precautions ] . • Extravasation and Tissue Necrosis: Extravasation of ELLENCE can result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate the drug and apply ice to the affected area [see Warnings and Precautions ] . • Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur [see Warnings and Precautions ] . WARNING: CARDIAC TOXICITY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS, and SEVERE MYELOSUPPRESSION See full prescribing information for complete boxed warning . • Cardiac Tox
5 WARNINGS AND PRECAUTIONS • Use in Patients with Hepatic Impairment: Monitor serum total bilirubin and AST levels before and during treatment with ELLENCE.
In patients with elevated serum AST or serum total bilirubin, dosage reductions or discontinuation may be required ( 2.3 , 5.5 ). • Tumor Lysis Syndrome: Evaluate blood uric acid levels, potassium, calcium, phosphate, and creatinine after initial treatment.
Consider hydration, urine alkalinization, and prophylaxis with allopurinol to minimize potential complications of hyperuricemia and tumor lysis syndrome . • Thrombophlebitis and Thromboembolic Events: Thrombophlebitis and thromboembolic events, including pulmonary embolism (in some cases fatal) have been reported with the use of ELLENCE.
Venous sclerosis may result from an injection into a small vessel or from repeated injections into the same vein . • Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including ELLENCE, may result in serious or fatal infections . • Potentiation of Radiation Toxicity and Radiation Recall: Administration of ELLENCE after previous radiation therapy may induce an inflammatory recall reaction at the site of the irradiation . • Embryo-Fetal Toxicity: ELLENCE can cause fetal harm.
Advise patients of the potential risk to a fetus and to use effective contraception ( 5.11 , 8.1 , 8.3 ).
5.1 Cardiac Toxicity ELLENCE and other anthracycline drugs can result in either early (or acute) or late (delayed) cardiac toxicity.
The principal manifestations of early cardiac toxicity are sinus tachycardia and/or electrocardiogram (ECG) abnormalities such as non-specific ST-T wave changes.
However, tachycardia (including premature ventricular contractions and ventricular tachycardia), bradycardia, as well as atrioventricular and bundle-branch block have been reported.
Early cardiac toxicity does not usually predict the subsequent occurrence of delayed cardiotoxicity and generally should not be considered a reason for suspending treatment with ELLENCE.
Delayed cardiac toxicity is manifested by reduced left ventricular ejection fraction (LVEF) and/or signs and symptoms of congestive heart failure (CHF).
If it occurs, late cardiotoxicity usually develops late during therapy with ELLENCE or within 2 to 3 months after completion of treatment, but there are reports of it occurring several months to years after treatment termination.
In a retrospective survey, including 9144 patients, mostly with solid tumors in advanced stages, the probability of developing CHF increased with increasing cumulative doses of ELLENCE (Figure 1).
In another retrospective survey of 469 ELLENCE-treated patients with metastatic or early breast cancer, the reported risk of CHF was comparable to that observed in the larger study of over 9000 patients.
Given the risk of cardiac toxicity, cumulative doses of 900 mg/m 2 ELLENCE should generally be avoided.
Risk of CHF in 9144 Patients Treated with ELLENCE Prior history of cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, and concomitant use of other cardiotoxic drugs, increase the risk of developing late cardiac toxicity.
Avoid administration of ELLENCE in combination with other cardiotoxic drugs.
Although not formally tested, it is probable that the toxicity of ELLENCE and other anthracyclines or anthracenediones is additive.
Cardiac toxicity with ELLENCE may occur at lower cumulative doses whether or not cardiac risk factors are present.
Patients receiving ELLENCE after stopping treatment with other cardiotoxic drugs, especially those with long half-lives such as trastuzumab, may be at increased risk of developing cardiotoxicity [see Dosage and Administration and Drug Interaction ] .
Perform a baseline ECG and evaluation of LVEF prior to initiating treatment with ELLENCE.
Monitor LVEF during the course of treatment and consider discontinuation of ELLENCE if LVEF decrease and/or signs or symptoms of CHF develop.
Closely monitor patients with other risk factors for cardiac toxicity, particularly prior administration of anthracycline or anthracenedione.
Figure 1 5.2 Secondary Malignancies The risk of developing secondary acute myelogenous leukemia and myelodysplastic syndrome (MDS), is increased following treatment with ELLENCE and other anthracyclines.
Cumulative risk of secondary acute myelogenous leukemia or myelodysplastic syndrome (AML/MDS) of about 0.27% at 3 years, 0.46% at 5 years, and 0.55% at 8 years.
These leukemias generally occur within 1 to 3 years of treatment [see Adverse Reactions ] .
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