Epirubicin

May cause severe myelosuppression, including leukopenia, thrombocytopenia, and anemia. Myelosuppression is the dose-limiting toxicity. Obtain baseline and periodic blood counts. Patients should recover from myelosuppression due to prior chemotherapy treatment before beginning treatments. Severe neutropenia and severe infections may require supportive care.

For IV administration only. Vesicant; if extravasation occurs, severe local tissue damage and necrosis may occur. Not for IM or SubQ use. Injection into a small vein or repeated administration in the same vein may result in venous sclerosis. Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. If perivenous infiltration occurs, immediately discontinue infusion and restart in another vein.

Epirubicin is associated with a moderate to high emetic potential (depending on regimen); antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016).

Myocardial toxicity, including fatal heart failure (HF) may occur, particularly in patients who have received prior anthracyclines (or anthracenediones), prior or concomitant radiotherapy to the mediastinal/pericardial area, who have preexisting cardiac disease (active or dormant), or with concomitant cardiotoxic medications. Cardiotoxicity may be concurrent or delayed (months to years after treatment). The risk of HF is ~0.9% at a cumulative dose of 550 mg/m2, ~1.6% at a cumulative dose of 700 mg/m2, and ~3.3% at a cumulative dose of 900 mg/m2. Cardiotoxicity may also occur at lower cumulative doses or without risk factors. The risk of delayed cardiotoxicity increases more steeply with cumulative doses >900 mg/m2, and this dose should be exceeded only with extreme caution. The maximum cumulative dose used in adjuvant studies was 720 mg/m2. Cardiotoxicity is dose-limiting. Early toxicity may consist of tachyarrhythmias, including sinus tachycardia, premature ventricular contractions, and ventricular tachycardia, as well as bradycardia. Electrocardiographic changes including ST-T wave changes, atrioventricular and bundle-branch block have also been reported. These effects are not necessarily predictive of subsequent delayed cardiotoxicity. Delayed toxicity is typically caused by cardiomyopathy which presents as decreased left ventricular ejection fraction (LVEF) and/or signs/symptoms of HF (eg, tachycardia, dyspnea, pulmonary edema, edema, hepatomegaly, ascites, pleural effusi

Treatment with anthracyclines (including epirubicin) may increase the risk of secondary acute myeloid leukemia (AML). AML is more common when given in combination with other antineoplastic agents, in patients who have received multiple courses of previous chemotherapy, or with escalated anthracycline doses. In breast cancer patients, the risk for treatment-related AML or myelodysplastic syndrome (MDS) was estimated at 0.27% at 3 years, 0.46% at 5 years, and 0.55% at 8 years after treatment. The latency period for secondary leukemias may be short (1 to 3 years).

Thrombophlebitis and thromboembolic phenomena (including pulmonary embolism) have occurred.

May cause tumor lysis syndrome (TLS). Although TLS does not generally occur in patients with breast cancer, if TLS risk is suspected, consider monitoring serum uric acid, potassium, calcium, phosphate and serum creatinine after initial administration; hydration and antihyperuricemic prophylaxis may minimize potential TLS complications. Disease-related concerns:

Dosage reduction is recommended in patients with mild-to-moderate hepatic impairment; use is not recommended in severe hepatic impairment. Evaluate hepatic function at baseline and during treatment. Epirubicin is predominantly hepatically eliminated; impaired hepatic function may lead to increased exposure and toxicity.

Dosage reduction is recommended in patients with serum creatinine >5 mg/dL. Evaluate renal function at baseline and during treatment. Has not been studied in patients on dialysis. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Women ≥70 years of age should be closely monitored for toxicity.

Children may be at increased risk for developing acute and delayed cardiotoxicity; long-term periodic cardiac function monitoring is recommended.

Epirubicin may have radiosensitizing activity; radiation recall (inflammatory) has also been reported. Other warnings/precautions:

Patients should recover from acute toxicities (stomatitis, myelosuppression, infections) prior to initiating treatment. Assess baseline labs (blood counts, bilirubin, ALT, AST, serum creatinine) and cardiac function (with LVEF). Prophylactic antibiotics should be administered with the CDF-120 regimen.

Should be administered under the supervision of an experienced cancer chemotherapy physician.

Patients should not be immunized with live viral vaccines during or shortly after treatment. Inactivated vaccines may be administered (response may be diminished).