Idarubicin Hydrochloride

5 WARNINGS AND PRECAUTIONS • Myelosuppression : Severe myelosuppression resulting in severe infection, septic shock, hemorrhage, or death may occur. Obtain complete blood counts prior to each treatment and closely monitor patients during treatment for possible clinical complications due to myelosuppression. (5.4) • Tumor Lysis Syndrome : During treatment, monitor blood chemistries and manage promptly. Treat as clinically indicated. (5.5) • Hypersensitivity : Monitor patients for hypersensitivity reactions and manage as clinically indicated. (5.6) • Renal Impairment : Assess renal function prior to and during treatment. Reduce the dose in patients on dialysis or those with GFR <30 mL/min. ( 2.3 , 5.7 , 8.6 ) • Hepatic Impairment : Obtain liver tests prior to and during therapy. Reduce dose in patients with serum bilirubin levels of 2.6 to 5 mg/dL. Avoid use in patients with serum bilirubin greater than 5 mg/dL. ( 2.4 , 5.8 , 8.7 ) • Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.9 , 8.1 , 8.3 ) 5.1 Cardiomyopathy IDAMYCIN PFS can cause myocardial damage, including left ventricular failure, or congestive heart failure (CHF). In pediatric patients, anthracycline-induced cardiomyopathy included impaired left ventricular systolic performance, reduced contractility, congestive heart failure, or death. Cardiomyopathy may develop during treatment with IDAMYCIN PFS or up to several years after completion of treatment. Cases of pericarditis and myocarditis have also been reported at a lower incidence and may not be dose related. The risk of cardiomyopathy is generally proportional to the cumulative exposure to anthracycline drugs. Include prior doses of other anthracyclines or anthracenediones in calculations of total cumulative dosage for idarubicin hydrochloride. In adult patients, at cumulative doses exceeding 90 mg/m 2 of idarubicin hydrochloride, there is an increased incidence of drug-induced congestive heart failure. The tolerable limit may be lower in patients who received radiation therapy to the mediastinum. Concomitant use of cardiotoxic drugs may increase the risk of idarubicin-induced cardiac toxicity or may result in cardiotoxicity at a lower cumulative anthracycline dose. Calculate the lifetime cumulative anthracycline exposure prior to each cycle of IDAMYCIN PFS. IDAMYCIN PFS use is not recommended in patients whose lifetime anthracycline exposure has reached the maximum cumulative limit. Assess left ventricular cardiac function (e.g., MUGA or echocardiogram) prior to initiation of IDAMYCIN PFS. Perform serial cardiac monitoring, which may include electrocardiograms and/or determination of systolic ejection fraction, in all patients during treatment to detect acute changes and after treatment to detect delayed cardiotoxicity. Increase the frequency of assessments as the cumulative anthracycline dose increases or in patients with risk factors for cardiac toxicity. Consider long-term periodic evaluation of cardiac function in these patients. Adults 65 years of age and older, or with pre-existing cardiac disease, may have an increased risk of anthracycline-induced cardiac toxicity, or may experience cardiotoxicity at a lower cumulative anthracycline dose. Discontinue IDAMYCIN PFS in patients who develop signs or symptoms of cardiomyopathy. 5.2 Secondary Malignancies The risk of developing secondary AML and myelodysplastic syndrome (MDS) is increased following treatment with IDAMYCIN PFS. AML and MDS have occurred in patients treated with anthracycline topoisomerase inhibitors when used in combination with other antineoplastic agents or radiation therapy. Monitor patients long-term for the development of secondary malignancies. 5.3 Severe Local Tissue Necrosis with Extravasation Extravasation of IDAMYCIN PFS at the site of intravenous administration can cause severe local tissue injury including blistering, ulceration, thrombophlebitis, and necrosis requiring wide excision of the affected area and skin grafting. Monitor patients during the IDAMYCIN PFS infusion for signs and symptoms of extravasation (including erythematous streaking, burning, or stinging sensations, thrombosis) or perivenous infiltration. If extravasation occurs during administration, immediately discontinue the intravenous injection or continuous intravenous infusion of IDAMYCIN PFS and manage per institutional guidelines [see Dosage and Administrations (2.6)]. 5.4 Severe Myelosuppression Severe myelosuppression resulting in severe infection, septic shock, hemorrhage, or death may occur during treatment with IDAMYCIN PFS, and some patients may require blood product transfusions. Obtain complete blood counts prior to each treatment and closely monitor patients during treatment for possible clinical complications due to myelosuppression. Delay next dose of IDAMYCIN PFS if severe myelosuppression has not improved. Consider dose reduction for patients with prolonged myelosuppression [see Dosage and Administrations (2.2) ] . Discontinue IDAMYCIN PFS in patients who develop severe myelosuppression. 5.5 Tumor Lysis Syndrome IDAMYCIN PFS may induce tumor lysis syndrome. Patients at risk of tumor lysis syndrome are those with rapidly growing tumors or high tumor burden prior to treatment. During and after initial treatment, monitor blood chemistries and manage abnormalities promptly. Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor lysis syndrome. 5.6 Hypersensitivity IDAMYCIN PFS can cause hypersensitivity reactions. Clinical signs and symptoms of hypersensitivity may include, but are not limited to, rash and urticaria [see Adverse Reactions (6.1) ] . Monitor patients for signs and symptoms of hypersensitivity during treatment with IDAMYCIN PFS and manage as clinically indicated. 5.7 Use in Patients with Renal Impairment Renal impairment may result in increased risk of toxicity in patients treated with IDAMYCIN PFS [see Use in Specific Populations (8.6) ] . Assess renal function prior to and during treatment with IDAMYCIN PFS. Reduce the dose of IDAMYCIN PFS in patients on dialysis or those with GFR <30 mL/min [see Dosage and Administration (2.3)]. 5.8 Use in Patients with Hepatic Impairment Hepatic impairment may result in increased risk of toxicity in patients treated with IDAMYCIN PFS [see Use in Specific Populations (8.7) ] . Obtain liver tests including ALT, AST, alkaline phosphatase, and bilirubin prior to and during therapy. Reduce the dose of IDAMYCIN PFS in patients with serum bilirubin levels of 2.6 to 5 mg/dL. Avoid use of IDAMYCIN PFS in patients with serum bilirubin greater than 5 mg/dL [see Dosage and Administration (2.4) ]. 5.9 Embryo-Fetal Toxicity Based on findings from animal reproductive studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , IDAMYCIN PFS can cause fetal harm when administered to pregnant women. Idarubicin hydrochloride was embryotoxic and teratogenic in rats at doses of 1.2 mg/m 2 /day or 0.1 times the human dose, which was not maternally toxic. Idarubicin hydrochloride was embryotoxic but not teratogenic in rabbits at doses of 2.4 mg/m 2 /day or 0.2 times the human dose, which was maternally toxic. Advise women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with IDAMYCIN PFS and for 6.5 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception for 3.5 months after the last dose [see Use in Specific Populations (8.1 , 8.3) and Nonclinical Toxicology (13.1) ].