Idarubicin Hydrochloride
FDA Drug Information • Also known as: Idamycin Pfs, Idarubicin Hydrochloride
- Brand Names
- Idamycin Pfs, Idarubicin Hydrochloride
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: CARDIOMYOPATHY, SECONDARY MALIGNANCIES, and EXTRAVASATION AND TISSUE NECROSIS
Cardiomyopathy: IDAMYCIN PFS can cause myocardial damage, including acute left ventricular failure, during or after termination of therapy. The risk of cardiomyopathy is increased in patients who have received prior anthracyclines or who have pre-existing cardiac disease. Assess left ventricular cardiac function prior to initiation of IDAMYCIN PFS and during and after treatment [see Warnings and Precautions (5.1) ] . Secondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including IDAMYCIN PFS [see Warnings and Precautions (5.2) ] . Extravasation and Tissue Necrosis: Extravasation of IDAMYCIN PFS during administration can result in local tissue injury and necrosis. Immediately terminate the infusion of IDAMYCIN PFS and institute the recommended management procedures [see Dosage and Administration (2.6) and Warnings and Precautions (5.3) ] . WARNING: CARDIOMYOPATHY, SECONDARY MALIGNANCIES, and EXTRAVASATION AND TISSUE NECROSIS See full prescribing information for complete boxed warning. Cardiomyopathy: Myocardial damage leading to congestive heart failure can occur with IDAMYCIN PFS. Assess left ventricular cardiac function prior to initiation of IDAMYCIN PFS and during and after treatment. (5.1) Secondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including IDAMYCIN PFS. (5.2) Extravasation of IDAMYCIN PFS during administration can result in local tissue injury and necrosis. Immediately discontinue the IDAMYCIN PFS infusion if extravasation occurs. ( 2.6 , 5.3 )Description
11 DESCRIPTION IDAMYCIN PFS contains idarubicin hydrochloride, which is an anthracycline topoisomerase inhibitor. Chemically, idarubicin hydrochloride is 5, 12-Naphthacenedione, 9-acetyl-7-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,9,11-trihydroxyhydrochloride, (7S- cis ). The structural formula is as follows: C 26 H 27 NO 9 ∙HCl M.W. 533.96 IDAMYCIN PFS injection, for intravenous use, is a sterile, orange-red, isotonic parenteral preservative-free solution, available in 5 mL (5 mg), 10 mL (10 mg), and 20 mL (20 mg) single-dose only vials. Each mL contains idarubicin hydrochloride, USP 1 mg (equivalent to 0.93 mg idarubicin free base) and the following inactive ingredients: Glycerin, USP 25 mg and Water for Injection, USP q.s. Hydrochloric Acid, NF is used to adjust the pH to a target of 3.5. chemical structure
What Is Idarubicin Hydrochloride Used For?
1 INDICATIONS AND USAGE IDAMYCIN PFS is indicated for the treatment of adult patients with acute myeloid leukemia (AML) as a component of a combination chemotherapy regimen. IDAMYCIN PFS is an anthracycline topoisomerase inhibitor indicated for the treatment of adult patients with acute myeloid leukemia (AML) as a component of a combination chemotherapy regimen. (1)
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Induction Therapy
12 mg/m 2 intravenously over 10 to 15 minutes on days 1, 2, and 3 of induction in combination with cytarabine 100 mg/m 2 by continuous intravenous infusion daily for 7 days or cytarabine 25 mg/m 2 intravenous bolus followed by cytarabine 200 mg/m 2 continuous intravenous infusion daily for 5 days. (2.1) IDAMYCIN PFS can be given as part of a combination regimen with other chemotherapeutic drugs. (2.1) Renal Impairment: Assess renal function prior to therapy. Reduce dosage in renal impairment. ( 2.3 , 8.6 ) Hepatic Impairment: Assess hepatic function prior to therapy. Avoid or reduce dosage in hepatic impairment. ( 2.4 , 8.7 ) See full prescribing information for preparation and administration instructions. (2.5 , 2.6) 2.1 Recommended Dosage Administer IDAMYCIN PFS 12 mg/m 2 intravenously over 10 to 15 minutes on days 1, 2, and 3 of induction in combination with cytarabine. The cytarabine may be given as 100 mg/m 2 by continuous intravenous infusion daily for 7 days or as cytarabine 25 mg/m 2 intravenous bolus followed by cytarabine 200 mg/m 2 continuous intravenous infusion daily for 5 days. If a response is not achieved with the first induction cycle, a second induction cycle may be administered. Other dosage regimens may be used for a second induction cycle. Individualize the dose and dosing schedule of IDAMYCIN PFS based on the specific regimen administered, disease state, response to treatment, and patient risk factors. 2.2 Dosage Modifications for Adverse Reactions Cardiomyopathy Discontinue IDAMYCIN PFS in patients who develop signs or symptoms of cardiomyopathy [see Warnings and Precautions (5.1) ] . Myelosuppression If patients develop severe myelosuppression, reduce the dose of IDAMYCIN PFS by 25% or as clinically indicated in subsequent cycles [see Warnings and Precautions (5.4)] . Mucositis If patients develop severe mucositis with IDAMYCIN PFS, reduce the dose by 25% in subsequent cycles. If a second cycle is planned, delay administration in patients who develop severe mucositis until this adverse reaction has resolved [see Adverse Reactions (6.1) ] . 2.3 Recommended IDAMYCIN PFS Dosage in Patients with Renal Impairment In patients with renal impairment, reduce the dose of IDAMYCIN PFS as described in Table 1 [see Use in Specific Populations (8.6) ] . Table 1: Recommended IDAMYCIN PFS Dosage for Patients with Renal Impairment Renal Impairment/Estimated GFR Dosage Modification GFR greater than or equal to 30 mL/min No adjustment needed GFR less than 30 mL/min Reduce the dose by 33% Hemodialysis Reduce the dose by 33% 2.4 Recommended IDAMYCIN PFS Dosage in Patients with Hepatic Impairment In patients with hepatic impairment, reduce the dose of IDAMYCIN PFS as described in Table 2 [see Use in Specific Populations (8.7) ] . Table 2: Recommended IDAMYCIN PFS Dosage for Patients with Hepatic Impairment Serum Bilirubin Dosage Less than or equal to 2.6 mg/dL No adjustment needed Greater...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:
Cardiomyopathy [see Warnings and Precautions (5.1) ] Secondary Malignancies [see Warnings and Precautions (5.2) ] Severe Local Tissue Necrosis with Extravasation [see Warnings and Precautions (5.3) ] Severe Myelosuppression [see Warnings and Precautions (5.4) ] Tumor Lysis Syndrome [see Warnings and Precautions (5.5) ] Hypersensitivity [see Warnings and Precautions (5.6) ] Most common adverse reactions (≥30%) are infection, nausea/vomiting, alopecia, abdominal pain/diarrhea, hemorrhage, mucositis, dermatologic, mental status changes, and pulmonary disorders. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials and Postmarketing Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of IDAMYCIN PFS in combination with cytarabine has been evaluated in four controlled clinical studies with 823 patients with AML randomized to receive idarubicin hydrochloride (n=401) or daunorubicin (n=422) [see Clinical Studies (14) ] . Southeastern Cancer Study Group (SEG) Table 3 below lists the adverse reactions that occurred in patients with AML who received idarubicin hydrochloride in the Southeastern Cancer Study Group (SEG) study. Table 3: Adverse Reactions (≥5%) in Patients with AML Who Received Idarubicin Hydrochloride as Induction Therapy in the SEG Trial Adverse Reactions Idarubicin with Cytarabine (N=110) Daunorubicin with Cytarabine (N=118) All Grades % All Grades % Infection 95 97 Nausea/Vomiting 82 80 Alopecia 77 72 Abdominal Pain/Diarrhea 73 68 Hemorrhage 63 65 Mucositis 50 55 Dermatologic 46 40 Mental Status Changes 41 34 Pulmonary Disorders 39 39 Fever 26 28 Headache 20 24 Cardiac Disorder 16 24 Peripheral Neuropathy 7 9 Clinically relevant adverse reactions in <5% of patients who received idarubicin hydrochloride included pulmonary allergy, seizure, and cerebellar adverse reactions. Other Clinical Trials The following additional adverse reactions associated with the use of idarubicin hydrochloride were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac Asymptomatic declines in Left Ventricular Ejection Fraction (LVEF) Chest pain Congestive heart failure Myocardial infarction Serious arrhythmias including atrial fibrillation Dermatologic Bullous erythrodermatous rash (palms and soles) Generalized rash Radiation recall (skin reaction) Urticaria Gastrointestinal Severe enterocolitis with perforation Hepatic Increased ALT/AST Renal Renal impairmentContraindications
4 CONTRAINDICATIONS None. None. (4)
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies and its mechanism of action, IDAMYCIN PFS can cause fetal harm when administered to a pregnant woman [see Warnings and Precautions (5.9) ] . There are no available data on the use of IDAMYCIN PFS in pregnant women to evaluate for a drug-associated risk. Idarubicin hydrochloride was embryotoxic and teratogenic in rats at doses of 1.2 mg/m 2 /day or 0.1 times the human dose. 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 [see Data ] . Advise women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Idarubicin hydrochloride was embryotoxic and teratogenic in the rat at a dose 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 the rabbit even at a dose of 2.4 mg/m 2 /day or 0.2 times the human dose, which was maternally toxic.
Overdosage
10 OVERDOSAGE There is no known antidote to idarubicin hydrochloride. Two cases of fatal overdosage in patients receiving therapy for AML have been reported. The doses were 135 mg/m 2 over 3 days and 45 mg/m 2 of idarubicin hydrochloride and 90 mg/m 2 of daunorubicin over a three-day period. Based on multicompartment and extravascular distribution, tissue binding, and low unbound fraction available in plasma, hemodialysis or peritoneal dialysis are unlikely to significantly reduce exposure during an overdosage.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied IDAMYCIN PFS (idarubicin hydrochloride) injection is a clear, orange-red, aqueous, preservative-free solution available as follows: Single-dose Cytosafe™ vials : Unit of Sale Concentration NDC 0013-2576-91 Carton of 1 Single-dose Vial 5 mg/5 mL (1 mg/mL) NDC 0013-2586-91 Carton of 1 Single-dose Vial 10 mg/10 mL (1 mg/mL) NDC 0013-2596-91 Carton of 1 Single-dose Vial 20 mg/20 mL (1 mg/mL) Single-dose glass vials : Unit of Sale Concentration NDC 0013-2576-05 Carton of 1 Single-dose Vial 5 mg/5 mL (1 mg/mL) NDC 0013-2586-10 Carton of 1 Single-dose Vial 10 mg/10 mL (1 mg/mL) NDC 0013-2596-20 Carton of 1 Single-dose Vial 20 mg/20 mL (1 mg/mL) Storage and Handling Store refrigerated at 2ºC to 8ºC (36ºF to 46ºF). Store and dispense in the original carton until time of use to protect from light. IDAMYCIN PFS is a hazardous drug. Follow applicable special handling and disposal procedures. 1
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.