Idamycin PFS

Boxed Warning 2/2026 Indications and Usage (1) 2/2026 Dosage and Administration (2) 2/2026 Warnings and Precautions (5) 2/2026

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)

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 than 2.6 mg/dL and less than 5 mg/dL Reduce the dose by 50% Greater than 5 mg/dL Avoid Use 2.5 Preparation • IDAMYCIN PFS is a hazardous drug. Follow applicable special handling and disposal procedures. 1 • Do not mix IDAMYCIN PFS or administer as an infusion with other drugs or heparin. • Avoid prolonged contact with any solution of an alkaline pH, as this will result in degradation of IDAMYCIN PFS. • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. • Withdraw the volume of IDAMYCIN PFS needed based on the required dose. • Do not further dilute prior to administration (see section 2.6 Administration). • Discard unused portion. 2.6 Administration • IDAMYCIN PFS is for intravenous infusion only. • Prior to administration, flush the intravenous catheter used for IDAMYCIN PFS administration to ensure patency and to minimize the risk of extravasation. • Administer IDAMYCIN PFS over …

3 DOSAGE FORMS AND STRENGTHS Injection: 5 mg/5 mL (1 mg/mL), 10 mg/10 mL (1 mg/mL), and 20 mg/20 mL (1 mg/mL) of idarubicin hydrochloride as a clear, orange-red, preservative-free aqueous solution in a single-dose vial. Injection: 5 mg/5 mL (1 mg/mL), 10 mg/10 mL (1 mg/mL), and 20 mg/20 mL (1 mg/mL) solution in a single-dose vial. (3)

4 CONTRAINDICATIONS None. None. (4)

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 impairment

8 USE IN SPECIFIC POPULATIONS • Lactation : Advise not to breastfeed. (8.2) • Infertility : May impair fertility. (8.3) 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. 8.2 Lactation Risk Summary There are no data on the presence of idarubicin hydrochloride or its metabolites in human milk, the effects on the breastfed child or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, including myelosuppression, cardiac toxicity and malignancy, advise women not to breastfeed during treatment with IDAMYCIN PFS and for 14 days after the last dose. 8.3 Females and Males of Reproductive Potential Based on mechanism of action and findings in animals, IDAMYCIN PFS can cause fetal harm [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify the pregnancy status of female patients of reproductive potential prior to initiating therapy with IDAMYCIN PFS. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with IDAMYCIN PFS and for 6.5 months after the last dose. Males Based on the genotoxicity potential, advise males with female partners of reproductive potential to use effective contraception during treatment with IDAMYCIN PFS and for 3.5 months after the last dose. Infertility Based on animal studies and mechanism of action, IDAMYCIN PFS may impair fertility in males and females of reproductive potential [see Nonclinical Toxicology (13.1) ] . It is not known if these effects are reversible. 8.4 Pediatric Use The safety and effectiveness of IDAMYCIN PFS in pediatric patients have not been established. Pediatric patients may be at greater risk for anthracycline-induced acute manifestations of cardiotoxicity or late cardiovascular dysfunction. The safety and effectiveness of idarubicin hydrochloride were assessed but not established in two open label clinical studies in pediatric patients aged 1 to <17 years with leukemia and solid tumors. The pharmacokinetics of idarubicin hydrochloride in these pediatric patients were within range of that observed in adult patients given a similar dose based on body surface area. Idarubicin hydrochloride and idarubicinol were detected in CSF samples obtained in these patients; the clinical relevance of these findings is unknown. 8.5 Geriatric Use Patients over 60 years of age who were undergoing induction therapy experienced congestive heart failure, serious arrhythmias, chest pain, myocardial infarction, and asymptomatic declines in LVEF more frequently than younger patients [see Adverse Reactions (6.1) ] . 8.6 Renal Impairment Reduce dosage of IDAMYCIN PFS in patients with GFR less than 30 mL/min and in patients on hemodialysis [see Dosage and Administration (2.3) ] . Renal function should be evaluated prior to and during treatment with IDAMYCIN PFS. The effect of renal impairment on …

12.1 Mechanism of Action Idarubicin hydrochloride has antimitotic and cytotoxic activity through forming complexes with the DNA, inhibiting nucleic acid synthesis, inhibiting topoisomerase II activity, and producing DNA-damaging free radicals.

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

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.

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 CytosafeTM 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