ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:oCardiomyopathy [see Warnings and Precautions (5.1)]oSecondary Malignancies [see Warnings and Precautions (5.2)]oSevere Local Tissue Necrosis with Extravasation [see Warnings and Precautions (5.3)]oSevere Myelosuppression [see Warnings and Precautions (5.4)]oTumor Lysis Syndrome [see Warnings and Precautions (5.5)]oHypersensitivity [see Warnings and Precautions (5.6)]. oCardiomyopathy [see Warnings and Precautions (5.1)]. oSecondary Malignancies [see Warnings and Precautions (5.2)]. oSevere Local Tissue Necrosis with Extravasation [see Warnings and Precautions (5.3)]. oSevere Myelosuppression [see Warnings and Precautions (5.4)]. oTumor Lysis Syndrome [see Warnings and Precautions (5.5)]. oHypersensitivity [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 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 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 TrialAdverse ReactionsIdarubicin with Cytarabine(N=110)Daunorubicin with Cytarabine(N=118)All Grades%All Grades%Infection9597Nausea/Vomiting8280Alopecia 7772Abdominal Pain/Diarrhea7368Hemorrhage6365Mucositis5055Dermatologic4640Mental Status Changes4134Pulmonary Disorders3939Fever 2628Headache2024Cardiac Disorder1624Peripheral Neuropathy79Clinically relevant adverse reactions in <5% of patients who received idarubicin hydrochloride included pulmonary allergy, seizure, and cerebellar adverse reactions. Other Clinical TrialsThe 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 population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. CardiacoAsymptomatic declines in Left Ventricular Ejection Fraction (LVEF)oChest painoCongestive heart failureoMyocardial infarctionoSerious arrhythmias including atrial fibrillationDermatologicoBullous erythrodermatous rash (palms and soles)oGeneralized rashoRadiation recall (skin reaction)oUrticariaGastrointestinaloSevere enterocolitis with perforationHepaticoIncreased ALT/ASTRenaloRenal impairment. oAsymptomatic declines in Left Ventricular Ejection Fraction (LVEF). oChest pain. oCongestive heart failure. oMyocardial infarction. oSerious arrhythmias including atrial fibrillation. oBullous erythrodermatous rash (palms and soles). oGeneralized rash. oRadiation recall (skin reaction). oUrticaria. oSevere enterocolitis with perforation. oIncreased ALT/AST. oRenal impairment.

BOXED WARNING SECTION.

WARNING: CARDIOMYOPATHY, SECONDARY MALIGNANCIES, and EXTRAVASATION AND TISSUE NECROSIS. oCardiomyopathy: 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)].oSecondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at higher incidence in patients treated with anthracyclines, including IDAMYCIN PFS [see Warnings and Precautions (5.2)].oExtravasation 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) ].. oCardiomyopathy: 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)].. oSecondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at higher incidence in patients treated with anthracyclines, including IDAMYCIN PFS [see Warnings and Precautions (5.2)].. oExtravasation 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.oCardiomyopathy: 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) oSecondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at higher incidence in patients treated with anthracyclines, including IDAMYCIN PFS. (5.2) oExtravasation 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). oCardiomyopathy: 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) oSecondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at higher incidence in patients treated with anthracyclines, including IDAMYCIN PFS. (5.2) oExtravasation 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).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with idarubicin hydrochloride. Idarubicin hydrochloride and related compounds have been shown to have mutagenic and carcinogenic properties when tested in experimental models (including bacterial systems, mammalian cells in culture and female Sprague Dawley rats).In male dogs given 1.8 mg/m2/day times/week (about one seventh the weekly human dose on mg/m2 basis) for 13 weeks, or times the human dose, testicular atrophy was observed with inhibition of spermatogenesis and sperm maturation with few or no mature sperm. These effects were not readily reversed after recovery of weeks.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY 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.. 12.2 Pharmacodynamics Idarubicin hydrochloride exposure-response relationships and the time course of pharmacodynamic response have not been fully characterized.. 12.3 Pharmacokinetics Idarubicin hydrochloride pharmacokinetics were determined in adult leukemia patients with normal renal and hepatic function following intravenous administration of idarubicin hydrochloride 10 to 12 mg/m2 daily for to days as single agent or combined with cytarabine.Accumulation is predicted to be 1.7-fold for idarubicin hydrochloride and 2.3-fold for idarubicinol following multiple idarubicin hydrochloride dosing.DistributionIdarubicin hydrochloride exhibits rapid distributive phase with very large volume of distribution. Idarubicin hydrochloride is approximately 97% and idarubicinol is 94% bound to plasma proteins and the binding is concentration independent.Concentrations of idarubicin hydrochloride and idarubicinol in nucleated blood and bone marrow cells are more than hundred times the plasma concentrations.EliminationIdarubicin hydrochloride mean (range) terminal half-life is 22 (4 to 48) hours when used as single agent and 20 (7 to 38) hours when used in combination with cytarabine. Idarubicin hydrochloride plasma clearance is twice the expected hepatic plasma flow.Idarubicinol mean terminal half-life exceeds 45 hours; hence, its plasma levels are sustained for period greater than days.MetabolismThe idarubicin hydrochloride is primary metabolized to the active metabolite idarubicinol which has cytotoxic activity that likely contributes to the effects of idarubicin hydrochloride.ExcretionIdarubicin hydrochloride is eliminated predominately by biliary excretion and to lesser extent by renal excretion, primarily as idarubicinol.Specific PopulationsThe effect of renal or hepatic impairment on idarubicin hydrochloride or idarubicinol pharmacokinetics is unknown.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES The efficacy of IDAMYCIN PFS was evaluated in four randomized, controlled clinical studies (Memorial Sloan Kettering Cancer Center (MSKCC), Southeastern Cancer Study Group (SEG), US Multicenter, and Gruppo Italiano Malattie Ematologiche Maligne dellAdulto (GIMEMA) trials) of 823 adult patients with newly-diagnosed AML. Patients were randomized to receive either idarubicin hydrochloride (IDR) or daunorubicin (DNR) in combination with cytarabine (Ara C) as induction therapy. Median age for IDR versus DNR in the MSKCC, SEG, US Multicenter, and GIMEMA studies was 36 versus 41, 60 versus 61, 56 versus 55, and 63 versus 62 years, respectively. Incidence of male sex was 45% versus 46%, 53% versus 47%, 57% versus 56%, and 52% versus 59%, respectively.Idarubicin hydrochloride was administered as an induction regimen of 12 mg/m2 (or 13 mg/m2 [1.1 times the recommended dosage] in US Multicenter study only) once day for days in combination with cytarabine. Daunorubicin was administered as an induction regimen of 45 mg/m2 (or 50 mg/m2 in MSKCC study only) daily for days. Cytarabine was administered 100 mg/m2 daily by continuous infusion for days or as 25 mg/m2 intravenous bolus followed by 200 mg/m2 daily for days continuous infusion (MSKCC only). Patients who had persistent leukemia after the first induction course could receive second course of induction therapy.Patients received the same anthracycline for consolidation as was used for induction, in combination with cytarabine (and 6-thioguanine for the SEG study only). The SEG study also included maintenance therapy with the same anthracycline used in induction in combination with cytarabine. The efficacy or safety have not been established for IDAMYCIN PFS for use as consolidation or maintenance therapy. Efficacy results for the four trials are provided in Table 4. Table 4: Efficacy Results in Patients with AML in MSKCC, SEG, US Multicenter, and GIMEMA StudiesAll randomized patients MSKCCSEGUS MulticenterGIMEMAIDR Ara CDNR Ara CIDR Ara CDNR Ara CIDR Ara CDNR Ara CIDR Ara CDNR Ara CComplete Remission Rate n/N (%)51/65Overall <0.05, unadjusted for prognostic factors or multiple endpoints (78%)38/65(58%)76/111 (68%)65/119(55%)68/101(67%)66/113(58%)49/124(40%)49/125(39%)Median Overall Survival (months)16.7 14.310.89.112.9 9.22.95.6.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS None.. None. (4).

DESCRIPTION SECTION.

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--L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,9,11-trihydroxyhydrochloride, (7S-cis). The structural formula is as follows:C26 H27 NO9 HCl M.W. 533.96IDAMYCIN PFS injection, for intravenous use, is sterile, orange-red, isotonic parenteral preservative-free solution, available in mL (5 mg), 10 mL (10 mg), and 20 mL (20 mg) single-dose only vials.Each mL contains idarubicin hydrochloride, USP 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 target of 3.5.. chemical structure.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION Induction Therapyo12 mg/m2 intravenously over 10 to 15 minutes on days 1, 2, and of induction in combination with cytarabine 100 mg/m2 by continuous intravenous infusion daily for days or cytarabine 25 mg/m2 intravenous bolus followed by cytarabine 200 mg/m2 continuous intravenous infusion daily for days. (2.1) oIDAMYCIN PFS can be given as part of combination regimen with other chemotherapeutic drugs. (2.1)oRenal Impairment: Assess renal function prior to therapy. Reduce dosage in renal impairment. (2.3, 8.6)oHepatic 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) o12 mg/m2 intravenously over 10 to 15 minutes on days 1, 2, and of induction in combination with cytarabine 100 mg/m2 by continuous intravenous infusion daily for days or cytarabine 25 mg/m2 intravenous bolus followed by cytarabine 200 mg/m2 continuous intravenous infusion daily for days. (2.1) oIDAMYCIN PFS can be given as part of combination regimen with other chemotherapeutic drugs. (2.1). oRenal Impairment: Assess renal function prior to therapy. Reduce dosage in renal impairment. (2.3, 8.6). oHepatic Impairment: Assess hepatic function prior to therapy. Avoid or reduce dosage in hepatic impairment. (2.4, 8.7). 2.1 Recommended Dosage Administer IDAMYCIN PFS 12 mg/m2 intravenously over 10 to 15 minutes on days 1, 2, and of induction in combination with cytarabine. The cytarabine may be given as 100 mg/m2 by continuous intravenous infusion daily for days or as cytarabine 25 mg/m2 intravenous bolus followed by cytarabine 200 mg/m2 continuous intravenous infusion daily for days.If response is not achieved with the first induction cycle, second induction cycle may be administered. Other dosage regimens may be used for 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 CardiomyopathyDiscontinue IDAMYCIN PFS in patients who develop signs or symptoms of cardiomyopathy [see Warnings and Precautions (5.1)].MyelosuppressionIf 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)] .MucositisIf patients develop severe mucositis with IDAMYCIN PFS, reduce the dose by 25% in subsequent cycles. If 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 [see Use in Specific Populations (8.6)].Table 1: Recommended IDAMYCIN PFS Dosage for Patients with Renal ImpairmentRenal Impairment/Estimated GFRDosage ModificationGFR greater than or equal to 30 mL/minNo adjustment neededGFR less than 30 mL/minReduce the dose by 33%HemodialysisReduce 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 [see Use in Specific Populations (8.7)].Table 2: Recommended IDAMYCIN PFS Dosage for Patients with Hepatic ImpairmentSerum BilirubinDosageLess than or equal to 2.6 mg/dLNo adjustment neededGreater than 2.6 mg/dL and less than mg/dLReduce the dose by 50%Greater than mg/dLAvoid Use. 2.5 Preparation oIDAMYCIN PFS is hazardous drug. Follow applicable special handling and disposal procedures.1 oDo not mix IDAMYCIN PFS or administer as an infusion with other drugs or heparin.oAvoid prolonged contact with any solution of an alkaline pH, as this will result in degradation of IDAMYCIN PFS.oParenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.oWithdraw the volume of IDAMYCIN PFS needed based on the required dose.oDo not further dilute prior to administration (see section 2.6 Administration).oDiscard unused portion.. oIDAMYCIN PFS is hazardous drug. Follow applicable special handling and disposal procedures.1 oDo not mix IDAMYCIN PFS or administer as an infusion with other drugs or heparin.. oAvoid prolonged contact with any solution of an alkaline pH, as this will result in degradation of IDAMYCIN PFS.. oParenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.. oWithdraw the volume of IDAMYCIN PFS needed based on the required dose.. oDo not further dilute prior to administration (see section 2.6 Administration).. oDiscard unused portion.. 2.6 Administration oIDAMYCIN PFS is for intravenous infusion only. oPrior to administration, flush the intravenous catheter used for IDAMYCIN PFS administration to ensure patency and to minimize the risk of extravasation.oAdminister IDAMYCIN PFS over 10 to 15 minutes into the tubing of freely running intravenous infusion of 0.9% Sodium Chloride Injection or 5% Dextrose Injection.oClosely monitor the infusion site for extravasation or drug infiltration during administration. Manage cases of extravasation as per institutional guidelines.oImmediately discontinue the infusion if extravasation occurs [see Warnings and Precautions (5.3)].. oIDAMYCIN PFS is for intravenous infusion only. oPrior to administration, flush the intravenous catheter used for IDAMYCIN PFS administration to ensure patency and to minimize the risk of extravasation.. oAdminister IDAMYCIN PFS over 10 to 15 minutes into the tubing of freely running intravenous infusion of 0.9% Sodium Chloride Injection or 5% Dextrose Injection.. oClosely monitor the infusion site for extravasation or drug infiltration during administration. Manage cases of extravasation as per institutional guidelines.. oImmediately discontinue the infusion if extravasation occurs [see Warnings and Precautions (5.3)].

DOSAGE FORMS & STRENGTHS SECTION.

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

FEMALES & MALES OF REPRODUCTIVE POTENTIAL SECTION.

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 TestingVerify the pregnancy status of female patients of reproductive potential prior to initiating therapy with IDAMYCIN PFS.ContraceptionFemalesAdvise females of reproductive potential to use effective contraception during treatment with IDAMYCIN PFS and for 6.5 months after the last dose.MalesBased 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.InfertilityBased 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.

GERIATRIC USE SECTION.

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)].

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING How SuppliedIDAMYCIN PFS (idarubicin hydrochloride) injection is clear, orange-red, aqueous, preservative-free solution available as follows:Single-dose Cytosafe(TM) vials:Unit of SaleConcentrationNDC 0013-2576-91Carton of Single-dose Vial5 mg/5 mL(1 mg/mL)NDC 0013-2586-91Carton of Single-dose Vial10 mg/10 mL(1 mg/mL)NDC 0013-2596-91Carton of Single-dose Vial20 mg/20 mL(1 mg/mL)Single-dose glass vials:Unit of SaleConcentrationNDC 0013-2576-05Carton of Single-dose Vial5 mg/5 mL(1 mg/mL)NDC 0013-2586-10Carton of Single-dose Vial10 mg/10 mL(1 mg/mL)NDC 0013-2596-20Carton of Single-dose Vial20 mg/20 mL(1 mg/mL)Storage and HandlingStore 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 hazardous drug. Follow applicable special handling and disposal procedures.1.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE IDAMYCIN PFS is indicated for the treatment of adult patients with acute myeloid leukemia (AML) as component of combination chemotherapy regimen.. IDAMYCIN PFS is an anthracycline topoisomerase inhibitor indicated for the treatment of adult patients with acute myeloid leukemia (AML) as component of combination chemotherapy regimen. (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION CardiomyopathyInform patients that IDAMYCIN PFS can cause irreversible myocardial damage. Advise patients to immediately contact their healthcare provider during or after treatment with IDAMYCIN PFS for symptoms of heart failure, including new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than pounds in 24 hours, dizziness, or loss of consciousness [see Warnings and Precautions (5.1)].Secondary MalignanciesInform patients that there is an increased risk of secondary malignancies with IDAMYCIN PFS [see Warnings and Precautions (5.2)].Extravasation and Tissue NecrosisInform patients that IDAMYCIN PFS can cause severe injection site reactions. Advise patients to contact healthcare provider if injection site pain occurs after receiving IDAMYCIN PFS [see Warnings and Precautions (5.3)].Severe MyelosuppressionInform patients that IDAMYCIN PFS causes bone marrow suppression at therapeutic doses resulting in an increased risk of infection or hemorrhage. Advise patients to contact their healthcare provider for new onset fever or symptoms of infection or hemorrhage [see Warnings and Precautions (5.4)].Tumor Lysis SyndromeAdvise patients to contact their healthcare provider promptly to report any signs and symptoms of tumor lysis syndrome (fever, chills, nausea, vomiting, confusion, shortness of breath, seizure, irregular heartbeat, dark or cloudy urine, unusual tiredness, muscle pain, and/or joint discomfort) [see Warnings and Precautions (5.5)].AlopeciaInform patients that IDAMYCIN PFS causes alopecia (usually reversible) in most patients [see Adverse Reactions (6.1)].Red Discoloration of Bodily FluidsInform patients that IDAMYCIN PFS may transiently impart red coloration to bodily fluids, including the urine, after administration. Gastrointestinal Adverse ReactionsInform patients that IDAMYCIN PFS can cause nausea, vomiting, diarrhea, and mucositis. Advise patients to contact healthcare provider if nausea, vomiting, diarrhea, or mucositis occur [see Adverse Reactions (6.1)].Embryo-Fetal ToxicityIDAMYCIN PFS can cause fetal harm. Advise females of reproductive potential to inform their healthcare provider of known or suspected pregnancy [see Warnings and Precautions (5.9), Use in Specific Populations (8.1, 8.3), and Nonclinical Toxicology (13.1)].Advise female patients of reproductive potential to use effective contraception during treatment with IDAMYCIN PFS and for 6.5 months after the last dose [see Warnings and Precautions (5.9), Use in Specific Populations (8.1, 8.3), and Nonclinical Toxicology (13.1)].Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3.5 months after the last dose of IDAMYCIN PFS. [see Warnings and Precautions (5.9) Use in Specific Populations (8.1, 8.3), and Nonclinical Toxicology (13.1)].LactationAdvise women not to breastfeed during treatment with IDAMYCIN PFS and for 14 days after the last dose [see Use in Specific Populations (8.2)].InfertilityAdvise male and female patients of reproductive potential that IDAMYCIN PFS may impair fertility [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1)].This products labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com.LAB-0131-10.0. Logo.

LACTATION SECTION.

8.2 Lactation Risk SummaryThere 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.

MECHANISM OF ACTION SECTION.

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.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with idarubicin hydrochloride. Idarubicin hydrochloride and related compounds have been shown to have mutagenic and carcinogenic properties when tested in experimental models (including bacterial systems, mammalian cells in culture and female Sprague Dawley rats).In male dogs given 1.8 mg/m2/day times/week (about one seventh the weekly human dose on mg/m2 basis) for 13 weeks, or times the human dose, testicular atrophy was observed with inhibition of spermatogenesis and sperm maturation with few or no mature sperm. These effects were not readily reversed after recovery of weeks.

OVERDOSAGE SECTION.

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/m2 over days and 45 mg/m2 of idarubicin hydrochloride and 90 mg/m2 of daunorubicin over 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.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 5 mg/5 mL Vial Label. NDC 0013-2576-915 mL Single-Dose CYTOSAFE(R) VialIdamycin PFS(R) idarubicin hydrochlorideinjection5 mg/5 mL(1 mg/mL)For IV use onlySterile, Isotonic SolutionRx only. PRINCIPAL DISPLAY PANEL 5 mg/5 mL Vial Label.

PEDIATRIC USE SECTION.

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 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 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.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics Idarubicin hydrochloride exposure-response relationships and the time course of pharmacodynamic response have not been fully characterized.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics Idarubicin hydrochloride pharmacokinetics were determined in adult leukemia patients with normal renal and hepatic function following intravenous administration of idarubicin hydrochloride 10 to 12 mg/m2 daily for to days as single agent or combined with cytarabine.Accumulation is predicted to be 1.7-fold for idarubicin hydrochloride and 2.3-fold for idarubicinol following multiple idarubicin hydrochloride dosing.DistributionIdarubicin hydrochloride exhibits rapid distributive phase with very large volume of distribution. Idarubicin hydrochloride is approximately 97% and idarubicinol is 94% bound to plasma proteins and the binding is concentration independent.Concentrations of idarubicin hydrochloride and idarubicinol in nucleated blood and bone marrow cells are more than hundred times the plasma concentrations.EliminationIdarubicin hydrochloride mean (range) terminal half-life is 22 (4 to 48) hours when used as single agent and 20 (7 to 38) hours when used in combination with cytarabine. Idarubicin hydrochloride plasma clearance is twice the expected hepatic plasma flow.Idarubicinol mean terminal half-life exceeds 45 hours; hence, its plasma levels are sustained for period greater than days.MetabolismThe idarubicin hydrochloride is primary metabolized to the active metabolite idarubicinol which has cytotoxic activity that likely contributes to the effects of idarubicin hydrochloride.ExcretionIdarubicin hydrochloride is eliminated predominately by biliary excretion and to lesser extent by renal excretion, primarily as idarubicinol.Specific PopulationsThe effect of renal or hepatic impairment on idarubicin hydrochloride or idarubicinol pharmacokinetics is unknown.

PREGNANCY SECTION.

8.1 Pregnancy Risk SummaryBased on findings from animal reproduction studies and its mechanism of action, IDAMYCIN PFS can cause fetal harm when administered to 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 drug-associated risk.Idarubicin hydrochloride was embryotoxic and teratogenic in rats at doses of 1.2 mg/m2/day or 0.1 times the human dose. Idarubicin hydrochloride was embryotoxic but not teratogenic in rabbits at doses of 2.4 mg/m2/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.DataAnimal DataIdarubicin hydrochloride was embryotoxic and teratogenic in the rat at dose of 1.2 mg/m2/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 dose of 2.4 mg/m2/day or 0.2 times the human dose, which was maternally toxic.

RECENT MAJOR CHANGES SECTION.

Boxed Warning2/2026Indications and Usage (1) 2/2026Dosage and Administration (2) 2/2026Warnings and Precautions (5) 2/2026.

REFERENCES SECTION.

15 REFERENCES 1.OSHA Hazardous Drugs. OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html.

SPL UNCLASSIFIED SECTION.

2.1 Recommended Dosage Administer IDAMYCIN PFS 12 mg/m2 intravenously over 10 to 15 minutes on days 1, 2, and of induction in combination with cytarabine. The cytarabine may be given as 100 mg/m2 by continuous intravenous infusion daily for days or as cytarabine 25 mg/m2 intravenous bolus followed by cytarabine 200 mg/m2 continuous intravenous infusion daily for days.If response is not achieved with the first induction cycle, second induction cycle may be administered. Other dosage regimens may be used for 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.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS oLactation: Advise not to breastfeed. (8.2)oInfertility: May impair fertility. (8.3). oLactation: Advise not to breastfeed. (8.2). oInfertility: May impair fertility. (8.3). 8.1 Pregnancy Risk SummaryBased on findings from animal reproduction studies and its mechanism of action, IDAMYCIN PFS can cause fetal harm when administered to 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 drug-associated risk.Idarubicin hydrochloride was embryotoxic and teratogenic in rats at doses of 1.2 mg/m2/day or 0.1 times the human dose. Idarubicin hydrochloride was embryotoxic but not teratogenic in rabbits at doses of 2.4 mg/m2/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.DataAnimal DataIdarubicin hydrochloride was embryotoxic and teratogenic in the rat at dose of 1.2 mg/m2/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 dose of 2.4 mg/m2/day or 0.2 times the human dose, which was maternally toxic.. 8.2 Lactation Risk SummaryThere 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 TestingVerify the pregnancy status of female patients of reproductive potential prior to initiating therapy with IDAMYCIN PFS.ContraceptionFemalesAdvise females of reproductive potential to use effective contraception during treatment with IDAMYCIN PFS and for 6.5 months after the last dose.MalesBased 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.InfertilityBased 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 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 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 idarubicin hydrochloride or idarubicinol pharmacokinetics is unknown [see Clinical Pharmacology (12.3)]. However, renal impairment can affect the disposition of idarubicin hydrochloride based on mechanistic understanding of idarubicin hydrochloride elimination. Treatment was not given if creatinine serum levels exceeded mg/dL in multiple clinical trials.. 8.7 Hepatic Impairment Reduce dosage of IDAMYCIN PFS in patients with serum bilirubin levels greater than 2.6 mg/dL and less than mg/dL [see Dosage and Administration (2.4)]. Do not administer IDAMYICN PFS in patients with serum bilirubin levels greater than mg/dL. Liver function should be evaluated prior to and during treatment with IDAMYCIN PFS.The effect of hepatic impairment on idarubicin hydrochloride or idarubicinol pharmacokinetics is unknown [see Clinical Pharmacology (12.3)]. However, hepatic impairment can affect the disposition of idarubicin hydrochloride based on mechanistic understanding of idarubicin hydrochloride elimination.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS oMyelosuppression: 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)oTumor Lysis Syndrome: During treatment, monitor blood chemistries and manage promptly. Treat as clinically indicated. (5.5)oHypersensitivity: Monitor patients for hypersensitivity reactions and manage as clinically indicated. (5.6)oRenal 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)oHepatic Impairment: Obtain liver tests prior to and during therapy. Reduce dose in patients with serum bilirubin levels of 2.6 to mg/dL. Avoid use in patients with serum bilirubin greater than mg/dL. (2.4, 5.8, 8.7)oEmbryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to fetus and to use effective contraception. (5.9, 8.1, 8.3). oMyelosuppression: 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). oTumor Lysis Syndrome: During treatment, monitor blood chemistries and manage promptly. Treat as clinically indicated. (5.5). oHypersensitivity: Monitor patients for hypersensitivity reactions and manage as clinically indicated. (5.6). oRenal 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). oHepatic Impairment: Obtain liver tests prior to and during therapy. Reduce dose in patients with serum bilirubin levels of 2.6 to mg/dL. Avoid use in patients with serum bilirubin greater than mg/dL. (2.4, 5.8, 8.7). oEmbryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to 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 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/m2 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 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 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 mg/dL. Avoid use of IDAMYCIN PFS in patients with serum bilirubin greater than 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/m2/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/m2/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)].