Rx only

FOR INTRAVENOUS USE ONLY

Idarubicin Hydrochloride Injection, USP contains idarubicin hydrochloride and is a sterile, semi-synthetic, preservative-free solution (PFS) antineoplastic anthracycline for intravenous use. Chemically, idarubicin hydrochloride is (1S,3S)-3-Acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-6,11-dioxo-1-naphthacenyl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside, hydrochloride. The structural formula is as follows:

C26H27NO9•HCl

M.W. 533.95

Idarubicin Hydrochloride Injection, USP​ is a sterile, red-orange, isotonic parenteral preservative-free solution, available in 5 mL (5 mg), 10 mL (10 mg) and 20 mL (20 mg) single-use-only vials.

Each mL contains idarubicin hydrochloride 1 mg and the following inactive ingredients: glycerin 25 mg and water for injection q.s. Hydrochloric acid is used to adjust the pH to a target of 3.5.

Four prospective randomized studies, three U.S. and one Italian, have been conducted to compare the efficacy and safety of idarubicin (IDR) to that of daunorubicin (DNR), each in combination with cytarabine as induction therapy in previously untreated adult patients with acute myeloid leukemia (AML). These data are summarized in the following table and demonstrate significantly greater complete remission rates for the IDR regimen in two of the three U.S. studies and significantly longer overall survival for the IDR regimen in two of the three U.S. studies.

There is no consensus regarding optional regimens to be used for consolidation; however, the following consolidation regimens were used in U.S. controlled trials. Patients received the same anthracycline for consolidation as was used for induction.

Studies 1 and 3 utilized 2 courses of consolidation therapy consisting of idarubicin 12 or 13 mg/m2 daily for 2 days, respectively (or DNR 50 or 45 mg/m2 daily for 2 days), and cytarabine, either 25 mg/m2 by IV bolus followed by 200 mg/m2 daily by continuous infusion for 4 days (Study 1), or 100 mg/m2 daily for 5 days by continuous infusion (Study 3). A rest period of 4 to 6 weeks is recommended prior to initiation of consolidation and between the courses. Hematologic recovery is mandatory prior to initiation of each consolidation course.

Study 2 utilized 3 consolidation courses, administered at intervals of 21 days or upon hematologic recovery. Each course consisted of idarubicin 15 mg/m2 IV for 1 dose (or DNR 50 mg/m2 IV for 1 dose), cytarabine 100 mg/m2 every 12 hours for 10 doses and 6-thioguanine 100 mg/m2 orally for 10 doses. If severe myelosuppression occurred, subsequent courses were given with 25% reduction in the doses of all drugs. In addition, this study included 4 courses of maintenance therapy (2 days of the same anthracycline as was used in induction and 5 days of cytarabine).

Toxicities and duration of aplasia were similar during induction on the 2 arms in the U.S. studies except for an increase in mucositis on the IDR arm in one study. During consolidation, duration of aplasia on the IDR arm was longer in all three studies and mucositis was more frequent in two studies. During consolidation, transfusion requirements were higher on the IDR arm in the two studies in which they were tabulated, and patients on the IDR arm in Study 3 spent more days on IV antibiotics (Study 3 used a higher dose of idarubicin).

The benefit of consolidation and maintenance therapy in prolonging the duration of remission and survival is not proven.

Intensive maintenance with idarubicin is not recommended in view of the considerable toxicity (including deaths in remission) experienced by patients during the maintenance phase of Study 2.

A higher induction death rate was noted in patients on the IDR arm in the Italian trial. Since this was not noted in patients of similar age in the U.S. trials, one may speculate that it was due to a difference in the level of supportive care.

Idarubicin Hydrochloride injection, USP in combination with other approved antileukemic drugs is indicated for the treatment of acute myeloid leukemia (AML) in adults. This includes French-American-British (FAB) classifications M1 through M7.

Idarubicin is intended for administration under the supervision of a physician who is experienced in leukemia chemotherapy.

Idarubicin is a potent bone marrow suppressant. Idarubicin should not be given to patients with pre-existing bone marrow suppression induced by previous drug therapy or radiotherapy unless the benefit warrants the risk.

Severe myelosuppression will occur in all patients given a therapeutic dose of this agent for induction, consolidation or maintenance. Careful hematologic monitoring is required. Deaths due to infection and/or bleeding have been reported during the period of severe myelosuppression. Facilities with laboratory and supportive resources adequate to monitor drug tolerability and protect and maintain a patient compromised by drug toxicity should be available. It must be possible to treat rapidly and completely a severe hemorrhagic condition and/or a severe infection.

Pre-existing heart disease and previous therapy with anthracyclines at high cumulative doses or other potentially cardiotoxic agents are co-factors for increased risk of idarubicin-induced cardiac toxicity and the benefit to risk ratio of idarubicin therapy in such patients should be weighed before starting treatment with idarubicin.

Myocardial toxicity as manifested by potentially fatal congestive heart failure, acute life-threatening arrhythmias or other cardiomyopathies may occur following therapy with idarubicin. Appropriate therapeutic measures for the management of congestive heart failure and/or arrhythmias are indicated.

Cardiac function should be carefully monitored during treatment in order to minimize the risk of cardiac toxicity of the type described for other anthracycline compounds. The risk of such myocardial toxicity may be higher following concomitant or previous radiation to the mediastinal-pericardial area or in patients with anemia, bone marrow depression, infections, leukemic pericarditis and/or myocarditis, active or dormant cardiovascular disease, previous therapy with other anthracyclines or anthracenediones, and concomitant use of drugs with the ability to suppress cardiace contractility or cardiotoxic drugs (e.g., trastuzumab, cyclophosphamide and paclitaxel). Do not administer idarubicin with other cardiotoxic agents unless the patient’s cardiac function is monitored frequently. Patients receiving anthracyclines after stopping treatment with other cardiotoxic agents, especially those with long half-lives, may also be at an increased risk of developing cardiotoxicity. Avoid the use of anthracycline-based therapy for at least 5 half-lives after discontinuation of the cardiotoxic agent. If anthracyclines are used before this time, carefully monitor the cardiac function. While there are no reliable means for predicting congestive heart failure, cardiomyopathy induced by anthracyclines is usually associated with a decrease of the left ventricular ejection fraction (LVEF) from pretreatment baseline values.

Since hepatic and/or renal function impairment can affect the disposition of idarubicin, liver and kidney function should be evaluated with conventional clinical laboratory tests (using serum bilirubin and serum creatinine as indicators) prior to and during treatment. In a number of Phase III clinical trials, treatment was not given if bilirubin and/or creatinine serum levels exceeded 2 mg%. However, in one Phase III trial, patients with bilirubin levels between 2.6 and 5 mg% received the anthracycline with a 50% reduction in dose. Dose reduction of idarubicin should be considered if the bilirubin and/or creatinine levels are above the normal range. (See DOSAGE AND ADMINISTRATION.)

   Pregnancy Category D - Idarubicin was embryotoxic and teratogenic in the rat at a dose of 1.2 mg/m2/day or one tenth the human dose, which was nontoxic to dams. Idarubicin was embryotoxic but not teratogenic in the rabbit even at a dose of 2.4 mg/m2/day or two tenths the human dose, which was toxic to dams. There is no conclusive information about idarubicin adversely affecting human fertility or causing teratogenesis. There has been one report of a fetal fatality after maternal exposure to idarubicin during the second trimester.

There are no adequate and well-controlled studies in pregnant women. If idarubicin is to be used during pregnancy, or if the patient becomes pregnant during therapy, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid pregnancy.

Approximately 550 patients with AML have received idarubicin in combination with cytarabine in controlled clinical trials worldwide. In addition, over 550 patients with acute leukemia have been treated in uncontrolled trials utilizing idarubicin as a single agent or in combination. The table below lists the adverse experiences reported in U.S. Study 2 (see CLINICAL STUDIES) and is representative of the experiences in other studies. These adverse experiences constitute all reported or observed experiences, including those not considered to be drug related. Patients undergoing induction therapy for AML are seriously ill due to their disease, are receiving multiple transfusions, and concomitant medications including potentially toxic antibiotics and antifungal agents. The contribution of the study drug to the adverse experience profile is difficult to establish.

The duration of aplasia and incidence of mucositis were greater on the IDR arm than the DNR arm, especially during consolidation in some U.S. controlled trials (see CLINICAL STUDIES).

The following information reflects experience based on U.S. controlled clinical trials.

There is no known antidote to idarubicin. Two cases of fatal overdosage in patients receiving therapy for AML have been reported. The doses were 135 mg/m2over 3 days and 45 mg/m2 of idarubicin and 90 mg/m2 of daunorubicin over a three day period.

It is anticipated that overdosage with idarubicin will result in severe and prolonged myelosuppression and possibly in increased severity of gastrointestinal toxicity. Adequate supportive care including platelet transfusions, antibiotics and symptomatic treatment of mucositis is required. The effect of acute overdose on cardiac function is not fully known, but severe arrhythmia occurred in 1 of the 2 patients exposed. It is anticipated that very high doses of idarubicin may cause acute cardiac toxicity and may be associated with a higher incidence of delayed cardiac failure.

Disposition studies with idarubicin in patients undergoing dialysis have not been carried out. The profound multicompartment behavior, extensive extravascular distribution and tissue binding, coupled with the low unbound fraction available in the plasma pool make it unlikely that therapeutic efficacy or toxicity would be altered by conventional peritoneal or hemodialysis.

(See WARNINGS)

For induction therapy in adult patients with AML the following dose schedule is recommended:

Idarubicin hydrochloride injection 12 mg/m2 daily for 3 days by slow (10 to 15 min) intravenous injection in combination with cytarabine. The cytarabine may be given as 100 mg/m2 daily by continuous infusion for 7 days or as cytarabine 25 mg/m2 intravenous bolus followed by cytarabine 200 mg/m2 daily for 5 days continuous infusion. In patients with unequivocal evidence of leukemia after the first induction course, a second course may be administered. Administration of the second course should be delayed in patients who experience severe mucositis, until recovery from this toxicity has occurred, and a dose reduction of 25% is recommended. In patients with hepatic and/or renal impairment, a dose reduction of idarubicin hydrochloride should be considered. Idarubicin hydrochloride should not be administered if the bilirubin level exceeds 5 mg%. (See WARNINGS.)

The benefit of consolidation in prolonging the duration of remissions and survival is not proven. There is no consensus regarding optional regimens to be used for consolidation. (See CLINICAL STUDIES for doses used in U.S. clinical studies.)

Idarubicin Hydrochloride Injection, USP Single Dose Glass Vials:

Sterile single use only, contains no preservative.

NDC 0143-9217-01 5 mg/5 mL vial (1 mg/mL), individually boxed.

NDC 0143-9218-01 10 mg/10 mL vial (1 mg/mL), individually boxed.

NDC 0143-9219-01 20 mg/20 mL vial (1 mg/mL), individually boxed.

Store under refrigeration 2° to 8°C (36° to 46°F), and protect from light. Retain in carton until time of use.

To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

For Product Inquiry call 1-877-845-0689.

1. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society. 1999: 32-41.

2. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. Washington, DC; Division of Safety, Clinical Center Pharmacy Department and Cancer Nursing Services, National institutes of Health; 1992. US Department of Health and Human Services, Public Health Service Publication NIH 92-2621.

3. AMA Council on Scientific Affairs. Guidelines for Handling Parenteral Antineoplastics. JAMA. 1985; 253: 1590-1591.

4. National Study Commission on Cytotoxic Exposure - Recommendations for Handling Cytotoxic Agents. 1987 Available from Louis P. Jeffrey, Sc. D., Chairman, National Study Commission on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115.5.

Clinical Oncological Society of Australia: Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia. 1983; 1:426-428.

6. Jones RB, Frank R, Mass T. Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center. CA Cancer J Clin. 1983; 33: 258-263.

7. American Society of Hospital Pharmacists. ASHP Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. Am J Hosp Pharm. 1990; 47: 1033-1049.

8. Controlling Occupational Exposure to Hazardous Drugs (OSHA Work-Practice Guidelines). Am J Health-Syst Pharm. 1996; 53: 1669-1685.

Manufactured by

THYMOORGAN PHARMAZIE GmbH,

Schiffgraben 23, 38690 Goslar, Germany

Distributed by

West-Ward Pharmaceuticals 

Eatontown, NJ 07724 USA

Revised March 2016

127.207.018/00

Idarubicin Hydrochloride Injection, USP 5 mg/5mL vial label

NDC 0143-9217-01 Rx only

Idarubicin Injection, USP

5 mg/5 mL

(1 mg/mL)

Sterile, Isotonic Solution

FOR IV USE ONLY

Idarubicin Hydrochloride Injection, USP 10 mg/10 mL vial label

NDC 0143-9218-01 Rx only

Idarubicin Injection, USP

10 mg/10 mL

(1 mg/mL)

Sterile, Isotonic Solution

FOR INTRAVENOUS USE ONLY

Idarubicin Hydrochloride Injection, USP 20 mg/20 mL vial label

NDC 0143-9219-01 Rx only

Idarubicin Hydrochloride Injection, USP

20 mg/20 mL

(1 mg/mL)

Sterile, Isotonic Solution

FOR INTRAVENOUS USE ONLY

Representative Carton Serialization Image

Representative Carton Serialization Image