Drug Facts
Composition & Profile
Identifiers & Packaging
HOW SUPPLIED 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.; Package/Label Display Panel NDC 0143-9217-01 Rx only Unit label Idarubicin Injection, USP 5 mg/5 mL (1 mg/mL) Sterile, Isotonic Solution FOR IV USE ONLY NDC 0143-9217-01 Rx only carton Idarubicin Injection, USP 5 mg/5 mL (1 mg/mL) Sterile, Isotonic Solution FOR IV USE ONLY Unit label carton; Package/Label Display Panel NDC 0143-9218-01 Rx only unit label Idarubicin Injection, USP 10 mg/10 mL (1 mg/mL) Sterile, Isotonic Solution FOR INTRAVENOUS USE ONLY NDC 0143-9218-01 Rx only carton Idarubicin Injection, USP 10 mg/10 mL (1 mg/mL) Sterile, Isotonic Solution FOR INTRAVENOUS USE ONLY unit label carton; Package/Label Display Panel NDC 0143-9219-01 Rx only unit label Idarubicin Hydrochloride Injection, USP 20 mg/20 mL (1 mg/mL) Sterile, Isotonic Solution FOR INTRAVENOUS USE ONLY NDC 0143-9219-01 Rx only carton Idarubicin Hydrochloride Injection, USP 20 mg/20 mL (1 mg/mL) Sterile, Isotonic Solution FOR INTRAVENOUS USE ONLY unit label carton; SERIALIZATION IMAGE 5 ML AND 10 ML CARTON Representative Carton Serialization Image Representative Carton Serialization Image; SERIALIZATION IMAGE 20 ML CARTON Representative Carton Serialization Image Representative Carton Serialization Image
- HOW SUPPLIED 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.
- Package/Label Display Panel NDC 0143-9217-01 Rx only Unit label Idarubicin Injection, USP 5 mg/5 mL (1 mg/mL) Sterile, Isotonic Solution FOR IV USE ONLY NDC 0143-9217-01 Rx only carton Idarubicin Injection, USP 5 mg/5 mL (1 mg/mL) Sterile, Isotonic Solution FOR IV USE ONLY Unit label carton
- Package/Label Display Panel NDC 0143-9218-01 Rx only unit label Idarubicin Injection, USP 10 mg/10 mL (1 mg/mL) Sterile, Isotonic Solution FOR INTRAVENOUS USE ONLY NDC 0143-9218-01 Rx only carton Idarubicin Injection, USP 10 mg/10 mL (1 mg/mL) Sterile, Isotonic Solution FOR INTRAVENOUS USE ONLY unit label carton
- Package/Label Display Panel NDC 0143-9219-01 Rx only unit label Idarubicin Hydrochloride Injection, USP 20 mg/20 mL (1 mg/mL) Sterile, Isotonic Solution FOR INTRAVENOUS USE ONLY NDC 0143-9219-01 Rx only carton Idarubicin Hydrochloride Injection, USP 20 mg/20 mL (1 mg/mL) Sterile, Isotonic Solution FOR INTRAVENOUS USE ONLY unit label carton
- SERIALIZATION IMAGE 5 ML AND 10 ML CARTON Representative Carton Serialization Image Representative Carton Serialization Image
- SERIALIZATION IMAGE 20 ML CARTON Representative Carton Serialization Image Representative Carton Serialization Image
Overview
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 (1 S ,3 S )-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: C 26 H 27 NO 9 •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. Structural Formula
Indications & Usage
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.
Dosage & Administration
( See WARNINGS ) For induction therapy in adult patients with AML the following dose schedule is recommended: Idarubicin hydrochloride injection 12 mg/m 2 daily for 3 days by slow (10 to 15 min) intravenous injection in combination with cytarabine. The cytarabine may be given as 100 mg/m 2 daily by continuous infusion for 7 days or as cytarabine 25 mg/m 2 intravenous bolus followed by cytarabine 200 mg/m 2 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.) Preparation and Administration Precautions Caution in handling the solution must be exercised as skin reactions associated with idarubicin hydrochloride may occur. Skin accidentally exposed to idarubicin hydrochloride should be washed thoroughly with soap and water and if the eyes are involved, standard irrigation techniques should be used immediately. The use of goggles, gloves, and protective gowns is recommended during preparation and administration of the drug. Care in the administration of idarubicin hydrochloride will reduce the chance of perivenous infiltration. It may also decrease the chance of local reactions such as urticaria and erythematous streaking. During intravenous administration of idarubicin hydrochloride extravasation may occur with or without an accompanying stinging or burning sensation even if blood returns well on aspiration of the infusion needle. If any signs or symptoms of extravasation have occurred, the injection or infusion should be immediately terminated and restarted in another vein. If it is known or suspected that subcutaneous extravasation has occurred, it is recommended that intermittent ice packs (1/2 hour immediately, then 1/2 hour 4 times per day for 3 days) be placed over the area of extravasation and that the affected extremity be elevated. Because of the progressive nature of extravasation reactions, the area of injection should be frequently examined and plastic surgery consultation obtained early if there is any sign of a local reaction such as pain, erythema, edema or vesication. If ulceration begins or there is severe persistent pain at the site of extravasation, early wide excision of the involved area should be considered. Idarubicin hydrochloride should be administered slowly (over 10 to 15 minutes) into the tubing of a freely running intravenous infusion of Sodium Chloride Injection (0.9%) or 5% Dextrose Injection. The tubing should be attached to a butterfly needle or other suitable device and inserted preferably into a large vein. Incompatibility Unless specific compatibility data are available, idarubicin hydrochloride should not be mixed with other drugs. Precipitation occurs with heparin. Prolonged contact with any solution of an alkaline pH will result in degradation of the drug. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and containers permit. Handling and Disposal: Procedures for handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. 1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
Warnings & Precautions
WARNINGS 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/m 2 /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/m 2 /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.
Boxed Warning
WARNINGS WARNINGS 1. Idarubicin Hydrochloride Injection should be given slowly into a freely flowing intravenous infusion. It must never be given intramuscularly or subcutaneously. Severe local tissue necrosis can occur if there is extravasation during administration. 2. As is the case with other anthracyclines the use of idarubicin Hydrochloride can cause myocardial toxicity leading to congestive heart failure. Cardiac toxicity is more common in patients who have received prior anthracyclines or who have pre-existing cardiac disease. 3. As is usual with antileukemic agents, severe myelosuppression occurs when idarubicin hydrochloride is used at effective therapeutic doses. 4. It is recommended that idarubicin hydrochloride be administered only under the supervision of a physician who is experienced in leukemia chemotherapy and in facilities with laboratory and supportive resources adequate to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The physician and institution must be capable of responding rapidly and completely to severe hemorrhagic conditions and/or overwhelming infection. 5. Dosage should be reduced in patients with impaired hepatic or renal function. (See DOSAGE AND ADMINISTRATION .)
Adverse Reactions
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. Induction Phase Percentage of Patients IDR DNR Adverse Experiences (N=110) (N=118) Infection 95% 97% Nausea & Vomiting 82% 80% Hair Loss 77% 72% Abdominal Cramps/Diarrhea 73% 68% Hemorrhage 63% 65% Mucositis 50% 55% Dermatologic 46% 40% Mental Status 41% 34% Pulmonary-Clinical 39% 39% Fever (not elsewhere classified) 26% 28% Headache 20% 24% Cardiac-Clinical 16% 24% Neurologic- Peripheral Nerves 7% 9% Pulmonary Allergy 2% 4% Seizure 4% 5% Cerebellar 4% 4% 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. Myelosuppression Severe myelosuppression is the major toxicity associated with idarubicin therapy, but this effect of the drug is required in order to eradicate the leukemic clone. During the period of myelosuppression, patients are at risk of developing infection and bleeding which may be life-threatening or fatal. Gastrointestinal Nausea and/or vomiting, mucositis, abdominal pain and diarrhea were reported frequently, but were severe (equivalent to WHO Grade 4) in less than 5% of patients. Severe enterocolitis with perforation has been reported rarely. The risk of perforation may be increased by instrumental intervention. The possibility of perforation should be considered in patients who develop severe abdominal pain and appropriate steps for diagnosis and management should be taken. Dermatologic Alopecia was reported frequently and dermatologic reactions including generalized rash, urticaria and a bullous erythrodermatous rash of the palms and soles have occurred. The dermatologic reactions were usually attributed to concomitant antibiotic therapy. Local reactions including hives at the injection site have been reported. Recall of skin reaction due to prior radiotherapy has occurred with idarubicin administration. Hepatic and Renal Changes in hepatic and renal function tests have been observed. These changes were usually transient and occurred in the setting of sepsis and while patients were receiving potentially hepatotoxic and nephrotoxic antibiotics and antifungal agents. Severe changes in renal function (equivalent to WHO Grade 4) occurred in no more than 1% of patients, while severe changes in hepatic function (equivalent to WHO Grade 4) occurred in less than 5% of patients. Cardiac Congestive heart failure (frequently attributed to fluid overload), serious arrhythmias including atrial fibrillation, chest pain, myocardial infarction and asymptomatic declines in LVEF have been reported in patients undergoing induction therapy for AML. Myocardial insufficiency and arrhythmias were usually reversible and occurred in the setting of sepsis, anemia and aggressive intravenous fluid administration. The events were reported more frequently in patients over age 60 years and in those with pre-existing cardiac disease.
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