Cerubidine (Daunorubicin hydrochloride) is the hydrochloride salt of an anthracycline cytotoxic antibiotic produced by a strain of . It is provided as a sterile reddish lyophilized powder in vials for intravenous administration only. Each vial contains 21.4 mg daunorubicin hydrochloride (equivalent to 20 mg of daunorubicin), and 100 mg mannitol. It is soluble in water when adequately agitated and produces a reddish solution. It has the following structural formula which may be described with the chemical name of (1,3)-3-Acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl 3-amino-2,3,6-trideoxy-α-L--hexopyranoside hydrochloride. Its molecular formula is CHNO•HCl with a molecular weight of 563.99. It is a hygroscopic crystalline powder. The pH of a 5 mg/mL aqueous solution is 4.5 to 6.5. The structural formula is as follows:

Cerubidine (Daunorubicin hydrochloride) has antimitotic and cytotoxic activity through a number of proposed mechanisms of action. Cerubidine (Daunorubicin hydrochloride) forms complexes with DNA by intercalation between base pairs. It inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. Single strand and double strand DNA breaks result.

Cerubidine (Daunorubicin hydrochloride) may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA.

Cerubidine (Daunorubicin hydrochloride) possesses an antitumor effect against a wide spectrum of animal tumors, either grafted or spontaneous.

In the treatment of adult acute nonlymphocytic leukemia, Cerubidine (Daunorubicin hydrochloride) , used as a single agent, has produced complete remission rates of 40 to 50%, and in combination with cytarabine, has produced complete remission rates of 53 to 65%.

The addition of Cerubidine (Daunorubicin hydrochloride) to the two-drug induction regimen of vincristine-prednisone in the treatment of childhood acute lymphocytic leukemia does not increase the rate of complete remission. In children receiving identical CNS prophylaxis and maintenance therapy (without consolidation), there is prolongation of complete remission duration (statistically significant, p
In adult acute lymphocytic leukemia, in contrast to childhood acute lymphocytic leukemia, Cerubidine (Daunorubicin hydrochloride) during induction significantly increases the rate of complete remission, but not remission duration, compared to that obtained with vincristine, prednisone, and L-asparaginase alone. The use of Cerubidine (Daunorubicin hydrochloride) in combination with vincristine, prednisone, and L-asparaginase has produced complete remission rates of 83% in contrast to a 47% remission in patients not receiving Cerubidine (Daunorubicin hydrochloride) .

Cerubidine (Daunorubicin hydrochloride) in combination with other approved anticancer drugs is indicated for remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.

Cerubidine (Daunorubicin hydrochloride) is contraindicated in patients who have shown a hypersensitivity to it.

Special attention must be given to the potential cardiac toxicity of Cerubidine (Daunorubicin hydrochloride) , particularly in infants and children. Pre-existing heart disease and previous therapy with doxorubicin are co-factors of increased risk of Cerubidine (Daunorubicin hydrochloride) -induced cardiac toxicity and the benefit-to-risk ratio of Cerubidine (Daunorubicin hydrochloride) therapy in such patients should be weighed before starting Cerubidine (Daunorubicin hydrochloride) . In adults, at total cumulative doses less than 550 mg/m, acute congestive heart failure is seldom encountered. However, rare instances of pericarditis-myocarditis, not dose-related, have been reported.

In adults, at cumulative doses exceeding 550 mg/m, there is an increased incidence of drug-induced congestive heart failure. Based on prior clinical experience with doxorubicin, this limit appears lower, namely 400 mg/m, in patients who received radiation therapy that encompassed the heart.

In infants and children, there appears to be a greater susceptibility to anthracycline-induced cardiotoxicity compared to that in adults, which is more clearly dose-related. Anthracycline therapy (including daunorubicin) in pediatric patients has been reported to produce impaired left ventricular systolic performance, reduced contractility, congestive heart failure or death. These conditions may occur months to years following cessation of chemotherapy. This appears to be dose-dependent and aggravated by thoracic irradiation. Long-term periodic evaluation of cardiac function in such patients should, thus, be performed. In both children and adults, the total dose of Cerubidine (Daunorubicin hydrochloride) administered should also take into account any previous or concomitant therapy with other potentially cardiotoxic agents or related compounds such as doxorubicin.

There is no absolutely reliable method of predicting the patients in whom acute congestive heart failure will develop as a result of the cardiac toxic effect of Cerubidine (Daunorubicin hydrochloride) . However, certain changes in the electrocardiogram and a decrease in the systolic ejection fraction from pre-treatment baseline may help to recognize those patients at greatest risk to develop congestive heart failure. On the basis of the electrocardiogram, a decrease equal to or greater than 30% in limb lead QRS voltage has been associated with a significant risk of drug-induced cardiomyopathy. Therefore, an electrocardiogram and/or determination of systolic ejection fraction should be performed before each course of Cerubidine (Daunorubicin hydrochloride) . In the event that one or the other of these predictive parameters should occur, the benefit of continued therapy must be weighed against the risk of producing cardiac damage.

Early clinical diagnosis of drug-induced congestive heart failure appears to be essential for successful treatment.

Therapy with Cerubidine (Daunorubicin hydrochloride) requires close patient observation and frequent complete blood-count determinations. Cardiac, renal, and hepatic function should be evaluated prior to each course of treatment.

Appropriate measures must be taken to control any systemic infection before beginning therapy with Cerubidine (Daunorubicin hydrochloride) .

Cerubidine (Daunorubicin hydrochloride) may transiently impart a red coloration to the urine after administration, and patients should be advised to expect this.

Cerubidine (Daunorubicin hydrochloride) , when injected subcutaneously into mice, causes fibrosarcomas to develop at the injection site. When administered to mice thrice weekly intraperitoneally, no carcinogenic effect was noted after 18 months of observation. In male rats administered Cerubidine (Daunorubicin hydrochloride) thrice weekly for 6 months, at 1/70th the recommended human dose on a body surface area basis, peritoneal sarcomas were found at 18 months. A single IV dose of Cerubidine (Daunorubicin hydrochloride) administered to rats at 1.6 fold the recommended human dose on a body surface area basis caused mammary adenocarcinomas to appear at 1 year. Cerubidine (Daunorubicin hydrochloride) was mutagenic (Ames assay, V79 hamster cell assay), and clastogenic (CCRFCEM human lymphoblasts) and (SCE assay in mouse bone marrow) tests.

In male dogs at a daily dose of 0.25 mg/kg administered intravenously, testicular atrophy was noted at autopsy. Histologic examination revealed total aplasia of the spermatocyte series in the seminiferous tubules with complete aspermatogenesis.

Use of Cerubidine (Daunorubicin hydrochloride) in a patient who has previously received doxorubicin increases the risk of cardiotoxicity. Cerubidine (Daunorubicin hydrochloride) should not be used in patients who have previously received the recommended maximum cumulative doses of doxorubicin or Cerubidine (Daunorubicin hydrochloride) . Cyclophosphamide used concurrently with Cerubidine (Daunorubicin hydrochloride) may also result in increased cardiotoxicity.

Dosage reduction of Cerubidine (Daunorubicin hydrochloride) may be required when used concurrently with other myelosuppressive agents.

Hepatotoxic medications, such as high-dose methotrexate, may impair liver function and increase the risk of toxicity.

Dose-limiting toxicity includes myelosuppression and cardiotoxicity (See ). Other reactions include:

Parenteral drug products should be inspected visually for particulate matter prior to administration, whenever solution and container permit.

In order to eradicate the leukemic cells and induce a complete remission, a profound suppression of the bone marrow is usually required. Evaluation of both the peripheral blood and bone marrow is mandatory in the formulation of appropriate treatment plans.

It is recommended that the dosage of Cerubidine (Daunorubicin hydrochloride) be reduced in instances of hepatic or renal impairment. For example, using serum bilirubin and serum creatinine as indicators of liver and kidney function, the following dose modifications are recommended:

Cerubine (daunorubicin HCl) for Injection, is available in butyl-rubber-stoppered vials, each containing 21.4 mg daunorubicin hydrochloride (equivalent to 20 mg of daunorubicin) and 100 mg of mannitol, as a sterile reddish lyophilized powder. When reconstituted with 4 mL of Sterile Water for Injection, USP, each mL contains 5 mg daunorubicin activity.