CERUBIDINE- daunorubicin hydrochloride injection, powder, for solution
Bedford Laboratories
Rx ONLY
WARNING
Cerubidine must be given into a rapidly flowing intravenous infusion. It must never be given by the intramuscular or subcutaneous route. Severe local tissue necrosis will occur if there is extravasation during administration.
Myocardial toxicity manifested in its most severe form by potentially fatal congestive heart failure may occur either during therapy or months to years after termination of therapy. The incidence of myocardial toxicity increases after a total cumulative dose exceeding 400 to 550 mg/m2 in adults, 300 mg/m2 in children more than 2 years of age, or 10 mg/kg in children less than 2 years of age.
Severe myelosuppression occurs when used in therapeutic doses; this may lead to infection or hemorrhage.
It is recommended that Cerubidine be administered only by physicians who are 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.
Dosage should be reduced in patients with impaired hepatic or renal function.
DESCRIPTION
Cerubidine (daunorubicin hydrochloride) is the hydrochloride salt of an anthracycline cytotoxic antibiotic produced by a strain of Streptomyces coeruleorubidus. 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 (1S ,3S)-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-?-L-lyxo -hexopyranoside hydrochloride. Its molecular formula is C27 H29 NO10 �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:
structural formula
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CLINICAL PHARMACOLOGY
Mechanism of Action
Cerubidine has antimitotic and cytotoxic activity through a number of proposed mechanisms of action. Cerubidine 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 may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA.
Cerubidine possesses an antitumor effect against a wide spectrum of animal tumors, either grafted or spontaneous.
