DAUNORUBICIN HYDROCHLORIDE- daunorubicin hydrochloride injection, solution
Teva Parenteral Medicines, Inc.
Package Insert
Rx only
WARNINGS
Daunorubicin hydrochloride injection 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 daunorubicin hydrochloride 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
Daunorubicin Hydrochloride Injection consists of the hydrochloride salt of an anthracycline cytotoxic antibiotic produced by a strain of Streptomyces coeruleorubidus. It is provided as a deep red sterile liquid in vials for intravenous administration only. Each mL contains daunorubicin hydrochloride, USP equivalent to 5 mg of daunorubicin, 9 mg sodium chloride, hydrochloric acid (to adjust pH), and water for injection, q.s. 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.
Structural Formula
(click image for full-size original)
C27 H29 NO10 �HCl M.W. 563.99
It is a hygroscopic crystalline powder. The pH of a 5 mg/mL aqueous solution is 3 to 4.
CLINICAL PHARMACOLOGY
Mechanism of Action
Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action. Daunorubicin 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.
Daunorubicin hydrochloride may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA.
Daunorubicin hydrochloride possesses an antitumor effect against a wide spectrum of animal tumors, either grafted or spontaneous.
