Store unused vials at 20C to 25C (68F to 77F). Prepare and handle cautiously to avoid adverse local dermatologic reactions. While doxorubicin treatment decreased ejection fraction 10% in normal animals, it had no effect on cardiovascular function in the knockout animals [109]. It is administered intravenously as a hydrochloride salt by various dose schedules in cancer patients. Available for Android and iOS devices. May potentiate toxicity of other antineoplastic agents. Redox cycling of anthracyclines by cardiac mitochondria I. Anthracycline radical formation by NADH dehydrogenase. Redox cycling of anthracyclines by cardiac mitochondria. Pap. Animal studies provide evidence for the cardioprotective properties of these agents, but these studies are limited in only examining the short term consequences and little is known about their potential protective role for late onset cardiac dysfunction. Drug class: Antineoplastic Agents The FDA approved drug dexrazoxane (Zinecard) is foremost used for cardioprotection from doxorubicin. May result in limitation of mobility of adjacent joints. Problematic in their study is the myriad of secondary pathways activated by these primary effects. Rafiyath S.M., Rasul M., Lee B., Wei G. Lamba G, and Liu D. Comparison of safety and toxicity of liposomal doxorubicin vs. conventional anthracyclines: a meta-analysis. Doxorubicin reportedly increases radiation-induced toxicity to myocardium, mucosae, skin, and liver. In patients with serum bilirubin concentrations of 1.23 mg/dL, administer 50% of usual dose; in those with serum bilirubin concentrations 3 mg/dL, administer 25% of usual dose. Doxorubicin accumulates in the nucleus and the mitochondria [69]. Severe myelosuppression may occur. There appears to be a relationship between delayed development of congestive heart failure and the cumulative dose of doxorubicin received. Simunek T., Sterba M., Popelova O., Adamcova M., Hrdina R., Gersl V. Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Similar results in animal studies indicate their value as suitable surrogates for the human condition [67], [68]. Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. Delayed effects have been reported in studies of childhood survivors 4 to 20years after doxorubicin treatment where significant decreases in fractional shortening and ejection fractions were observed [2], [30], [31], [33], [42], [54], [55], [89], [90]. ), Reduce dosage in patients with hepatic impairment. Similar reactions not reported with conventional doxorubicin. The efficacy of doxorubicin as a cancer treatment is attributed to the various cytotoxic mechanisms by which it acts, most notably by inducing DNA damage through interaction with topoisomerase II and production of free radicals through interaction with intracellular oxidoreductases. Further study is needed to establish role of liposomal doxorubicin in the treatment of advanced epithelial ovarian cancer. Miyagawa K., Emoto N., Widyantoro B., Nakayama K., Yagi K., Rikitake Y., Suzuki T., Hirata K. Attenuation of doxorubicin-induced cardiomyopathy by endothelin-converting enzyme-1 ablation through prevention of mitochondrial biogenesis impairment. Liposomal doxorubicin: Undetectable or low plasma concentrations of doxorubicinol reported after single-dose IV administration; suggests that drug is not released appreciably from circulating liposomes or that some doxorubicin may be released but the rate of doxorubicinol elimination greatly exceeds the release rate; doxorubicin hydrochloride encapsulated in liposomes that have not been PEG-stabilized is metabolized to doxorubicinol. To avoid potential risks associated with reconstitution of the powder, commercially available injection can be used; however, handling of solution is not without risk. Extravasation and Tissue Necrosis: Extravasation of this drug can result in severe local tissue injury and necrosis requiring wide excision and skin grafting. Exp. Use within 1 hour. At this dose, the elimination half life of liposomal doxorubicin is expected to be longer and the clearance lower compared to a 20 mg/m dose. At least six isoforms of topoisomerase are present in the nucleus and mitochondria of the cardiomyocyte [58], [104], [108]. Purpose Cumulative anthracycline dose is one of the strongest predictors of heart failure (HF) after cancer treatment. Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy. Transition metals, such as iron, are known to catalyze the production of free radicals, thus doxorubicinol secondarily contributes to the oxidative stress seen in cells. However, the differential risk for cardiotoxicity between daunorubicin and doxorubicin has not been rigorously evaluated among survivors of childhood cancer. Dexrazoxane's protective effects appear in part to be that of protecting the cardiac mitochondria. Duration of therapy depends on patient response and tolerance. Fallah-Rad N., Walker J.R., Wassef A., Lytwyn M., Bohonis S., Fang T., Tian G., Kirkpatrick I.D., Singal P.K., Krahn M., Grenier D., Jassal D.S. Frequency and risk factors of anthracycline-induced clinical heart failure in children: a systematic review. Jaenke R.S. However, these actions of the drug also result in various hematological and gastrointestinal toxicities. Not perfect but good, it has been suggested in some studies that dexrazoxane may diminish the antineoplastic actions of doxorubicin when administered in conjunction. Contrary to these ideas is evidence for an increase in the Bcl2:Bax ratio as a function of a decline in Bax, a shift which is antiapoptotic. Kingma P.S., Osheroff N. Spontaneous DNA damage stimulates topoisomerase II-mediated DNA cleavage. The recommended dosage of Doxorubicin Hydrochloride Injection/for Injection is 60 mg/m2 administered as an intravenous bolus on day 1 of each 21-day treatment cycle, in combination with cyclophosphamide, for a total of four cycles. If the extravasation is in an extremity, elevate the extremity. The drug should be administered under the supervision of an experienced cancer chemotherapy physician. Do not administer IM or sub-Q. This drug is compatible with 0.9% sodium chloride injection or dextrose 5% injection. Save 2.20. Anthracyclines, including doxorubicin, are some of the most efficacious anticancer drugs available. Cancer Chemother. Bu'Lock F.A., Mott M.G., Oakhill A., Martin R.P. Department of Physiology, New York Medical College, Valhalla, NY, United States. Did you find an answer to your question? Gently shake vial until the contents have dissolved. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. The recommended dose of doxorubicin HCl, when administered in combination with other chemotherapy drugs, is 40 to 75 mg/m. Administer only under the supervision of qualified clinician experienced in the use of cancer chemotherapeutic agents. 20 mg/m2 by IV infusion once every 3 weeks. In children >2 years of age, clearance of nonencapsulated doxorubicin was increased compared with that in adults; clearance in children <2 years of age was decreased compared with that in older children and approached range reported for adults. Anemia occurred most commonly; neutropenia, leukopenia, and thrombocytopenia also occurred. Rossi F., Filippelli W., Russo S., Filippelli A., Berrino L. Cardiotoxicity of doxorubicin: effects of drugs inhibiting the release of vasoactive substances. Bai P., Mabley J.G., Liaudet L., Virag L., Szabo C., Pacher P. Matrix metalloproteinase activation is an early event in doxorubicin-induced cardiotoxicity. When possible, do not use veins over joints or in extremities with compromised venous or lymphatic drainage. Alteration of endothelin-1 expression in cardiomyocytes seen after treatment with doxorubicin provides an additional mechanism of cardiotoxicity. Cardiomyopathy: Myocardial damage can occur with doxorubicin hydrochloride with incidences from 1% - 20% for. What is the chemo drug called the Red Devil? Bruynzeel A.M., Niessen H.W., Bronzwaer J.G., van der Hoeven J.J., Berkhof J., Bast A., van der Vijgh W.J., van Groeningen C.J. Other isoforms are present in other cell populations within the heart. However, some studies have demonstrated that administering doxorubicin and verapamil in conjunction actually further potentiates cardiotoxicity. Nishimura Y., Kondo C., Morikawa Y., Tonomura Y., Torii M., Yamate J., Uehara T. Plasma miR-208 as a useful biomarker for drug-induced cardiotoxicity in rats. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Treatment cycles repeated every 3 weeks for a total of 6 cycles. Doxorubicin cardiomyopathy. Clinicians should consult the appropriate references to verify the dose. Efficacy and safety of anti-obesity drugs in children and adolescents: systematic review and meta-analysis. Thrombocytopenia and anemia may also occur. Carvedilol has also been shown to have antioxidant properties as well as protect against calcium dysregulation by blocking the doxorubicin-induced down-regulation of sarcoplasmic reticular calcium pumps [44]. Administer to patients with history of cardiovascular disease only when benefits outweigh risk. Applies to the following strengths: 10 mg; 20 mg; 50 mg; 150 mg; 2 mg/mL; 75 mg; 100 mg. This drug is not interchangeable with other formulations of doxorubicin. Table 1. Cardiomyopathy: Myocardial damage, including acute left ventricular failure, can occur Do not initiate Doxorubicin Hydrochloride Injection/for Injection; The recommended dosage of Doxorubicin Hydrochloride Injection/for Injection when used as a single agent is 60 mg/m, The recommended dosage of Doxorubicin Hydrochloride Injection/for Injection, when administered in combination with other chemotherapy drugs, is 40 mg/m. Dosage Modification of Liposomal Doxorubicin Hydrochloride for Palmar-Plantar Erythrodysesthesia. Childs A.C., Phaneuf S.L., Dirks A.J., Phillips T., Leeuwenburgh C. Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2:Bax ratio. Bethesda, MD 20894, Web Policies Apoptosis in adriamycin cardiomyopathy and its modulation by probucol. Administer only under constant supervision of qualified clinician experienced in cancer chemotherapy. (See Hematologic Effects under Cautions. However, there is a rapid escalation in risk of congestive heart failure to 36% as cumulative doses exceeded 600mg/m2 Manufacturer recommends the following dosage modifications based on drug-induced adverse effects. Conventional doxorubicin: Alopecia, nausea, vomiting, mucositis, myelosuppression. In instances where a patient's cumulative dose of doxorubicin exceeded 300mg/m2, such as in treatment of advanced metastatic breast cancer, dexrazoxane treatment did significantly lower incidence of congestive heart failure with little effect on time to cancer progression [92], [93]. Possible potentiation of toxicities associated with doxorubicin and/or other antineoplastic agents (see Toxicity Potentiation with Concomitant Therapy under Cautions), Most patients receiving liposomal doxorubicin to date received antiviral therapy concomitantly, but potential for interaction not evaluated, Calcium-channel blocking agents (e.g., verapamil), Possible increased risk of doxorubicin-induced cardiotoxicity, Possible increased AUCs of doxorubicin and doxorubicinol, possibly due to decreased doxorubicin clearance and decreased metabolism of doxorubicinol, Potential for more severe and prolonged hematologic toxicity, Administration sequence of paclitaxel followed by doxorubicin resulted in substantially decreased doxorubicin clearance, with more profound neutropenia and stomatitis, than did the reverse sequence of administration, Enhanced doxorubicin-induced neutropenia and thrombocytopenia reported, Possible inhibition of doxorubicin metabolism, Potentially hazardous in immunosuppressed patients, including those undergoing cytotoxic chemotherapy. Heart & Vasculature, http://www.labeling.pfizer.com/showlabeling.aspx?id=530. Cumulative and irreversible cardiac mitochondrial dysfunction induced by doxorubicin. Was 21.99. Place gelled product at room temperature (15C to 30C (59F to 86F)] for 2 to 4 hours to return the product to a slightly viscous, mobile solution. Conventional doxorubicin: Approximately 5085%. Dosage reduction may be necessary in patients who have received extensive prior radiation therapy or in those whose bone marrow has been infiltrated with malignant cells, since severe myelosuppression is likely to occur. Surprisingly, salicylate an active metabolite of acetylsalicylic acid (aspirin) has been reported as an inhibitor of topoisomerase II and should in theory be protective of the myocardium [6]. While as anti-cancer drugs this approach holds a great deal of promise, it is not without some drawbacks. 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