Doxorubicin

Cardiomyopathy Doxorubicin hydrochloride can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy is generally proportional to the cumulative exposure. Include prior doses of other anthracyclines or anthracenediones in calculations of total cumulative dosage for doxorubicin hydrochloride. Cardiomyopathy may develop during treatment or up to several years after completion of treatment and can include decrease in LVEF and signs and symptoms of congestive heart failure (CHF). The probability of developing cardiomyopathy is estimated to be 1 to 2% at a total cumulative dose of 300 mg/m 2 of doxorubicin hydrochloride, 3 to 5% at a dose of 400 mg/m 2, 5 to 8% at a dose of 450 mg/m 2, and 6 to 20% at a dose of 500 mg/m 2, when doxorubicin hydrochloride is administered every 3 weeks. There is an additive or potentially synergistic increase in the risk of cardiomyopathy in patients who have received radiotherapy to the mediastinum or concomitant therapy with other known cardiotoxic agents, such as cyclophosphamide and trastuzumab. Pericarditis and myocarditis have also been reported during or following doxorubicin hydrochloride treatment. Assess left ventricular cardiac function (e.g., MUGA or echocardiogram) prior to initiation of Doxorubicin Hydrochloride Injection/for Injection, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Increase the frequency of assessments as the cumulative dose e...

2.2 Recommended Dosage for Other Cancers • The recommended dosage of Doxorubicin Hydrochloride Injection/for Injection when used as a single agent is 60 mg/m 2 to 75 mg/m 2 intravenously every 21 days. • The recommended dosage of Doxorubicin Hydrochloride Injection/for Injection, when administered in combination with other chemotherapy drugs, is 40 mg/m 2 to 75 mg/m 2 intravenously every 21 to 28 days. • Consider use of the lower Doxorubicin Hydrochloride Injection/for Injection dose in the recommended dosage range or longer intervals between cycles for heavily pretreated patients, elderly patients, or obese patients. • Cumulative doses above 550 mg/m 2 are associated with an increased risk of cardiomyopathy [see 2.4 Dosage Modifications for Hepatic Impairment Doxorubicin Hydrochloride Injection/for Injection is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C or serum bilirubin greater than 5 mg/dL) [see Dosage modifications for Doxorubicin Hydrochloride Injection/for Injection in patients with elevated serum total bilirubin concentrations [see Table 1. Recommended Dosage Modification for Elevated Serum Total Bilirubin Serum total bilirubin concentration Dosage Modification 1.2 – 3 mg/dL 50% 3.1 – 5 mg/dL 75% greater than 5 mg/dL Do not initiate Doxorubicin Hydrochloride Injection/for Injection; discontinue Doxorubicin Hydrochloride Injection/for Injection Reconstitution of Doxorubicin Hydrochloride for Injection • Reconstitute Doxorubicin Hy...

Overview • The chemotherapy (“chemo”) drug “The Red Devil” is • Doxorubicin may also cause your urine or other body fluids to turn a reddish color for 1 to 2 days after a dose is given, which is normal and temporary. • Doxorubicin can cause harsh side effects such as heart toxicity (heart failure), severe nausea and vomiting, and total hair loss (alopecia). • The brand name product Adriamycin has now been discontinued in the U.S., but the generic doxorubicin is still on the market. Doxorubicin, in the drug class known as anthracyclines, has been used for decades in the treatment of various solid cancers such as breast cancer and ovarian cancer, or blood cancers like leukemia or lymphoma. It works by inhibiting an enzyme known as topoisomerase 2 and blocking RNA and DNA synthesis, which leads to cell death. Because of its heart toxicity (cardiotoxicity), doxorubicin has a maximum cumulative dose that can be given to each patient. The higher the total dose you receive over time, the greater your chance for heart side effects. Your doctor will monitor your heart before, during and after doxorubicin treatment. Patients typically receive injections every 21 to 28 days on a specific cycle, but your dose schedule may be different. You may NOT be able to use doxorubicin if you have severe heart disease or severe liver disease. Contact your doctor right away if you feel extremely weak or tired, have a fast heartbeat, any level of shortness of breath, or swelling in your ankles or f...

Doxorubicin (Dox) is a secondary metabolite of the mutated strain of Streptomyces peucetius var. Caesius and belongs to the anthracyclines family. The anti-cancer activity of Dox is mainly exerted through the DNA intercalation and inhibiting topoisomerase II enzyme in fast-proliferating tumors. However, Dox causes cumulative and dose-dependent cardiotoxicity, which results in increased risks of mortality among cancer patients and thus limiting its wide clinical applications. There are several mechanisms has been proposed for doxorubicin-induced cardiotoxicity and oxidative stress, free radical generation and apoptosis are most widely reported. Apart from this, other mechanisms are also involved in Dox-induced cardiotoxicity such as impaired mitochondrial function, a perturbation in iron regulatory protein, disruption of Ca 2+ homeostasis, autophagy, the release of nitric oxide and inflammatory mediators and altered gene and protein expression that involved apoptosis. Dox also causes downregulation of DNA methyltransferase 1 (DNMT1) enzyme activity which leads to a reduction in the DNA methylation process. This hypomethylation causes dysregulation in the mitochondrial genes like peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1-alpha (PGC‐1α), nuclear respiratory factor 1 (NRF‐1) and mitochondrial transcription factor A (TFAM) unit in the heart. Apart from DNA methylation, Dox treatment also alters the micro RNAs levels and histone deacetylase (HDAC) acti...

Hero Images / Getty Images Doxorubicin May Cause Heart Damage It is well recognized that doxorubicin may cause damage to the heart in some individuals. While other anthracyclines (like epirubicin and mitoxantrone) may also cause heart damage, the chances are more common with doxorubicin. Doxorubicin causes both early and late heart damage (also called cardiotoxicity). The early damage occurs immediately after drug administration or within 1 to 2 days. There are minor effects that are picked up on the electrocardiogram (EKG) and in most cases resolve without causing any major problems. It is the late-starting damage that is important and more serious. How Does Doxorubicin Damage the Heart? Doxorubicin reacts with some chemicals in the body (called enzymes) to produce harmful substances called free radicals. The production of these harmful free radicals is enhanced in organs like the heart where there are more oxygen and iron. While some organs have special enzymes to destroy these free radicals, the heart has a relatively poor supply of these enzymes. This makes the heart muscles susceptible to damage with free radicals. • A high dose of doxorubicin is more likely to produce heart damage. At higher doses, the chances of heart damage increase. The total dose of doxorubicin received during a person’s life should be ideally less than 450mg per square meter (of the body surface). The risk of CHF depends on the dose, ranging from about 4 to 36%. Fortunately, most chemo schedules...

What is doxorubicin? Doxorubicin is used to treat different types of cancers that affect the breast, bladder, kidneys, ovaries, thyroid, stomach, lungs, bones, nerve tissues, joints, and soft tissues. Doxorubicin is also used to treat Doxorubicin may also be used for purposes not listed in this medication guide. Warnings You should not use doxorubicin if you have severe liver disease, severe heart problems, very low blood cell counts caused by prior chemotherapy, or if you recently had a Doxorubicin can weaken your immune system. Your blood may need to be tested often. Tell your doctor if you have unusual bruising or bleeding, or signs of Doxorubicin may cause dangerous effects on your heart. Call your doctor at once if you feel very weak or tired, or have fast heartbeats, shortness of breath (even with mild exertion), or swelling in your ankles or feet. Before taking this medicine You should not use this medicine if you are allergic to doxorubicin or similar medications (doxorubicin, • very low blood cell counts caused by chemotherapy you received in the past; • severe liver disease; • severe heart problems; or • if you have recently had a heart attack. Tell your doctor if you have ever had: • severe liver disease; • heart disease or • radiation treatment to your chest. Tell your doctor about all other Using doxorubicin may increase your risk of developing a bone marrow disease or other types of leukemia later in life. Ask your doctor about your specific risk. You may nee...

Adriamycin, Doxil, Myocet Generic Name Doxorubicin DrugBank Accession Number DB00997 Background Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius along side with daunorubicin, another cytotoxic agent, in 1970. Type Small Molecule Groups Approved, Investigational Structure Close Weight Average: 543.5193 Monoisotopic: 543.174060775 Chemical Formula C 27H 29NO 11 Synonyms • (1S,3S)-3-glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside • (8S-cis)-10-((3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione • 14-hydroxydaunomycin • 14-hydroxydaunorubicine • Doxorubicin • Doxorubicina • Hydroxydaunorubicin Pharmacology Indication Doxorubicin is indicated for the treatment of neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin and non-Hodgkin lymphoma, metastatic breast cancer, metastatic Wilms’ tumor, metastatic neuroblastoma, metastatic soft tissue and bone sarcomas, metastatic ovarian carcinoma, metastatic transitional cell bladder carcinoma, metastatic thyroid carcinoma, metastatic gastric carcinoma, and metastatic bronchogenic carcinoma. Learn more Pharmacodynamics Doxorubicin is a cytotoxic, cell-cycle non-specific anthracycline antibiotic. Mechanism of action Generally, doxorubicin is thought to exert its an...