Doxorubicin

PDF of Stat Consult 0810

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Drug type

• An anthracycline antibiotic that has antineoplasticactivity

• Also available in a liposomal version

• The dose of liposomal doxorubicin is different from that of conventional doxorubicin, and the two formulations are not interchangeable

• Liposomal delivery improves drug penetration into tumors and decreases drug clearance, therebyincreasing the duration of therapeutic drug effects

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Indications

• Used to treat acute lymphoblastic leukemia, acute myeloblastic leukemia, breast cancer, bronchogenic lungcancer, gastric cancer, Kaposi sarcoma related to AIDS, malignant lymphoma (Hodgkin and non-Hodgkin), neuroblastoma, ovarian cancer, soft tissue and osteogenic sarcomas, thyroid cancer, transitional cell bladder cancer, Wilms tumor

• Also used to treat Ewing tumor; squamous cell carcinoma of the head, neck, cervix, and vagina; carcinoma of the testes, prostate, and uterus; and refractory multiple myeloma

Mechanism of action

• Intercalates between base pairs in the DNA helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis

• Inhibits topoisomerase II, which results in an increased and stabilized cleavable enzyme-DNA linked complex during DNA replication and subsequently prevents the ligation of the nucleotide strand after double-strand breakage

• Forms oxygen free radicals resulting in cytotoxicitysecondary to lipid peroxidation of cell membrane lipids; the formation of oxygen free radicals also contributes to drug toxicity, namely the cardiac and cutaneous vascular effects

How to administer

• IV adminstration only (potent vesicant)

—If extravasation occurs, it may lead to severe local tissue damage resulting in ulceration, necrosis, and pain

Dosage and administration

• Children

—35-75 mg/m² q21d, or 20-30 mg/m²/wk, or 60-90 mg/m² continuous IV infusion over 96 hours q3-4wk

• Adults

—60-75 mg/m² IV injection q21d, or 60 mg/m² q2wk, or 40-60 mg/m² q3-4wk

—20-30 mg/m² for 2-3 days q4wk

—20 mg/m² once a week

—Dose adjustments are based on hepatic impairment and the severity of neutropenic fever/infection

Pregnancy category: D

Lactation

• Enters into breast milk

• Breast-feeding while taking doxorubicin is not recom-mended

Black box warning

• May cause cumulative, dose-related myocardial toxicity (early or delayed)

• Probability of developing impaired myocardial function based on a combined index of signs, symptoms, and decline in left ventricular ejection fraction is estimated to be

—1% to 2% at a total cumulative dose of 300 mg/m²

—3% to 5% at a dose of 400 mg/m²

—5% to 8% at a dose of 450 mg/m²

—6% to 20% at a dose of 500 mg/m²

• Risk of developing heart failure (HF) increases rapidly with increasing total cumulative doses of more than 450 mg/m²

Cautions and adverse effects

• Pediatric: Risk of delayed cardiotoxicity and HF, prepubertal growth failure

• Geriatric: Cardiotoxicity more frequent, bone marrow reserves may be inadequate

• Most frequently reported adverse reactions: alopecia, esophagitis, infection, leukopenia, nausea, stomatitis, urine or tear discoloration, vomiting

• Less frequent: chronic HF, diarrhea, GI ulcer, hyper-uricemia, injection site sequelae, nail discoloration, phlebosclerosis, postirradiation erythema, skin thickening, thrombocytopenic disorder, tissue necrosis, uric acid nephropathy, gout

• Rare: allergic dermatitis, allergic reactions, anaphylaxis, bronchospastic pulmonary disease, cardiotoxicity, drug fever, dyspnea, extravasation injury, myelodysplastic syndrome, pruritus of skin, severe bone marrow depression, skin rash, urticaria, wheezing

Drug interactions

• Clearly contraindicated drug combinations

—Immunosuppressives, immunomodulators/efalizumab (Raptiva), natalizumab (Tysabri), live vaccines

• Severe interaction

—Doxorubicin may increase the concentrations of 2B6 substrates, leflunomide (Arava, generics), vitamin K antagonists

—Levels of doxorubicin may be increased by bevacizumab (Avastin), cyclosporine (Neoral, Sandimmune, Gengraf, generics), darunavir (Prezista), dasatinib (Sprycel), sorafenib (Nexavar)

• Herbals:

—Avoid St. John’s Wort, echinacea, black cohosh, and dong quai

• Severe interaction

—Selected chemotherapy agents: bevacizumab, dasatinib, trastuzumab (Herceptin), taxanes, sorafenib

—Stavudine (Zerit, generics), zidovudine (Retrovir, generics), warfarin (Coumadin, Jantoven, generics)

• Moderate interaction

—Digoxin (Digitek, Lanoxicaps, Lanoxin, generics)

What to tell your patient

• Doxorubicin is a chemotherapy drug that works by slowing or stopping the growth of cancer cells

• Your doctor has prescribed this medication because he or she has judged that the benefit is greater than the risk of side effects

• Many patients on doxorubicin do not have serious side effects

• Contact your health care provider immediately if you should experience any of the following symptoms:

—Fever of 100.5ºF (38ºC), chills (possible infection)

—Blistering, pain, burning sensation, or swelling at the IV site

—Shortness of breath, wheezing, difficulty breathing, closing up of the throat, swelling of facial features, hives (possible allergic reactions)

• Contact your health care provider within 24 hours of noticing any of the following:

—Mouth sores (painful redness, swelling, or ulcers)

—Nausea (interferes with ability to eat and unrelieved with prescribed medication)

—Vomiting (vomiting more than 4 to 5 times in a 24-hour period)

—Diarrhea (4 to 6 episodes in a 24-hour period)

—Fast or irregular heartbeats

—Unusual bleeding or bruising

—Black or tarry stools or blood in your stools or urine

—Extreme fatigue (bad enough that you cannot carry on self-care activities)

—Swelling of the feet or ankles ONA

Prepared by Bette Weinstein Kaplan. Reviewed by Maribel Pereiras, PharmD, BCPS, BCOP.

From the August 01, 2010 Issue of Oncology Nurse Advisor