Doxorubicin

Doxorubicin is a cytotoxic, anthracycline, topoisomerase II inhibitor indicated as a component of multi-agent adjuvant chemotherapy for treatment of women with axillary lymph node involvement following resection of primary breast cancer.

Doxorubicin is also indicated for the treatment of cancers of the ovary, prostate, stomach, and thyroid; small cell cancer of the lung, and liver; squamous cell cancer of the head and neck; multiple myeloma, Hodgkin's disease, lymphomas, acute lymphocytic leukemia (ALL), and acute myeloid leukemia (AML).

• Doxorubicin is available under the following different brand names: Adriamycin, Caelyx, Lipodox, Rubex

Common side effects of Doxorubicin include:

• hair loss, 
• thinning hair, 
• nausea, 
• vomiting, 
• sores in the mouth, 
• skin darkening on the palms or feet, and 
• diarrhea

Serious side effects of Doxorubicin include:

• fast or irregular heartbeat, 
• shortness of breath, 
• swelling of the feet and ankles, 
• cough, 
• hoarseness, 
• fever, 
• chills, 
• redness or darkening of the skin, 
• joint pain, 
• lower back or side pain, 
• pain at the injection site, 
• painful or difficult urination, 
• red streaks along the injected vein, 
• stomach pain, 
• black or tarry stools, 
• blood in the urine, 
• pinpoint red spots on the skin, 
• easy bruising, and
• unusual bleeding

Rare side effects of Doxorubicin include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; sudden dizziness, lightheartedness, or passing out.

Adult and pediatric dosage

Injectable solution

• 2 mg/mL

Powder for injection

• 10 mg
• 50 mg

Cancers

Adult dosage

• 60-75 mg/m2 IV every 21 days or 
• 60 mg/m2 IV every 14 days or
• 40-60 mg/m2 IV every 21-28 days or
• 20 mg/m2/dose every week

Pediatric dosage

• 35-75 mg/m2 IV every 21 days or
• 20-30 mg/m2/dose every week
• 60-90 mg/m2 IV over 96 hours every 3-4 weeks 

Renal Impairment

• Dose adjustment is not necessary

Hepatic Impairment

• Serum bilirubin less than 1.2 mg/dL: Dose adjustment not necessary
• Serum bilirubin 1.2-3 mg/dL [20.5-51.3 micromoles/L]: Give 50% dose
• Serum bilirubin: 3.1-5 mg/dL [53-85.5 micromoles/L]: Give 25% dose
• Severe hepatic impairment: Contraindicated

Administration

• Limit lifetime cumulative dose to less than 550 mg/m² to reduce the risk of cardiotoxic
• Monitor: complete blood count (CBC), cardiac function, liver function tests (LFTs)

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

• Doxorubicin has severe interactions with no other drugs. 
• Doxorubicin has serious interactions with at least 33 other drugs. 
• Doxorubicin has moderate interactions with at least 136 other drugs. 
• Doxorubicin has minor interactions with the following drugs:
  • amobarbital
  • artemether/lumefantrine
  • dactinomycin
  • progesterone, natural
  • rifapentine
  • ruxolitinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Contraindications

• Hypersensitivity
• Active infection
• Severe hepatic impairment
• Baseline neutrophil count under 1500/mm3
• Recent MI or severe myocardial insufficiency
• Prior treatment max dose of doxorubicin, daunorubicin, idarubicin, or other anthracyclines
• Cardiomyopathy, CHF, impaired cardiac function
• IM/SC administration

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Doxorubicin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Doxorubicin?”

Cautions

Vesicant

• Pericarditis and myocarditis reported during or following treatment; assess left ventricular cardiac function (eg, MUGA or echocardiogram) before initiation of doxorubicin; discontinue in patients who develop signs or symptoms of cardiomyopathy; consider the use of dexrazoxane to reduce incidence and severity of cardiomyopathy due to administration in patients who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m2 and who will continue to receive doxorubicin hydrochloride
• The risk of developing secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) is increased following treatment with doxorubicin hydrochloride. Cumulative incidences ranged from 0.2% at five years to 1.5% at 10 years in two separate trials involving the adjuvant treatment of women with breast cancer. These leukemias generally occur within 1 to 3 years of treatment
• Drug clearance of doxorubicin is decreased in patients with elevated serum bilirubin with increased risk of toxicity; reduce dose in patients with serum bilirubin levels of 1.2 to 5 mg/dL; obtain liver tests including ALT, AST, alkaline phosphatase, and bilirubin before and during therapy
• Doxorubicin hydrochloride can induce tumor lysis syndrome in patients with rapidly growing tumors; evaluate blood uric acid levels, potassium, calcium, phosphate, and creatinine after initial treatment; hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor lysis syndrome
• Therapy can increase radiation-induced toxicity to myocardium, mucosa, skin, and liver; radiation recall, including but not limited to cutaneous and pulmonary toxicity, can occur in patients who receive drugs after prior radiation therapy
• Secondary oral cancers, primarily squamous cell carcinoma, reported with long-term (i.e., over 1 year)
• Use caution in the elderly, liver impairment, and concomitant radiotherapy
• Not effective in malignant melanoma, kidney CA, bowel CA, brain tumors, CNS metastasis
• Therapy can cause myelosuppression; dose-dependent, reversible neutropenia is predominant manifestation of myelosuppression from therapy; obtain complete blood counts before each treatment and carefully monitor patients during treatment for possible clinical complications due to myelosuppression; delay next dose if severe myelosuppression has not improved; consider dose reduction for patients with prolonged myelosuppression based on the severity of the reaction

Extravasation

• Extravasation of doxorubicin hydrochloride can cause severe local tissue injury manifesting as blistering, ulceration, and necrosis requiring wide excision of the affected area and skin grafting
• Extravasation should be considered if a patient experiences a burning or stinging sensation or shows other evidence indicating peri-venous infiltration or extravasation; however, extravasation may be present in patients who do not experience a stinging or burning sensation or when blood return is present on the aspiration of the infusion needle
• When given via a peripheral venous line, infuse over 10 minutes or less to minimize the risk of thrombosis or perivenous extravasation
• If extravasation is suspected, immediately discontinue intravenous injection or continuous intravenous infusion; apply ice to site intermittently for 15 minutes, 4 times a day for 3 days; in adults, if appropriate, administer dexrazoxane at the site of extravasation as soon as possible and within the first 6 hours after extravasation

Arrhythmias

• Therapy can result in arrhythmias, including life-threatening arrhythmias, during or within a few hours after treatment and at any time point during treatment; tachyarrhythmias, including sinus tachycardia, premature ventricular contractions, and ventricular tachycardia, as well as bradycardia, can occur
• Electrocardiographic changes, including non-specific ST-T wave changes, atrioventricular and bundle-branch block can also occur; these electrocardiographic changes may be transient and self-limited and may not require a dosage modification of doxorubicin hydrochloride

Pediatric patients

• Based on postmarketing reports, pediatric patients are at risk for developing late cardiovascular dysfunction
• Risk factors include young age at treatment (especially over 5 years), high cumulative doses and receipt of combined modality therapy; long-term periodic cardiovascular monitoring recommended for all pediatric patients
• The drug, as a component of intensive chemotherapy regimens administered to pediatric patients, may contribute to prepubertal growth failure and may also contribute to gonadal impairment, which is usually temporary

Pregnancy and Lactation

• Based on findings in animals and its mechanism of action, the drug can cause fetal harm when administered to a pregnant woman; avoid use during 1st trimester; available human data do not establish presence or absence of major birth defects and miscarriage related to use during 2nd and 3rd trimesters; the drug was teratogenic and embryotoxic in rats and embryotoxic in rabbits when administered during organogenesis at doses approximately 0.07 times (based on body surface area) recommended human dose of 60 mg/m2; advise pregnant women of the potential risk to a fetus
• Verify pregnancy status of females of reproductive potential before initiating therapy
• In females of reproductive potential, the drug may cause infertility and result in amenorrhea; premature menopause can occur; recovery of menses and ovulation is related to age at treatment

Contraception

• Females: Treatment can cause fetal harm when administered to pregnant women; advise female patients of reproductive potential to use highly effective contraception during treatment and for 6 months after treatment
• Males: Treatment may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities; due to potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after treatment; males with pregnant partners should use condoms during treatment and for at least 10 days after the final dose

Lactation

• Data are not available regarding effects on breastfed children or milk production
• Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 10 days after the final dose