- Injection, solution 2 mg/mL
- Injection, lyophilized powder for solution 10 mg
- Injection, lyophilized powder for solution 20 mg
- Injection, lyophilized powder for solution 50 mg
Cells treated with doxorubicin have been shown to manifest the characteristic morphologic changes associated with apoptosis or programmed cell death. Doxorubicin-induced apoptosis may be an integral component of the cellular mechanism of action relating to therapeutic effects, toxicities, or both.
Distribution half-life is approximately 5 min. Vd is 809 to 1,214 L/m 2 . 74% to 76% protein bound.
Metabolized to doxorubicinol (active).
The half-life is 20 to 48 h. Cl is 324 to 809 mL/min/m 2 . Approximately 40% is excreted in the bile and 5% to 12% in the urine in 5 days.
Special PopulationsRenal Function Impairment
The influence of renal function on the pharmacokinetics has not been evaluated.Hepatic Function Impairment
Excretion is slower, resulting in increased retention and accumulation. Reduce dose in those with elevated bilirubin.Elderly
No dosage adjustment is recommended based on age.Children
Cl in children older than 2 y was increased compared with adults.Gender
Cl appears to be higher in men than women; however, the half-life was longer in men compared with women.Race
The influence of race on the pharmacokinetics has not been evaluated.
Indications and Usage
Produce regression of disseminated neoplastic conditions, such as acute lymphoblastic leukemia, acute myeloblastic leukemia, breast carcinoma, gastric carcinoma, Hodgkin disease, malignant lymphoma and bronchogenic carcinoma, neuroblastoma, ovarian carcinoma, soft tissue and bone sarcomas, thyroid carcinoma, transitional cell bladder carcinoma, Wilms tumor; component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer.
Multiple myeloma; endometrial, islet cell, Merkel cell carcinoma; thymic carcinoma or thymoma; AIDS-related Kaposi sarcoma.
Baseline neutrophil count less than 1,500 cells/mm 3 ; severe hepatic impairment; recent MI; severe myocardial insufficiency; severe arrhythmias; previous treatment with complete cumulative doses of doxorubicin, daunorubicin, idarubicin, or other anthracyclines and anthracenediones; hypersensitivity to doxorubicin, any of its excipients, or other anthracyclines or anthracenediones.
Dosage and AdministrationSingle Agent Therapy
Adults and children
IV 60 to 75 mg/m 2 as a single dose every 21 days.Combination Therapy
Adults and children
IV 40 to 60 mg/m 2 as a single dose every 21 to 28 days.Adjuvant Therapy in Breast Cancer
IV 60 mg/m 2 with cyclophosphamide 600 mg/m 2 IV on day 1 of each 21-day treatment cycle for 4 cycles. For patients who develop neutropenic fever/infection, decrease doses to 75% of the starting doses. When necessary, the next cycle can be delayed until the ANC is at least 1,000 cells/mm 3 , platelet count is at least 100,000 cells/mm 3 , and nonhematologic malignancies have resolved.Patients With Elevated Bilirubin
If serum bilirubin is 1.2 to 3 mg/dL, give 50% of adjusted dose from prior course. If serum bilirubin is 3.1 to 5 mg/dL, give 25% of adjusted dose from prior course. Some clinicians recommend not giving doxorubicin to patients with a bilirubin above 5 mg/dL.
- Calculate dosage using the lower of ideal body weight or actual body weight.
- The lower dosage should be given to patients with inadequate marrow reserves due to old age, prior therapy, or neoplastic marrow infiltration.
- Do not mix doxorubicin with other drugs.
- Dilute lyophilized powder with 5, 10, or 25 mL of sodium chloride 0.9% for the 10, 20, or 50 mg vial, respectively (final concentration, 2 mg/mL).
- Administer IV infusion slowly into a freely running IV infusion of sodium chloride injection or dextrose 5% injection. Attach tubing to a butterfly needle inserted into a large vein. Avoid veins over joints or in extremities with compromised venous or lymphatic drainage. Administer over at least 3 to 5 min. Local erythematous streaking along the vein, as well as facial flushing, may indicate too rapid administration.
- Caregivers of children receiving doxorubicin should be counseled to take precautions (such as wearing latex gloves) to prevent contact with the patient's urine and other body fluids for at least 5 days after each treatment.
Store lyophilized powder between 59° and 86°F and protect from light. Refrigerate solution and protect from light. Reconstituted solution is stable for 7 days between 59° and 86°F and under normal room light, and 15 days under refrigeration (36° to 46°F). Protect from sunlight. Discard any of the unused solution from the single-dose vials.
Drug InteractionsBarbiturates (eg, phenobarbital)
Elimination of doxorubicin may be increased. Monitor the clinical response. The doxorubicin dose may need to be adjusted when barbiturates are started or stopped.Calcium channel blockers (eg, diltiazem)
Studies have suggested that coadministration of doxorubicin and calcium channel blockers may increase the risk of doxorubicin cardiotoxicity. Closely monitor for signs of cardiac dysfunction.Cardiotoxic agents (eg, trastuzumab)
Doxorubicin should not be administered with other cardiotoxic drugs unless cardiac function is closely monitored. Patients receiving doxorubicin after stopping treatment with other cardiotoxic agents, especially those with long half-lives, such as trastuzumab, may be at increased risk for developing cardiotoxicity. Closely monitor for signs of cardiac dysfunction.Cyclophosphamide
Cyclophosphamide-induced hemorrhagic cysts may be exacerbated; risk of occurrence of acute myeloid leukemia may be increased. The risk of cardiotoxicity may be increased. Monitor for symptoms of heart failure.Cyclosporine
Doxorubicin and doxorubinol concentrations may be increased. Profound and prolonged hematologic toxicity, as well as coma and seizures, have been reported. Close clinical and laboratory monitoring is warranted.Cytarabine
Bloody stools, life-threatening reactions, and necrotizing colitis have been reported.Dactinomycin
Pediatric patients receiving concomitant doxorubicin and dactinomycin have manifested acute “recall” pneumonitis at variable times after local radiation therapy.Digoxin
Doxorubicin may decrease oral absorption of digoxin tablets. Monitor digoxin serum concentrations and the patient for evidence of clinical deterioration (eg, worsening CHF); adjust the digoxin dosage accordingly.Paclitaxel
Risk of cardiotoxicity may be increased.Palifermin
Coadministration of palifermin and doxorubicin within the same 24-h time period may increase the severity and duration of oral mucositis. Palifermin should not be administered within 24 h before, during, or 24 h after administration of doxorubicin.Phenytoin
Concentrations may be reduced by doxorubicin. Monitor phenytoin plasma concentrations, seizure frequency, and phenytoin toxicity during and after chemotherapy treatment cycles; adjust the phenytoin dosage as needed.Progesterone
Risk of neutropenia and thrombocytopenia may be increased.Radiation
Radiation-induced toxicity to the myocardium, mucosa, skin, and liver has been increased by doxorubicin administration.Sorafenib
In clinical studies, both an increase and no changes in the AUC of doxorubicin were observed. The clinical importance of these findings is unknown.Streptozocin
Doxorubicin concentrations may be elevated. Close clinical and laboratory monitoring is warranted.Vaccines
Administration of live or live-attenuated vaccines may result in serious or fatal infections. Vaccination with live vaccines should be avoided. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.Warfarin
Hypoprothrombinemic effects of warfarin may be increased by doxorubicin. Monitor anticoagulant activity and adjust the warfarin dose as needed.
Coma; malaise/asthenia; peripheral neurotoxicity; seizures.
Alopecia (92%); facial flushing; hyperpigmentation of nail beds and dermal creases; itching; onycholysis; photosensitivity; radiation recall; rash.
Conjunctivitis, keratitis, lacrimation.
Vomiting (37%); nausea (16%); abdominal pain; anorexia; dehydration; diarrhea; esophagitis; hyperpigmentation of the oral mucosa; mucositis; necrotizing colitis; stomatitis; ulceration and necrosis of the colon.
Leukopenia (3%); bone marrow suppression.
Anaphylaxis; chills; fever; urticaria.
Weight gain (11%); weight loss (6%).
Shock/sepsis, systemic infection (2%).
Severe local tissue necrosis will occur if there is extravasation during administration. Must not be given by the IM or subcutaneous route.Cardiotoxicity
Myocardial toxicity manifested in its most severe form by potentially fatal CHF may occur during therapy or months to years after termination of therapy. The risk of developing CHF increases rapidly with increasing total cumulative doses of doxorubicin in excess of 400 mg/m 2 . Risk factors (active or dormant CV disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, concomitant use of other cardiotoxic drugs) may increase the risk of cardiotoxicity. Cardiac toxicity with doxorubicin may occur at lower cumulative doses whether or not cardiac risk factors are present. Pediatric patients are at an increased risk for developing delayed cardiotoxicity.Secondary malignancy
Secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome have been reported. The occurrence of refractory secondary AML or myelodysplastic syndrome is more common when anthracyclines are given in combination with DNA-damaging antineoplastic agents or radiotherapy, when patients have been heavily pretreated with cytotoxic drugs, or when doses or anthracyclines have been escalated. Pediatric patients are also at risk of developing secondary AML.Hepatic function impairment
Reduce doxorubicin doses.Myelosuppression
Severe myelosuppression may occur.
Perform a careful baseline assessment of blood cell counts; serum levels of total bilirubin, AST, and creatinine; and cardiac function as measured by left ventricular ejection function (LVEF). Carefully monitor patients for possible clinical complications of myelosuppression. Assess total and differential WBC, RBC, and platelet counts before and during each cycle of therapy. Periodically monitor hepatic function tests. Evaluate blood uric acid levels, potassium, calcium, phosphate, and creatinine after initial treatment. Perform repeated evaluations of LVEF, particularly with higher, cumulative doxorubicin doses. Because children are at increased risk for developing delayed cardiotoxicity, follow-up cardiac evaluations are recommended periodically to monitor for delayed cardiotoxicity.
Category D .
Excreted in breast milk.
Children are at increased risk for developing delayed cardiotoxicity and for developing AML and other neoplasms. Doxorubicin may contribute to prepubertal growth failure. It may also contribute to gonadal impairment, which is usually temporary.
Oligospermia or azoospermia may occur in men and can be permanent. Sperm counts may return to normal several years after the end of therapy. Men should use effective contraception. May cause amenorrhea, premature menopause, and infertility in women.
Doxorubicin is emetogenic. Consider prophylactic use of antiemetics prior to administration of doxorubicin, especially when given in conjunction with other emetogenic agents.
Abnormalities of hepatic function tests may occur.
Phlebosclerosis may result from injection into a small vessel or from repeated injections into the same vein. Following recommended administration procedures may minimize the risk of phlebitis/thrombophlebitis at injection site.
Tumor lysis syndrome
May occur. Hydration, urinary alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor lysis syndrome.
Cardiomyopathy/CHF, leukopenia, mucositis, thrombocytopenia.
- Advise patients, families, or caregivers that medication will be prepared and administered by a health care provider in a health care setting.
- Advise patients, families, or caregivers that medication may be used in combination with other agents to achieve maximum benefit possible.
- Review dosing schedule with patients, families, or caregivers.
- Advise patients, families, or caregivers that this medication will usually cause a red coloration of the urine for 1 to 2 days after administration. Advise patients that this is not a problem and is expected because the medication is eliminated in the urine.
- Advise patients, families, or caregivers that this medication may cause hair loss but that this is reversible when therapy is stopped.
- Advise patients, families, or caregivers to immediately report any of the following to their health care provider: chest pain; chills or other signs of infection; difficulty breathing; fever; hives; pain, redness, or swelling at injection site; rash; sores in mouth; unusual bleeding or bruising.
- Advise patients, families, or caregivers to report any of the following to their health care provider: persistent appetite loss, diarrhea, nausea, or vomiting; persistent or worsening general body weakness.
- Caution women of childbearing potential to avoid becoming pregnant while being treated.
- Advise men to use effective contraception during treatment.
- Inform women that treatment with doxorubicin may lead to irreversible amenorrhea or premature menopause.
- Advise patients that following discharge from the hospital, frequent follow-up visits, ECGs or heart function tests, and laboratory tests will be required to monitor therapy, and to keep appointments.
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