Classifications: antineoplastic; antibiotic; Therapeutic: antineoplastic
Pregnancy Category: D
10 mg, 20 mg, 50 mg, 100 mg, 150 mg powder for injection; 2 mg/mL injection; 20 mg liposomal injection
Cytotoxic antibiotic with wide spectrum of antitumor activity and strong immunosuppressive properties. Intercalates with
preformed DNA residues, blocking effective DNA and RNA transcription. A potent radiosensitizer capable of enhancing radiation
Highly destructive to rapidly proliferating cells and slowly developing carcinomas; selectively toxic to cardiac tissue.
Doxorubicin: To produce regression in neoplastic conditions, including acute lymphoblastic and myeloblastic leukemias, transitional
cell bladder cancer, breast cancer, Hodgkin's disease, ovarian cancer, small-cell lung cancer, non-Hodgkin's lymphoma, thyroid
cancer, Wilms' tumor, soft tissue and bone sarcomas. Generally used in combined modalities with surgery, radiation, and
immunotherapy. Effective pretreatment to sensitize superficial tumors to local radiation therapy. Liposome Doxorubicin: Kaposi's sarcoma, progressive/refractory ovarian cancer, relapsed/refractory multiple myeloma.
Myelosuppression, thrombocytopenia; impaired cardiac function, obstructive jaundice, previous treatment with complete cumulative
doses of doxorubicin or daunorubicin; lactation; pregnancy (category D).
Impaired hepatic or renal function; patients who have received cyclophosphamide or pelvic irradiation or radiotherapy to
areas surrounding heart; history of atopic dermatitis.
Route & Dosage
| CONVENTIONAL DOXORUBICIN
Acute Lymphatic Leukemia
Adult/Child: IV 30 mg/m2 weekly x 4 wk
Acute Myelogenous Leukemia
Adult/Child: IV 30 mg/m2 x 3 d (with cytarabine)
Transitional Bladder Cell Cancer
Adult: IV 30 mg/m2/dose once monthly
Adult/Child: IV 25 mg/m2 days 1 and 15, repeat q28d
Adult/Child: IV 6075 mg/m2 q3wk
Adult: IV 4050 mg/m2 usually in combination with other agents (max: total cumulative lifetime dose 500550 mg/m2)
Child: IV 3575 mg/m2 as single dose, repeat at 21-d interval, or 2030 mg/m2 once weekly (max: total cumulative lifetime dose 500550 mg/m2)
Bilirubin 1.23 mg/dL: reduce dose by 50%; bilirubin 35 mg/dL: reduce dose by 75%; bilirubin >5 mg/dL:
Adult: IV 20 mg/m2 every 3 wk. Infuse over 30 min (do not use in-line filters).
Progressive/Refractory Ovarian Cancer
Adult: IV 50 mg/m2 q4wk, minimum of 4 courses
Relapsed/Refractory Multiple Myeloma
Adult: IV 45 mg/m2 q4wk, up to 6 cycles
Bilirubin 1.23 mg/dL: reduce dose 50%; bilirubin 35 mg/dL: reduce dose by 75%
- IV administration to infants and children: Verify correct IV concentration and rate of infusion with physician.
- Wear gloves and use caution when preparing drug solution. If powder or solution contacts skin or mucosa, wash copiously with
soap and water.
- Exposure to doxorubicin during the first trimester of pregnancy can result in losing the fetus.
PREPARE: Direct: Vial reconsitution: Dilute with 1 mL of nonbacteriostatic NS for each 2 mg of doxorubicin to yield a final concentraion of 2 mg/mL. For each
mL of NS added, withdraw an equal volume of air from vial to minimize pressure buildup. Shake to dissolve. ?? Doxorubicin solutions: Solutions of 2 mg/mL are available that can be further diluted in 50 mL or more of NS or D5W.
ADMINISTER: Direct: Give bolus dose slowly into Y-site of freely running IV infusion of NS or D5W. If possible, use IV tubing attached to a
needle inserted into a larger vein with a butterfly needle. ??Usually infused over 35 min. ??Monitor for red streaking along vein or facial flushing which indicates need to slow infusion rate.
PREPARE: IV Infusion: Dilute doses up to 90 mg in 250 mL of D5W and doses >90 mg in 500 mL D5W. Solution will be translucent but not clear, and
will be red in color. ??DO NOT use filters during preparation or administration.
ADMINISTER: IV Infusion: DO NOT give bolus injection or undiluted solution. ??Infuse at 1 mg/min initially; may increase rate to complete infusion in 1 h if no adverse reactions occur. Slow infusion
rate as warranted if an adverse reation occurs.??Do not use a filter.
INCOMPATIBILITIES Solution/additive: Conventional doxorubicin: Aminophylline, diazepam, fluorouracil. Y-site: Conventional doxorubicin: Allopurinol, amphotericin B cholesteryl sulfate, cefepime, gallium, ganciclovir, lansoprazole, pemetrexed, prochlorperazine, propofol, TPN. Doxorubicin liposomal: Amphotericin B, amphotericin B cholesteryl complex, hydroxyzine, mannitol, meperidine, metoclopramide, mitoxantrone, morphine, paclitaxel, piperacillin/tazobactam, promethazine, sodium bicarbonate.
- Facial flushing and local red streaking along the vein may occur if drug is administered too rapidly.
- Avoid using antecubital vein or veins on dorsum of hand or wrist, if possible, where extravasation could damage underlying
tendons and nerves. Also avoid veins in extremity with compromised venous or lymphatic drainage.
- Store reconstituted solution for 24 h at room temperature; refrigerated at 4°10° C (39°50°
F) for 48 h. Protect from sunlight; discard unused solution.
Adverse Effects (≥1%) Body as a Whole:
Hypersensitivity (red flare around injection site, erythema
, skin rash, pruritus, angioedema, urticaria, eosinophilia, fever,
chills, anaphylactoid reaction
). CV: Serious, irreversible myocardial toxicity with delayed CHF, ventricular arrhythmias, acute left ventricular failure,
hypertension, hypotension, cardiomyopathy. GI: Stomatitis,
esophagitis with ulcerations; nausea, vomiting, anorexia, inanition, diarrhea
. Hematologic: Severe myelosuppression
(6085% of patients); leukopenia (principally granulocytes) , thrombocytopenia
Hyperpigmentation of nail beds, tongue, and buccal mucosa
(especially in blacks); complete alopecia
(reversible), hyperpigmentation of dermal creases (especially in children), rash, recall phenomenon (skin reaction due to prior radiotherapy). Other:
Lacrimation, drowsiness, fever, facial flush with too rapid IV
infusion rate, microscopic hematuria, hyperuricemia, hand-foot syndrome. With extravasation: severe cellulitis, vesication, tissue necrosis,
may decrease effects by increasing its hepatic metabolism
may prolong doxorubicin half-life
; agents affecting QT interval (e.g., Bepridil, droperidol, erythromycin, halpperidol, methadone, phenothiazine
, etc.) may increase risk of cardiac side effects
. Conventional formulation: Avoid use with zidovudine.
Widely distributed; does not cross bloodbrain barrier; 75% protein binding; does not cross placenta; passes into
breast milk. Metabolism:
Metabolized in liver to active metabolite
Excreted primarily in bile. Half-Life:
3050 h. Doxorubicin Liposomal: Distribution:
Vascular fluid. Metabolism:
Metabolized in plasma
and liver. Elimination:
In urine. Half-Life:
Assessment & Drug Effects
- Care should be taken to avoid extravasation. Stop infusion, remove IV needle, and notify physician promptly if patient complains
of stinging or burning sensation at the injection site.
- Monitor any area of extravasation closely for 34 wk. If ulceration begins (usually 14 wk after extravasation),
a plastic surgeon should be consulted.
- Begin a flow chart to establish baseline data. Include temperature, pulse, respiration, BP, body weight, laboratory values,
and I&O ratio and pattern.
- Lab tests: Baseline and periodic hepatic function, renal function, CBC with differential throughout therapy.
- Note: The nadir of leukopenia (an expected 1000/mm3) typically occurs 1014 d after single dose, with recovery occurring within 21 d.
- Evaluate cardiac function (ECG) prior to initiation of therapy, at regular intervals, and at end of therapy.
- Be alert to and report early signs of cardiotoxicity (see Appendix F). Acute life-threatening arrhythmias may occur within
a few hours of drug administration.
- Report promptly objective signs of hepatic dysfunction (jaundice, dark urine, pruritus) or kidney dysfunction (altered I&O
ratio and pattern, local discomfort with voiding).
- Promote fastidious oral hygiene, especially before and after meals. Stomatitis, generally maximal in second week of therapy,
frequently begins with a burning sensation accompanied by erythema of oral mucosa that may progress to ulceration and dysphagia
in 2 or 3 d.
- Report signs of superinfection (see Appendix F) promptly; these may result from antibiotic therapy during leukopenic period.
- Avoid rectal medications and use of rectal thermometer; rectal trauma is associated with bloody diarrhea resulting from
an antiblastic effect on rapidly growing intestinal mucosal cells.
Patient & Family Education
- Note: Complete loss of hair (reversible) is an expected adverse effect. It may also involve eyelashes and eyebrows, beard and
mustache, pubic and axillary hair. Regrowth of hair usually begins 23 mo after drug is discontinued.
- Drug turns urine red for 12 d after administration.
- Keep hands away from eyes to prevent conjunctivitis. Increased tearing for 510 d after a single dose is possible.