DOXORUBICIN HYDROCHLORIDE

(dox-oh-roo'bi-sin)

Adriamycin, Rubex
DOXORUBICIN LIPOSOME
Doxil
Classifications: antineoplastic; antibiotic;
Therapeutic: antineoplastic
Pregnancy Category: D

Availability

10 mg, 20 mg, 50 mg, 100 mg, 150 mg powder for injection; 2 mg/mL injection; 20 mg liposomal injection

Action

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 reactions.

Therapeutic Effect

Highly destructive to rapidly proliferating cells and slowly developing carcinomas; selectively toxic to cardiac tissue.

Uses

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.

Contraindications

Myelosuppression, thrombocytopenia; impaired cardiac function, obstructive jaundice, previous treatment with complete cumulative doses of doxorubicin or daunorubicin; lactation; pregnancy (category D).

Cautious Use

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

Hodgkin's Disease
Adult/Child: IV 25 mg/m² days 1 and 15, repeat q28d

Thyroid Cancer
Adult/Child: IV 60–75 mg/m² q3wk

Other Neoplasms
Adult: IV 40–50 mg/m² usually in combination with other agents (max: total cumulative lifetime dose 500–550 mg/m²)
Child: IV 35–75 mg/m² as single dose, repeat at 21-d interval, or 20–30 mg/m² once weekly (max: total cumulative lifetime dose 500–550 mg/m²)

Hepatic Impairment
Bilirubin 1.2–3 mg/dL: reduce dose by 50%; bilirubin 3–5 mg/dL: reduce dose by 75%; bilirubin >5 mg/dL: stop therapy

DOXORUBICIN LIPOSOME

Kaposi's Sarcoma
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

Hepatic Impairment
Bilirubin 1.2–3 mg/dL: reduce dose 50%; bilirubin 3–5 mg/dL: reduce dose by 75%

Administration

Intravenous

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.

Conventional Doxorubicin

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 3–5 min. ??Monitor for red streaking along vein or facial flushing which indicates need to slow infusion rate.

Lyophilized Doxorubicin

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 (60–85% of patients); leukopenia (principally granulocytes) , thrombocytopenia, anemia. Skin: 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, lymphangitis, phlebosclerosis.

Interactions

Drug: barbiturates may decrease effects by increasing its hepatic metabolism; streptozocin 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.

Pharmacokinetics

Distribution: Widely distributed; does not cross blood–brain barrier; 75% protein binding; does not cross placenta; passes into breast milk. Metabolism: Metabolized in liver to active metabolite. Elimination: Excreted primarily in bile. Half-Life: 30–50 h. Doxorubicin Liposomal: Distribution: Vascular fluid. Metabolism: Metabolized in plasma and liver. Elimination: In urine. Half-Life: 44–55 h.

Nursing Implications

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 3–4 wk. If ulceration begins (usually 1–4 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 10–14 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 2–3 mo after drug is discontinued.
Drug turns urine red for 1–2 d after administration.
Keep hands away from eyes to prevent conjunctivitis. Increased tearing for 5–10 d after a single dose is possible.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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