Doxorubicin hydrochloride


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Doxorubicin hydrochloride
(ADR)

Doxorubicin hydrochloride (Adriamycin PFS, Adriamycin RDF)
ADR (Adriamycin PFS, Adriamycin RDF)
Doxorubicin
(dox-oh- ROO-bih-sin)
Pregnancy Category: D Adriamycin PFS Adriamycin RDF Rubex (Rx)
Doxorubicin hydrochloride liposomal
Doxorubicin hydrochloride liposomal
Doxorubicin
Pregnancy Category: D Doxil (Rx)

Classification: Antineoplastic, anthracycline antibiotic

See Also: See also Antineoplastic Agents .

Action/Kinetics: Produced by Streptomyces peucetius. Cell-cycle specific for the S phase of cell division. Antineoplastic activity may be due to binding to DNA by intercalating between base pairs resulting in inhibition of synthesis of DNA and RNA by template disordering and steric obstruction. The liposomal product is produced with surface-bound methoxypolyethylene in order to protect liposomes from detection by mononuclear phagocytes and to increase blood circulation time. It is believed the liposomes are able to penetrate altered and often compromised vasculature of tumors. Conventional doxorubicin is significantly bound to tissue and plasma proteins whereas the liposomal product is confined mostly to the vascular fluid and does not bind to plasma proteins. Metabolized in the liver to the active doxorubicinol as well as inactive metabolites, which are excreted through the bile. t 1/2, doxorubicin, conventional: triphasic: 12 min, 3.3 hr, and 29.6 hr. t 1/2, liposomes: About 55 hr.

Uses: Conventional doxorubicin: Acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms' tumor, soft tissue and osteogenic sarcomas, neuroblastoma, cancer of the breast, ovaries, lungs, bladder, and thyroid, lymphomas (Hodgkin's and non-Hodgkin's), bronchogenic carcinoma (especially small cell histologic type) and gastric carcinoma. Investigational (conventional): Cancer of the head and neck, cervix, liver, pancreas, prostate, testes, and endometrium.
Liposomal doxorubicin: AIDS-related Kaposi's sarcoma in clients where the disease has progressed on prior combination therapy or in those who are intolerant of such therapy. Third-line treatment of metastatic ovarian cancer in women who have failed or relapsed after cisplatin- or paclitaxel-based chemotherapy.

Contraindications: Malignant melanoma, cancer of the kidney, large bowel carcinoma, brain tumors and metastases to the CNS (not responsive to doxorubicin therapy). Initiation of therapy in those with marked myelosuppression induced by previous treatment with other drugs or with radiotherapy. Use in preexisting heart disease. Previous treatment with complete cumulative doses of doxorubicin or daunorubicin. Lactation. Depressed bone marrow or cardiac disease. IM or SC use.

Special Concerns: Use with caution in impaired hepatic function and necrotizing colitis. Cardiotoxicity may be more frequent in children.

Additional Side Effects: Myocardial toxicity: Potentially fatal CHF. Infusion reactions liposomal product: Flushing, SOB, facial swelling, headache, chills, back pain, tightness in chest and throat, hypotension. GI: N&V, mucositis (stomatitis, esophagitis), anorexia, diarrhea. Ulceration and necrosis of the colon. Dermatologic: Reversible complete alopecia, hyperpigmentation of nail beds and dermal creases (especially in children), onycholysis, recall of skin reaction to prior radiotherapy, palmar-plantar erythrodysesthesia (swelling, pain, erythema, and desquamation of the skin on the hands and feet). Local: Severe cellulitis, vesication, and tissue necrosis if the drug is extravasated. Erythematous streaking along the vein next to injection site. Hypersensitivity: Fever, chills, urticaria, cross-sensitivity with lincomycin, anaphylaxis. Hematologic: Myelosuppression. Ophthalmic: Conjunctivitis, lacrimation.

Overdose Management: Symptoms: Mucositis, leukopenia, thrombocytopenia, pancytopenia. Increased risk of cardiomyopathy and subsequent CHF with chronic overdosage. Treatment: If the client is myelosuppressed, antibiotics and platelet and granulocyte transfusions may be necessary. Treat symptoms of mucositis. Treat CHF with digitalis preparations and diuretics as well as peripheral vasodilators.

Drug Interactions: Barbiturates / Plasma clearance of doxorubicin Cyclophosphamide / Risk of hemorrhagic cystitis Digoxin / Digoxin plasma levels and renal excretion 6-Mercaptopurine / Risk of hemorrhagic cystitis

How Supplied: Conventional. Aqueous Injection: 2 mg/mL; Powder for injection, lyophilized: 10 mg, 20 mg, 50mg, 100 mg, 150 mg. Liposomal. Injection: 20 mg

Dosage
?IV Only ?Conventional Doxorubicin
Adults, highly individualized: 60-75 mg/m 2 as a single injection q 21 days. Alternatively, 30 mg/m 2 for 3 successive days q 4 weeks, or 20 mg/m 2 q week. Do not exceed a total dose of 550 mg/m 2 (440 mg/m 2 in clients with previous chest irradiation or medications increasing cardiotoxicity). Pediatric: 30 mg/m 2 on 3 successive days q 4 weeks. Use reduced dosage in clients with hepatic dysfunction, depending on serum bilirubin level. If bilirubin is 1.2-3 mg/100 mL, give 50% of usual dose; if it is greater than 3 mg/100 mL, give 25% of usual dose.
?Liposomal Doxorubicin AIDS-related Kaposi's sarcoma.
Adults: 20 mg/m 2 over 30 min once q 3 weeks, as long as the client responds satisfactorily and tolerates the drug. For clients with hepatic dysfunction, use the same dosing schedule as conventional doxorubicin.
Metastatic ovarian carcinoma.
50 mg/m 2 at an initial rate of 1 mg/min. If no adverse effects occur, increase the rate of infusion to complete administration in 1 hr.

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