Dose-limiting toxicities of therapy are myelosuppression and cardiotoxicity (see WARNINGS). Other reactions reported are:
Cardiotoxicity: (See WARNINGS.)
Cutaneous: Reversible complete alopecia occurs in most cases. Hyperpigmentation of nailbeds and dermal creases, primarily in children, and onycholysis have been reported in a few cases. Recall of skin reaction due to prior radiotherapy has occurred with doxorubicin administration.
Gastrointestinal: Acute nausea and vomiting occurs frequently and may be severe. This may be alleviated by antiemetic therapy. Mucositis (stomatitis and esophagitis) may occur 5 to 10 days after administration. The effect may be severe leading to ulceration and represents a site of origin for severe infections. The dosage regimen consisting of administration of doxorubicin on 3 successive days results in the greater incidence and severity of mucositis. Ulceration and necrosis of the colon, especially the cecum, may occur leading to bleeding or severe infections which can be fatal. This reaction has been reported in patients with acute non-lymphocytic leukemia treated with a 3-day course of doxorubicin combined with cytarabine. Anorexia and diarrhea have been occasionally reported.
Vascular: Phlebosclerosis has been reported especially when small veins are used or a single vein is used for repeated administration. Facial flushing may occur if the injection is given too rapidly.
Local: Severe cellulitis, vesication and tissue necrosis will occur if extravasation of doxorubicin occurs during administration. Erythematous streaking along the vein proximal to the site of the injection has been reported (see DOSAGE AND ADMINISTRATION).
Hematologic: The occurrence of secondary acute myeloid leukemia with or without a preleukemic phase has been reported in patients concurrently treated with doxorubicin in association with DNA-damaging antineoplastic agents. Such cases could have a short (1-3 years) latency period. An analysis of 1474 breast cancer patients who received adjuvant doxorubicin treatment in clinical trials, showed a 10-year estimated risk of developing treatment-related leukemia at 2.5% (95% confidence interval [CI], 1.0% to 5.1%) for the 810 patients receiving radiotherapy plus chemotherapy and 0.5% (95% CI, 0.1% to 2.4%) for the 664 patients receiving chemotherapy alone. The overall risk was 1.5% (95% CI, 0.7%-2.9%) at 10 years for the entire patient population. Pediatric patients are also at risk of developing secondary acute myeloid leukemia.
Hypersensitivity: Fever, chills, and urticaria have been reported occasionally. Anaphylaxis may occur. A case of apparent cross-sensitivity to lincomycin has been reported.
Other: Conjunctivitis and lacrimation occur rarely.