Sign Out
DOXORUBICIN should be administered only under the supervision of a doctor experienced in cancer chemotherapy.
Patients should be advised not to conceive and the use of contraceptives are advised.
Patients should recover from acute toxicities of prior cytotoxic treatment (such as stomatitis, neutropenia, thrombocytopenia and generalised infections) before beginning treatment with doxorubicin.
Doxorubicin is incompatible with heparin and should also not be mixed with other medicines.
Doxorubicin should be given with great care, in reduced doses, to elderly patients and to those with hepatic impairment.
The systemic clearance of doxorubicin is reduced in obese patients (i.e. >130% ideal body weight; See Dosage & Administration).
Cardiac function: Cardiotoxicity is a risk of anthracycline treatment that may be manifested by early (i.e. acute) or late (i.e. delayed) events.
Early events: This consists mainly of sinus tachycardia and/or ECG abnormalities such as non-specific ST-T wave changes. Tachyarrhythmias, including premature ventricular contractions and ventricular tachycardia, bradycardia as well as atrioventricular and bundle-branch block have also been reported. These events do not usually predict subsequent development of delayed cardiotoxicity, are rarely of clinical importance, and are generally not a consideration for discontinuation of doxorubicin treatment.
Late events: Delayed cardiotoxicity usually develops late in the course of therapy with doxorubicin or within 2 to 3 months after treatment termination, but later events, several months to years after completion of treatment, have also been reported. Delayed cardiomyopathy is manifested by reduced left ventricular ejection fraction (LVEF) and/or signs and symptoms of congestive heart failure (CHF) such as dyspnea, pulmonary oedema, dependent oedema, cardiomegaly and hepatomegaly, oliguria, ascites, pleural effusion and gallop rhythm. Subacute effects such as pericarditis/myocarditis have also been reported. Life-threatening CHF is the most severe form of anthracycline-induced cardiomyopathy and represents the cumulative dose-limiting toxicity of the drug.
Cardiac function should be assessed before patients undergo treatment with doxorubicin and must be monitored throughout therapy to minimise the risk of incurring severe cardiac impairment. The risk may be decreased through regular monitoring of LVEF during the course of treatment with prompt discontinuation of doxorubicin at the first sign of impaired function. The appropriate quantitative method for repeated assessment of cardiac function (evaluations of LVEF) includes multi-gated radionuclide angiography or echocardiography (ECHO). A baseline cardiac evaluation with an ECG and either a multi-gated radionuclide angiography scan or an ECHO is recommended, especially in patients with risk factors for increased cardiotoxicity. Repeated multi-gated radionuclide angiography or ECHO determinations of LVEF should be performed, particularly with higher, cumulative anthracycline doses.
Haematologic toxicity: DOXORUBICIN may produce myelosuppression. Haematologic profiles should be assessed before and during each cycle of therapy with doxorubicin, including differential white blood cell (WBC) counts. A dose-dependent, reversible leukaemia and/or granulocytopenia (neutropenia) is the predominant manifestation of doxorubicin haematologic toxicity and is the most common acute dose-limiting toxicity of this drug. Leukopenia and neutropenia generally reach the nadir between days 10-14 after drug administration; the WBC/neutrophil counts return to normal values in most cases by day 21. Thrombocytopenia and anaemia may also occur. Clinical consequences of severe myelosuppression include fever, infections, sepsis/septicemia, septic shock, haemorrhage, tissue hypoxia or death.
Secondary leukaemia: See Precautions.
Gastro-intestinal: Doxorubicin is emetogenic. Mucositis/stomatitis generally appears early after drug administration and, if severe, may progress over a few days to mucosal ulcerations. Most patients recover from this adverse event by the third week of therapy.
Liver function: The major route of elimination of doxorubicin is the hepatobiliary system. Serum total bilirubin should be monitored before and during treatment with doxorubicin. Patients with elevated bilirubin may experience slower clearance of the drug with an increase in overall toxicity. Lower dose are recommended in these patients (see Dosage & Administration). Patients with severe hepatic impairment should not receive doxorubicin (see Contraindications).
Effects at site of injection: Phlebosclerosis may result from an injection into a small vessel or from repeated injections into the same vein. Following the recommended administration procedures may minimise the risk of phlebitis/thrombophlebitis at the injection site.
Extravasation: Extravasation of doxorubicin during intravenous injection may produce local pain, severe tissue lesions (vesication, severe cellulitis) and necrosis. Should signs or symptoms of extravasation occur during intravenous administration of doxorubicin, the drug infusion should be stopped immediately.
Initial treatment calls for a careful baseline monitoring of various laboratory parameters and cardiac function. Blood counts and measurement of haemoglobin concentration should be carried out routinely.
The occurrence of secondary acute myeloid leukaemia with or without a pre-leukaemic phase has been reported rarely in patients concurrently treated with doxorubicin in association with DNA-damaging antineoplastic agents. Such cases could have a short (1-3 years) latency period.
Fertility impairment: In women, doxorubicin may cause infertility during the time of drug administration. Doxorubicin may cause amenorrhoea. Ovulation and menstruation appear to return after termination of therapy, although premature menopause can occur. Doxorubicin is mutagenic and can induce chromosomal damage in human spermatozoa. Oligospermia or azoospermia may be permanent. Men undergoing doxorubicin treatment should use effective contraceptive methods.
