Doxorubicin Ebewe Dosage/Direction for Use

Doxorubicin may be given by: intravenous (bolus) injection over 2-5 minutes or as continuous infusion into a running infusion of sodium chloride 0.9% w/v intravenous injection, dextrose intravenous injection 5% w/v or sodium chloride and dextrose intravenous injection.
Bolus injection causes higher peak plasma-concentrations and therefore is probably more cardiotoxic.
Adult dosage: Monotherapy: Dosage depends on tumor type, cardiac or hepatic function, and concurrent chemotherapy.
The recommended dose as single agent: The commonly recommended dosage schedule as single agent is 60-75mg/m² by intravenous injection, once every three weeks. An alternative dose schedule is 20mg/m² intravenously, for three consecutive days, once every three weeks.
The maximum cumulative dose: 550mg/m² should not be exceeded.
Administration of doxorubicin in a weekly regimen has been shown to be as effective as the 3-weekly regimen whilst reducing cardiac toxicity. The recommended dosage is 20mg/m² weekly, although objective responses have been seen with doses between 6 and 12mg/m².
Combination therapy: Dosage should be decreased when combination with other cytostatic drugs with any similar toxicity is used.
The maximum cumulative dose: If a patient received mediastinal irradiation, has concomitant heart disease, or is also treated with other cardiotoxic, non-anthracycline oncolytics, a maximal cumulative dose of 450mg/m² is recommended.
Dosage adjustments in specific patient groups: Hepatic dysfunction: Dosage should be reduced in patients with impaired hepatic function. Doxorubicin dosage should be reduced if the bilirubin is elevated as follows: serum bilirubin 12 to 30mg - give ½ of the normal dose, bilirubin > 30mg - give ¼ of the normal dose.
Renal dysfunction: In general, impaired renal function does not require dose reduction.
Patients with cardiac risk: Patients at increased risk for cardiotoxicity should be considered for treatment with a 24 hours continuous infusion, rather than bolus injection. In this way, cardiotoxicity may be less frequent, without a reduction in therapeutic efficacy. In these patients, the ejection fraction should be measured before each course.
The risk of development of cardiomyopathy gradually increases with the dosage. A cumulative lifetime dose of 450-550mg/m² should not be exceeded.
In case of preexisting heart disease or prior radiotherapy to the heart or the mediastinum, cumulative doses of more than 400mg should be avoided (Monitoring of the cardiac function - see Precautions).
In combination with other oncolytics doses of 50-75mg/m² are administered. Myelosuppression may be more pronounced because of the additive effects of the drugs.
Dosage in children: Dosage for children should be lowered since they have an increased risk of cardiotoxicity especially delayed cardiotoxicity and therefore follow-up cardiac evaluation is recommended.
Myelotoxicity should be anticipated, with nadirs at 10 to 14 days after start of treatment, but is usually followed by a rapid recovery due to the large bone marrow reserve of children as compared to adults.
Superficial bladder carcinoma and bladder carcinoma in situ: The recommended dosage is 50mg in 50ml normal saline, administered via a sterile catheter. Initially, this dose is given weekly, later on monthly. The optimal duration of treatment has not yet been determined; it ranges from 6 to 12 months.
Restrictions regarding the maximal cumulative dose, as with intravenous administration, do not apply to intravesical administration, because systemic absorption of doxorubicin is negligible.
Take care in the administration to avoid the possibility of perivenous infiltration resulting in local necrosis and thrombophlebitis.
Doxorubicin must not be given intrathecally or intramuscularly, subcutaneously or by long term infusion. (Since doxorubicin is reported to form precipitates in combination with heparin and 5-fluorouracil, it should not be mixed with any other drug.)