Epirubicin hydrochloride is mainly used in combination with other cytotoxic medicinal products. Additive toxicity may occur especially with regard to bone marrow/haematologic and gastrointestinal effects (see Precautions). The use of epirubicin hydrochloride in combination chemotherapy with other potentially cardiotoxic medicinal products, as well as the concomitant use of other cardioactive compounds (e.g., calcium channel blockers), requires monitoring of cardiac function throughout treatment.
Epirubicin hydrochloride is extensively metabolised by the liver. Changes in hepatic function induced by concomitant therapies may affect epirubicin hydrochloride metabolism, pharmacokinetics, therapeutic efficacy and/or toxicity (see Precautions).
Anthracyclines including epirubicin hydrochloride should not be administered in combination with other cardiotoxic agents unless the patient's cardiac function is closely monitored. Patients receiving anthracyclines after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity.
Because the half-life of trastuzumab is approximately 28-38 days, trastuzumab may persist in the circulation for up to 27 weeks after stopping trastuzumab treatment. Patients who receive anthracyclines such as epirubicin hydrochloride after stopping trastuzumab may possibly be at an increased risk of cardio toxicity. If possible, physicians should avoid anthracycline-based therapy for up to 27 weeks after stopping trastuzumab. If anthracyclines such as epirubicin hydrochloride are used, the patient's cardiac function should be monitored carefully.
Vaccination with a live vaccine should be avoided in patients receiving epirubicin hydrochloride. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.
Cimetidine increased the AUC of epirubicin hydrochloride by 50% and should be discontinued during treatment with epirubicin hydrochloride.
When given prior to epirubicin hydrochloride, paclitaxel can cause increased plasma concentrations of unchanged epirubicin hydrochloride and its metabolites, the latter being, however, neither toxic nor active. Co-administration of paclitaxel or docetaxel did not affect the pharmacokinetics of epirubicin hydrochloride when epirubicin hydrochloride was administered prior to the taxane.
This combination may be used if using staggered administration between the two agents. Infusion of epirubicin hydrochloride and paclitaxel should be performed with at least a 24 hour interval between the 2 agents.
Dexverapamil may alter the pharmacokinetics of epirubicin hydrochloride and possibly increase its bone marrow depressant effects.
One study found that docetaxel may increase the plasma concentrations of epirubicin hydrochloride metabolites when administered immediately after epirubicin hydrochloride.
Quinine may accelerate the initial distribution of epirubicin hydrochloride from blood into the tissues and may have an influence on the red blood cells partitioning of epirubicin hydrochloride.
The co-administration of interferon α2b may cause a reduction in both the terminal elimination half-life and the total clearance of epirubicin hydrochloride.
The possibility of a marked disturbance of haematopoiesis needs to be kept in mind with a (pre) treatment with medications which influences the bone marrow (i.e. cytostatic agents, sulphonamide, chloramphenicol, diphenylhydantoin, amidopyrine-derivative, antiretroviral agents).
Increase of myelosuppression may occur in patients receiving combination therapy of anthracycline and dexrazoxane.