Antharin-50 Drug Interactions

Doxorubicin is a major substrate of cytochrome P450 CYP3A4 and CYP2D6, and P-glycoprotein (P-gp). Clinically significant interactions have been reported with inhibitors of CYP3A4, CYP2D6, and/or P-gp (e.g, verapamil), resulting in increased concentration and clinical effect of doxorubicin. Inducers of CYP3A4 (e.g, phenobarbital, phenytoin, St. John's Wort) and P-gp inducers may decrease the concentration of doxorubicin.
The addition of cyclosporine to doxorubicin may result in increases in area under the concentration-time curve (AUC) for both doxorubicin and doxorubicinol, possibly due to a decrease in clearance of the parent drug and a decrease in metabolism of doxorubicinol. Literature reports suggest that adding cyclosporine to doxorubicin results in more profound and prolonged haematologic toxicity than that observed with doxorubicin alone. Coma and seizures have also been described with concomitant administration of cyclosporine and doxorubicin.
High dose cyclosporine increases the serum levels and myelotoxicity of doxorubicin.
Doxorubicin is mainly used in combination with other cytotoxic drugs. Additive toxicity may occur especially with regard to bone marrow/haematologic and gastrointestinal effects. The use of doxorubicin in combination chemotherapy with other potentially cardiotoxic drugs, as well as the concomitant use of other cardioactive compounds (e.g. calcium channel blockers), require monitoring of cardiac function throughout treatment. Changes in hepatic function induced by concomitant therapies may affect doxorubicin metabolism, pharmacokinetics, therapeutic efficacy and/or toxicity.
Paclitaxel can cause increased plasma-concentrations of doxorubicin and/or its metabolites when given prior to doxorubicin. Certain data indicate that a smaller increase is observed when doxorubicin is administered prior to paclitaxel.
The use of trastuzumab in combination with anthracyclines (such as doxorubicin hydrochloride) is associated with an increased cardiotoxic risk. Trastuzumab and anthracyclines should currently not be used in combination, except for well controlled clinical studies with monitoring of cardiac function.
In a clinical study, an increase in doxorubicin AUC of 21% was observed when given with sorafenib 400 mg twice daily. The clinical significance of this finding is unknown.