Rubicin Drug Interactions

Doxorubicin is extensively metabolized by the liver. Changes in hepatic function induced by concomitant therapies may affect doxorubicin metabolism, pharmacokinetics, therapeutic efficacy, and/or toxicity. Toxicities associated with doxorubicin, especially hematologic and gastrointestinal events, may be increased when doxorubicin is used in combination with other cytotoxic drugs.
Bone marrow depressants or radiation therapy: Additive bone marrow depression may occur. Adjust Doxorubicin dosage when two or more bone marrow depressants, including radiation therapy, are used concurrently or consecutively.
Cardiotoxic agents (e.g., trastuzumab): Doxorubicin should not be administered in combination with other cardiotoxic agents unless the patient's cardiac function is closely monitored. Patients receiving doxorubicin 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. Physicians should avoid doxorubicin-based therapy for up to 24 weeks after stopping trastuzumab when possible. If doxorubicin is used before this time, careful monitoring of cardiac functions is recommended (see Warnings and Precautions).
Cyclophosphamide: The addition of cyclophosphamide to doxorubicin treatment does not affect exposure to Doxorubicin, but may increase exposure to doxorubicinol. Cyclophosphamide-induced hemorrhagic cystitis may be exacerbated and cardiotoxicity may be enhanced. High-dose cyclophosphamide in combination with 2 to 3 times the recommended dosage of doxorubicin has also been reported to cause seizures. Studies show that AML as a second malignancy was shown after treatment with doxorubicin and cyclophosphamide.
Ciclosporin: The use of ciclosporin in combination with doxorubicin may result in an increase in the area under the plasma concentration-time (AUC) for both doxorubicin and doxorubicinol, possibly due to a decrease in doxorubicin clearance and a decrease in metabolism of doxorubicinol. Evidence suggests that the concomitant use of ciclosporin may result in a more severe and prolonged hematologic toxicity associated with doxorubicin. In addition, seizures and/or coma have occurred in patients receiving doxorubicin and ciclosporin concomitantly.
Paclitaxel: Compared with administration of doxorubicin followed by paclitaxel, initial administration of paclitaxel (by infusion over 24 hours) followed by doxorubicin administered over 48 hours) was shown to result in a decrease in doxorubicin clearance and an increase in the severity of neutropenia and stomatitis.
Verapamil: A study of the effects of verapamil on the acute toxicity of doxorubicin in mice showed higher initial peak concentrations of Doxorubicin in the heart with a higher incidence and severity of degenerative changes in cardiac tissue resulting in a shorter survival.
Daunorubicin, Idarubicin, Mitoxantrone, and Irradiation of the cardiac region: Concurrent administration may increase plasma concentrations of doxorubicin and/or its metabolites and increase cardiotoxicity. The maximum cumulative dose of doxorubicin should be reduced.
Phenobarbital: Increases elimination of doxorubicin.
Phenytoin: Phenytoin levels may be decreased by doxorubicin.
Sorafenib: Increases systemic exposure to doxorubicin.
6-mercaptopurine: Concomitant use may enhance hepatotoxicity of 6-mercaptopurine.
Streptozocin, Methotrexate, and Valspodar: Concurrent therapy may inhibit hepatic metabolism of doxorubicin and prolong doxorubicin's half-life. Reduce doxorubicin dose.
Dactinomycin: Concomitant use with doxorubicin therapy produces "recall" acute pneumonitis at variable times after local radiation therapy in children.
Dexrazoxane: A clinical study showed a lower tumor response in women with metastatic breast cancer who were concurrently using the cardioprotectant dexrazoxane with the initiation of a regimen of fluorouracil, doxorubicin and cyclophosphamide. Dexrazoxane is only indicated for women with metastatic breast cancer who have received a cumulative Doxorubicin dose of 300 mg/m² and are continuing Doxorubicin therapy.
Cytarabine: Doxorubicin given by IV push daily for 3 days with cytarabine given by continuous infusion daily for 7 or more days resulted in necrotizing colitis manifested by typhlitis (cecal inflammation), bloody stools and severe and sometimes fatal infections.
Thalidomide: A clinical study cited that the addition of thalidomide to doxorubicin in patients with multiple myeloma increased the risk of deep-vein thrombosis.
Calcium-channel Blocking Agents: Studies suggest that doxorubicin-induced cardiotoxicity may be potentiated by concomitant use of calcium-channel blocking agents.
Progesterone: Exacerbation of doxorubicin-induced neutropenia and thrombocytopenia has been reported in patients with advanced malignancies receiving high doses of progesterone (up to 10 g IV over 24 hours) concomitantly with doxorubicin (60 mg/m² by IV bolus).
Other Drugs: Saquinavir in combination with cyclophosphamide, doxorubicin and etoposide increased mucosal toxicity in patients with HIV-associated non-Hodgkin's lymphoma. Doxorubicin is reported to inhibit the intracellular activation of stavudine, inhibiting its antiviral effect.
Seizures and/or coma have occurred in patients receiving Doxorubicin and vincristine concomitantly.
Vaccine use: Concurrent use with a live virus vaccine may potentiate virus replication, may increase side effects of vaccine virus, and/or may decrease patient's antibody response to killed virus vaccines. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient’s ability to respond to the vaccine depends on many factors; estimates vary from 3 months to 1 year.