Cyclophosphamideinteractions

Cyclophosphamide is a pro-drug that is activated by cytochrome P450s. An increase of the concentration of cytotoxic metabolites may occur with: Protease inhibitors: Concomitant use of protease inhibitors may increase the concentration of cytotoxic metabolites. Use of protease inhibitor-based regimens was found to be associated with a higher incidence of infections and neutropenia in patients receiving cyclophosphamide, doxorubicin, and etoposide (CDE) than use of a Non-Nucleoside Reverse Transcriptase Inhibitor-based regimen.Combined or sequential use of cyclophosphamide and other agents with similar toxicities can potentiate toxicities. Increased hematotoxicity and/or immunosuppression may result from a combined effect of cyclophosphamide and, for example: ACE inhibitors: ACE inhibitors can cause leukopenia.

Natalizumab Paclitaxel: Increased hematotoxicity has been reported when cyclophosphamide was administered after paclitaxel infusion. Thiazide diuretics Zidovudine Increased cardiotoxicity may result from a combined effect of cyclophosphamide and, for example: Anthracyclines Cytarabine Pentostatin Radiation therapy of the cardiac region Trastuzumab Increased pulmonary toxicity may result from a combined effect of cyclophosphamide and, for example: Amiodarone G-CSF, GM-CSF (granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor): Reports suggest an increased risk of pulmonary toxicity in patients treated with cytotoxic chemotherapy that includes cyclophosphamide and G-CSF or GMCSF. Increased nephrotoxicity may result from a combined effect of cyclophosphamide and, for example: Amphotericin B Indomethacin: Acute water intoxication has been reported with concomitant use of indomethacin Increase in other toxicities: Azathioprine: Increased risk of hepatotoxicity (liver necrosis) Busulfan: Increased incidence of hepatic veno-occlusive disease and mucositis has been reported.

Protease inhibitors: Increased incidence of mucositis Increased risk of hemorrhagic cystitis may result from a combined effect of cyclophosphamide and past or concomitant radiation treatment.

Etanercept: In patients with Wegener's granulomatosis, the addition of etanercept to standard treatment, including cyclophosphamide, was associated with a higher incidence of non-cutaneous malignant solid tumors.

Metronidazole: Acute encephalopathy has been reported in a patient receiving cyclophosphamide and metronidazole. Causal association is unclear. In an animal study, the combination of cyclophosphamide with metronidazole was associated with increased cyclophosphamide toxicity.

Tamoxifen: Concomitant use of tamoxifen and chemotherapy may increase the risk of thromboembolic complications.

Coumarins: Both increased and decreased warfarin effect have been reported in patients receiving warfarin and cyclophosphamide.

Cyclosporine: Lower serum concentrations of cyclosporine have been observed in patients receiving a combination of cyclophosphamide and cyclosporine than in patients receiving only cyclosporine. This interaction may result in an increased incidence of graft-versus-host disease.

Depolarizing muscle relaxants: Cyclophosphamide treatment causes a marked and persistent inhibition of cholinesterase activity. Prolonged apnea may occur with concurrent depolarizing muscle relaxants (e.g., succinylcholine). If a patient has been treated with cyclophosphamide within 10 days of general anesthesia, alert the anesthesiologist.