Cyclophosphamide metabolized mainly in the liver by the action of microsomal oxidase system, forming active alkylating metabolites methenolone enanthate), part of which is subjected to further transformation to inactive metabolites, some are transported into cells, where under the influence phosphatases are converted into metabolites possess cytotoxic action. The concentration of metabolites in the plasma reaches a maximum 2-3 hours after intravenous administration. Communication unchanged drug to plasma proteins is negligible (12-14%), but some metabolites bind more than 60%. Penetrates through the blood-brain barrier to a limited extent.
Cyclophosphamide is excreted mainly by the kidneys in the form of a metabolite, but 5 to 25% of the administered dose is excreted in the urine in an unmodified form as well as in the bile. The half-life is 3-12 hours.
Acute lymphoblastic and chronic lymphocytic leukemia, Hodgkin’s disease, non-Hodgkin’s lymphoma, multiple myeloma, breast cancer, ovarian, neuroblastoma, retinoblastoma, mycosis fungoides. Cyclophosphamide is also used in combination with other anticancer drugs for the treatment of lung cancer, germ cell tumors, cancer, cervical methenolone enanthate cancer, bladder cancer, soft tissue sarcoma, reticulosarcoma, Ewing’s sarcoma, Wilms tumor, prostatic cancer.
As immunosuppressive agents cyclophosphamide used in progressive autoimmune diseases (rheumatoid arthritis, psoriatic arthritis, collagen diseases, autoimmune hemolytic anemia, nephrotic syndrome) and for the suppression of transplant rejection reactions.
- Hypersensitivity to cyclophosphamide or any other component of the formulation.
- Severe violation of bone marrow function.
- Urinary retention.
- Pregnancy and lactation.
- Active infection.
Precautions : in severe diseases of the heart, liver and kidneys, adrenalectomy, gout (in history), nefrourolitiaze, methenolone enanthate suppression of bone marrow function, bone marrow infiltration by tumor cells prior to radiation or chemotherapy.
Dosing and Administration
Is administered intravenously or as an infusion, intramuscular injection.
Is part of many chemotherapy regimens, and therefore, the choice of a particular route of administration, regime and doses in each methenolone enanthate individual case should be guided by the data of literature.
The most common applied doses and regimens for adults and children:
When using cyclophosphamide in combination with other anticancer drugs may require dose reduction of both cyclophosphamide and other .
After addition of the solvent vial is shaken vigorously in order to completely dissolve the drug. If rapid and complete dissolution is not reached, the vial should be left to stand for several minutes.
To. solution for infusion of the drug to the resulting solution was added Cyclophosphamide Ringer’s, 0.9% sodium chloride solution or dextrose solution, so that the total liquid volume was approximately 500 ml.
Side effects Hematopoietic system : leukopenia, neutropenia; rarely, thrombocytopenia, anemia. The largest decrease in the number of white blood cells and platelets usually occurs 7-14 days of treatment.Recovery leukopenia usually begins 7-10 days after discontinuation of treatment. On the part of the digestive system : nausea, vomiting, anorexia, stomatitis, less often, discomfort or pain in the abdomen, diarrhea or constipation, there are isolated reports of the development of hemorrhagic colitis, jaundice. Rarely, abnormal liver function, manifested an increase in transaminases, alkaline phosphatase and bilirubin in blood serum. In 15-50% of patients receiving high, dose cyclophosphamide in combination with busulfan and. total irradiation during allogeneic bone marrow transplantation develop veno-occlusive disease of the liver. A similar reaction in very rare cases are also observed in patients receiving high doses of cyclophosphamide methenolone enanthate in patients with aplastic anemia. The syndrome usually develops within 1-3 weeks after transplantation of the bone marrow and is characterized by rapid weight gain, hepatomegaly, ascites and hyperbilirubinaemia.