Endoxan (cyclophosphamide) 500 mg. powder for solution for injections 500 mg. vial №1

Description

Endoxan powder Dosage form
Powder for solution for injection.

Basic physical and chemical properties: white crystalline substance.

Endoxan powder Pharmacotherapeutic group
Antineoplastic agents. Alkylating compounds. Analogs of nitrogen mustard. Cyclophosphamide. ATX code L01A A01.

Endoxan powder Pharmacological properties

Pharmacodynamics.

Cyclophosphamide is an antineoplastic agent of the oxazaphosphorine class. It is related to nitrogen mustard.

Cyclophosphamide is inactive in vitro. Its activation occurs in vivo mainly by microsomal enzymes in the liver, where it is converted to 4-hydroxycyclophosphamide, which is in equilibrium with its tautomer – aldophosphamide. These tautomers undergo partially spontaneous, partially enzymatic conversion into inactive and active metabolites (especially mustard phosphoramide and acrolein).

The cytotoxic effect of cyclophosphamide is based on the interaction between its alkylating metabolites and DNA. This alkylation results in the rupture and cross-linking of DNA strands and DNA proteins. In the cell cycle, the course of the G2 phase slows down. The cytotoxic effect is not specific to the phase of the cell cycle, but specific to the entire cell cycle. Acrolein has no antineoplastic activity, but it is responsible for urotoxic side effects. In addition, the immunosuppressive effect of cyclophosphamide is discussed.

Cross-resistance cannot be ruled out, especially with cytostatics of a similar structure, such as ifosfamide, as well as with other alkylating agents.

Pharmacokinetics.

Blood levels after intravenous and oral administration are bioequivalent.

Absorption

Cyclophosphamide is almost completely absorbed from the gastrointestinal tract. In humans, after a single intravenous injection of radiolabeled cyclophosphamide for 24 hours, there is a significant decrease in the concentration of cyclophosphamide and its metabolites in plasma, but levels that can be detected in blood plasma persist for up to 72 hours.

Indication
ENDOXAN® is intended for use in chemotherapy of the following tumors in combination with other antineoplastic agents:

induction of remission and consolidation therapy in acute lymphoblastic leukemia;
induction of remission in Hodgkin’s disease;
non-Hodgkin’s lymphomas (depending on the histological type and the stage of the disease also in the form of monotherapy);
chronic lymphocytic leukemia (CLL) after the lack of effectiveness of standard therapy (chlorambucil / prednisone);
induction of remission in plasmacytoma (also in combination with prednisone);
adjuvant therapy for breast cancer after tumor resection or mastectomy;
palliative therapy for advanced breast cancer;
common ovarian cancer;
small cell lung cancer;
Ewing’s sarcoma;
neuroblastoma;
rhabdomyosarcoma in children;
osteosarcoma.
Preparation before allogeneic bone marrow transplantation in:

severe aplastic anemia – as monotherapy or in combination with antiplatelet globulin;
acute myeloid and acute lymphoblastic leukemia – in combination with whole-body irradiation or busulfan;
chronic myeloid leukemia – in combination with whole body irradiation or busulfan.
Progressive autoimmune diseases: severe progressive forms of lupus nephritis and Wegener’s granulomatosis.

Contraindication
ENDOXAN® is contraindicated in:

hypersensitivity to cyclophosphamide, its metabolites or to other components of the drug;
severe bone marrow dysfunction (myelosuppression, especially in patients previously treated with cytotoxic drugs and / or radiotherapy);
inflammation of the bladder (cystitis);
urinary tract obstruction;
active infections;
pregnancy or breastfeeding.
General contraindications for allogeneic bone marrow transplantation, such as upper age limit 50-60 years, bone marrow contamination with metastases of malignant (epithelial) tumors, as well as the lack of HLA -identity with the planned donor in the case of chronic myeloid leukemia, which must be carefully clarified before the beginning of preparatory therapy with the drug ENDOXAN®.