Product Information
Registration Status: ActiveENDOXAN FOR INJECTION 500mg/VIAL is approved to be sold in Singapore with effective from 1988-09-06. It is marketed by BAXTER HEALTHCARE (ASIA) PTE LTD, with the registration number of SIN01748P.
This product contains Cyclophosphamide 500mg/vial in the form of INJECTION, POWDER, FOR SOLUTION. It is approved for INTRAVENOUS use.
This product is manufactured by BAXTER ONCOLOGY GMBH in GERMANY.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [PubChem]
Indication
Cyclophosphamide is indicated for the treatment of malignant lymphomas, multiple myeloma, leukemias, mycosis fungoides (advanced disease), neuroblastoma (disseminated disease), adenocarcinoma of the ovary, retinoblastoma, and carcinoma of the breast. It is also indicated for the treatment of biopsy-proven minimal change nephrotic syndrome in pediatric patients.
Mechanism of Action
Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.
Pharmacokinetics
- Absorption
- After oral administration, peak concentrations occur at one hour.
- Distribution
- 30-50 L
- Metabolism
- Metabolism and activation occurs at the liver. 75% of the drug is activated by cytochrome P450 isoforms, CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18, and 2C19. The CYP2B6 isoform is the enzyme with the highest 4-hydroxylase activity. Cyclophosphamide undergoes activation to eventually form active metabolites, phosphoramide mustard and acrolein. Cyclophosphamide appears to induce its own metabolism which results in an overall increase in clearance, increased formation of 4-hydroxyl metabolites, and shortened t1/2 values following repeated administration.
- Elimination
Clearance
Total body clearance = 63 ± 7.6 L/kg.
Toxicity
Adverse reactions reported most often include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea.
Active Ingredient/Synonyms
(+-)-Cyclophosphamide | (RS)-Cyclophosphamide | 2-[Bis(2-chloroethylamino)]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide | Anhydrous cyclophosphamide | Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester | Ciclofosfamida | Ciclofosfamide | Cyclophosphamid | Cyclophosphamide | Cyclophosphamide anhydrous | Cyclophosphamidum | Cytophosphane | Ledoxina | N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide | Cyclophosphamide |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.