ASTA;Asta B 518;Clafen;Claphene;CP;CPA;CTX;CY;Cyclophosphamid;Cyclophosphamide Monohydrate;Cyclophosphamide Sterile;Cyclophosphamidum;Cyclophosphan;Cyclophosphane;Cyclophosphoramide;Cyclostin;Cyklofosfamid;Cytophosphan;Cytoxan;Cytoxan Lyoph;Endoxan;Endoxan R;Endoxan-Asta;Endoxana;Endoxanal;Endoxane;Enduxan;Genoxal;Hexadrin;Lyophilized Cytoxan;Mitoxan;Neosar;Procytox;Rcra Waste Number U058;Revimmune;Semdoxan;Sendoxan;Senduxan;Zyklophosphamid;

cyclophosphamide;

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]

• Baxter healthcare corp
• Baxter healthcare corp anesthesia and critical care
• Roxane laboratories inc
• Teva parenteral medicines inc

Synthesis Reference	Not Available
General Reference	Brock N: The history of the oxazaphosphorine cytostatics. Cancer. 1996 Aug 1;78(3):542-7. Pubmed Brock N: Oxazaphosphorine cytostatics: past-present-future. Seventh Cain Memorial Award lecture. Cancer Res. 1989 Jan 1;49(1):1-7. Pubmed

Form	Route	Strength
Powder, for solution	Intravenous
Solution	Intravenous
Tablet	Oral

Unit description	Cost	Unit
Cyclophosphamide 500 mg vial	37.76 USD	vial
Cyclophosphamide 100% powder	33.66 USD	g
Cytoxan 500 mg vial	15.25 USD	vial
Cytoxan 50 mg tablet	4.14 USD	tablet
Cyclophosphamide 50 mg tablet	3.92 USD	tablet
Cytoxan 25 mg tablet	2.26 USD	tablet
Cyclophosphamide 25 mg tablet	2.09 USD	tablet

Type	small molecule

Classes

Nitrogen Mustards

Substructures

Organophosphate Esters Phosphoric Acids and Derivatives Alkyl Halides Heterocyclic compounds Nitrogen Mustards

Cancer 癌症;

Indication	For management of malignant lymphomas, multiple myeloma,leukemias, mycosis fungoides (advanced disease), neuroblastoma (disseminated disease), adenocarcinoma of the ovary, retinoblastoma and carcinoma of the breast
Pharmacodynamics	Cyclophosphamide is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
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.
Absorption	90-100%
Volume of distribution	Not Available
Protein binding	>60%
Metabolism	hepatic Enzyme Metabolite Reaction Km Vmax Cytochrome P450 3A4 4-Hydroxycyclophosphamide 4-hydroxylation 1800 104.63 Cytochrome P450 3A4 Dechloroethyl cyclophosphamide Cytochrome P450 2C9 4-Hydroxycyclophosphamide Cytochrome P450 2C19 4-hydroxycyclophosphamide 4-hydroxylation 0 0 Cytochrome P450 2B6 4-Hydroxycyclophosphamide 4-hydroxylation 2000 319.82
Route of elimination	It is eliminated primarily in the form of metabolites, but from 5% to 25% of the dose is excreted in urine as unchanged drug.
Half life	3-12 hours
Clearance	Not Available
Toxicity	infection, myelosuppression, and cardiac toxicity
Affected organisms	Humans and other mammals
Pathways	Pathway Name SMPDB ID Cyclophosphamide Pathway SMP00447

Properties
State	solid
Melting point	41-45 oC
Experimental Properties	Property Value Source water solubility Soluble. 1-5 g/100 mL at 23 oC PhysProp logP 0.8 PhysProp
Predicted Properties	Property Value Source water solubility 1.51e+01 g/l ALOGPS logP 0.76 ALOGPS logP 0.10 ChemAxon Molconvert logS -1.24 ALOGPS pKa ChemAxon Molconvert hydrogen acceptor count 2 ChemAxon Molconvert hydrogen donor count 1 ChemAxon Molconvert polar surface area 41.57 ChemAxon Molconvert rotatable bond count 5 ChemAxon Molconvert refractivity 58.48 ChemAxon Molconvert polarizability 23.72 ChemAxon Molconvert

Drug	Interaction
Acenocoumarol	The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of acenocoumarol.
Anisindione	The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of anisindione.
Dicumarol	The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of dicumarol.
Digoxin	The antineoplasic agent decreases the effect of digoxin
Fluconazole	Fluconazole reduces metabolism and clearance of cyclophosphamide.
Pentostatin	Increased toxicity of cyclophosphamide
Succinylcholine	Cyclophosphamide may increase the effect of succinylcholine.
Thiotepa	Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Cyclophosphamide, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Cyclophosphamide if Thiotepa is initiated, discontinued or dose changed.
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Warfarin	The antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of warfarin.

• Drink liberally- 2 to 3 liters/day.
• Take with food to reduce irritation.