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

pharmacology

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.

toxicity

infection, myelosuppression, and cardiac toxicity

biotransformation

hepatic

absorption

90-100%

half life

3-12 hours

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.

drug interactions

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.