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General principles of the use of cyclophosphamide in rheumatic diseases

W. Joseph McCune, MD, MACR
Megan B Clowse, MD, MPH
Section Editor
Daniel E Furst, MD
Deputy Editor
Monica Ramirez Curtis, MD, MPH


Cyclophosphamide (CYC), an alkylating agent, is one of the most potent immunosuppressive therapies available. It has been used extensively to treat severe manifestations of a variety of autoimmune and inflammatory diseases. Examples include organ-threatening manifestations of rheumatic diseases such as systemic lupus erythematosus (SLE), granulomatosis with polyangiitis (GPA; Wegener's), microscopic polyangiitis (MPA), polyarteritis nodosa, eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome), Behçet's syndrome, primary angiitis of the central nervous system, and isolated vasculitic neuropathy.

It is a prodrug that is converted to its active form in the liver and, to a lesser extent, in other organs. It can be administered either orally or intravenously. Oral administration usually corresponds to daily dosing and intravenous use to intermittent dosing (eg, every two to four weeks), but some exceptions exist. For example, extremely ill patients who are unable to ingest medications orally may receive daily doses of CYC via the intravenous route at the same doses they would otherwise receive orally.

Although very effective, CYC has the potential for devastating toxicity both in the short and long term (even after the medication has been stopped). Concerns about such drug toxicity, especially malignancy, have restricted its use to patients with the most severe disease. Newer, short-term protocols using significantly reduced cumulative doses of CYC have reduced, but not eliminated, associated risks.

Two major aims govern the use of CYC:

Prompt control of the underlying disease, to limit the extent and severity of damage

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Literature review current through: Nov 2017. | This topic last updated: Jun 22, 2016.
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