Dosage cyclophosphamide

The long-term prognosis for sperm counts after chemotherapy with and without radiation in 71 males treated for non-Hodgkin s lymphoma on the CHOP-Bleomycin combination has been studied (262). Pelvic radiotherapy and cumulative cyclophosphamide dosages of greater than 9.5 g/m are associated independently and in combination with a greater risk of permanent sterility. 

HI. Disruption of cell metabolism with inhibition of proliferation. At dosages below those needed to treat malignancies, some cytostatics are also employed for immunosuppression, e.g., azathioprine, methotrexate, and cyclophosphamide (p. 298). The antiproliferative effect is not specific for lymphocytes and involves both T- and B-cells. 

Cyclophosphamide is active against rheumatoid arthritis when given orally at dosages of 2 mg/kg/d but not when given intravenously. It is used regularly to treat systemic lupus erythematosus, vasculitis, Wegener s granulomatosis, and other severe rheumatic diseases. 

When chemotherapeutic mercaptopurines (eg, azathioprine) are given concomitantly with allopurinol, their dosage must be reduced by about 75%. Allopurinol may also increase the effect of cyclophosphamide. Allopurinol inhibits the metabolism of probenecid and oral anticoagulants... 

Cyclophosphamide is a prodrug which is converted into active metabolites in the liver. Urotoxic side effects must be anticipated they can be suppressed by the additional administration of sodium-2 mercaptoethanesulphonate. This alkylating substance has a strong immunosuppressive effect therefore, it is occasionally used to prevent graft rejection or (at a low dosage) in autoimmune hepatitis, (s. p. 686)... 

Cardiac toxicity can be observed at high doses of cyclophosphamide (usually over 1.5 g/m /day), and acute myocardial necrosis or severe cardiac failure have been anecdotally reported after smaller dosages (SEDA-21,386). 

Allopurinol inhibits the enzymatic inactivation of mercaptopurine and its derivative azathio-prine by xanthine oxidase. Thus, when allopurinol is used concomitantly with oral mercaptopurine or azathioprine, dosage of the antineoplastic agent must be reduced by 25-33% (see Chapters 38 and 51). This is of importance when treating gout in the transplant recipient. The risk of bone marrow suppression also is increased when allopurinol is administered with cytotoxic agents that are not metabolized by xanthine oxidase, particularly cyclophosphamide. 

A man well stabilised on warfarin had a marked reduction in his anticoagulant response on two occasions while taking mercaptopurine, but no changes occurred when he took busulfan, cyclophosphamide, cytarab-ine, hydroxycarbamide, mitobronitol, demecolcine or melphalan. A woman needed a marked increase in her dosage of acenocoumarol, from 21 to 70 mg weekly, when she was given mercaptopurine 100 mg daily. Another patient required about a 25% increase in warfarin dose while taking mercaptopurine 1(X) mg daily. 

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