Complications
All patients on supraphysiological doses of corticosteroids are at increased risk for development of osteoporosis and should be evaluated for other risk factors.
Supplemental calcium and vitamin D, and consideration of bisphosphonate therapy, may be appropriate.
Cytopenias occur commonly, and a FBC should be obtained 2 weeks after a dose increase, and then every 4 to 6 weeks when the dose is stable.
Drug-induced hepatitis may also occur, and monitoring of liver enzymes every 2 months is reasonable.
In terms of infertility, oligospermia may be seen in men and is generally reversible on discontinuation of therapy.
Cytopenias are common, and a FBC should be obtained every 2 weeks while on oral cyclophosphamide; a decrease in the total WBC count to <3.5 should prompt dose reduction.
Renal function should be monitored monthly, as a decline in renal function warrants dose adjustment. Urinalysis for the detection of haematuria should be done monthly.
Metabolites of cyclophosphamide may cause cystitis: patients should be encouraged to maintain adequate fluid intake of at least 2 L/day.
Because of teratogenesis, patients must be reminded of, and counselled on, the importance of effective contraception.
Because of the risk for infertility, sperm banking and hormonal manipulation to preserve ovarian function should be discussed prior to initiation of therapy.
Bladder malignancies may develop years after therapy has been completed, and early referral for cystoscopy should be sought for persistent haematuria.
Patients on cyclophosphamide are at increased risk of opportunistic infections, including Pneumocystis jirovecii. All patients should be placed on prophylactic therapy and have their vaccinations updated prior to initiation of therapy and should not receive live vaccines while being treated with immunosuppressive regimens.
The American College of Rheumatology guidelines for monitoring methotrexate toxicity (based on use of methotrexate in the treatment for rheumatoid arthritis) recommend baseline determination of FBC, renal function, liver enzymes, albumin, and hepatitis B and C serologies prior to initiation of methotrexate use.[54]
Liver enzymes and albumin should be monitored every 4 to 8 weeks, and referral for liver biopsy done if persistent elevations of the AST are noted or if albumin falls below the normal range.
A baseline CXR is indicated.
The British Association of Dermatologists recommend checking varicella zoster virus (VZV) serology in patients without a history of chickenpox. VZV vaccination is considered where serology is negative.[55]
Referral for liver biopsy prior to therapy should be considered in patients who have a history of significant alcohol intake; have persistent baseline abnormalities of liver transaminases; or are positive for chronic hepatitis B or C serology.
Methotrexate is not recommended for use in women of childbearing age.
Alcohol should not be consumed while taking methotrexate.
Administration of folic acid (1 mg/day) may decrease the incidence of side effects and is recommended for all patients.
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