What affects cyclosporine absorption? Cyclosporine is poorly absorbed from the gut with a bioavailability of 30% though with substantial variability among individuals. A high-fat meal can increase absorption. Grapefruit juice and marmalade from Seville oranges contain dihydroxy-bergamottin, which inhibits the cytochrome P450 enzyme in the small intestine, resulting in increased absorption and decreased metabolism of …
What other alkylating agent has been used to treat rheumatic diseases? Chlorambucil (Leukeran) has been used to treat several rheumatic diseases. The usual dose is 0.1 mg/kg per day (2–8 mg/day). It has been used primarily to treat the ocular and neuropsychiatric complications of Behçet’s disease. It has also been used in cryoglobulinemia, refractory dermatomyositis, …
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What are the major toxicities of cyclophosphamide? What can be done to prevent them? • Bone marrow suppression: the WBC nadir after a dose is 8 to 14 days later. Start at 50 mg/day orally with slow escalation and close monitoring. • Infection (all types, especially herpes viruses): screen for hepatitis B and C, human immunodeficiency virus, and tuberculosis …
In which rheumatic diseases is cyclophosphamide therapy indicated? How effective is it? • Granulomatosus with polyangiitis (Wegener’s). • SLE (particularly lupus nephritis, severe manifestations). • ILD in systemic sclerosis patients. • Other systemic vasculitis syndromes. • Other rheumatic diseases refractory to conventional therapy. Cyclophosphamide is considered to be one of the most potent immunosuppressive drugs available. Its use has succeeded …
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MOA and metabolism of cyclophosphamide Cyclophosphamide is an inactive prodrug that is activated by hepatic cytochrome P-450 enzymes. Genetic polymorphisms of cytochrome P-450 enzymes can affect response to cyclophosphamide. The major active metabolite is phosphoramide mustard, which alkylates DNA and results in crosslinking of DNA, breaks in DNA, decreased DNA synthesis, and apoptosis. Cyclophosphamide synthesis …
Use of cyclophosphamide in rheumatic diseases Pearl: dose of cyclophosphamide is based on actual body weight even if patient is obese. A study review included 31 patients taking cyclophosphamide and 39 patients taking placebo. Patients taking cyclophosphamide had improved tender and swollen joint scores. Patients receiving placebo were six times more likely to discontinue treatment because …
What rheumatic diseases have been treated successfully with MMF? Which diseases have not been treated successfully with MMF? Use is similar to AZA. Good success has been seen in lupus nephritis (diffuse proliferative glomerulonephritis membranous) especially in African-American and Hispanic patients. It has been used successfully for treating cutaneous lupus (discoid and subacute cutaneous lupus), …
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