Immunosuppression via inhibition of guanosine synthesis.
Selected Indications RA.
Mycophenolate mofetil is rapidly absorbed and then hydrolyzed to its active metabolite, mycophenolic acid. Food does not affect absorption. Mycophenolic acid is later inactivated by hepatic glucuronidation. The inactive metabolites are mostly excreted in urine (93%), with the remainder excreted in feces.
Gastrointestinal effects, including nausea, diarrhea, mucosal hemorrhage, and ulceration, can occur. Leukopenia and infections, especially by opportunistic organisms, are also potential problems. In the renal transplant population, there may be an increased risk for lymphoproliferative and non-melanoma skin carcinomas.
Complete blood cell counts should be obtained initially weekly and then monthly. A rapid fall in leukocyte count requires a decrease in dosage or discontinuation of the drug. Serum liver chemistries should be checked periodically. Vigilance for infection and malignancy should be maintained. Mycophenolate should be avoided in pregnant and nursing women. Dose adjustment is necessary in severe renal insufficiency.
Tablets, 250 and 500 mg. Dosage
Initially 500 mg twice daily; can be increased as indicated to 1,000 mg twice daily. D-Penicillamine (Cuprimine, Depen)
Mode of action in RA is unknown. D-Penicillamine decreases circulating immune complexes and rheumatoid factor titer and inhibits lymphocyte responsiveness to mitogens. A latent period of 2 to 3 months is often observed between initiation of therapy and clinical response.
Selected Indications RA, systemic sclerosis.
Well absorbed from gastrointestinal tract and rapidly excreted in urine. It should be administered on an empty stomach (1 to 2 hours after a meal) to avoid interference of absorption by dietary metals.
Pruritus and skin rash represent the most common side effects and can occur at any time. They can be treated by either lowering the dosage or administering antihistamines. If necessary, the therapy may be interrupted until the rash resolves. Stomatitis also occurs. Alteration of taste is frequent, independent of dosage, and self-limited, with resolution in 2 to 3 months despite continued drug administration. Bone marrow depression may occur precipitously at any time. If the platelet count falls below 80,000 to 100,000, therapy must be discontinued. The most common late toxic effect is immune complex nephropathy. Proteinuria may be seen in 20% of patients. If proteinuria exceeds 1 g/d, the dosage should be reduced. Nephrotic syndrome, hypoalbuminemia, or hematuria requires discontinuation of the drug. Less common side effects include autoimmune syndromes (lupus syndromes, Goodpasture's syndrome, myasthenia gravis, pemphigus, stenosing alveolitis, polymyositis), which necessitate prompt discontinuation of the drug.
Penicillamine administration is contraindicated in patients who are receiving gold compounds, immunosuppressive drugs, or phenylbutazone. Renal insufficiency and pregnancy are further contraindications. A history of penicillin allergy does not preclude use of penicillamine. All patients should have a complete blood cell count, including platelets, and a urinalysis at 2-week intervals for the first 6 months of therapy and monthly thereafter. An unreliable patient is a relative contraindication.
Capsules, 125 and 250 mg. Dosage
Initially, a single daily dose of 250 mg, which is increased in 2 to 3 months to 375 or 500 mg daily if clinical response is insufficient. Further increases to the maximum dose of 750 mg daily may be made after 2 to 3 months.
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