Mycophenolate mofetil drug interactions

Sirolimus is currently the only FDA-approved ToR inhibitor. One of its derivatives, everolimus, is in phase III clinical trials and has been approved for use in some European countries.30 Sirolimus is a macrolide antibiotic that has no effect on cal-cineurin phosphatase.11,31,32 Sirolimus inhibits T cell activation and proliferation by binding to and inhibiting the activation of the mammalian ToR, which suppresses cellular response to IL-2 and other cytokines (i.e., IL-4 and IL-15J.11,31 Studies have shown that sirolimus may be used safely and effectively with either cyclosporine or tacrolimus as a replacement for either azathioprine or mycophenolate mofetil.33 However, when using both sirolimus and cyclosporine as part of a patient s immunosuppressant therapy, because of a drug interaction between the two resulting in a marked increase in sirolimus concentrations, it is recommended to separate the sirolimus and cyclosporine doses by at least 4 hours. Sirolimus also can be used as an alternative agent for patients who do not tolerate calcineurin inhibitors due to nephrotoxicity or other adverse events.34... 

Drug interactions In a randomized, double-blind study, Zenapax or placebo was added to an immunosuppressive regimen of cyclosporine, mycophenolate mofetil, and steroids to assess tolerability, pharmacokinetics, and drug interactions. The addition of Zenapax did not result in an increased incidence of adverse events or a change in the types of adverse events reported. The following medications have been administered in clinical trials with Zenapax with no incremental increase in adverse reactions cyclosporine, mycophenolate mofetil, ganciclovir, acyclovir, azathioprine, and corticosteroids. 

Drug interactions No formal drug-drug interaction studies have been conducted. The following medications have been administered in clinical trials with Simulect with no incremental increase in adverse reactions azathioprine, corticosteroids, cyclosporine, mycophenolate mofetil, and muromonab-CD3. 

Mycophenolate mofetil is available in both oral and intravenous forms. The oral form is rapidly metabolized to mycophenolic acid. Although the cytochrome P450 system is not involved, some drug interactions still occur. Plasma drug levels are frequently monitored, similar to the calcineurin inhibitors and PSIs. 

Drug Interactions Acyclovir Antacids with magnesium and aluminum hydroxides Cholestyramine Drugs that alter gastrointestinal flora may interact with mycophenolate mofetil by disrupting enterohepatic recirculation Probenecid... 

Hubner GI, Eismann R, Sziegoleit W. Drug interaction between mycophenolate mofetil and tacrolimus detectable within therapeutic mycophenolic acid monitoring in renal transplant patients. Ther Drug Monit 1999 21(5) 536-9. 

See Chap. 87 on solid organ transplantation for a discussion of drug interactions involving mycophenolate mofetil. 

Therapeutic Uses Mycophenolate mofetil is indicated for prophylaxis of transplant rejection, and it typically is used in combination with glucocorticoids and a calcineurin inhibitor, but not with azathioprine. Combined treatment with siroUmus is possible, although potential drug interactions necessitate careful monitoring of drug levels. For renal transplants, 1 g is administered orally or intravenously (over 2 hours) twice daily (2 g/day). A higher dose, 1.5 g twice daily (3 g/day), is recommended for African American renal transplant patients and all cardiac transplant patients. 

Shah J, Juan D, Bullingham R, Wong B, Wong R, Fu C. A single dose drug interaction study of mycophenolate mofetil and acyclovir in normal subjects. J Clin Pharmacol (1994) 34, 1029. 

S3mtex. A single-dose, pharmacokinetic drug interaction study of oral mycophenolate mofetil and oral acyclovir in normal subjects. Data on file, 1994. 

A study in patients with rheumatoid arthritis found that the combination of methotrexate and mycophenolate mofetil was well tolerated and there were no pharmacokinetic interactions. There would appear to be no need for dose adjustments if both drugs are given for rheumatoid arthritis. 

Drug-drug interactions Mycophenolate mofetil In a pharmacokinetic study of telmisartan, valsartan, and candesartan in combination with mycophenolate mofetil in renal transplant patients, telmisartan increased the elimination of mycophenolic acid there was no interaction with valsartan or candesartan [57 ]. It was suggested that this was due to activation by... 

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