Jane S. Ricciuti, RPh, MS


March 19, 2003

In This Article

Immunosuppressive Agents


Manufacturer: Novartis Pharmaceuticals Corporation

Drug Approval Classification: Supplemental New Drug Application (Approval Date: 02/14/03)

Precautions: The "Precautions" section of the Sandimmune (cyclosporine) label was changed to include the following new precautions and statements:

The following drugs were added to the list of nonsteroidal anti-inflammatory drugs: naproxen, sulindac, and colchicine.

  • Compounds that decrease cyclosporine absorption, such as orlistat, should be avoided.

  • The following drugs were added to the list of antibiotics that increase cyclosporine concentrations: quinupristin and dalfopristin.

  • The HIV protease inhibitors (eg, indinavir, nelfinavir, ritonavir, and saquinavir) are known to inhibit cytochrome P-450 3A and thus could potentially increase the concentrations of cyclosporine; however, no formal studies of the interaction are available. Care should be exercised when these drugs are administered concomitantly.

  • Grapefruit and grapefruit juice affect metabolism, increasing blood concentrations of cyclosporine, and thus should be avoided.

  • The dietary supplement St. John's wort and orlistat were added to the table for Drugs/Dietary Supplements That Decrease Cyclosporine Concentrations. Below this table, the following sentences were added:

    There have been reports of a serious drug interaction between cyclosporine and the herbal dietary supplement, St. John's wort. This interaction has been reported to produce a marked reduction in the blood concentrations of cyclosporine, resulting in subtherapeutic levels, rejection of transplanted organs, and graft loss.

  • Rifabutin is known to increase the metabolism of other drugs metabolized by the cytochrome P-450 system. The interaction between rifabutin and cyclosporine has not been studied. Care should be exercised when these 2 drugs are administered concomitantly.

  • A new subsection was added to "Precautions," " Nonsteroidal Anti-inflammatory Drug (NSAID) Interactions " containing the following language:

    Clinical status and serum creatinine should be closely monitored when cyclosporine is used with nonsteroidal anti-inflammatory agents in rheumatoid arthritis patients.

  • Pharmacodynamic interactions have been reported to occur between cyclosporine and both naproxen and sulindac, in that concomitant use is associated with additive decreases in renal function, as determined by 99mTc-diethylenetriamine penta-acetic acid (DTPA) and (p-aminohippuric acid) PAH clearances. Although concomitant administration of diclofenac does not affect blood levels of cyclosporine, it has been associated with approximate doubling of diclofenac blood levels and occasional reports of reversible decreases in renal function. Consequently, the dose of diclofenac should be in the lower end of the therapeutic range.

  • A new subsection was added to "Precautions," " Methotrexate Interaction " containing the following language:

    Preliminary data indicate that when methotrexate and cyclosporine were co-administered to rheumatoid arthritis patients (N = 20), methotrexate concentrations (AUCs) were increased approximately 30% and the AUCs of its metabolite, 7-hydroxy methotrexate, were decreased by approximately 80%. The clinical significance of this interaction is not known. Cyclosporine concentrations do not appear to have been altered (N = 6).

  • The following changes were made to the "Precautions: Other Drug Interactions " subsection:

    Psoriasis patients receiving other immunosuppressive agents or radiation therapy (including PUVA and UVB) should not receive concurrent cyclosporine because of the possibility of excessive immunosuppression.

  • Sandimmune (cyclosporine) Labeling

    Sandimmune (cyclosporine)


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