ity. The risk increases with increasing doses of cyclosporine. Renal dysfunction including structural kidney damage is a potential consequence of Gengraf and therefore renal function must be monitored during therapy. Care should be taken in using cyclosporine with nephrotoxic drugs (see PRECAUTIONS).
Patients receiving Gengraf require frequent monitoring of serum creatinine (see Special Monitoring under DOSAGE AND ADMINISTRATION). Elderly patients should be monitored with particular care, since decreases in renal function also occur with age. If patients are not properly monitored and doses are not properly adjusted, cyclosporine therapy can be associated with the occurrence of structural kidney damage and persistent renal dysfunction.
An increase in serum creatinine and BUN may occur during Gengraf therapy and reflect a reduction in the glomerular filtration rate. Impaired renal function at any time requires close monitoring, and frequent dosage adjustment may be indicated. The frequency and severity of serum creatinine elevations increase with dose and duration of cyclosporine therapy. These elevations are likely to become more pronounced without dose reduction or discontinuation.
Because Gengraf (cyclosporine oral solution, USP [MODIFIED]) is not bioequivalent to Sandimmune® (Cyclosporine Oral Solution), conversion from Gengraf to Sandimmune® using a 1:1 ratio (mg/kg/day) may result in lower cyclosporine blood concentrations. Conversion from Gengraf to Sandimmune ® should be made with increased monitoring to avoid the potential of underdosing.
Kidney, Liver, and Heart Transplant
Cyclosporine, the active ingredient of Gengraf (cyclosporine oral solution, USP [MODIFIED]), can cause nephrotoxicity and hepatotoxicity when used in high doses. It is not unusual for serum creatinine and BUN levels to be elevated during cyclosporine therapy. These elevations in renal transplant patients do not necessarily indicate rejection, and each patient must be fully eva luated before dosage adjustment is initiated.
Based on the historical Sandimmune® experience with oral solution, nephrotoxicity associated with cyclosporine had been noted in 25% of cases of renal transplantation, 38% of cases of cardiac transplantation, and 37% of cases of liver transplantation. Mild nephrotoxicity was generally noted 2-3 months after renal transplant and consisted of an arrest in the fall of the pre-operative elevations of BUN and creatinine at a range of 35-45 mg/dL and 2-2.5 mg/dL respectively. These elevations were often responsive to cyclosporine dosage reduction.
More overt nephrotoxicity was seen early after transplantation and was characterized by a rapidly rising BUN and creatinine. Since these events are similar to renal rejection episodes, care must be taken to differentiate between them. This form of nephrotoxicity is usually responsive to cyclosporine dosage reduction.
Although specific diagnostic criteria which reliably differentiate renal graft rejection from drug toxicity have not been found, a number of parameters have been significantly associated with one or the other. It should be noted however, that up to 20% of patients may have simultaneous nephrotoxicity and rejection.
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Nephrotoxicity vs. Rejection |
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a p < 0.05, b p < 0.01, c p < 0.001, d p & |
