The initial dose of Gengraf® Oral Solution (cyclosporine oral solution, USP [MODIFIED]) should be 2.5 mg/kg/day. Gengraf® should be taken twice daily, as a divided (1.25 mg/kg BID) oral dose. Patients should be kept at that dose for at least 4 weeks, barring adverse events. If significant clinical improvement has not occurred in patients by that time, the patient's dosage should be increased at 2-week intervals. Based on patient response, dose increases of approximately 0.5 mg/kg/day should be made to a maximum of 4.0 mg/kg/day. 

Dose decreases by 25% to 50% should be made at any time to control adverse events, e.g., hypertension, elevations in serum creatinine (≥ 25% above the patient's pretreatment level), or clinically significant laboratory abnormalities. If dose reduction is not effective in controlling abnormalities, or if the adverse event or abnormality is severe, Gengraf® should be discontinued (see Special Monitoring for Psoriasis Patients). 

Patients generally show some improvement in the clinical manifestations of psoriasis in 2 weeks. Satisfactory control and stabilization of the disease may take 12 to 16 weeks to achieve. Results of a dose-titration clinical trial with Gengraf® indicate that an improvement of psoriasis by 75% or more (based on PASI) was achieved in 51% of the patients after 8 weeks and in 79% of the patients after 16 weeks. Treatment should be discontinued if satisfactory response cannot be achieved after 6 weeks at 4 mg/kg/day or the patient's maximum tolerated dose. Once a patient is adequately controlled and appears stable the dose of Gengraf® should be lowered, and the patient treated with the lowest dose that maintains an adequate response (this should not necessarily be total clearing of the patient). In clinical trials, cyclosporine doses at the lower end of the recommended dosage range were effective in maintaining a satisfactory response in 60% of the patients. Doses below 2.5 mg/kg/day may also be equally effective. 

Upon stopping treatment with cyclosporine, relapse will occur in approximately 6 weeks (50% of the patients) to 16 weeks (75% of the patients). In the majority of patients rebound does not occur after cessation of treatment with cyclosporine. Thirteen cases of transformation of chronic plaque psoriasis to more severe forms of psoriasis have been reported. There were 9 cases of pustular and 4 cases of erythrodermic psoriasis. Long term experience with Gengraf® in psoriasis patients is limited and continuous treatment for extended periods greater than one year is not recommended. Alternation with other forms of treatment should be considered in the long-term management of patients with this lifelong disease. 

Gengraf® Oral Solution (Cyclosporine Oral Solution, USP [MODIFIED])-Recommendations for Administration 

To make Gengraf® Oral Solution (cyclosporine oral solution, USP [MODIFIED]) more palatable, it should be diluted with orange or apple juice that is at room temperature. Patients should avoid switching diluents frequently. Grapefruit juice affects metabolism of cyclosporine and should be avoided. The combination of Gengraf® solution with milk can be unpalatable. The effect of milk on the bioavailability of cyclosporine when administered as Gengraf® Oral Solution (cyclosporine oral solution, USP [MODIFIED]) has not been evaluated. 

Take the prescribed amount of Gengraf® Oral Solution (cyclosporine oral solution, USP [MODIFIED]) from the container using the dosing syringe supplied, and transfer the solution to a glass of orange or apple juice. Stir well and drink at once. Do not allow diluted oral solution to stand before drinking. Use a glass container (not plastic). Rinse the glass with more diluent to ensure that the total dose is consumed. After use, dry the outside of the dosing syringe with a clean towel and store in a clean, dry place. Do not rinse the dosing syringe with water or other cleaning agents. If the syringe requires cleaning, it must be completely dry before resuming use.