ne (30% above patient's pretreatment level) or clinically significant laboratory abnormalities (see WARNINGS and PRECAUTIONS). If dose reduction is not effective in controlling abnormalities or if the adverse event or abnormality is severe, Gengraf should be discontinued. The same initial dose and dosage range should be used if Gengraf is combined with the recommended dose of methotrexate. Most patients can be treated with Gengraf doses of 3 mg/kg/day or below when combined with methotrexate doses of up to 15 mg/week (see CLINICAL PHARMACOLOGY - Clinical Trials).
There is limited long-term treatment data. Recurrence of rheumatoid arthritis disease activity is generally apparent within four weeks after stopping cyclosporine.
Psoriasis
The initial dose of Gengraf (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 mg/kg/day.
Dose decreases by 25%-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 PRECAUTIONS - Special Monitoring of 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 12-16 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 six 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 life long disease.
Geng
