In transplanted patients who are considered for conversion to Gengraf from Sandimmune (cyclosporine), Gengraf should be started with the same daily dose as was previously used with Sandimmune* (cyclosporine) (1:1 dose conversion). The Gengraf dose should subsequently be adjusted to attain the pre conversion cyclosporine blood trough concentration. Using the same trough concentration target range for Gengraf as for Sandimmune* (cyclosporine) results in greater cyclosporine exposure when Gengraf is administered (see CLINICAL PHARMACOLOGY -Pharmacokinetics, Absorption). Patients with suspected poor absorption of Sandimmune* (cyclosporine) require different dosing strategies (see DOSAGE AND ADMINISTRATION - Transplant Patients with Poor Absorption of Sandimmune* (cyclosporine), below). In some patients, the increase in blood trough concentration is more pronounced and may be of clinical significance.

Until the blood trough concentration attains the pre-conversion value, it is strongly recommended that the cyclosporine blood trough concentration be monitored every 4 to 7 days after conversion to Gengraf. In addition, clinical safety parameters such as serum creatinine and blood pressure should be monitored every two weeks during the first two months after conversion. If the blood trough concentrations are outside the desired range and/or if the clinical safety parameters worsen, the dosage of Gengraf must be adjusted accordingly.

Transplant Patients with Poor Absorption of Sandimmune®* (Cyclosporine)

Patients with lower than expected cyclosporine blood trough concentrations in relation to the oral dose of Sandimmune* (cyclosporine) may have poor or inconsistent absorption of cyclosporine from Sandimmune* (cyclosporine). After conversion to Gengraf (cyclosporine oral solution, USP [MODIFIED]), patients tend to have higher cyclosporine concentrations. Due to the increase in bioavailability of cyclosporine following conversion to Gengraf, the cyclosporine blood trough concentration may exceed the target range. Particular caution should be exercised when converting patients to Gengraf at doses greater than 10 mg/kg/day. The dose of Gengraf should be titrated individually based on cyclosporine trough concentrations, tolerability, and clinical response. In this population the cyclosporine blood trough concentration should be measured more frequently, at least twice a week (daily, if initial dose exceeds 10 mg/kg/day) until the concentration stabilizes within the desired range.

Rheumatoid Arthritis

The initial dose of Gengraf (cyclosporine oral solution, USP [MODIFIED]) is 2.5 mg/kg/day, taken twice daily as a divided (BID) oral dose. Salicylates, nonsteroidal anti-inflammatory agents, and oral corticosteroids may be continued (see WARNINGS and PRECAUTIONS - Drug Interactions). Onset of action generally occurs between 4 and 8 weeks. If insufficient clinical benefit is seen and tolerability is good (including serum creatinine less than 30% above baseline), the dose may be increased by 0.5 to 0.75 mg/kg/day after 8 weeks and again after 12 weeks to a maximum of 4 mg/kg/day. If no benefit is seen by 16 weeks of therapy, Gengraf therapy should be discontinued.

Dose decreases by 25%-50% should be made at any time to control adverse events, e.g., hypertension elevations in serum creatini