Other therapies should be considered for MCD patients with frequent relapses and steroid toxicity. A course of treatment with alklylating agents such as cyclophosphamide or chlorambucil has been shown to lead to a prolonged remission in children who are frequent relapsers. Cyclophosphamide (2 mg/kg) for 12 weeks is more commonly used and may induce remission lasting several years. Patients must be monitored for bone marrow toxicity with weekly complete blood counts and prompt treatment with varicella-zoster immune globulin if they are not immune to varicella infection. Courses longer than 12 weeks may lead to gonadal toxicity. In practice, many patients begin cyclophosphamide therapy while on alternate day steroids, which are weaned gradually over the course of 3–6 months. If patients resume a frequently relapsing course after receiving a course of cyclophosphamide, alternate day steroid therapy, levamisole (unavailable in the United States) or a course of cyclosporine may be tried. Levamisole has been shown to reduce the incidence of relapses in children with frequent relapses but not in children with steroid dependence. If the patient has not yet had a kidney biopsy, most pediatric nephrologists will perform one prior to using cyclosporine. Cyclosporine has been shown to be useful therapy in the patient with frequent relapsing, steroid- dependent, and probably even steroid-resistant MCD. Because of its toxicity profile, cyclosporine should be prescribed only by physicians who are experienced in its use. Side effects of treatment include hirsuitism, gingival hyperplasia, hypertension, hypomagnesemia, and nephrotoxicity. The usual starting dose is 5–6 mg/kg/day divided in two doses with close monitoring of cyclosporine levels (target trough levels of 50–125 ng/mL), renal function, and magnesium levels. The typical course of therapy is 1–2 years, followed by a slow taper. Many patients experience relapses after discontinuation of cyclosporine; if continued therapy is needed, kidney biopsies should be performed to monitor for nephrotoxicity. Many patients also require alternate day steroid therapy in conjunction with cyclosporine. Tacrolimus, also a calcineurin inhibitor, also shows some promise for therapy of patients with therapy-resistant nephrotic syndrome. Recent reports have suggested that mycophenolate mofetil (MMF), a purine synthesis inhibitor, may be useful in the treatment of children with steroid-dependent nephrotic syndrome.