Table 3.

Steroid-sparing immunosuppressive agents for frequent relapses and/or steroid dependence

	Indication in the scientific information	Recommended dose	Side effects	Monitoring	Therapy duration	Advantage/indication
Cyclosporine	Steroid-dependent and steroid-resistant nephrotic syndrome resulting from primary glomerular diseases such as minimal change nephropathy, focal segmental glomerulosclerosis or membranous glomerulonephritis	150 mg/m2 divided into two oral doses, in the further course adjustments after blood trough levels might be necessary	Kidney dysfunction, tremor, hypertrichosis, hypertension, diarrhea, anorexia, nausea and vomiting, gingival hyperplasia	Blood trough level (80–120 ng/mL initial, later lower, 50–80 ng/mL) Serum Creatinine	1–4 years	Good effectiveness in long-term therapy
Tacrolimus	Off-label	0.1–0.15 mg/kg divided into two oral doses, in the further course adjustments after blood trough levels might be necessary	Kidney dysfunction, tremor, hypertension, diarrhea, anorexia, nausea, vomiting, diabetes mellitus	Blood trough level 3–5 (-8) ng/mL Serum Creatinine	1–4 years	Good effectiveness in long-term therapy, fewer cosmetic side effects (gingival hyperplasia, hypertrichosis)
Mycophenolic acid	Off-label	1200 mg/m2 divided into two oral doses, in the course adjustments according to MPA-AUC might be necessary	Diarrhea and vomiting, leukocytopenia, sepsis, increased infection rate. Contraindicated in pregnancy	Blood count controls, plasma predose concentration, if necessary determination of total exposure (AUC kinetics) for individual dose finding	1–4 years	Good effectiveness with adequate exposure
Cyclophosphamide	Threatening “autoimmune diseases,” severe, progressive forms of lupus nephritis and granulomatosis with polyangiitis (GPA)	2–3 mg/kg per day in one oral dose for 8–12 weeks	Myelosuppression especially leukocytopenia, hemorrhagic cystitis	Blood count checks initially weekly	8–12 weeks	Short therapy duration,potentially permanent remission
Levamisole	Off-label	2–2.5 mg/kg every second day as a single oral dose (max. 150 mg)	Leukocytopenia, allergic reactions, gastrointestinal disorders, skin necrosis, ANCA-positive vasculitis	First weekly blood count, then at 4–12 weekly intervals	1.5–2 years	Efficacy especially for frequent relapses, less for steroid dependence
Rituximab	Off-label	375 mg/m2 intravenously as a single dose	Potentially fatal infections, neutropenia, drop in IgG and IgM, skin reactions, cytokine release syndrome, progressive multifocal leukoencephalopathy	Blood count controls, control of immunoglobulins G and M, prophylaxis of Pneumocystis jirovecii infection	If necessary, repeat the application during the course of the treatment (e.g., after B-cell monitoring)	Good efficacy, side effect profile in this indication still insufficiently documented. Only indicated if the usual therapy is not sufficiently effective