Table 5.

Dose, monitoring, adverse effects, and cost of all agents used as maintenance in FRNS and SDNS patients

Therapeutic agent Dose	Monitoring	Adverse Effects	Cost
Low Dose Alternate-Day PDN  ≤ 0.5 mg/kg/alt day, max 20 mg alt day	Quarterly: blood pressure, height, weight Yearly: ophthalmological examination	Obesity/weight gain, hypertension, diabetes mellitus, behavioral/psychiatric disorders, sleep disruption, growth failure, cushingoid features, striae rubrae/distensae, glaucoma, cataract, bone pain, avascular necrosis	Low
Low Dose Daily PDN  ≤ 0.25 mg/kg/day, max 10 mg/day
Calcineurin inhibitors Cyclosporin A Start: 3–5 mg/kg per day (maximum dose 250 mg) in 2 divided doses, Target: C0 60–100 ng/mL or C2 300–550 ng/mL (aiming for the lowest possible dose to maintain remission) Tacrolimus Start: 0.1–0.2 mg/kg per day (maximum dose 10 mg) in 2 divided doses Target: C0 level between 3 and 7 ng/mL (aiming for the lowest possible dose to maintain remission)	Quarterly: Blood pressure CBC, creatinine, eGFR, K+ LFTs, lipids Uric acid (CsA) Mg+ (TAC) Fasting glucose (TAC) Drug levels Consider discontinuation or a kidney biopsy after 2–3 years to avoid/detect toxicity	Acute and chronic nephrotoxicity, hypertension, seizures, tremor, posterior reversible encephalopathy syndrome (PRES) Hirsutism (CsA), gum hyperplasia (CsA), diabetes mellitus (TAC) TAC drug levels can increase in case of intense diarrhea Consider risk of toxicity due to drug interactions (e.g., macrolide antibiotics, certain anti-epileptic agents, and grapefruit juice increase drug levels)	Intermediate price, CsA less than TAC
Cyclophosphamide 2 mg/kg per day (maximum dose 150 mg) over 12 weeks (oral) or 3 mg/kg per day (maximum dose 150 mg) over 8 weeks Single morning dose preferable No more than a single course (max TCD 168 mg/kg) Give in conjunction with alternate day oral PDN starting with a dose of 40 mg/m2 (1.5 mg/kg) and reducing to 10 mg/m2 (0.3 mg/kg) over the duration of treatment	CBC every 14 days during therapy	Leukopenia, severe infections, alopecia, nail discoloration, seizure, infertility, GI upset (abdominal pain, diarrhea), hemorrhagic cystitis, jaundice Fertile individuals must be warned of the need to avoid unplanned pregnancy (CYC can cause fetal malformation)	Low
Levamisole 2–2.5 mg/kg/alternate day (maximum dose 150 mg) In some cases, LEV is initially alternated with oral PDN on non-LEV days	Quarterly: CBC, LFTs Twice-yearly: ANCA titers (also at baseline)	Arthritis, vasculitic rash, neutropenia, abnormal LFTs	Low
Mycophenolate mofetil (MMF)/mycophenolic sodium (MPS) MMF: Start: 1200 mg/m2 per day in two divided doses every 12 hoursa (maximum dose 3000 mg) MPS: 360 mg corresponds to 500 mg of MMF Therapeutic drug monitoring using a limited sampling strategy: The most effective MPA AUC0–12 is above 50 mg × h/Lb	Quarterly: CBC LFTs	Abdominal pain, diarrhea, weight loss (may be improved by the use of MPS). Leukopenia, anemia and abnormal LFTs Verrucae Fertile females must be warned of the need to avoid unplanned pregnancy (MMF/MPS can cause fetal malformations)	High; MPS more expensive than MMF
Rituximab 375 mg/m2 for 1–4 doses per course (maximum single dose 1000 mg) at weekly intervals Aim for CD19 depletion (< 5 cells/mm3 or < 1% total lymphocytes) Premedication is often used with antihistamine, paracetamol and steroids Repeated courses can be given Administer in remission after appropriate pre-medication under close supervision and monitoring Exclude hepatitis B and C, HIV, EBV, tuberculosis / any active infection	Quarterly: CBC LFTs CD19 counts and % IgG (at baseline, quarterly in the 1st year, then yearly)	Infusion reactions, infection, activation of latent viruses, transient or persistent IgG deficiency Serious adverse effects: tuberculosis, hepatitis B, or JC virus infection, myocardial dysfunction, risk of progressive multifocal leukoencephalopathy (PML) If infection is suspected, undertake diagnostic work-up including chest x-ray etc	High

CBC complete blood count, C₀ trough level, C₂ 2 h post dosing, eGFR estimated glomerular filtration rate, CBC complete blood cells, LFTs liver function test, LEV levamisole; cyclosporin A, CsA; TAC, tacrolimus; GI gastrointestinal, AUC area under the curve

Evidence and grading are given in the text

^aPatients may be started on half dose. Dosage may be increased after 1 week in case of no side effects, e.g., leucopenia or GI discomfort

^bA limited sampling strategy for assessing pharmacokinetic profiles was validated in children with NS being in remission on MMF monotherapy. It requires three measurements of plasma MPA at times 0 min (before administration, C₀), 60 min (C₁), 120 min (C₂) after administration), and allows a good estimation of MPA-AUC_0-12 using the formula eMPA − AUC₀₋₁₂ = 8.70 + 4.63 * C₀ + 1.90 * C₁ + 1.52 * C₂ [152]. Alternatively, the formula: eMPA—AUC₀₋₁₂ = 7.75 + (6.49 * C₀) + (0.76 * C_0.5) + (2.43 * C₂) which was originally established in adult heart transplant patients treated with concomitant CsA can be used [108, 152, 153]