Off‐label use of tacrolimus in children with glomerular disease: Effectiveness, safety and pharmacokinetics

Abstract

Glomerular diseases are leading causes of end‐stage renal disease in children. Tacrolimus is frequently used off‐label in the treatment of glomerular diseases. The effectiveness, safety and pharmacokinetic data of tacrolimus in the treatment of glomerular diseases in children are reviewed in this paper to provide evidence to support its rational use in clinical practice. The remission rates in previously published studies were different. In 19 clinical trials on children with nephrotic syndrome, the overall remission rate was 52.6‐97.6%. In four clinical trials on children with lupus nephritis, the overall remission rate was 81.8‐89.5%. In a pilot study with paediatric Henoch‐Schönlein purpura nephritis patients, the overall remission rate was 100.0%. Infection, nephrotoxicity, gastrointestinal symptoms and hypertension are the most common adverse events. Body weight, age, CYP3A5 genotype, cystatin‐C and daily dose of tacrolimus may have significant effects on the pharmacokinetics of tacrolimus in children with glomerular disease. More prospective controlled trials with long follow‐up are needed to demonstrate definitely the effectiveness, safety and pharmacokinetics of tacrolimus in children with glomerular diseases.

Steroid Sensitive Nephrotic Syndrome: Revised Guidelines

“…Calcineurin inhibitors: Observational studies indicate that CNI (cyclosporine 4-6 mg/kg/day, tacrolimus 0.1-0.2 mg/ kg/day, in two divided doses) maintain remission and enable steroid-sparing in 60-90% patients with frequent relapses or steroid dependence who have failed treatment with alkylating agents [82][83][84]. These agents have not been compared to placebo or to each other in controlled studies for SSNS.…”

“…Chief adverse effects of CNI include acute and chronic nephrotoxicity (with both agents), hirsutism, gum hypertrophy, hypertension and hyperlipidemia (with cyclosporine), and hyperglycemia or seizures (with tacrolimus) [82,83]. While tacrolimus is preferred to cyclosporine due to lack of cosmetic effects, only the latter is available as an oral suspension for young children.…”

Monitoring tacrolimus whole blood concentrations

“…Несмотря на то что CYP3A5 может объяснить до 45% фармакокинетической вариабельности TAC между индивидуумами, другие факторы также могут влиять на TAC: различия скорости опорожнения желудка или неспособность ТАС растворяться в желудочном содержимом. Следует учитывать влияние иммуносупрессантов на рост и развитие детей, особенно на протекание инфекционных процессов и более высокие показатели посттрансплантационной лимфопролиферативной заболеваемости [14,15].…”

The efficacy and safety of tacrolimus in treating refractory IgA vasculitis nephritis: a single-center retrospective study on 16 cases

“…Tacrolimus (TAC) is a potent immunosuppressant applied in the clinic. It has a strong inhibitory effect on T-cell proliferation and can be widely used in glomerular diseases, especially refractory glomerular diseases [ 8 ]. It has been reported in the literature that TAC can alleviate proteinuria in children with steroid-resistant nephrotic syndrome [ 9 ] and can also be used to treat refractory IgA nephropathy [ 10 ], which can significantly decrease proteinuria and haematuria in patients with fewer adverse effects.…”