Ciclosporin

CEILING, WITH ITS SPC QUALIFIER (this sentence sits inside the §4.2 block headed 'Non-transplantation indications', which opens 'When using Capimune in any of the established non-transplantation indications, the following general rules should be adhered to'): 'Except in patients with sight-threatening endogenous uveitis and in children with nephrotic syndrome, the total daily dose must never exceed 5 mg/kg.' It does NOT cap the transplantation regimens below. GENERAL RULES FOR NON-TRANSPLANT USE (§4.2): establish a reliable baseline of renal function by at least two measurements before starting (eGFR by MDRD in adults, an appropriate formula in children); 'If eGFR decreases by more than 25% below baseline at more than one measurement, the dosage of Capimune should be reduced by 25 to 50%. If the eGFR decrease from baseline exceeds 35%, further reduction of the dose of Capimune should be considered... If dose reduction is not successful in improving eGFR within one month, Capimune treatment should be discontinued.' 'For maintenance treatment the lowest effective and well tolerated dosage should be determined individually.' Treatment should be discontinued where no adequate response is achieved in the stated time or the effective dose is incompatible with the safety guidelines (psoriasis: 'in patients in whom sufficient response of psoriatic lesions cannot be achieved within 6 weeks on 5 mg/kg/day'). Atopic dermatitis: 'Although an 8-week course of therapy may be sufficient to achieve clearing, up to 1 year of therapy has been shown to be effective and well tolerated, provided the monitoring guidelines are followed.' PRESCRIBER/BRAND: 'Capimune should only be prescribed by, or in close collaboration with, a physician with experience of immunosuppressive therapy and/or organ transplantation'; psoriasis and atopic dermatitis treatment 'should be initiated by physicians with experience in the diagnosis and treatment' of the condition. 'The switch from one oral ciclosporin formulation to another should be made under physician supervision, including monitoring of blood levels of ciclosporin for transplantation patients.' OTHER NON-TRANSPLANT INDICATIONS IN THE SAME SPC (different indications — do not apply to the above): endogenous uveitis, 'initially 5 mg/kg/day orally given in 2 divided doses... In refractory cases, the dose can be increased to 7 mg/kg/day for a limited period', with systemic corticosteroid 0.2 to 0.6 mg/kg prednisone or equivalent if needed; nephrotic syndrome, recommended daily dose in 2 divided oral doses — 'adults: 5 mg/kg; children: 6 mg/kg', and 'In patients with impaired renal function, the initial dose should not exceed 2.5 mg/kg/day', not exceeding 5 mg/kg/day in adults and 6 mg/kg/day in children. TRANSPLANTATION REGIMENS FROM THE SAME SPC — SEPARATE INDICATION, HIGHER DOSES, THE 5 mg/kg NON-TRANSPLANT CEILING DOES NOT APPLY: solid organ transplantation, 'initiated within 12 hours before surgery at a dose of 10 to 15 mg/kg given in two divided doses', maintained 1-2 weeks post-operatively then gradually reduced to 'a recommended maintenance dose of about 2 to 6 mg/kg given in 2 divided doses' (lower doses, e.g. 3-6 mg/kg in two divided doses initially, when combined with corticosteroids or in triple/quadruple therapy); bone marrow transplantation, intravenous 3 to 5 mg/kg/day from the day before transplantation for up to 2 weeks, then oral maintenance 'at daily doses of about 12.5 mg/kg given in 2 divided doses' (12.5 to 15 mg/kg/day in 2 divided doses if oral therapy is used to initiate), maintenance for at least 3 months and preferably 6 months before tapering to zero by 1 year; GVHD occurring after discontinuation — 'an initial oral loading dose of 10 to 12.5 mg/kg should be given, followed by daily oral administration of the maintenance dose previously found to be satisfactory'. PAEDIATRIC (§4.2): 'Clinical studies have included children from 1 year of age. In several studies, paediatric patients required and tolerated higher doses of ciclosporin per kg body weight than those used in adults. Use of Capimune in children for non-transplantation indications other than nephrotic syndrome cannot be recommended.' paedDose is therefore null for this page's indications — verify any paediatric use against a children's formulary. ELDERLY (§4.2): experience is limited; in rheumatoid arthritis trials patients aged 65 or older 'were more likely to develop systolic hypertension on therapy, and more likely to show serum creatinine rises >= 50% above the baseline after 3 to 4 months of therapy'; start at the low end of the dosing range. SOURCE LIMITS: §4.4, §4.6 and §4.8 were truncated at the source-fetch limit, and the §4.3 bullet list ends mid-item, so neither the contraindication list nor the adverse-reaction table below is complete.