Rheumatoid arthritis

When using ciclosporin in any of the established non-transplantation indications, the following general rules should be adhered to:

Before initiation of treatment a reliable baseline level of renal function should be established by at least two measurements. The estimated glomerular filtration rate (eGFR) by the MDRD formula can be used for estimation of renal function in adults and an appropriate formula should be used to assess eGFR in paediatric patients. Since ciclosporin can impair renal function, it is necessary to assess renal function frequently. If eGFR decreases by more than 25% below baseline at more than one measurement, the dosage of ciclosporin should be reduced by 25 to 50%. If the eGFR decrease from baseline exceeds 35%, further reduction of the dose of ciclosporin should be considered. These recommendations apply even if the patient’s values still lie within the laboratory’s normal range. If dose reduction is not successful in improving eGFR within one month, ciclosporin treatment should be discontinued.

Regular monitoring of blood pressure is required.

The determination of bilirubin and parameters that assess hepatic function are required prior to starting therapy and close monitoring during treatment is recommended. Determinations of serum lipids, potassium, magnesium and uric acid are advisable before treatment and periodically during treatment.

Occasional monitoring of ciclosporin blood levels may be relevant in non-transplant indications, e.g. when ciclosporin is co-administered with substances that may interfere with the pharmacokinetics of ciclosporin, or in the event of unusual clinical response (e.g. lack of efficacy or increased drug intolerance such as renal dysfunction).

The normal route of administration is by mouth. If the concentrate for solution for infusion is used, careful consideration should be given to administering an adequate intravenous dose that corresponds to the oral dose. Consultation with a physician with experience of use of ciclosporin is recommended.

Except in patients with sight-threatening endogenous uveitis and in children with nephrotic syndrome, the total daily dose must never exceed 5 mg/kg.

For maintenance treatment the lowest effective and well tolerated dosage should be determined individually.

In patients in whom within a given time no adequate response is achieved or the effective dose is not compatible with the established safety guidelines, treatment with ciclosporin should be discontinued.

Rheumatoid arthritis

For the first 6 weeks of treatment the recommended dose is 3 mg/kg/day orally given in 2 divided doses. If the effect is insufficient, the daily dose may then be increased gradually as tolerability permits, but should not exceed 5 mg/kg. To achieve full effectiveness, up to 12 weeks of Neoral therapy may be required.

For maintenance treatment the dose has to be titrated individually to the lowest effective level according to tolerability.

Ciclosporin can be given in combination with low-dose corticosteroids and/or non-steroidal anti-inflammatory drugs (NSAIDs). Neoral can also be combined with low-dose weekly methotrexate in patients who have insufficient response to methotrexate alone, by using 2.5 mg/kg ciclosporin in 2 divided doses per day initially, with the option to increase the dose as tolerability permits.