Ciclosporin rheumatoid arthritis

Gastrointestinal symptoms due to ciclosporin are usually mild and transient. In rheumatoid arthritis, gastrointestinal intolerance has been reported in 50% of patients, being the main cause for withdrawal of ciclosporin in 8% (83). Whereas worsening colitis did not occur in patients with inflammatory bowel disease, ciclosporin was involved in the development of acute colitis in isolated reports (SED-13,1125). 

In an 8-year-old girl with rheumatoid arthritis, the combination of ciclosporin with NSAIDs (indometacin and diclofenac) was suggested to have caused biopsy-proven, non-specific colitis, because her symptoms occurred only when the combination was used (279). 

In patients with rheumatoid arthritis, steady-state coadministration of diclofenac with ciclosporin was associated with a significant rise in serum creatinine concentration. 

Cyclospasmol cyclandelate. cyclosporin [ban] (ciclosporin [inn.jan] cyclosporine [usan] cyclosporin A Neoral Sandimmune ) is a cyclic polypeptide ANTIBIOTIC, possessing IMMUNOSUPPRESSIVE properties (with a specific action on T-lymphocytes). It also has ANTIFUNGAL activity and can be used clinically as an immunosuppressant after transplant surgery, and to treat severe autoimmune diseases including rheumatoid arthritis, cyclosporin A cyclosporine, cyclothiazide [ban. inn. usan] is a (thiazide) diuretic which can be used in ANTIHYPERTENSIVE therapy, cyclovalone [inn] (DVC) is a cyclohexanone, a choleretic... 

Three patients had rapid rises in serum ciclosporin levels, with evidence of nephrotoxicity in two of them, when they were given chloroquine. Some loss of renal function has even been seen with low doses of ciclosporin used with chloroquine for rheumatoid arthritis. Hydroxychloroquine is expected to interact similarly... 

A randomised, controlled study in 88 patients with recent onset rheumatoid arthritis found that the addition of ciclosporin (1.25 or 2.5 mg/kg daily) to chloroquine 100 mg daily was moderately effective, but changes in serum creatinine levels occurred. In the presence of chloroquine the creatinine was not significantly altered by placebo or ciclosporin 1.25 mg/kg, but was raised by 10 micromol/L by ciclosporin2.5 mg/kg, indicating that some renal effects can occur. ... 

A 6-month study in 20 patients with severe rheumatoid arthritis given diclofenac 100 to 200 mg with ciclosporin 3 mg/kg daily found that the AUC of diclofenac was doubled and serum creatinine levels raised from 71 to 88.4 micromol/L. The overall pattern of adverse events and laboratory abnormalities were similar to those in patients with rheumatoid arthritis treated with ciclosporin and other NSAIDs. It was suggested that it would be prudent to start with low doses of diclofenac and to monitor well. A study in 24 healthy subjects found that diclofenac 50 mg every 8 hours for 8 days caused no changes in the pharmacokinetics of ciclosporin, but there was some inconclusive evidence that diclofenac serum levels were increased. ... 

A child with rheumatoid arthritis taking ciclosporin 10 mg/kg daily developed colitis when diclofenac was given. The NSAID was stopped and her symptoms resolved while the ciclosporin was continued. ... 

A study in 16 healthy subjects found that indometacin 100 mg twice daily for 9 days reduced the maximum blood levels of a single 300-mg dose of ciclosporin by 18% and slowed its absorption (time to maximum concentration increased by 30 minutes) but the extent of absorption was not changed, indicating the absence of a clinically relevant pharmacokinetic interaction. Further, the pharmacokinetics of indometacin were not affected by ciclosporin. A study in rheumatoid arthritis patients taking ciclosporin 2.5 mg/kg daily, found that creatinine clearances were reduced by 6% in those taking indometacin 50 mg four times daily, but this was not considered to be clinically important. An experimental study in healthy subjects found that ciclosporin 10 mg/kg twice daily for 4 days had no effect on effective renal plasma flow (ERPF) or the glomerular filtration rate (GFR), but when indometacin 50 mg twice daily was added the ERPF fell by 32% and the GFR by 37%. ... 

A study in rheumatoid arthritis patients taking ciclosporin 2.5 mg/kg daily, found that creatinine clearances were reduced by 2.3% in those taking ketoprofen 50 mg four times daily, but this was not considered to be clin-... 

In 11 patients with rheumatoid arthritis taking ciclosporin, naproxen and sulindac increased serum creatinine levels by 24% and reduced renal function (glomerular filtration rate reduced from 98 niL/minute at baseline to 67 mL/minute while taking an NSAID and ciclosporin). All patients had a clinical improvement in their rheumatoid arthritis. 

Piroxicam is reported to have increased the serum creatinine levels ofa patient with rheumatoid arthritis by an unknown amount (but classed as a significant adverse event). This resolved when the piroxicam was withdrawn. A study in healthy subjects given piroxicam 20 mg daily for 11 days and a single 300-mg dose of ciclosporin on day 10 found no clinically relevant pharmacokinetic interaction. ... 

A patient with a kidney transplant had a rise in serum creatinine levels when sulindac was used. Ciclosporin blood levels fell and rose again when the sulindac was stopped. Another report states that the ciclosporin levels of a woman with a kidney transplant were more than doubled within 3 days of her starting to take sulindac 150 mg twice daily. In 11 patients with rheumatoid arthritis taking ciclosporin, both sulindac and naproxen increased serum creatinine levels by 24% and reduced renal function (glomerular filtration rate reduced from 98 mL/minute at baseline to 67 mL/minute while taking an NSAID and ciclosporin). All patients had a clinical improvement in their rheumatoid arthritis. "... 

Another report describes a patient with rheumatoid arthritis taking ciclosporin who developed increased serum creatinine levels when given ketoprofen, but not when given sulindac. ... 

Information about the NSAIDs listed here is sparse and limited, but the overall picture appears to be that concurrent use in rheumatoid arthritis need not be avoided but renal function should be very well monitored. The manufacturers of ciclosporin also specifically recommend that patients... 

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