Diclofenac Ciclosporin

CICLOSPORIN ANALGESICS-NSAIDs 1. t risk of renal failure with NSAIDs 2. Diclofenac levels t by ciclosporin 3. Rofecoxib 1 plasma concentrations of ciclosporin, with risk of transplant rejection 1. Additive effect both can cause renal insufficiency 2. Uncertain 3. Rofecoxib is a mild inducer of CYP3A4 and not a substrate of CYP3A4 1. Monitor renal function closely 2. Halve dose of diclofenac 3. Be aware. May not be clinically significant... 

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). 

The risk of ciclosporin-induced nephrotoxicity can be increased when NSAIDs are also used (44,45). Diclofenac in particular should be avoided, because it is more likely to cause deterioration of renal function in patients taking ciclosporin (SEDA-15, 100) (SEDA-17, 107). There is also a pharmacokinetic interaction, which may be caused by inhibition by ciclosporin of the first-pass metabolism of diclofenac (SEDA-21,104). 

In 16 healthy volunteers there were no important pharmacokinetic changes when a single dose of ciclosporin was taken during steady-state administration of aspirin, indometacin, or piroxicam, but there was an interaction with diclofenac, whose AUC was doubled in the presence of ciclosporin (46). 

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

NSAIDs sometimes reduce renal function in individual patients, which is reflected in serum creatinine level rises and possibly in changes in ciclosporin levels, but concurrent use can also be uneventful Diclofenac serum levels can be doubled by ciclosporin. There is an isolated report of colitis in a child treated with ciclosporin and diclofenac or indometacin. 

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. ... 

The occurrence of colitis in a child receiving ciclosporin and either diclofenac or indometacin appeared to be independent of changes in ciclosporin levels and may be a result of additive effects of both drugs. ... 

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