Nephrotoxicity diclofenac

Concomitant administration of methotrexate and Voltarol, a proprietary preparation of diclofenac, a non-steroidal anti-inflammatory drug, may result in accumulation of methotrexate as its excretion is reduced. The use of diclofenac and diuretics such as bendroflumethiazide may increase the risk of nephrotoxicity. Concomitant use of alcohol and an angiotensin-converting enzyme inhibitor such as lisinopril (Zestril) may result in an enhanced hypotensive effect. Alcohol and the benzodiazepine diazepam (Valium) may result in enhanced sedation. 

Recently, a case of vulture mortality was reported from the Indian subcontinent related to NS AID toxicity. Diclofenac is a widely available veterinary NS AID in the Indian subcontinent, used in domestic livestock. Vultures were exposed to the drug when they consumed carcasses of cattle that were treated with diclofenac shortly before death. Experimental studies of this drug in vultures showed marked nephrotoxicity. The gross observations were primarily deposits of urate on the surface of internal organs related to renal failure. Histopathological findings were acute necrosis of the proximal renal tubular epithelium with minimal inflammatory response and deposits of urate crystals (Oaks et al, 2004 Meteyer et al, 2005). 

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). 

Deray G, Le Hoang P, Aupetit B, Achour A, Rottembourg J, Baumelou A. Enhancement of cyclosporine A nephrotoxicity by diclofenac. Clin Nephrol 1987 27(4) 213-14. 

Diclofenac An HIV-l-positive patient who had taken long-term tenofovir developed severe acute tubular necrosis with proximal tubular dysfunction when she also started to take diclofenac [134 ]. Since she had tolerated tenofovir well for several years, the authors suggested that diclofenac had interfered with tenofovir clearance, thereby causing nephrotoxicity. However, the effect could have been due to the diclofenac alone. 

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