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Diclofenac, tenofovir combination may increase acute kidney injury risk
BRUSSELS — Drug-to-drug interaction caused by diclofenac could increase tenofovir-associated nephrotoxicity and should be prescribed with caution for patients receiving tenofovir disoproxil fumarate therapy, according to a presenter here at EACS 2013.
To determine the prevalence of nephrotoxicity in patients with HIV who received nonsteroidal anti-inflammatory drugs, Markus Bickel, MD, and colleagues from the department of infectious disease and internal medicine at JW Goethe University Clinic in Frankfurt, Germany, conducted retrospective analysis of patients in a hospital-based HIV cohort who received a prescription for diclofenac from January 2008 to June 2012.
According to data analysis, of the 89 cohort patients who were prescribed diclofenac, 61 were treated with tenofovir (Viread, Gilead Sciences) and 28 with tenofovir-sparing combination antiretroviral therapy.
Researchers identified 13 patients who developed acute kidney injuries shortly after beginning diclofenac. Acute kidney injury appeared exclusively in the tenofovir-treated group, which all had previously exhibited stable renal function. All incidences were accompanied by new onset of no less than two parameters indicating proximal tubular damage, including normoglycemic glycosuria and hypophosphatemia.
In addition, 11.5% of patients receiving tenofovir were found to have newly developed proximal tubular damage, yet maintained glomerular filtration rate. However, patients receiving diclofenac exhibited no change in renal function while receiving tenofovir-sparing combination ART.
In a univariate analysis, risk factors for acute kidney injury were tenofovir-sparing combination ART (P=.0076) and pre-existing hypophosphatemia (P=.0086).
“Physicians and patients should be aware that co-administration of diclofenac and tenofovir could increase the risk for proximal tubular dysfunction,” Bickel said. “Patients with hypophosphatemia who could possibly already have a subclinical toxicity from treatment or those patients who require diclofenac treatment should consider treatment with combination ART.”
For more information:
Bickel M. #PS 1/1. Presented at: 14th European AIDS Conference; Oct. 16-19, 2013; Brussels.
Perspective
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The prescribing patterns of physicians, in general, has varied dramatically from country to country, and even varied within countries from clinic to clinic. The relationship between diclofenac and renal dysfunction is not new, but is very well described and is something that many physicians will regularly come across in the general treatment population, not just specifically HIV.
The interesting element of this study is that it examined diclofenac that was prescribed for a prolonged period of time — the author outlined that patients had been on it for about 3 months concurrently with tenofovir on a regular dose. This is a drug that can be used regularly as a short-term pain relief medication.
It is a very specific use of this drug in this setting, and a relatively small number of patients who have come up with this very significant and very dramatic effect. In terms of what recommendations physicians should make based on this study, if physicians choose to prescribe diclofenac regularly to patients with HIV for prolonged periods of time — which, personally, I don’t do — then they need to monitor these patients very carefully.