The U.S. Food and Drug Administration has received 30 reports of kidney stones over a four-year period among HIV-positive patients being treated with Reyataz® (atazanavir). While it is not yet clear if the crystallized deposits are common among patients taking Bristol-Myers Squibb's protease inhibitor (PI), the agency says that the drug's package insert has been updated to reflect the possibility of this side effect.
Kidney stones, also known as nephrolithiasis, are not a new side effect of antiretroviral treatment. In clinical trials of Crixivan® (indinavir), one of the first PIs approved, kidney stones were documented in approximately 9% of patients taking the drug. To reduce the risk of this often painful – and potentially serious – adverse effect, patients on Crixivan are usually counseled to consume at least eight glasses of water a day.
The brief paper from the FDA, published in the May 31 issue of AIDS, suggests that Reyataz takers may also need to maximize their fluid intake.
Between December 2002 and January 2007, the agency's Adverse Event Reporting System (AERS) received 30 cases of kidney stones that were likely associated with Reyataz treatment. The AERS database, Kirk Chan-Tack, MD, of the FDA and his colleagues write, is based on volunteer reports filed by healthcare providers, patients, and manufacturers from the United States and other countries.
Twenty-one patients were men and five were women; the genders of the remaining four were not reported.
Many of the reports filed with the FDA did not include full medical histories, but the available information indicated that three patients had pre-existing kidney disease and five patients had a history of kidney stones.
Of the 20 cases reporting complete HIV treatment information, including all of the medications and doses being taken, 17 patients were receiving Reyataz boosted with low-dose Norvir® (ritonavir) and 13 were also taking tenofovir (as Viread®, its brand name, or as a component of Truvada®).
Fourteen of the kidney stones collected from the patients were submitted to the FDA for analysis. Twelve of the stones contained crystallized Reyataz, a sign of the drug's possible involvement.
Although some patients evidently passed their stones spontaneously, eight of the patients required interventions such as a stent or tube insertion. Reyataz was stopped in eight patients; the experiences of those who continued on Reyataz treatment were not discussed in the paper.
In conclusion, Dr. Chan-Tack and his colleagues pointed out that the mechanism by which Reyataz causes kidney stones has not yet been determined. Additional data are also needed to determine whether patients with pre-existing kidney disease or a history of kidney stones are at an increased risk, or if kidney stones are more likely to develop in patients who have been on the PI for an extended period of time.
Until these data are collected and reported, however, the FDA stresses that "healthcare professionals and patients should be informed that nephrolithiasis is a possible adverse event with the use of atazanavir."
If signs or symptoms of kidney stones occur – these include excruciating pain in the lower back, side, or groin, as well as blood in the urine – patients should consult with their healthcare providers immediately. According the FDA, temporarily or permanently stopping Reyataz may be necessary.
Source:
Chan-Tack KM, Truffa MM, Struble KA, et al. Atazanavir-associated nephrolithiasis: cases from the US Food and Drug Administration's Adverse Event Reporting System. AIDS 21:9, 2007.
