Indinavir Nephrolithiasis in Warm Climates

To The Editor: The recent release of indinavir, a potent protease inhibitor of HIV, has resulted in fairly dramatic widespread addition of this agent to the antiretroviral armamentarium for patients with high viral loads of HIV RNA. As noted in the package insert, one of the few side effects of this agent is nephrolithiasis(1). Four percent (79/2205) of patients in the clinical studies required for the NDA has been listed as the approximate frequency of this adverse reaction, which is believed to be crystallization of indinavir in the urine. Therapy includes hydration with resulting dissolution of the crystallized product or, if necessary, discontinuation of the drug. Patients are therefore being instructed to drink~1.5 L of fluid in a 24-h period. Since we have begun using this agent in our practice, despite very careful instructions to our patients about the need for adequate hydration, we have had 7 of 14 patients(50%) develop symptomatic nephrolithiasis, manifested as acute flank or groin pain associated with microscopic and sometimes even gross hematuria. On detailed questioning of these patients, they all claimed to have been taking adequate amounts of fluid. We have observed, however, some features peculiar to our "Southern coastal climate." Many of these patients have been at the beach, working outdoors in their yards during the hot and often humid days, or visiting health spas and exercising, as well as sometimes taking a sauna. All but one have successfully resumed therapy after hydration. It is our opinion that in these particular situations, the vigilance for even greater fluid intake for even greater fluid needs must be emphasized. We suspect that in warmer climates the incidence of nephrolithiasis may in fact be higher unless there is adequate fluid intake. We recommend 2 to 3 L of fluid per day. Michael C. Bach Eliot W.