Sucroferric Oxyhydroxide Does Not Interact With Oral VDRAs
Intact parathyroid hormone decreased in dialysis patients taking sucroferric oxyhydroxide but increased in those taking sevelamer carbonate.
Sucroferric oxyhydroxide, unlike sevelamer carbonate, does not reduce the therapeutic activity of oral vitamin D receptor agonists (VDRA) in controlling secondary hyperparathyroidism (SHPT), a new study finds.
Stuart M. Sprague, DO, of NorthShore University HealthSystem in Illinois, and colleagues, investigated potential drug-drug interactions between phosphate binders and oral VDRAs in a post hoc analysis of a phase 3 study on sucroferric oxyhydroxide, sevelamer carbonate, and VDRA activity. Of 1059 dialysis patients with hyperphosphatemia, 710 randomly received sucroferric oxyhydroxide (1 to 3 g daily) and 349 sevelamer carbonate (2.4 to 14.4 g daily) for up to 52 weeks. The investigators used serum intact parathyroid hormone (iPTH) as a surrogate for serum levels of VDRAs.
Dr Sprague and his team compared 3 exclusive populations: Patients taking oral VDRAs, no VDRAs, or intravenous (IV) paricalcitol. In the population taking oral VDRAs only, iPTH decreased in the sucroferric oxyhydroxide group (–25.3 pg/mL) but increased in the sevelamer group (+89.8 pg/mL), according to results published online ahead of print in the American Journal of Nephrology. Among patients with no VDRA therapy, iPTH increased at similar rates in both groups. Among patients receiving IV paricalcitol, iPTH decreased comparably in both groups (–29.6 and –11.4 pg/mL for sucroferric oxyhydroxide and sevelamer, respectively).
Sucroferric oxyhydroxide did not hinder the ability of oral VDRAs to lower iPTH over 52 weeks, according to the investigators. Similar decreases in iPTH were observed in patients taking sucroferric oxyhydroxide whether with oral or intravenous VDRAs.
Conversely, sevelamer carbonate, may interact with oral VDRAs. iPTH increased in patients taking sevelamer and oral VDRA, whereas it decreased in those given IV paricalcitol. The results on sevelamer carbonate concur with a previous pharmacokinetic study, the investigators noted. SHPT rates also were significantly lower with sucroferric oxyhydroxide than sevelamer carbonate.
Investigators observed no significant differences in 25-hydroxyvitamin D concentrations among the groups. Also, both phosphate binders resulted in similar phosphorus reductions.
"The use of oral VDRAs have increased in recent years, thus it is important that concomitant medications, such as phosphate binders, do not affect the biologic activity of VDRAs," Dr Sprague told Renal & Urology News. "Our findings demonstrate that sucroferric oxyhydroxide does not interfere with the biologic effect of oral VDRAs."
Among the limitations, the investigators acknowledged that their research was not a true pharmacodynamic study because it used iPTH as a proxy for VDRA activity. In addition, it's possible that unrecorded medications or supplements may have influenced iPTH levels.
The study was funded by Vifor Pharma, which produces sucroferric oxyhydroxide (Velphoro®). Several study authors disclosed consultancy and/or lecture fees from the company.
1. 1. Sprague SM1, Covic AC, Floege J, Ketteler M, Botha J, Chong EM, and Rastogi A. Pharmacodynamic Effects of Sucroferric Oxyhydroxide and Sevelamer Carbonate on Vitamin D Receptor Agonist Bioactivity in Dialysis Patients. Am J Nephrol. 2016 Jul 20;44(2):104-112. doi: 10.1159/000447600. [Epub ahead of print]