Drug–drug interactions between sucroferric oxyhydroxide and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects

Abstract

BackgroundThe novel iron-based phosphate binder sucroferric oxyhydroxide is being investigated for the treatment of hyperphosphatemia. Patients with chronic kidney disease often have multiple comorbidities that may necessitate the daily use of several types of medication. Therefore, the potential pharmacokinetic drug–drug interactions between sucroferric oxyhydroxide and selected drugs commonly taken by dialysis patients were investigated.MethodsFive Phase I, single-center, open-label, randomized, three-period crossover studies in healthy volunteers investigated the effect of a single dose of sucroferric oxyhydroxide 1 g (based on iron content) on the pharmacokinetics of losartan 100 mg, furosemide 40 mg, omeprazole 40 mg, digoxin 0.5 mg and warfarin 10 mg. Pharmacokinetic parameters [including area under the plasma concentration–time curve (AUC) from time 0 extrapolated to infinite time (AUC0–∞) and from 0 to 24 h (AUC0–24)] for these drugs were determined: alone in the presence of food; with sucroferric oxyhydroxide in the presence of food; 2 h after food and sucroferric oxyhydroxide administration.ResultsSystemic exposure based on AUC0–∞ for all drugs, and AUC0–24 for all drugs except omeprazole (for which AUC 0–8 h was measured), was unaffected to a clinically significant extent by the presence of sucroferric oxyhydroxide, irrespective of whether sucroferric oxyhydroxide was administered with the drug or 2 h earlier.ConclusionsThere is a low risk of drug–drug interactions between sucroferric oxyhydroxide and losartan, furosemide, digoxin and warfarin. There is also a low risk of drug–drug interaction with omeprazole (based on AUC0–∞ values). Therefore, sucroferric oxyhydroxide may be administered concomitantly without the need to adjust the dosage regimens of these drugs.

Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide

“…Then, their dosage does not need to be adjusted if sucroferric oxyhydroxide is simultaneously administered. 52 However, a potential adsorption of levothyroxine by sucroferric oxyhydroxide has been reported; then, it is recommended that levothyroxine should not be prescribed with this phosphate binder. 49,53 Comparative efficacy, safety, and tolerability studies of iron oxyhydroxide in CKD Over recent years, various clinical studies have been carried out to evaluate efficacy, safety, and tolerability of sucroferric …”

“…As mentioned before, the risk turned out to be low with losartan, furosemide, omeprazole, digoxin, and warfarin. 52 Another Phase I study recruited patients with stage 3-4 CKD, patients on hemodialysis, and healthy subjects. The aim was to evaluate the effects of 1-week treatment with sucroferric oxyhydroxide 10 g/day on serum phosphate concentrations and the potential risk for iron overload.…”

Sucroferric Oxyhydroxide: A Review in Hyperphosphataemia in Chronic Kidney Disease Patients Undergoing Dialysis

“…In healthy volunteers, there were no clinically relevant effects on the systemic exposure of digoxin, furosemide, losartan, omeprazole or warfarin when these agents were administered simultaneously or 2 h after a single dose of sucroferric oxyhydroxide 1000 mg [17]. In this study, peak serum concentrations (C max ) of digoxin, furosemide, losartan and omeprazole were decreased when administered with sucroferric oxyhydroxide and food compared with administration 2 h after food and sucroferric oxyhydroxide.…”

“…In this study, peak serum concentrations (C max ) of digoxin, furosemide, losartan and omeprazole were decreased when administered with sucroferric oxyhydroxide and food compared with administration 2 h after food and sucroferric oxyhydroxide. While it was considered possible that the differences in C max were due to the effect of food, a direct effect of sucroferric oxyhydroxide on the absorption rate of these medications could not be excluded [17].…”

A Review of Sucroferric Oxyhydroxide for the Treatment of Hyperphosphatemia in Patients Receiving Dialysis

“…6 Losartan, digoxin, warfarin, furosemide, and omeprazole were chosen for these studies. The pharmacokinetic parameters of interest were AUC 0-24 , AUC 0-1 , C max , t max , and t ½ .…”