Sucroferric oxyhydroxide

Clinical data
Trade names Velphoro
AHFS/Drugs.com Consumer Drug Information
Pregnancy
category
  • US: B (No risk in non-human studies)
  • EU, Japan (No risk in non-human studies)
Legal status
  • US: ℞-only
  • EU, Japan (prescription only)
Routes of
administration		 Oral (chewable tablets)
Identifiers
ATC code V03AE05
Chemical data
Formula Varies

Sucroferric oxyhydroxide (INN; trade name Velphoro, by Vifor Fresenius Medical Care Renal Pharma) is a non-calcium, iron-based phosphate binder used for the control of serum phosphorus levels in adult patients with chronic kidney disease (CKD) on haemodialysis (HD) or peritoneal dialysis (PD).[1] It is used in form of chewable tablets.

Hyperphosphataemia

In a healthy person, normal serum phosphate levels are maintained by the regulation of dietary absorption, bone formation and resorption, equilibration with intracellular stores, and renal excretion.[2] When kidney function is impaired, phosphate excretion declines. Without specific treatment, hyperphosphataemia occurs almost universally, despite dietary phosphate restriction and conventional dialysis treatment.[2][3] In patients on dialysis, hyperphosphataemia is an independent risk factor for fractures, cardiovascular disease and mortality.[4][5] Abnormalities in phosphate metabolism such as hyperphosphatemia are included in the definition of the new chronic kidney disease–mineral and bone disorder (CKD-MBD).[5]

Structure and mechanism of action

Sucroferric oxyhydroxide comprises a polynuclear iron(III)-oxyhydroxide core that is stabilised with a carbohydrate shell composed of sucrose and starch.[6][7] The carbohydrate shell stabilises the iron(III)-oxyhydroxide core to preserve the phosphate adsorption capacity.

Dietary phosphate binds strongly to sucroferric oxyhydroxide in the gastrointestinal (GI) tract. The bound phosphate is eliminated in the faeces and thereby prevented from absorption into the blood. As a consequence of the decreased dietary phosphate absorption, serum phosphorus concentrations are reduced.

Medical uses

Sucroferric oxyhydroxide is approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the control of serum phosphorus levels in patients with chronic kidney disease (CKD) on dialysis.[1][8]

Adverse effects

The most frequently reported adverse drug reactions reported from trials were diarrhoea and discoloured faeces.[1][8] The vast majority of gastrointestinal adverse events occurred early during treatment and abated with time under continued dosing.[1]

Interactions

Drug-interaction studies and post hoc analyses of Phase 3 studies showed no clinically relevant interaction of sucroferric oxyhydroxide with the systemic exposures to losartan, furosemide, omeprazole, digoxin, and warfarin,[9] the lipid-lowering effects of statins,[10] and oral vitamin D receptor agonists.[11] According to the European label (Summary of Product Characteristics), medicinal products that are known to interact with iron or have the potential to interact with Velphoro should be administered at least one hour before or two hours after Velphoro.[1] According to the US prescribing information, Velphoro should not be prescribed with oral levothyroxine.[8]

Chewability

The chewability of sucroferric oxyhydroxide compares well with that of Calcimagon, a calcium containing tablet used as a standard for very good chewability.[12] Tablets of sucroferric oxyhydroxide easily disintegrated in artificial saliva.

Effectiveness and phosphate binding

Clinical Phase 3 studies showed that sucroferric oxyhydroxide achieves and maintains phosphate levels in compliance with the KDOQI guidelines.[13][14] The reduction in serum phosphate levels of sucroferric oxyhydroxide-treated patients was non-inferior to that in sevelamer-treated patients. The required daily pill burden was lower with sucroferric oxyhydroxide.[13]

Sucroferric oxyhydroxide binds phosphate under empty and full stomach conditions and across the physiologically relevant pH range of the GI tract.[7]

References

  1. 1 2 3 4 5 Velphoro (sucroferric oxyhydroxide). Summary of Product Characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002705/WC500175254.pdf/. Accessed 24 October 2014.
  2. 1 2 Jha V, Garcia-Garcia G, Iseki K et al. (2013). "Chronic kidney disease: global dimension and perspectives". Lancet 382 (9888): 260–72. doi:10.1016/S0140-6736(13)60687-X. PMID 23727169.
  3. ↑ Hutchison AJ, Smith CP, Brenchley PE (2011). "Pharmacology, efficacy and safety of oral phosphate binders". Nat Rev Nephrol 7 (10): 578–89. doi:10.1038/nrneph.2011.112. PMID 21894188.
  4. ↑ Isakova T, Gutierrez OM, Chang Y et al. (2009). "Phosphorus binders and survival on hemodialysis". Am Soc Nephrol 20 (2): 388–96. doi:10.1681/ASN.2008060609. PMC 2637053. PMID 19092121.
  5. 1 2 Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group (2009). "KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)". Kidney Int Supplement 76 (113): S1–130. doi:10.1038/ki.2009.188. PMID 19644521.
  6. ↑ Vifor Fresenius Medical Care Renal Pharma. Product Monograph 2015.
  7. 1 2 Wilhelm M, Gaillard S, Rakov V et al. (2014). "The iron-based phosphate binder PA21 has potent phosphate binding capacity and minimal iron release across a physiological pH range in vitro". Clin Nephrol 81: 251−8.
  8. 1 2 3 Fresenius Medical Care North America. Prescribing information. http://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=237da26c-f38c-4faa-93ad-735e71c9d0c1&type=pdf&name=237da26c-f38c-4faa-93ad-735e71c9d0c1.
  9. ↑ Chong E, Kalia V, Willsie S et al. (2014). "Drug−drug interactions between VELPHORO and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects". J Nephrol 27: 659−66.
  10. ↑ Levesque V, Chong EMF, Moneuse P (2013). "Post-hoc analysis of pharmacodynamic interaction of PA21 with statins in a Phase 3 study of PA21 in dialysis patients with hyperphosphatemia". J Am Soc Nephrol 24: 758A.
  11. ↑ Floege J, Botha J, Chong E et al. (2014). „PA21 does not interact with oral vitamin D receptor agonists: a post hoc analysis of a Phase 3 study”. Poster presented at the ERA-EDTA congress, Amsterdam, The Netherlands, 31 May–3 June 2014. [Abstract no. SP257].
  12. ↑ Lanz M, Baldischweiler J, Kriwet B et al. (2014). "Chewability testing in the development of a chewable tablet for hyperphosphatemia". Drug Dev Ind Pharm 40: 1623−31.
  13. 1 2 Floege J, Covic AC, Ketteler M et al. (2014). "A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients". Kidney Int 86: 638−47.
  14. ↑ Floege J, Covic AC, Ketteler M et al. (2015). "Long-term effects of iron-based phosphate binder, sucroferric oxyhydroxide, in dialysis patients". Nephrol Dial Transplant 30: 1037−46.
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