Sucroferric oxyhydroxide explained

Tradename:Velphoro
Dailymedid:Sucroferric oxyhydroxide
Routes Of Administration:By mouth
Atc Prefix:V03
Atc Suffix:AE05
Legal Au:S4
Legal Au Comment:[1]
Legal Ca:Rx-only
Legal Ca Comment:[2]
Legal Uk:POM
Legal Uk Comment:[3]
Legal Us:Rx-only
Legal Eu:Rx-only
Cas Number:20344-49-4
Unii:87PZU03K0K
Pubchem:91663255
Drugbank:DB09146
Kegg:D04616

Sucroferric oxyhydroxide, sold under the brand name Velphoro, is a non-calcium, iron-based phosphate binder used for the control of serum phosphorus levels in adults with chronic kidney disease (CKD) on haemodialysis (HD) or peritoneal dialysis (PD).[4] It is used in form of chewable tablets.

Sucroferric oxyhydroxide is also known as a mixture of polynuclear iron(III)-oxyhydroxide, sucrose and starches.[5]

The most common side effects include diarrhea and discolored feces, which may become less frequent with continued treatment.

It was approved for medical use in the United States in November 2013, and in the European Union in August 2014.[6]

Medical uses

Sucroferric oxyhydroxide is approved by the U.S. 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.[7]

Adverse effects

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

Interactions

Drug-interaction studies and post hoc analyses of Phase III studies showed no clinically relevant interaction of sucroferric oxyhydroxide with the systemic exposures to losartan, furosemide, omeprazole, digoxin, and warfarin,[8] the lipid-lowering effects of statins,[9] and oral vitamin D receptor agonists.[10] According to the European label (Summary of Product Characteristics), medicinal products that are known to interact with iron (e.g. doxycycline) or have the potential to interact with Velphoro should be administered at least one hour before or two hours after Velphoro. This allows sucroferric oxyhydroxide to bind phosphate as intended and be excreted without coming into contact with medications in the gut that it might interact with. According to the US prescribing information, Velphoro should not be prescribed with oral levothyroxine. The combination of sucroferric oxyhydroxide and levothyroxine is contraindicated because sucroferric oxyhydroxide contains iron, which may cause levothyroxine to become insoluble in the gut, thereby preventing the intestinal absorption of levothyroxine.[11]

Hyperphosphatemia

See main article: Hyperphosphatemia. 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.[12] When kidney function is impaired, phosphate excretion declines. Without specific treatment, hyperphosphataemia occurs almost universally, despite dietary phosphate restriction and conventional dialysis treatment.[13] In patients on dialysis, hyperphosphataemia is an independent risk factor for fractures, cardiovascular disease and mortality.[14] [15] Abnormalities in phosphate metabolism such as hyperphosphatemia are included in the definition of the new chronic kidney disease–mineral and bone disorder (CKD-MBD).

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.[16] [17] 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.

Chewability

The chewability of sucroferric oxyhydroxide compareswell with that of Calcimagon, a calcium containing tablet used as a standard for very good chewability.[18] Tablets of sucroferric oxyhydroxide easily disintegrated in artificial saliva.

Effectiveness and phosphate binding

Clinical Phase III studies showed that sucroferric oxyhydroxide achieves and maintains phosphate levels in compliance with the KDOQI guidelines.[19] [20] 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.

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

In a retrospective, real-world study, hyperphosphatemic peritoneal dialysis patients who were prescribed to switch to sucroferric oxyhydroxide from sevelamer, lanthanum carbonate, or calcium acetate had significant reductions in serum phosphorus levels, along with a 53% decrease in the prescribed daily pill burden.[21]

Notes and References

  1. Web site: Prescription medicines: registration of new chemical entities in Australia, 2014 . Therapeutic Goods Administration (TGA) . 21 June 2022 . 10 April 2023 . 10 April 2023 . https://web.archive.org/web/20230410065838/https://www.tga.gov.au/resources/resource/guidance/prescription-medicines-registration-new-chemical-entities-australia-2014 . live .
  2. Web site: Regulatory Decision Summary for Velphoro . 23 October 2014 . 11 April 2023 . 5 January 2023 . https://web.archive.org/web/20230105002046/https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00419 . live .
  3. Web site: Velphoro 500 mg chewable tablets - Summary of Product Characteristics (SmPC) . (emc) . 9 April 2019 . 1 June 2020 . 2 July 2020 . https://web.archive.org/web/20200702102904/https://www.medicines.org.uk/emc/product/3532/smpc . live .
  4. Web site: Velphoro Product Information . European Medicines Agency (EMA) . 24 October 2014 . live . 29 August 2021 . https://web.archive.org/web/20210829073419/https://www.ema.europa.eu/en/documents/product-information/velphoro-epar-product-information_en.pdf .
  5. Web site: Velphoro EPAR . European Medicines Agency (EMA) . 13 October 2014 . 30 June 2020 . 1 July 2020 . https://web.archive.org/web/20200701014816/https://www.ema.europa.eu/en/medicines/human/EPAR/velphoro . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. Web site: Velphoro (sucroferric oxyhydroxide) Chewable Tablet NDA #205109 . U.S. Food and Drug Administration (FDA) . 24 December 1999 . 30 June 2020 . 29 March 2021 . https://web.archive.org/web/20210329215008/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205109Orig1s000TOC.cfm . live .
  7. Web site: Velphoro- sucroferric oxyhydroxide tablet, chewable . DailyMed . 23 April 2020 . 1 June 2020 . 1 July 2020 . https://web.archive.org/web/20200701052940/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=237da26c-f38c-4faa-93ad-735e71c9d0c1 . live .
  8. Chong E, Kalia V, Willsie S, Winkle P . Drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects . Journal of Nephrology . 27 . 6 . 659–66 . December 2014 . 24699894 . 4242982 . 10.1007/s40620-014-0080-1 .
  9. Levesque V, Chong EM, 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.
  10. Floege J, Botha J, Chong E . PA21 does not interact with oral vitamin D receptor agonists: a post hoc analysis of a Phase 3 study . ERA-EDTA congress. Amsterdam, the Netherlands. 31 May 2014. Abstract no. SP257. etal.
  11. Book: Prescribing Information. Synthroid (levothyroxine).. 1 March 2008. Abbott Laboratories. Chicago, IL.
  12. Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang CW . Chronic kidney disease: global dimension and perspectives . Lancet . 382 . 9888 . 260–72 . July 2013 . 23727169 . 10.1016/S0140-6736(13)60687-X . 5508863 .
  13. Hutchison AJ, Smith CP, Brenchley PE . Pharmacology, efficacy and safety of oral phosphate binders . Nature Reviews. Nephrology . 7 . 10 . 578–89 . September 2011 . 21894188 . 10.1038/nrneph.2011.112 . 19833271 .
  14. Isakova T, Gutiérrez OM, Chang Y, Shah A, Tamez H, Smith K, Thadhani R, Wolf M . Phosphorus binders and survival on hemodialysis . Journal of the American Society of Nephrology . 20 . 2 . 388–96 . February 2009 . 19092121 . 2637053 . 10.1681/ASN.2008060609 .
  15. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) . Kidney International Supplements . 76 . 113 . S1-130 . August 2009 . 19644521 . 10.1038/ki.2009.188 . Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group . free .
  16. Vifor Fresenius Medical Care Renal Pharma. Product Monograph 2015.
  17. Wilhelm M, Gaillard S, Rakov V, Funk F . The iron-based phosphate binder PA21 has potent phosphate binding capacity and minimal iron release across a physiological pH range in vitro . Clinical Nephrology . 81 . 4 . 251–8 . April 2014 . 24656315 . 10.5414/cn108119 .
  18. Lanz M, Baldischweiler J, Kriwet B, Schill J, Stafford J, Imanidis G . Chewability testing in the development of a chewable tablet for hyperphosphatemia . Drug Development and Industrial Pharmacy . 40 . 12 . 1623–31 . December 2014 . 24010939 . 10.3109/03639045.2013.838583 . 21386803 .
  19. Floege J, Covic AC, Ketteler M, Rastogi A, Chong EM, Gaillard S, Lisk LJ, Sprague SM . A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients . Kidney International . 86 . 3 . 638–47 . September 2014 . 24646861 . 4150998 . 10.1038/ki.2014.58 .
  20. Floege J, Covic AC, Ketteler M, Mann JF, Rastogi A, Spinowitz B, Chong EM, Gaillard S, Lisk LJ, Sprague SM . Long-term effects of the iron-based phosphate binder, sucroferric oxyhydroxide, in dialysis patients . Nephrology, Dialysis, Transplantation . 30 . 6 . 1037–46 . June 2015 . 25691681 . 4438742 . 10.1093/ndt/gfv006 .
  21. Kalantar-Zadeh K, Parameswaran V, Ficociello LH, Anderson L, Ofsthun NJ, Kwoh C, Mullon C, Kossmann RJ, Coyne DW . Real-World Scenario Improvements in Serum Phosphorus Levels and Pill Burden in Peritoneal Dialysis Patients Treated with Sucroferric Oxyhydroxide . American Journal of Nephrology . 47 . 3 . 153–161 . 2018 . 29514139 . 5906196 . 10.1159/000487856 .

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