Sucroferric oxyhydroxide

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Sucroferric oxyhydroxide
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Trade names Velphoro
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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 hemodialysis (HD) or peritoneal dialysis (PD). [6] It is used in form of chewable tablets. [5]

Contents

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. [5]

It was approved for medical use in the United States in November 2013, and in the European Union in August 2014. [7] [5]

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. [6] [4] [5]

Adverse effects

The most frequently reported adverse drug reactions reported from trials were diarrhoea and discoloured faeces. [6] [4] The vast majority of gastrointestinal adverse events occurred early during treatment and abated with time under continued dosing. [6]

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. [6] 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. [4] 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

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. [12] [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). [15]

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 compares well 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. [19]

Sucroferric oxyhydroxide binds phosphate under empty and full stomach conditions and across the physiologically relevant pH range of the GI tract. [17]

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]

Related Research Articles

Nephrology is a specialty for both adult internal medicine and pediatric medicine that concerns the study of the kidneys, specifically normal kidney function and kidney disease, the preservation of kidney health, and the treatment of kidney disease, from diet and medication to renal replacement therapy. The word "renal" is an adjective meaning "relating to the kidneys", and its roots are French or late Latin. Whereas according to some opinions, "renal" and "nephro" should be replaced with "kidney" in scientific writings such as "kidney medicine" or "kidney replacement therapy", other experts have advocated preserving the use of renal and nephro as appropriate including in "nephrology" and "renal replacement therapy", respectively.

<span class="mw-page-title-main">Kidney failure</span> Disease where the kidneys fail to adequately filter waste products from the blood

Kidney failure, also known as end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as either acute kidney failure, which develops rapidly and may resolve; and chronic kidney failure, which develops slowly and can often be irreversible. Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications of acute and chronic failure include uremia, hyperkalemia, and volume overload. Complications of chronic failure also include heart disease, high blood pressure, and anaemia.

<span class="mw-page-title-main">Hyperparathyroidism</span> Increase in parathyroid hormone levels in the blood

Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands or as response to external stimuli. Symptoms of hyperparathyroidism are caused by inappropriately normal or elevated blood calcium excreted from the bones and flowing into the blood stream in response to increased production of parathyroid hormone. In healthy people, when blood calcium levels are high, parathyroid hormone levels should be low. With long-standing hyperparathyroidism, the most common symptom is kidney stones. Other symptoms may include bone pain, weakness, depression, confusion, and increased urination. Both primary and secondary may result in osteoporosis.

<span class="mw-page-title-main">Chronic kidney disease</span> Abnormal kidney structure or gradual loss of kidney function

Chronic kidney disease (CKD) is a type of long-term kidney disease, in which either there is a gradual loss of kidney function which occurs over a period of months to years, or an abnormal kidney structure. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications can relate to hormonal dysfunction of the kidneys and include high blood pressure, bone disease, and anemia. Additionally CKD patients have markedly increased cardiovascular complications with increased risks of death and hospitalization. CKD can lead to kidney failure requiring kidney dialysis or kidney transplantation.

<span class="mw-page-title-main">Hyperphosphatemia</span> Excess phosphate in the blood

Hyperphosphatemia is an electrolyte disorder in which there is an elevated level of phosphate in the blood. Most people have no symptoms while others develop calcium deposits in the soft tissue. The disorder is often accompanied by low calcium blood levels, which can result in muscle spasms.

<span class="mw-page-title-main">Metabolic acidosis</span> Imbalance in the bodys acid-base equilibrium

Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys to excrete excess acids. Metabolic acidosis can lead to acidemia, which is defined as arterial blood pH that is lower than 7.35. Acidemia and acidosis are not mutually exclusive – pH and hydrogen ion concentrations also depend on the coexistence of other acid-base disorders; therefore, pH levels in people with metabolic acidosis can range from low to high.

Phosphate binders are medications used to reduce the absorption of dietary phosphate; they are taken along with meals and snacks. They are frequently used in people with chronic kidney failure (CKF), who are less able to excrete phosphate, resulting in an elevated serum phosphate.

Renal osteodystrophy is currently defined as an alteration of bone morphology in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure.

<span class="mw-page-title-main">Sevelamer</span> Chemical compound

Sevelamer (rINN) is a phosphate binding medication used to treat hyperphosphatemia in patients with chronic kidney disease. When taken with meals, it binds to dietary phosphate and prevents its absorption. Sevelamer was invented and developed by GelTex Pharmaceuticals. Sevelamer is marketed by Sanofi under the brand names Renagel and Renvela.

<span class="mw-page-title-main">Lanthanum carbonate</span> Ore of lanthanum metal

Lanthanum carbonate, La2(CO3)3, is the salt formed by lanthanum(III) cations and carbonate anions. It is an ore of lanthanum metal (bastnäsite), along with monazite.

<span class="mw-page-title-main">Secondary hyperparathyroidism</span> Medical condition

Secondary hyperparathyroidism is the medical condition of excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia, with resultant hyperplasia of these glands. This disorder is primarily seen in patients with chronic kidney failure. It is sometimes abbreviated "SHPT" in medical literature.

Phosphate nephropathy or nephrocalcinosis is an adverse renal condition that arises with a formation of phosphate crystals within the kidney's tubules. This renal insufficiency is associated with the use of oral sodium phosphate (OSP) such as C.B. Fleet's Phospho soda and Salix's Visocol, for bowel cleansing prior to a colonoscopy.   

<span class="mw-page-title-main">Calciphylaxis</span> Painful, necrotic skin lesions associated with chronic kidney disease

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA) or “Grey Scale”, is a rare syndrome characterized by painful skin lesions. The pathogenesis of calciphylaxis is unclear but believed to involve calcification of the small blood vessels located within the fatty tissue and deeper layers of the skin, blood clots, and eventual death of skin cells due to lack of blood flow. It is seen mostly in people with end-stage kidney disease but can occur in the earlier stages of chronic kidney disease and rarely in people with normally functioning kidneys. Calciphylaxis is a rare but serious disease, believed to affect 1-4% of all dialysis patients. It results in chronic non-healing wounds and indicates poor prognosis, with typical life expectancy of less than one year.

<span class="mw-page-title-main">Robert Provenzano</span> American physician

Robert Provenzano is an American nephrologist. He is also an Associate Clinical Professor of Medicine at Wayne State University School of Medicine.

Potassium binders are medications that bind potassium ions in the gastrointestinal tract, thereby preventing its intestinal absorption. This category formerly consisted solely of polystyrene sulfonate, a polyanionic resin attached to a cation, administered either orally or by retention enema to patients who are at risk of developing hyperkalaemia. Newer drugs include: another polyanionic polymer, patiromer, which exchanges calcium for potassium; and Sodium zirconium cyclosilicate crystals, which exchange sodium for potassium

Calcium acetate/magnesium carbonate is a fixed-dose combination drug that contains 110 mg calcium and 60 mg magnesium ions and is indicated as a phosphate binder for dialysis patients with hyperphosphataemia. It is registered by Fresenius Medical Care under the trade names Renepho (Belgium) and OsvaRen.

<span class="mw-page-title-main">Tenapanor</span> Medication

Tenapanor, sold under the brand name Ibsrela among others, is a medication used for the treatment of adults with a disease of the gut called irritable bowel syndrome with constipation commonly referred to as IBS-C. It is used in form of tenapanor hydrochloride. It is also used in the treatment of chronic kidney disease. Tenapanor is a sodium hydrogen exchanger 3 (NHE3) inhibitor.

Chronic kidney disease–mineral and bone disorder (CKD–MBD) is one of the many complications associated with chronic kidney disease. It represents a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:

CSL Vifor is a global specialty pharmaceuticals company in the treatment areas of iron deficiency, dialysis, nephrology & rare disease. It is headquartered in Switzerland and consists of CSL Vifor, Vifor Fresenius Medical Care Renal Pharma (VFMCRP) and Sanifit Therapeutics.

A renal diet is a diet aimed at keeping levels of fluids, electrolytes, and minerals balanced in the body in individuals with chronic kidney disease or who are on dialysis. Dietary changes may include the restriction of fluid intake, protein, and electrolytes including sodium, phosphorus, and potassium. Calories may also be supplemented if the individual is losing weight undesirably.

References

  1. ↑ "Prescription medicines: registration of new chemical entities in Australia, 2014". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.
  2. ↑ "Regulatory Decision Summary for Velphoro". 23 October 2014. Archived from the original on 5 January 2023. Retrieved 11 April 2023.
  3. ↑ "Velphoro 500 mg chewable tablets - Summary of Product Characteristics (SmPC)". (emc). 9 April 2019. Archived from the original on 2 July 2020. Retrieved 1 June 2020.
  4. 1 2 3 4 "Velphoro- sucroferric oxyhydroxide tablet, chewable". DailyMed. 23 April 2020. Archived from the original on 1 July 2020. Retrieved 1 June 2020.
  5. 1 2 3 4 5 6 "Velphoro EPAR". European Medicines Agency (EMA). 13 October 2014. Archived from the original on 1 July 2020. Retrieved 30 June 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. 1 2 3 4 5 "Velphoro Product Information" (PDF). European Medicines Agency (EMA). Archived (PDF) from the original on 29 August 2021. Retrieved 24 October 2014.
  7. ↑ "Velphoro (sucroferric oxyhydroxide) Chewable Tablet NDA #205109". U.S. Food and Drug Administration (FDA). 24 December 1999. Archived from the original on 29 March 2021. Retrieved 30 June 2020.
  8. ↑ Chong E, Kalia V, Willsie S, Winkle P (December 2014). "Drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects". Journal of Nephrology. 27 (6): 659–66. doi:10.1007/s40620-014-0080-1. PMC   4242982 . PMID   24699894.
  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, et al. (31 May 2014). 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. Abstract no. SP257.
  11. ↑ Prescribing Information. Synthroid (levothyroxine). Chicago, IL: Abbott Laboratories. 1 March 2008.
  12. 1 2 Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. (July 2013). "Chronic kidney disease: global dimension and perspectives". Lancet. 382 (9888): 260–72. doi:10.1016/S0140-6736(13)60687-X. PMID   23727169. S2CID   5508863.
  13. ↑ Hutchison AJ, Smith CP, Brenchley PE (September 2011). "Pharmacology, efficacy and safety of oral phosphate binders". Nature Reviews. Nephrology. 7 (10): 578–89. doi:10.1038/nrneph.2011.112. PMID   21894188. S2CID   19833271.
  14. ↑ Isakova T, Gutiérrez OM, Chang Y, Shah A, Tamez H, Smith K, et al. (February 2009). "Phosphorus binders and survival on hemodialysis". Journal of the American Society of Nephrology. 20 (2): 388–96. doi:10.1681/ASN.2008060609. PMC   2637053 . PMID   19092121.
  15. 1 2 Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group (August 2009). "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. doi: 10.1038/ki.2009.188 . PMID   19644521.
  16. ↑ Vifor Fresenius Medical Care Renal Pharma. Product Monograph 2015.
  17. 1 2 Wilhelm M, Gaillard S, Rakov V, Funk F (April 2014). "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. doi:10.5414/cn108119. PMID   24656315.
  18. ↑ Lanz M, Baldischweiler J, Kriwet B, Schill J, Stafford J, Imanidis G (December 2014). "Chewability testing in the development of a chewable tablet for hyperphosphatemia". Drug Development and Industrial Pharmacy. 40 (12): 1623–31. doi:10.3109/03639045.2013.838583. PMID   24010939. S2CID   21386803.
  19. 1 2 Floege J, Covic AC, Ketteler M, Rastogi A, Chong EM, Gaillard S, et al. (September 2014). "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. doi:10.1038/ki.2014.58. PMC   4150998 . PMID   24646861.
  20. ↑ Floege J, Covic AC, Ketteler M, Mann JF, Rastogi A, Spinowitz B, et al. (June 2015). "Long-term effects of the iron-based phosphate binder, sucroferric oxyhydroxide, in dialysis patients". Nephrology, Dialysis, Transplantation. 30 (6): 1037–46. doi:10.1093/ndt/gfv006. PMC   4438742 . PMID   25691681.
  21. ↑ Kalantar-Zadeh K, Parameswaran V, Ficociello LH, Anderson L, Ofsthun NJ, Kwoh C, et al. (2018). "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. doi:10.1159/000487856. PMC   5906196 . PMID   29514139.
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