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 Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

(CKD) on

haemodialysis Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...

(HD) or

peritoneal dialysis Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte prob ...

(PD). It is used in form of chewable tablets. Sucroferric oxyhydroxide is also known as a mixture of polynuclear iron(III)-oxyhydroxide, sucrose and starches. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. 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.

Medical uses

Sucroferric oxyhydroxide is approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) and the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA) for the control of serum phosphorus levels in patients with

(CKD) on

dialysis Dialysis may refer to: *Dialysis (chemistry), a process of separating molecules in solution **Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...

Adverse effects

The most frequently reported adverse drug reactions reported from trials were

diarrhoea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

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 Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin II receptor antagonist, angiotensin receptor blocker (ARB) family of medication, and is consider ...

furosemide Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by mouth ...

omeprazole Omeprazole, sold under the brand names Prilosec and Losec, among others, is a medication used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome. It is also used to prevent upper g ...

digoxin Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is on ...

, and

warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent strok ...

, the lipid-lowering effects of

statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low- ...

s, and oral

vitamin D receptor The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then forms a heterodimer ...

agonists. According to the European label (

Summary of Product Characteristics A package insert is a document included in the package of a medication that provides information about that drug and its use. For prescription medications, the insert is technical, providing information for medical professionals about how to pre ...

), medicinal products that are known to interact with iron (e.g.

doxycycline Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, an ...

) 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 Levothyroxine, also known as -thyroxine, is a manufactured form of the thyroid hormone thyroxine (T4). It is used to treat hypothyroidism, thyroid hormone deficiency (hypothyroidism), including a severe form known as myxedema coma. It may also ...

. 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.

Hyperphosphatemia

In a healthy person, normal serum phosphate levels are maintained by the regulation of dietary absorption,

bone formation Ossification (also called osteogenesis or bone mineralization) in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in t ...

and

resorption Resorption is the absorption of cells or tissue into the circulatory system, usually by osteoclasts. Types of resorption include: * Bone resorption * Herniated Disc Resorption * Tooth resorption * Fetal resorption * Blood resorption See also ...

, equilibration with intracellular stores, and

renal excretion In pharmacology, clearance is a pharmacokinetics, pharmacokinetic measurement of the volume of blood plasma, plasma from which a substance is completely removed per unit time. Usually, clearance is measured in L/h or mL/min. The quantity reflects t ...

. When kidney function is impaired, phosphate excretion declines. Without specific treatment, hyperphosphataemia occurs almost universally, despite dietary phosphate restriction and conventional

treatment. In patients on dialysis, hyperphosphataemia is an independent risk factor for

fractures Fracture is the separation of an object or material into two or more pieces under the action of stress. The fracture of a solid usually occurs due to the development of certain displacement discontinuity surfaces within the solid. If a displa ...

cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...

and

mortality Mortality is the state of being mortal, or susceptible to death; the opposite of immortality. Mortality may also refer to: * Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...

. 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 In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...

shell composed of

sucrose Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula . For human consumption, sucrose is extracted and refined ...

and

starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human diets ...

. 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. Tablets of sucroferric oxyhydroxide easily disintegrated in artificial

saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...

Effectiveness and phosphate binding

Clinical Phase III studies showed that sucroferric oxyhydroxide achieves and maintains phosphate levels in compliance with the KDOQI guidelines. The reduction in serum phosphate levels of sucroferric oxyhydroxide-treated patients was non-inferior to that in

sevelamer 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 ...

-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.

References

External links

* {{Portal bar , Medicine Phosphate binders