Sodium zirconium cyclosilicate, sold under the brand name Lokelma, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used to treat high blood potassium. Onset of effects occurs in one to six hours. It is taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

. Common side effects include swelling and low blood potassium. Use is likely safe in pregnancy and breastfeeding. It works by binding

potassium Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...

ions An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

which is then lost in the stool. Sodium zirconium cyclosilicate was approved for medical use in the European Union and in the United States in 2018. It was developed by

AstraZeneca AstraZeneca plc () (AZ) is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, UK. It has a portfolio of products for major diseases in areas includi ...

Medical use

Sodium zirconium cyclosilicate is used to treat high blood potassium. Onset of effects occurs in one to six hours.

Mechanism of action

ZS-9 is a

zirconium silicate Zirconium silicate, also zirconium orthosilicate, ZrSiO4, is a chemical compound, a silicate of zirconium. It occurs in nature as zircon, a silicate mineral. Powdered zirconium silicate is also known as zircon flour. Zirconium silicate is usual ...

. Zirconium silicates have been extensively used in medical applications because of their proven safety. 11 zirconium silicates were screened by an iterative optimization process. ZS-9 selectively captures potassium ions, presumably by mimicking the actions of physiologic

potassium channels Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of ...

. ZS-9 is an inorganic cation exchanger crystalline with a high capacity to entrap monovalent cations, specifically potassium and

ammonium Ammonium is a modified form of ammonia that has an extra hydrogen atom. It is a positively charged (cationic) polyatomic ion, molecular ion with the chemical formula or . It is formed by the protonation, addition of a proton (a hydrogen nucleu ...

ions, in the

GI tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...

Background

Hyperkalemia is rare among those who are otherwise healthy. Among those who are in hospital, rates are between 1% and 2.5%. Common causes include

kidney failure Kidney failure, also known as renal failure or 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 fa ...

hypoaldosteronism Hypoaldosteronism is an endocrinological disorder characterized by decreased levels of the hormone aldosterone. Similarly, isolated hypoaldosteronism is the condition of having lowered aldosterone without corresponding changes in cortisol. (The ...

, and

rhabdomyolysis Rhabdomyolysis (shortened as rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some o ...

. A number of medications can also cause high blood potassium including

spironolactone Spironolactone, sold under the brand name Aldactone among others, is classed as a diuretic medication. It can be used to treat edema, fluid build-up due to hepatic cirrhosis, liver disease or kidney disease. It is also used to reduce risk o ...

, NSAIDs, and

angiotensin converting enzyme inhibitors Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decr ...

. There is no universally accepted definition of what level of hyperkalemia is mild, moderate, or severe. However, if hyperkalemia causes any

ECG Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity through repeated cardiac cycles. It is an electrogram of the heart which is a graph of voltage versus time of ...

change it is considered a

medical emergency A medical emergency is an acute injury or illness that poses an immediate risk to a person's life or long-term health, sometimes referred to as a situation risking "life or limb". These emergencies may require assistance from another, qualified ...

due to a risk of potentially fatal abnormal heart rhythms and is treated urgently. Potassium levels greater than 6.5 to 7.0

mmol/L Molar concentration (also called molarity, amount concentration or substance concentration) is the number of moles of solute per liter of solution. Specifically, It is a measure of the concentration of a chemical species, in particular, of a sol ...

in the absence of ECG changes are managed aggressively. Several approaches are used to treat hyperkalemia. Other approved potassium binders in the United States include

patiromer Patiromer, sold under the brand name Veltassa, is a medication used to treat high blood potassium. It is taken by mouth. It works by binding potassium in the gut. Common side effects include constipation, low blood magnesium, and abdominal p ...

and

sodium polystyrene sulfonate Polystyrene sulfonates are a group of medications used to treat high blood potassium. Effects generally take hours to days. They are also used to remove potassium, calcium, and sodium from solutions in technical applications. Common side effe ...

. Hyperkalemia, particularly if severe, is a marker for an increased risk of death. However, there is disagreement regarding whether a modestly elevated levels directly causes problems. One viewpoint is that mild to moderate hyperkalemia is a secondary effect that denotes underlying medical problems. Accordingly, these problems are both proximate and ultimate causes of death,

History

In the United States, regulatory approval of ZS-9 was rejected by the

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 respo ...

(FDA) in May 2016, due to issues associated with manufacturing. On 18 May 2018, the FDA approved sodium zirconium cyclosilicate for treatment of adults with hyperkalemia. It was first practically synthesized by UOP in the late 1990s. (reference -zirconium silicate and zirconium germate

molecular sieve A molecular sieve is a material with pores of uniform size comparable to that of individual molecules, linking the interior of the solid to its exterior. These materials embody the molecular sieve effect, in which molecules larger than the pore ...

s and the process of using the same, US Patent 5,888,472) the recognition of the unique ion exchange properties and the potential use to remove toxins from the body were identified shortly thereafter ("process for removing toxins from bodily fluids using zirconium or titanium microporous compositions, US Patent 6,332,985).

Research

One review found a decrease in potassium of 0.17 mEq/L at one hour and 0.67 mEq/L at 48 hours. It appears effective in people with

chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

, and

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

. Use has been studied for up to a year.

Medical use

Mechanism of action

Background

History

Research

References

Further reading