Sodium zirconium cyclosilicate (ZS-9), sold under the brand name Lokelma, is a medication used to treat

high blood potassium Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...

. Onset of effects occurs in one to six hours. It is taken by mouth. Common side effects include swelling and

low blood potassium Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abnor ...

. Use is likely safe in pregnancy and breastfeeding. It works by binding

potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...

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 conven ...

in the

gastrointestinal 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 GI tract contains all the major organ (biology), organs of the digestive syste ...

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

Medical use

Sodium zirconium cyclosilicate is used to treat

. Onset of effects occurs in one to six hours. 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 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 ...

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

, and

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

. Use has been studied for up to a year.

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 and dental 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 cel ...

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

ammonium The ammonium cation is a positively-charged polyatomic ion with the chemical formula or . It is formed by the protonation of ammonia (). Ammonium is also a general name for positively charged or protonated substituted amines and quaternary a ...

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 GI tract contains all the major organs of the digestive system, in humans and ...

. ZS-9 is not systemically absorbed; accordingly, the risk of systemic toxicity may be minimized.

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 end-stage kidney disease, 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 eit ...

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. (T ...

, and

rhabdomyolysis Rhabdomyolysis (also called 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 of th ...

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

spironolactone Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood pressure ...

, 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. They work by causing relaxation of blood vessels as well as a decrease in blood volum ...

. 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. It is an electrogram of the heart which is a graph of voltage versus time of the electrical activity of the hear ...

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 p ...

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 a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of solut ...

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 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 effects ...

. 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

Regulatory

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 respon ...

(FDA) in May 2016, due to issues associated with manufacturing. On May 18, 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 sieves 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).

References

External links

* {{Portal bar , Medicine Chelating agents used as drugs Nephrology procedures Zirconium compounds AstraZeneca brands Potassium