Sodium zirconium cyclosilicate (ZS-9), sold under the brand name Lokelma, is a medication used to treat high blood potassium. Onset of effects occurs in one to six hours. It is taken by mouth. Common side effects include swelling and low blood potassium. 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 atmosp ...

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 conve ...

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 organs of the digestive system, in humans a ...

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 includ ...

Medical use

Sodium zirconium cyclosilicate is used to treat high blood potassium. 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, ...

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 ...

, 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, ...

. Use has been studied for up to a year.

Mechanism of action

ZS-9 is a zirconium silicate. 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. 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 quaternar ...

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 an ...

. 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, 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 t ...

. 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 pressur ...

, 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 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 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 solu ...

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. Common side effects include constipation, low blood magnesium, and abdominal pain. It works by binding potassium in the gut ...

and sodium polystyrene sulfonate. Hyperkalemia, particularly if severe, is a

marker The term Marker may refer to: Common uses * Marker (linguistics), a morpheme that indicates some grammatical function * Marker (telecommunications), a special-purpose computer * Boundary marker, an object that identifies a land boundary * Marke ...

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 federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(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