Clinical data | |
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Trade names | Lokelma |
Other names | ZS-9 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a618035 |
License data | |
Routes of administration | By mouth |
ATC code | |
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Legal status | |
Pharmacokinetic data | |
Bioavailability | Not absorbed |
Excretion | Feces |
Identifiers | |
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CAS Number | |
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Chemical and physical data | |
Formula | (2Na·H2O·3H4SiO4·H4ZrO6)n |
Sodium zirconium cyclosilicate, sold under the brand name Lokelma, is a medication used to treat high blood potassium. [4] Onset of effects occurs in one to six hours. [4] It is taken by mouth. [4]
Common side effects include swelling and low blood potassium. [4] Use is likely safe in pregnancy and breastfeeding. [4] It works by binding potassium ions in the gastrointestinal tract which is then lost in the stool. [4] [5]
Sodium zirconium cyclosilicate was approved for medical use in the European Union and in the United States in 2018. [4] [3] [6] It was developed by AstraZeneca. [4]
Sodium zirconium cyclosilicate is used to treat high blood potassium. [4] Onset of effects occurs in one to six hours. [4]
ZS-9 is a zirconium silicate. Zirconium silicates have been extensively used in medical and dental applications because of their proven safety. [7] 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. [8] ZS-9 is an inorganic cation exchanger crystalline with a high capacity to entrap monovalent cations, specifically potassium and ammonium ions, in the GI tract.
Hyperkalemia is rare among those who are otherwise healthy. [9] Among those who are in hospital, rates are between 1% and 2.5%. [10] Common causes include kidney failure, hypoaldosteronism, and rhabdomyolysis. [11] A number of medications can also cause high blood potassium including spironolactone, NSAIDs, and angiotensin converting enzyme inhibitors. [11]
There is no universally accepted definition of what level of hyperkalemia is mild, moderate, or severe. [12] However, if hyperkalemia causes any ECG change it is considered a medical emergency [12] due to a risk of potentially fatal abnormal heart rhythms and is treated urgently. [12] Potassium levels greater than 6.5 to 7.0 mmol/L in the absence of ECG changes are managed aggressively. [12] Several approaches are used to treat hyperkalemia. [12] Other approved potassium binders in the United States include patiromer and sodium polystyrene sulfonate. [13]
Hyperkalemia, particularly if severe, is a marker for an increased risk of death. [14] 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. [14] Accordingly, these problems are both proximate and ultimate causes of death, [14]
In the United States, regulatory approval of ZS-9 was rejected by the Food and Drug Administration (FDA) in May 2016, due to issues associated with manufacturing. [15] On 18 May 2018, the FDA approved sodium zirconium cyclosilicate for treatment of adults with hyperkalemia. [16]
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).
One review found a decrease in potassium of 0.17 mEq/L at one hour and 0.67 mEq/L at 48 hours. [17]
It appears effective in people with chronic kidney disease, diabetes, and heart failure. [5] Use has been studied for up to a year. [5]
Angiotensin-converting-enzyme 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 decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be absent, mild or severe. Mild symptoms include a decreased ability to think, headaches, nausea, and poor balance. Severe symptoms include confusion, seizures, and coma; death can ensue.
Potassium is the main intracellular ion for all types of cells, while having a major role in maintenance of fluid and electrolyte balance. Potassium is necessary for the function of all living cells, and is thus present in all plant and animal tissues. It is found in especially high concentrations within plant cells, and in a mixed diet, it is most highly concentrated in fruits. The high concentration of potassium in plants, associated with comparatively very low amounts of sodium there, historically resulted in potassium first being isolated from the ashes of plants (potash), which in turn gave the element its modern name. The high concentration of potassium in plants means that heavy crop production rapidly depletes soils of potassium, and agricultural fertilizers consume 93% of the potassium chemical production of the modern world economy.
Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in those with a high calcium level in the urine. Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness. Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis. This initially increases urine volume and lowers blood volume. It is believed to reduce peripheral vascular resistance.
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasionally when severe it can cause palpitations, muscle pain, muscle weakness, or numbness. Hyperkalemia can cause an abnormal heart rhythm which can result in cardiac arrest and death.
Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, fluid balance, oxygen delivery, acid–base balance and much more. Electrolyte imbalances can develop by consuming too little or too much electrolyte as well as excreting too little or too much electrolyte. Examples of electrolytes include calcium, chloride, magnesium, phosphate, potassium, and sodium.
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 abnormal heart rhythm, which is often too slow and can cause cardiac arrest.
Hyperkalemic periodic paralysis is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is characterized by muscle hyperexcitability or weakness which, exacerbated by potassium, heat or cold, can lead to uncontrolled shaking followed by paralysis. Onset usually occurs in early childhood, but it still occurs with adults.
Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium-sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. It is taken by mouth. Onset of action is about two hours and it lasts for about a day.
Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of prostaglandins, endogenous signaling molecules known to cause these symptoms. It does this by inhibiting cyclooxygenase, an enzyme that catalyzes the production of prostaglandins.
Lisinopril is a medication belonging to the drug class of angiotensin-converting enzyme (ACE) inhibitors and is used to treat hypertension, heart failure, and heart attacks. For high blood pressure it is usually a first-line treatment. It is also used to prevent kidney problems in people with diabetes mellitus. Lisinopril is taken orally. Full effect may take up to four weeks to occur.
Potassium-sparing diuretics or antikaliuretics refer to drugs that cause diuresis without causing potassium loss in the urine. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The steroidal aldosterone antagonists can also be used for treatment of primary hyperaldosteronism. Spironolactone, a steroidal aldosterone antagonist, is also used in management of female hirsutism and acne from PCOS or other causes.
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.
Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth.
Magnesium deficiency is an electrolyte disturbance in which there is a low level of magnesium in the body. It can result in multiple symptoms. Symptoms include tremor, poor coordination, muscle spasms, loss of appetite, personality changes, and nystagmus. Complications may include seizures or cardiac arrest such as from torsade de pointes. Those with low magnesium often have low potassium.
A mineralocorticoid receptor antagonist or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure. Spironolactone, the first member of the class, is also used in the management of hyperaldosteronism and female hirsutism. Most antimineralocorticoids, including spironolactone, are steroidal spirolactones. Finerenone is a nonsteroidal antimineralocorticoid.
Calcium gluconate is the calcium salt of gluconic acid and is used as a mineral supplement and medication. As a medication it is used by injection into a vein to treat low blood calcium, high blood potassium, and magnesium toxicity. Supplementation is generally only required when there is not enough calcium in the diet. Supplementation may be done to treat or prevent osteoporosis or rickets. It can also be taken by mouth but is not recommended for injection into a muscle.
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
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.
Roxadustat, sold under the brand name Evrenzo, is an anti-anemia medication. Roxadustat is a HIF prolyl-hydroxylase inhibitor that increases endogenous production of erythropoietin and stimulates production of hemoglobin and red blood cells. It was investigated in clinical trials for the treatment of anemia caused by chronic kidney disease (CKD). It is taken by mouth. The drug was developed by FibroGen, in partnership with AstraZeneca.