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]
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]
Medical use
Sodium zirconium cyclosilicate is used to treat high blood potassium.[4] Onset of effects occurs in one to six hours.[4]
Mechanism of action
Cross-sections of ZS-9 pores with three different ions (K⁺ = potassium, Na⁺ = sodium, Ca²⁺ = calcium). The specificity for potassium is thought to be caused by the diameter and composition of the pores, which resembles potassium channels.
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.
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]
History
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).
Research
One review found a decrease in potassium of 0.17 mEq/L at one hour and 0.67 mEq/L at 48 hours.[17]
