Introduction
Hyperkalaemia, defined as a serum potassium level greater than 5.5 mmol/L, is one of the most common laboratory electrolyte abnormalities. It can develop as a result of both acute and chronic conditions that interfere with the body’s ability to excrete potassium, particularly through the kidneys. Hyperkalaemia is not uncommon in people living with other chronic conditions such as heart failure, diabetes, and hypertension, and it occurs at a notable rate among those with CKD. It is also seen frequently in transplant recipients treated with medications such as cyclosporin or tacrolimus. 1
For many years, treatment options for chronic hyperkalaemia were quite limited, often focusing on dietary potassium restriction, adjusting or stopping certain medications, or using therapies like diuretics or mineralocorticoids. However, these approaches could be difficult to maintain or were not always effective.
Potassium binders were developed to directly help the body remove excess potassium. These are artificial resins that work inside the gut by swapping sodium or calcium for potassium, which is then excreted in the stool. In recent years, newer potassium binders such as patiromer and sodium zirconium cyclosilicate (ZS-9) have been developed to expand treatment options.1
Background of Potassium Binders
Lokelma® (sodium zirconium cyclosilicate, SZC), Kayexalate® (sodium polystyrene sulfonate, SPS), and Veltassa® (patiromer) are cation exchange resins used to help remove excess potassium from the body through the gastrointestinal tract. They work by exchanging sodium or calcium for potassium, allowing potassium to be excreted in the stool.2
Kayexalate has been in use the longest, approved by the FDA in 1958, but its evidence base is limited to a small number of low-quality studies. It has been associated with serious risks such as fatal intestinal ischemia, colonic necrosis, disturbances in calcium and magnesium levels due to its non-selective binding, and edema from its high sodium and fluid load. In addition, its onset of action is highly variable, making it less suitable for quickly lowering potassium in urgent situations like in the emergency department. 2
Lokelma, in contrast, was FDA approved much more recently in 2018 after phase 2 and phase 3 clinical trials established its safety and effectiveness. It has been shown to reduce potassium levels significantly within 1 hour of a single dose. Lokelma is highly selective for potassium and ammonium, and its sodium content is much lower than that of Kayexalate. Because of its faster onset of action, Lokelma may be more useful in the acute phase of hyperkalemia treatment.2
Veltassa is another option in this group, though there are no published studies directly comparing these agents head-to-head. Each of them has a role in managing high potassium, but their differences in safety, selectivity, and speed of action are important factors for treatment consideration. 2
Approved Use
Lokelma is prescribed for adults to help manage hyperkalemia, which means having higher-than-normal levels of potassium in the blood. By lowering potassium, it helps bring these levels back into balance.3
It is important to know that Lokelma is not meant to be used in emergency situations where hyperkalemia is life-threatening. This is because the medicine takes time to start working and does not act immediately. 3
Mechanism of Action
LOKELMA (sodium zirconium cyclosilicate) works inside the gut without being absorbed into the body. It acts like a potassium “trapper,” where it captures excess potassium in exchange for small amounts of hydrogen and sodium. Laboratory studies show that it has a strong ability to bind to potassium, even when other minerals like calcium and magnesium are also present.
By holding on to potassium in the digestive tract, LOKELMA helps the body get rid of it through stools. This reduces the amount of free potassium in the gut, which in turn helps bring down the potassium levels in the blood.3
Administration Overview
For the initial treatment of high potassium, the recommended dose of Lokelma is 10 g taken three times a day for up to 48 hours. After this, for continued treatment, the usual dose is 10 g once daily. In patients on chronic hemodialysis, Lokelma is taken only on non-dialysis days, starting at 5 g once daily. In some cases, if potassium levels are above 6.5 mEq/L, the starting dose may be 10 g once daily on non-dialysis days. Lokelma should always be taken by mouth as a suspension in water. To prepare a dose, the full contents of the packet should be emptied into a glass with about three tablespoons of water, stirred well, and drunk immediately. If powder remains, add water again, stir, and drink right away, repeating until the glass is clear. Other oral medicines should be taken at least two hours before or two hours after Lokelma. 3
Adverse Effects
In clinical studies, the most commonly reported side effect of LOKELMA was edema, which refers to swelling caused by fluid buildup in the body. The chances of developing edema appeared to increase with higher doses. For example, in placebo-controlled trials where patients were treated for up to 28 days, 4.4% of those receiving 5 g, 5.9% of those receiving 10 g, and 16.1% of those receiving 15 g of LOKELMA reported edema, compared to 2.4% in the placebo group. 3
Another side effect observed was hypokalemia, which means that potassium levels in the blood became lower than normal. This usually improved when the dose was lowered or when the treatment was stopped.3
Monitoring Requirements
While on Lokelma, potassium levels in the blood need to be checked regularly to ensure they stay within the desired target range. The dose may be adjusted depending on these results, with changes usually made at intervals of one week or longer. If potassium levels fall below the target range, the dose may be lowered or the medicine stopped. In patients receiving chronic hemodialysis, monitoring is especially important after the long gap between dialysis sessions, as this is when potassium levels guide dose adjustments. In such cases, the medicine should be reduced or discontinued if potassium becomes too low or if low potassium symptoms are clinically significant.3
Clinical Evidence
LOKELMA has been studied in several clinical trials for people with high potassium. In one large study of 753 patients (average age 66, many with kidney disease, diabetes or on RAAS medicines), LOKELMA lowered potassium within 48 hours in a dose-dependent way. At the highest dose (10 g three times a day), potassium fell by an average of 0.7 mEq/L. Patients with higher starting potassium saw a greater drop, and the effect was consistent across those with kidney disease, heart failure, and diabetes. In the same study, patients who continued LOKELMA once daily were more likely to keep potassium in the normal range compared to placebo. 3
Another study of 258 patients showed potassium levels fell from 5.6 to 4.5 mEq/L after 48 hours of treatment. Of these, 92% reached the normal range and went into a longer phase. Over 28 days, LOKELMA kept potassium lower than placebo at all doses tested, with up to 94% of patients staying in the normal range compared with 46% on placebo.
Long-term results from a 12-month study in 751 patients showed that 99% reached normal potassium within 72 hours, and control was maintained with continued, adjusted dosing. In patients on chronic hemodialysis, LOKELMA helped more patients keep potassium between 4.0–5.0 mEq/L compared with placebo (41% vs 1%), showing benefit even in this high-risk group.3
Conclusion
Lokelma (sodium zirconium cyclosilicate) is a newer potassium binder that has been shown in multiple clinical trials to lower and maintain normal blood potassium levels in people with hyperkalemia, including those with chronic kidney disease, diabetes, heart failure, and patients on hemodialysis. It works selectively in the gut to trap excess potassium, helping restore balance safely over time. While effective, regular monitoring is essential to avoid potassium levels dropping too low and to manage side effects such as edema. Lokelma provides a more reliable and faster-acting option compared to older binders, offering doctors and patients an important tool for managing high potassium.
Note:
This information is provided for educational purposes only and is not a substitute for professional medical advice. Lokelma should only be taken under the guidance of a qualified healthcare provider. Patients should always consult their doctor or pharmacist for advice on diagnosis, treatment, and medication use, and should not make changes to their prescribed therapy without medical supervision.
Disclaimer:
Rx4U procures prescribed medicines directly from manufacturers or authorized distributors. It does not claim ownership of any trademarks and complies with the provisions of the Trademark Act, 1999, particularly Sections 30 and 30(1) concerning ‘Fair Use’. It solely facilitates access to new launches through named patient import.
References
- Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020;6(6):CD013165. Published 2020 Jun 26. doi:10.1002/14651858.CD013165.pub2
- Hasara S, Dubey J, Amatea J, Finnigan N. Sodium polystyrene sulfonate versus sodium zirconium cyclosilicate for the treatment of hyperkalemia in the emergency department. Am J Emerg Med. 2023;65:59-64. doi:10.1016/j.ajem.2022.12.043
- LOKELMA PRESCRIBING INFORMATION
