LOKELMA can cause swelling (edema) caused by fluid retention in your body (such as hands, ankles, feet). Gastrointestinal Adverse Events in Patients with Motility Disorders: In a clinical trial of LOKELMA in patients on chronic hemodialysis in which most patients were treated with doses of. Mechanism of action Hyperkalemia is a condition defined by elevated potassium levels in the blood, often caused by cardiovascular, renal, and metabolic diseases. Potassium binders for hyperkalemia in chronic kidney disease–diet, renin-angiotensin-aldosterone system inhibitor therapy, and hemodialysis. For patients on chronic hemodialysis, administer Lokelma only on non-dialysis days. Clinical pharmacology does not correlate with efficacy or safety. The active ingredient in LOKELMA is sodium zirconium cyclosilicate, a potassium binder. Last updated on Oct 1, 2020. 4. 2015;66(4):731-738. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. You may report side effects related to AstraZeneca products by clicking here. n = Number of patients with non-missing potassium measurements at a particular visit. Stir well and drink immediately. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS: Lokelma (sodium zirconium cyclosilicate) is a non-absorbed zirconium silicate that preferentially captures potassium in exchange for hydrogen and sodium. AstraZeneca has picked up FDA approval for its hyperkalaemia treatment Lokelma, allowing it to compete head-to-head with rival Vifor Pharma on both sides of the Atlantic. 2017;37(4):401-411. Medically reviewed by Drugs.com. ©2020 AstraZeneca. As displayed in Table 1 for the secondary endpoint of potassium change from baseline, Lokelma showed dose-dependent reductions in serum potassium at 2.5, 5 and 10 g. In patients administered 10 g TID, the mean serum potassium reduction was -0.7 mEq/L at 48 hours. LOKELMA increases fecal potassium excretion LOKELMA contains 400 mg of sodium in each 5 g dose. Following the acute phase of the study, there was a double-blind randomized withdrawal phase where patients who achieved potassium levels between 3.5 and 5 mEq/L were randomized to one of three doses of Lokelma administered once-daily for 28 days, or placebo just before breakfast. During maintenance treatment, up-titrate based on the serum potassium level at intervals of 1-week or longer and in increments of 5 g. Decrease the dose of Lokelma or discontinue if the serum potassium is below the desired target range. LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action. 6. Veltassa® (patiromer) [prescribing information]. 9. A greater proportion of patients were responders in the Lokelma arm as compared to placebo (41% vs 1%, respectively; p<0.001). Thirty-six (36) drugs were tested to determine potential interactions with Lokelma. The dose of Lokelma may need to be adjusted. In a study in healthy adult subjects, Lokelma administered as 5 g or 10 g once daily for four days caused a dose-dependent increase in fecal potassium excretion. Advise patients who are taking other oral medications to separate dosing of Lokelma by at least 2 hours (before or after) [see Drug Interactions (7)]. Lokelma can transiently increase gastric pH. Patients on hemodialysis may be prone to acute illness that can increase the risk of hypokalemia on Lokelma (e.g., illnesses associated with decreased oral intake, diarrhea). The recommended maintenance dose range is from 5 g every other day to 15 g daily. Expert opinion: ZS-9 has a unique mechanism of action consisting of thermodynamically favorable sequestration of potassium ions, enabling rapid trapping and removal of excess potassium. During initiation and after a dose adjustment, assess serum potassium after one week. Avoid use of Lokelma in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders, because Lokelma has not been studied in patients with these conditions and may be ineffective and may worsen gastrointestinal conditions. Watch the video to find out more about LOKELMA's mechanism of action. Sodium zirconium cyclosilicate is a non-absorbed zirconium silicate that preferentially exchanges potassium for hydrogen and sodium. Given that zirconium cyclosilicate is not genotoxic, not absorbed from the gastrointestinal tract, and did not cause local gastrointestinal alterations in a chronic toxicity study in dogs, carcinogenicity studies in animals to evaluate tumorigenic potential of sodium zirconium cyclosilicate were not deemed to be necessary. In the first phase of the trial (the acute phase), 753 patients were randomized to receive one of four doses of Lokelma (1.25, 2.5, 5 or 10 g) or placebo, administered three times daily for the initial 48 hours with meals. In placebo-controlled trials in which patients who were not on dialysis were treated with once daily doses of Lokelma for up to 28 days, edema was reported in 4.4% of patients receiving 5 g, 5.9% of patients receiving 10 g and 16.1% of patients receiving 15 g Lokelma compared to 2.4% of patients receiving placebo. It is an insoluble, non-absorbed sodium zirconium silicate agent classified as a cation exchange resin. There are 4 published studies on the use of Lokelma for treating hyperkalemia in patients with mild hyperkalemia in CKD. Generic Name: sodium zirconium cyclosilicate Challenges in treating cardiovascular disease: restricting sodium and managing hyperkalemia. In patients with hyperkalemia treated with Lokelma 10 g three times a day for up to 48 hours, reductions in serum potassium were observed one hour after initiation of therapy; serum potassium concentrations continued to decline over the 48-hour treatment period [see Clinical Studies (14.2)]. The treatment effect on serum potassium was maintained during continued therapy. Watch for signs of swelling in your body especially if you limit sodium in your diet or are likely to have fluid retention in your body due to heart or kidney problems. The primary endpoint in the trial was the proportion of responders, defined as patients who maintained a pre-dialysis serum potassium between 4.0 and 5.0 mEq/L on at least 3 out of 4 dialysis treatments after the long inter-dialytic interval and who did not receive rescue therapy during the evaluation period. 1. For initial treatment of hyperkalemia, the recommended dose of Lokelma is 10 g administered three times a day for up to 48 hours. Corresponding dose-dependent decreases in urinary potassium excretion and serum potassium were also observed. Sodium zirconium cyclosilicate is a non-absorbed zirconium silicate that preferentially exchanges potassium for hydrogen and sodium. [see Warnings and Precautions (5.3)]. Lokelma (sodium zirconium cyclosilicate) is a non-absorbed zirconium silicate that preferentially captures potassium in exchange for hydrogen and sodium. Lokelma (sodium zirconium cyclosilicate or ZS-9) has been cleared by the FDA as an oral treatment for hyperkalaemia (elevated potassium levels) in adults, a potentially life-threatening condition caused by cardiovascular, renal and … The following tests for mutagenic potential of sodium zirconium cyclosilicate were negative: (1) the Ames (S. typhimurium and E. coli) test; (2) chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells; and (3) in vivo rat micronucleus assay. Our Lokelma (sodium zirconium cyclosilicate) for Oral Suspension Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication. Meaney CJ, Beccari MV, Yang Y, Zhao J. In vitro, Lokelma has a high affinity for potassium ions, even in the presence of other cations such as calcium and magnesium. For maintenance treatment, the initial dosage of Lokelma was 5 g once daily and was adjusted to a minimum of 5 g every other day up to maximum of 15 g once daily, based on serum potassium level. Lokelma is not absorbed systemically following oral administration, and breastfeeding is not expected to result in exposure of the child to Lokelma. Consider a starting dose of 10 g once daily on non-dialysis days in patients with serum potassium greater than 6.5 mEq/L. Non-emergent hyperkalemia is generally treated by addressing the reversible causes, such as removing drugs that may be causing The total exposure to Lokelma in the safety and efficacy clinical trials of patients not on dialysis with hyperkalemia was 1,760 patients with 652 patients exposed to Lokelma for at least 6 months and 507 patients exposed for at least one year. In a clinical trial of Lokelma in patients on chronic hemodialysis, 5% of patients developed pre-dialysis hypokalemia (serum potassium <3.5 mEq/L) in both the Lokelma and placebo groups; 3% and 1% of patients developed a serum potassium < 3.0 mEq/L in the Lokelma and placebo groups, respectively. Watch the video to find out more about LOKELMA's mechanism of action. Sodium zirconium cyclosilicate (ZS-9), sold under the brand name Lokelma, is a medication used to treat high blood potassium. In longer-term uncontrolled trials in which most patients were maintained on doses <15 g once daily, adverse reactions of edema (edema, generalized edema and peripheral edema) were reported in 8% to 11% of patients. However, there was an increase in systemic exposure to weak acids such as furosemide and atorvastatin, and a decrease in systemic exposure to weak bases such as dabigatran when co-administered with Lokelma, as shown in Figure 2. This is not a complete list of side effects and others may occur. In patients not continuing Lokelma, potassium levels increased. Figure 5: Mean Pre-Dialysis Serum Potassium Levels Over Time in Patients on Chronic Hemodialysis. LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action. 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. U.S. Patent No: 6332985, 8808750, 8877255, 8802152, 9592253, Manufactured by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850, NDC 0310-1105-30 Contains 30 packets, NDC 0310-1110-30 Contains 30 packets, sodium bicarbonate, Kayexalate, insulin regular, calcium gluconate, Humulin R, Veltassa. Veltassa is a registered trademark of Relypsa, Inc., a Vifor Pharma Group Company. The effectiveness of Lokelma in lowering serum potassium was studied in a double-blind, placebo-controlled trial of 196 chronic hemodialysis patients (mean age 58 years, range 20 to 86 years) with persistent pre-dialysis hyperkalemia (mean baseline potassium 5.8 mEq/L) who were randomized to receive Lokelma 5 g or placebo once daily on non-dialysis days (NCT03303521). During the dose adjustment period (initial 4 weeks), the dose was adjusted weekly in 5 g increments up to 15 g once daily based on pre-dialysis serum potassium measurement after the long inter-dialytic interval to achieve a pre-dialysis serum potassium level between 4.0-5.0 mEq/L. Redwood City, CA: Relypsa, Inc; May 2018. LOKELMA is a modern K+ binder that preferentially captures K+ and exchanges it for hydrogen and sodium.1,2 LOKELMA has a unique crystal lattice structure.2 LOKELMA is insoluble and does not expand in water, so it is not expected to swell within the GI tract.2. Each 5 g dose of Lokelma contains about 400 mg of sodium. 2016;21(5):456-465. hyperkalemia because of its delayed onset of action; reduction in serum potassium is seen within 1 hour of administration, potassium levels continue to decline over the 48 hours of treatment period. Instruct dialysis patients who experience acute illness (e.g., decreased oral intake of food or fluids, diarrhea) to contact the health care provider. On average, onset of action was around 1 hour and median time to achieving normal potassium was 2.2 hours. Following the acute phase treatment of Lokelma 10 g three times a day, patients who achieved normokalemia (3.5-5.0 mEq/L) within 72 hours (n=746; 99%) entered the maintenance phase. †In vitro, LOKELMA has a high affinity for K+, even in the presence of other cations such as calcium and magnesium.1, ‡In vitro study; based on simulated intestinal fluid.2, §Based on nonclinical and early phase studies.11, ||The sodium content/unit dose of LOKELMA is 400 mg/5 g, but the extent of absorption by the patient is unknown. Systematic review and meta-analysis of patiromer and sodium zirconium cyclosilicate: a new armamentarium for the treatment of hyperkalemia. Patients with higher starting serum potassium levels or receiving a higher dose have greater reductions in serum potassium. Lokelma was effective in lowering potassium levels in patients with chronic kidney disease, heart failure, diabetes mellitus and those taking RAAS inhibitor therapy. Regulatory Status Hypertension. Fertility in male and female rats has been assessed at doses up to a Human Equivalent Dose (HED) of 58 g per day (the maximum feasible dose) with no adverse effects. GI=gastrointestinal; qod=every other day. US-39847; US-42950 Last Updated 11/20. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Watch for signs of swelling in your body especially if you limit sodium in your diet or are likely to have fluid retention in your body due to heart or kidney problems. 3. Mechanism Of Action. Call your doctor for medical advice about side effects. The FDA approval is supported by data from three double-blind, placebo-controlled trials and two open-label trials, which showed that for patients receiving Lokelma, the onset of action … Am J Med. DOSING: Non-hemodialysis Patients For initial treatment of hyperkalemia, the recommended starting dose is 10 g administered three times a day up to 48 hours. LOKELMA increases fecal potassium excretion through binding of potassium in the … The primary endpoint in the acute phase was the difference in the exponential rate of change in serum potassium levels during the initial 48 hours of study drug treatment, comparing placebo-treated patients and Lokelma-treated patients.
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