Figure 3: Study 2 - Mean Serum Potassium Levels in the Acute and Randomized Withdrawal Phases, Intent-to-Treat population includes subjects with at least one valid serum potassium measurement on or after Day 8. Li L, Harrison SD, Cope MJ, et al. Monitor serum potassium and adjust the dose of LOKELMA … Sixteen (16) drugs tested did not show an in vitro interaction with Lokelma (allopurinol, apixaban, aspirin, captopril, cyclosporine, digoxin, ethinyl estradiol, lisinopril, magnesium, metformin, phenytoin, prednisone, propranolol, quinapril, spironolactone and ticagrelor). All rights reserved. … It is … All three doses (5, 10 and 15 g) of once daily Lokelma maintained mean potassium at lower levels than placebo (mean serum potassium was 4.8, 4.5, and 4.4 mEq/L for the 5, 10 and 15 g dose groups, respectively, vs. 5.1 mEq/L in the placebo group, p≤0.001 for all doses, Figure 3, right). LOKELMA contains 400 mg of sodium in each 5 g dose. Lokelma should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action… Am J Med. LOKELMA is indicated for the treatment of hyperkalemia in adults. LOKELMA can cause swelling (edema) caused by fluid retention in your body (such as hands, ankles, feet). … Mayo Clin Proc. LOKELMA can cause swelling (edema) caused by fluid retention in your body (such as hands, ankles, feet). Lokelma (sodium zirconium cyclosilicate) is a potassium binder indicated for the treatment of hyperkalemia in adults. St. Michael, Barbados: Concordia Pharmaceuticals Inc.; 2017. During initiation and after a dose adjustment, assess serum potassium after one week. Figure 5: Mean Pre-Dialysis Serum Potassium Levels Over Time in Patients on Chronic Hemodialysis. Mechanism of action and pharmacology of patiromer, a nonabsorbed cross-linked polymer that lowers serum potassium concentration in patients with hyperkalemia. Hypertension. For oral suspension: 5 g or 10 g of white to grey powder in a foil-lined packet. This site is intended for US Healthcare Professionals only. The active ingredient in Lokelma, sodium zirconium cyclosilicate, has a high affinity for potassium ions. 6. Lokelma can transiently increase gastric pH. … ©2020 AstraZeneca. Lokelma causes a small dose-dependent increase in serum bicarbonate concentrations (1.1 mmol/L at 5 g once daily, 2.3 mmol/L at 10 g once daily and 2.6 mmol/L at 15 g once daily as compared with a mean increase of 0.6 mmol/L in patients treated with placebo). New potassium binders for the treatment of hyperkalemia: current data and opportunities for the future. FDA Approved Indication(s) Lokelma is indicated for the treatment of hyperkalemia in adults. 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. 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. The mean age of patients was 66 years, 59% of patients were men, and 86% were Caucasian. Each 5 g of sodium zirconium cyclosilicate contains 400 mg of sodium. US-39847; US-42950 Last Updated 11/20. It is a non-absorbed zirconium silicate that preferentially captures potassium in … 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. In general, other oral medications should be administered at least 2 hours before or 2 hours after Lokelma [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)]. The treatment effect on serum potassium was maintained during continued therapy. 8. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. 2017;92(8):1248-1260. Advise patients to adjust dietary sodium, if appropriate. Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (e.g., heart failure or renal disease). The following adverse reactions are discussed in greater detail elsewhere in the label: Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. 2017;37(4):401-411. In clinical trials of Lokelma in patients who were not on dialysis, edema was observed and was generally mild to moderate in severity and was more commonly seen in patients treated with 15 g once daily. In the open-label acute phase of Study 2, 258 patients with hyperkalemia (baseline mean 5.6 mEq/L, range 5.1 to 7.4 mEq/L) received 10 g of Lokelma administered three times daily with meals for 48 hours. Limitation(s) of use: Lokelma should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action… 1. References: 1. Characterization of structure and function of ZS-9, a K+ selective ion trap. Instruct dialysis patients who experience acute illness (e.g., decreased oral intake of food or fluids, diarrhea) to contact the health care provider. 2. Sodium zirconium cyclosilicate contained in Lokelma is an insoluble, non-absorbable inorganic crystalline compound that works as a potassium blinder. J Cardiovasc Pharmacol Ther. Lien YH. 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 … In clinical trials of Lokelma in patients who were not on dialysis, edema was observed and was generally mild to moderate in severity and was more commonly seen in patients treated with 15 g once daily. Losartan, glipizide and levothyroxine did not show any changes in exposure when co-administered with Lokelma. Lokelma binds to potassium and exchanges it for hydrogen and sodium. Increase the dose of diuretics as needed [see Adverse Reactions (6)]. Patients who achieved a potassium level between 3.5 and 5 mEq/L after receiving Lokelma during the acute phase were re-randomized to receive once daily placebo or 1.25, 2.5, 5 or 10 g of once daily Lokelma for 12 days together with breakfast. Advise patients to adjust dietary sodium, if appropriate. Lokelma is a powder for oral suspension. Systematic review and meta-analysis of patiromer and sodium zirconium cyclosilicate: a new armamentarium for the treatment of hyperkalemia. In clinical trials in patients who were not on dialysis, 4.1% of Lokelma-treated patients developed hypokalemia with a serum potassium value less than 3.5 mEq/L, which resolved with dosage reduction or discontinuation of Lokelma. Lokelma is used to treat hyperkalemia (high levels of potassium in the blood) in adults. The recommended maintenance dose range is from 5 g every other day to 15 g daily. If powder remains in the drinking glass, add water, stir and drink immediately. LOKELMA (sodium zirconium cyclosilicate) is a non-absorbed zirconium silicate that preferentially captures potassium in exchange for hydrogen and sodium. It attaches to … Last updated on Oct 1, 2020. Patients with higher starting serum potassium levels or receiving a higher dose have greater reductions in serum potassium. 1,2 LOKELMA has a unique crystal lattice structure. The mean baseline potassium level in this study was 5.6 mEq/L. 10. The recommended starting dose is 5 g once daily on non-dialysis days. LOKELMA (sodium zirconium cyclosilicate) is a non-absorbed zirconium silicate that preferentially captures potassium in exchange for hydrogen and sodium. Palmer BF. Veltassa® (patiromer) [prescribing information]. … Beccari MV, Meaney CJ. Advise patients to adjust dietary sodium, if appropriate [see Warnings and Precautions (5.2)]. The recommended starting dose is 5 g once daily on non-dialysis days. 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)]. Figure 4 shows that the treatment effect on serum potassium was maintained during continued therapy. 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. Consider a starting dose of 10 g once daily on non-dialysis days in patients with serum potassium greater than 6.5 mEq/L. Patients had hyperkalemia in association with comorbid diseases such as chronic kidney disease, heart failure, and diabetes mellitus. It binds potassium in exchange for sodium and hydrogen. 2018;131(5):459-460. Lokelma’s mechanism of action. Lokelma should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action [see Clinical Pharmacology (12.2) and Clinical Studies (14)]. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. ADVERSE REACTIONS: The most common adverse reaction in non-dialysis patients with LOKELMA was mild to moderate edema. Instruct patients to empty the entire contents of the packet(s) into a drinking glass containing approximately 3 tablespoons of water or more if desired. 2 LOKELMA is insoluble and does not … LOKELMA is a modern K+ binder that preferentially captures K + and exchanges it for hydrogen and sodium. On average, onset of action was around 1 hour and median time to … 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). Lokelma increases fecal potassium excretion through binding of potassium in the lumen of the gastrointestinal tract. Meaney CJ, Beccari MV, Yang Y, Zhao J. Thirty-six (36) drugs were tested to determine potential interactions with Lokelma. LOKELMA contains 400 mg of sodium in each 5 g dose. Mechanism of action and pharmacology of patiromer, a nonabsorbed cross-linked polymer that lowers serum potassium concentration in patients with … Lokelma (sodium zirconium cyclosilicate) is a non-absorbed zirconium silicate that … Lokelma and Veltassa are indicated for the treatment of hyperkalemia. In vitro, Lokelma has a high affinity for potassium ions, even in the presence of other cations such as calcium and magnesium. 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. It has a mean particle size of 20 µm and includes no more than 3% of particles with a diameter below 3 µm. Lokelma is not absorbed systemically following oral administration, and breastfeeding is not expected to result in exposure of the child to Lokelma. Inform the patient that it is necessary to drink the full dose [see Dosage and Administration (2.3)]. 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. 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. 12.1 Mechanism of Action LOKELMA (sodium zirconium cyclosilicate) is a non-absorbed zirconium silicate that preferentially captures potassium in exchange for hydrogen and sodium. For initial treatment of hyperkalemia, the recommended dose of Lokelma is 10 g administered three times a day for up to 48 hours. The potassium lowering action … Hyperkalemia, used to describe an elevated level of potassium in the blood, occurs when there is a disturbance in the balance between intake and elimination or a shift of potassium between the … Each 5 g dose of Lokelma contains approximately 400 mg of sodium, but the extent of absorption by the patient is unknown. An in vivo mass balance study in rats showed that Lokelma was recovered in the feces with no evidence of systemic absorption. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. Watch for signs of swelling in your body … LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action. Sodium zirconium cyclosilicate is a non-absorbed zirconium silicate that preferentially exchanges potassium for hydrogen and sodium. n = Number of patients with non-missing potassium measurements at a particular visit. Dosage Form: powder, for oral suspension. These changes are consistent with the hypothesis that Lokelma, by elevating gastric pH, affects the systemic exposure of co-administered drugs whose solubility is pH-dependent [see Drug Interactions (7)]. What is Lokelma? *Brand names for sodium polystyrene sulfonate (SPS) include Kayexalate® and Kionex®. Li L, Harrison SD, Cope MJ, et al. Safety and effectiveness in pediatric patients have not been established. 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)]. Monitor serum potassium and adjust the dose of Lokelma based on the pre-dialysis serum potassium value after the long inter-dialytic interval and desired target range. LOKELMA is a registered trademark and AZ&Me is a trademark of the AstraZeneca group of companies. Patients with higher starting potassium levels had a greater response to Lokelma. Dosage Adjustment for Patients on Chronic Hemodialysis For patients on chronic hemodialysis, administer LOKELMA only on non-dialysis days.