LOKELMA US Label Updated to Include Dosing Guidance for the Treatment of Hyperkalemia in Patients With End-Stage Renal Disease on Hemodialysis

Label replace relies on knowledge from Part IIIb DIALIZE trial

Right this moment, the US Meals and Drug Administration (FDA) authorized a label replace within the US for AstraZeneca’s LOKELMA^® (sodium zirconium cyclosilicate) to incorporate a dosing routine particularly to deal with hyperkalemia in sufferers with end-stage renal illness on persistent hemodialysis.

The approval by the US FDA was based mostly on constructive outcomes from the Part IIIb DIALIZE trial, the primary ever randomized, placebo-controlled trial to guage a potassium binder in sufferers on secure hemodialysis. The DIALIZE trial confirmed {that a} considerably increased proportion of sufferers within the LOKELMA group (41.2%) met the first endpoint and had been categorized as responders (maintained serum potassium 4-5 mmol/L throughout at the very least three out of 4 hemodialysis classes after the lengthy interdialytic interval [LIDI] of the final 4 weeks of therapy and didn’t require pressing rescue remedy) in comparison with sufferers within the placebo group (1.0%), making it a statistically vital (P<0.001) and clinically significant enchancment. Rescue remedy was outlined as any pressing therapeutic intervention thought-about needed to cut back serum potassium for extreme hyperkalemia (serum potassium >6.Zero mmol/L). The protection profile of LOKELMA noticed in DIALIZE was per earlier trials.

LOKELMA is a potassium binder indicated for the therapy of hyperkalemia in adults. LOKELMA shouldn’t be used as an emergency therapy for life-threatening hyperkalemia due to its delayed onset of motion. That is the primary label replace for LOKELMA within the US following its FDA approval in 2018 to deal with adults with hyperkalemia. The label replace now features a dosing routine for sufferers on persistent hemodialysis with a beginning dose of 5 g as soon as each day on non-dialysis days and a beginning dose of 10 g as soon as each day on non-dialysis days in sufferers with serum potassium higher than 6.5 mmol/L.

Mene Pangalos, Government Vice President, BioPharmaceuticals R&D, mentioned: “Greater than 500,000 sufferers within the US live with dialysis-dependent end-stage renal illness and could possibly be in danger for dangerously excessive ranges of potassium. With this FDA authorized replace, the LOKELMA label now contains necessary dosing steerage for treating hyperkalemia in sufferers on hemodialysis.”

LOKELMA is presently authorized within the US, EU, Canada, Hong Kong, China, Russia and Japan for the therapy of sufferers with hyperkalemia. LOKELMA just lately obtained a constructive opinion from The Committee for Medicinal Merchandise for Human Use (CHMP) of the European Medicines Company (EMA) on a dosing and administration label replace to incorporate sufferers with hyperkalemia on secure hemodialysis. A last resolution is anticipated from the European Fee within the near-future.

IMPORTANT SAFETY INFORMATION FOR LOKELMA^® 5 g and 10 g (sodium zirconium cyclosilicate)

WARNINGS AND PRECAUTIONS:

• Gastrointestinal Hostile Occasions in Sufferers with Motility Issues: Keep away from LOKELMA in sufferers with extreme constipation, bowel obstruction or impaction, together with irregular post-operative bowel motility issues. LOKELMA has not been studied in sufferers with these situations and it could be ineffective and should worsen gastrointestinal situations.
• Edema: Every 5-g dose of LOKELMA incorporates roughly 400 mg of sodium, however the extent of absorption by the affected person is unknown. In medical trials of LOKELMA in sufferers who weren’t on dialysis, edema was noticed and was usually gentle to reasonable in severity and was extra generally seen in sufferers handled with 15 g as soon as each day. Monitor for indicators of edema, significantly in sufferers who ought to limit their sodium consumption or are susceptible to fluid overload (eg, coronary heart failure or renal illness). Advise sufferers to regulate dietary sodium, if acceptable. Improve the dose of diuretics as wanted.

  In a medical trial of LOKELMA in sufferers on persistent hemodialysis through which most sufferers had been handled with doses of 5 g to 10 g as soon as each day on non-dialysis days, there was no distinction within the imply change from baseline in interdialytic weight achieve (a measure of fluid retention) between the LOKELMA and placebo teams.

• Hypokalemia in Sufferers on Hemodialysis: Sufferers on hemodialysis could also be susceptible to acute sickness that may improve the chance of hypokalemia on LOKELMA (eg, sicknesses related to decreased oral consumption, diarrhea). Think about adjusting LOKELMA dose based mostly on potassium ranges in these settings.

ADVERSE REACTIONS: The most typical opposed response in non-dialysis sufferers with LOKELMA was gentle to reasonable edema. In placebo-controlled trials as much as 28 days, edema was reported in 4.4%, 5.9%, 16.1% of non-dialysis sufferers handled with 5 g, 10 g, and 15 g of LOKELMA as soon as each day, respectively vs 2.4% of non-dialysis sufferers receiving placebo.

DRUG INTERACTIONS: LOKELMA can transiently improve gastric pH. Generally, oral drugs with pH-dependent solubility needs to be administered at the very least 2 hours earlier than or 2 hours after LOKELMA. Spacing shouldn’t be wanted if it has been decided the concomitant treatment doesn’t exhibit pH-dependent solubility.

INDICATION AND LIMITATION OF USE

LOKELMA is indicated for the therapy of hyperkalemia in adults.

LOKELMA shouldn’t be used as an emergency therapy for life-threatening hyperkalemia due to its delayed onset of motion.

DOSING

• Non-hemodialysis Sufferers
  For preliminary therapy of hyperkalemia, the really helpful beginning dose is 10 g administered 3 times a day as much as 48 hours. For upkeep therapy, the really helpful beginning dose is 10 g as soon as each day. Monitor serum potassium and regulate dose of LOKELMA at 1-week intervals or longer in increments of 5 g based mostly on serum potassium and desired goal vary. The really helpful upkeep dose vary is from 5 g each different day to 15 g each day. Discontinue or lower the dose of LOKELMA if serum potassium is beneath the specified goal vary.

• Hemodialysis Sufferers
  For sufferers on persistent hemodialysis, administer LOKELMA solely on non‑dialysis days. The really helpful beginning dose is 5 g as soon as each day on non-dialysis days. Think about a beginning dose of 10 g as soon as each day on non-dialysis days in sufferers with serum potassium higher than 6.5 mEq/L. Monitor serum potassium and regulate the dose of LOKELMA based mostly on the pre‑dialysis serum potassium worth after the lengthy interdialytic interval and desired goal vary. Throughout initiation and after dose adjustment, assess serum potassium after one week. Discontinue or lower the dose of LOKELMA if serum potassium falls beneath the specified goal vary based mostly on pre-dialysis worth after the lengthy interdialytic interval or the affected person develops clinically vital hypokalemia. The really helpful upkeep dose vary is from 5 g to 15 g as soon as each day, on non-dialysis days.

PLEASE READ FULL PRESCRIBING INFORMATION.

Hyperkalemia

Hyperkalemia is characterised by excessive ranges of potassium within the blood, usually categorized as higher than 5 mmol/l. Many individuals residing with persistent kidney illness (CKD) have hyperkalemia regardless of being on hemodialysis and infrequently expertise fluctuations of their potassium ranges. Sufferers with excessive variability in potassium ranges between dialysis classes are at vital threat of arrhythmias which might result in cardiac arrest. Hyperkalemia happens in 23% to 47% of sufferers with CKD and/or coronary heart failure with an estimated 700 million and 64 million folks respectively, residing with every situation worldwide.

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