lokelma vs kayexalate for the treatment of Hyperkalemia

Lokelma vs Kayexalate - summarizes the major differences between Lokelma and kayexalate. Lokelma is the brand name of Sodium zirconium cyclosilicate. It is a novel drug used to treat chronic hyperkalemia.

Another drug recently approved for the treatment of hyperkalemia is Patiromer (Veltassa). Until now, treatment of hyperkalemia focused on dietary restriction, avoiding drugs that cause hyperkalemia, drugs acting via the renal tubules such as diuretics, and increasing potassium elimination via the gastrointestinal tract with sodium polystyrene sulfonate or kayexalate.

The novel drugs Lokelma (Sodium Zirconium cyclosilicate) and Patiromer (Veltassa) have been approved by both the FDA and EMA for the chronic treatment of hyperkalemia. Their efficacy has been confirmed in various clinical trials.

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What is Lokelma (Sodium Zirconium Cyclosilicate)?

It is an orally administered drug available as a powder formulation. It is tasteless and odorless. Before administering, it is mixed with water to form a soluble suspension. Lokelma acts within the whole gastrointestinal tract.

It acts by binding potassium within the gastrointestinal tract in exchange for Sodium and Hydrogen ions resulting in the excretion of potassium ions. Lokelma (Sodium Zirconium Cyclosilicate) is a highly selective inorganic molecule that acts immediately after ingestion. It does not bind calcium and magnesium ions and is not systemically absorbed.


What is Kayexalate (Sodium polystyrene sulfonate)?

Kayexalate (sodium polystyrene sulfonate) is a potassium-binding resin. It was approved in 1958 when clinical efficacy and safety were not measured in clinical trials prior to approval. It removes potassium ions in exchange for sodium ions in the intestine (in particular the large intestine).

It has an onset of action of 2 - 24 hours and is not absorbed into the systemic circulation. Because it is a sodium-containing resin, it may cause hypernatremia. Furthermore, it is a non-specific resin, therefore, it binds calcium, magnesium, and potassium.

Hence it may result in hypocalcemia and hypomagnesemia. It may also result in some serious side effects like intestinal ulceration, perforation, and ischemic colitis.


Lokelma vs Kayexalate - The main differences

Lokelm and Kayexalate are both resins that lower plasma potassium by inhibiting their absorption. Another potassium-lowering drug that is considered safer than kayexalate is Veltassa (Read: Veltassa vs Kayexalate).

Below is a table comparing Lokelma (Sodium Zirconium Cyclosilicate) and Kayexalate (Sodium Polystyrene sulfonate) [Ref]:

Lokelma vs Kayexalate

 

Lokelma (Sodium Zirconium cyclosilicate)

Kayexalate (sodium polystyrene sulfonate)

Date of FDA approval

May 2018

June 1958

Date of EMA approval

March 2018

NA

Chemical properties

  • Nonpolymer
  • nonabsorbed zirconium silicate
  • Resin/polymer
  • the sodium salt of polystyrene sulfonic acid

Sodium content

80 mg/gm

100 mg/gm

Mechanism of action

Preferentially captures K+ in exchange for hydrogen and sodium

Sodium-K+ exchange resin/polymer, nonspecifically binds K+, magnesium, and calcium

Onset of action

1 hour

Hours to days

Dose

Initial:

  • 10 g three times a day for up to 48 hours

Maintenance:

  • 10 g QD (adjust dose at weekly intervals in 5-g increments to obtain the desired serum K+ range)

Usual maintenance dose:

  • 5 g to 15 g QD

15 g (4 level teaspoons) 1 - 4 times a day

Preparation

Combine powder with 45 mL ( 3 tablespoons ) of water, stir well, and drink immediately

Combine with a small quantity of water or for greater palatability, the syrup may also give by a nasogastric tube or as an enema

Administration

Can be taken with or without food

Oral suspension or enema

Appearance and texture

Free-flowing, odorless, insoluble white powder for oral suspension

Cream to light brown finely ground powder

storage

15 - 30 C (59 - 86 F)

25 C (77 F, excursions to 15 - 30 C permitted)

Site of K+ binding

GI tract

GI tract or colon when administered by enema

Adverse effects

Edema (mild to moderate) hypokalemia

  • Intestinal necrosis
  • electrolyte disturbances (including hypokalemia)
  • nausea
  • vomiting
  • constipation
  • diarrhea
  • fluid overload in patients sensitive to high sodium intake
  • risk of aspiration

Drug interactions

Oral medications that exhibit pH-dependent solubility should be administered 2 h before or 2 h after their administration

  • Take other orally administered drugs 3 h before or 3 h after their intake
  • cation-donating antacids may reduce potassium exchange and increase the risk of systemic alkalosis
  • concomitant use of sorbitol may contribute to the risk of intestinal necrosis and is not recommended

Sodium Zirconium cyclosilicate (Lokelma) and Patiromer have proven efficacy and safety in major trials, notably the Harmonize and Harmonize-GL trials.