Sodium Zirconium Cyclosilicate - Uses, Side Effects, and Pharmacology

Overview:

Sodium zirconium cyclosilicate is a medication used to treat hyperphosphatemia, characterized by elevated levels of phosphate in the blood and often associated with chronic kidney disease (CKD). CKD can lead to impaired kidney function, making it difficult for the kidneys to effectively filter and remove excess phosphate from the body. When phosphate levels become too high in individuals with CKD, it can lead to various complications, including bone problems and cardiovascular issues. This medication was first approved by the FDA (United Food and Drug Safety Administration) on May 18, 2018.

Drug Group:

Sodium zirconium cyclosilicate belongs to a drug group known as phosphate binders. Phosphate binders are medications used to lower and control high phosphate levels in the blood, particularly in individuals with conditions like chronic kidney disease (CKD) or end-stage renal disease (ESRD).

Available Doses and Dosage Forms:

The specific available doses and dosage forms may vary depending on the manufacturer and region, but common forms include:

• Powder for Oral Suspension: Sodium zirconium cyclosilicate is often available as a 10 g powder that can be mixed with water or another suitable liquid and taken orally. This form allows for flexibility in dosing, as the healthcare provider can adjust the amount of powder to achieve the desired dose.

• Oral Suspension (Liquid): Some formulations of sodium zirconium cyclosilicate are liquid, which can be easier to administer for some patients, particularly those with difficulty swallowing pills or powders. It is used as 5 g (grams) or 10 g of white to grey powder in a foil-lined packet.

• Tablets: In some regions, Sodium zirconium cyclosilicate may be available in 5-10g tablet, which can be taken orally with water. Tablets may come in different strengths to allow for various dosing options.

For Patients:

What Is Hyperphosphatemia Associated With Chronic Kidney Disease?

Hyperphosphatemia is a medical condition characterized by abnormally high levels of phosphate in the blood. When this condition is associated with chronic kidney disease (CKD), it is referred to as "hyperphosphatemia associated with chronic kidney disease." This condition occurs primarily because the kidneys play a crucial role in regulating the balance of minerals, including phosphate, in the body.

In individuals with healthy kidneys, excess phosphate is efficiently filtered out of the bloodstream and excreted in the urine. However, the kidneys cannot adequately remove phosphate from the blood in CKD. As a result, phosphate levels in the blood can become elevated.

Hyperphosphatemia associated with CKD is a concern for several reasons:

• Bone and Mineral Metabolism: Elevated phosphate levels can disrupt the body's normal bone and mineral metabolism. It can lead to calcium release from bones, potentially causing bone weakening and disorders.

• Cardiovascular Complications: High phosphate levels have been linked to an increased risk of cardiovascular complications, including blood vessel calcification and heart disease risk.

• Secondary Hyperparathyroidism: Persistent hyperphosphatemia can stimulate the parathyroid glands to release more parathyroid hormone (PTH). Elevated PTH levels can further affect calcium and phosphate balance and contribute to bone and mineral abnormalities.

• Symptoms: Hyperphosphatemia may not cause noticeable symptoms, but its complications, such as bone pain, bone fractures, itching, and cardiovascular issues, can result in discomfort and reduced quality of life.

How Does Sodium Zirconium Cyclosilicate Work?

Sodium zirconium cyclosilicate, marketed under the brand name Lokelma, is a medication used to treat hyperphosphatemia associated with chronic kidney disease (CKD). It works by binding to phosphate in the gastrointestinal tract, preventing its absorption into the bloodstream.

Here is how sodium zirconium cyclosilicate works:

• When sodium zirconium cyclosilicate is ingested orally, it enters the digestive tract.

• Within the gastrointestinal tract, the medication undergoes ion exchange. The sodium ions in sodium zirconium cyclosilicate are exchanged for phosphate ions.

• The bound phosphate forms a complex with sodium zirconium cyclosilicate, which is then excreted from the body through the feces. This process reduces phosphate absorption from food, helping lower phosphate levels in the bloodstream.

By reducing phosphate absorption from the diet, sodium zirconium cyclosilicate helps maintain normal phosphate levels in individuals with CKD and hyperphosphatemia.

Dosage of Sodium Zirconium Cyclosilicate:

The recommended starting dose for this treatment is 10 grams, administered three times a day and continued for up to 48 hours. Following the initial phase, the recommended dose is 10 grams once daily for maintenance treatment.

How Effective Is Sodium Zirconium Cyclosilicate?

Studies have shown that sodium zirconium cyclosilicate is effective in rapidly lowering and maintaining normal potassium levels in individuals with hyperkalemia. The medication is generally well-tolerated, and its efficacy has been demonstrated in short-term and long-term treatment scenarios.

What Are the Things to Inform the Doctor Before Taking Sodium Zirconium Cyclosilicate?

Here are some specific things to inform the doctor before starting sodium zirconium cyclosilicate:

• Inform the doctor if people have any allergies, especially if they have a known allergy to sodium zirconium cyclosilicate or its ingredients.

• Provide a complete medical history, including kidney problems, heart conditions, electrolyte imbalances, digestive issues, or other relevant medical conditions.

• List all the current medications, including prescription drugs, over-the-counter medications, vitamins, and supplements. It is important to check for potential drug interactions.

• Discuss with the doctor if people are pregnant, planning to become pregnant, or breastfeeding. The safety of sodium zirconium cyclosilicate during pregnancy and breastfeeding is not well established, and the doctor will help weigh the potential risks and benefits.

• Inform the doctor if people have experienced significant electrolyte imbalances, as sodium zirconium cyclosilicate can affect electrolyte levels in the body.

• If people have a history of gastrointestinal problems, such as bowel obstructions or severe constipation, let the doctor know, as sodium zirconium cyclosilicate is taken orally and can affect the digestive system.

• Mention any other health conditions people may have, as they could influence the decision to prescribe this medication.

• Share information about the diet, dietary restrictions or changes people follow, and overall lifestyle habits.

• Inform the doctor about alcohol and tobacco use, as these substances can interact with medications.

• If people have had recent surgeries or are planning any surgeries, including dental procedures, make sure the doctor is aware. Sodium zirconium cyclosilicate may need to be adjusted or temporarily discontinued in some cases.

• Discuss any concerns or questions about taking the medication, including potential side effects, and ensure people understand how to take it correctly.

How Is Sodium Zirconium Cyclosilicate Administered?

Sodium zirconium cyclosilicate is typically administered orally, and the healthcare provider should provide the specific administration instructions found in the medication's packaging.

What Are the Side Effects of Sodium Zirconium Cyclosilicate?

Common Side Effects:

• Gastrointestinal Symptoms: These are the most commonly reported side effects and may include diarrhea, nausea, vomiting, abdominal discomfort, and flatulence (accumulation of gas in the alimentary canal)

Serious Side Effects:

• Hypokalemia: Low potassium levels in the blood can occur as a serious side effect of sodium zirconium cyclosilicate. Symptoms of hypokalemia (decreased potassium level) can include muscle weakness, irregular heartbeat, and fatigue.

• Hypomagnesemia: Rarely, the medication can lead to low magnesium levels in the blood, which may cause symptoms such as muscle spasms, irregular heartbeat, and weakness.

• Allergic Reactions: Although uncommon, allergic reactions to medications can occur. Signs of an allergic reaction may include hives, difficulty breathing, and swelling of the face, lips, tongue, or throat. Allergic reactions are considered serious and require immediate medical attention.

Dietary Considerations:

• If people take sodium zirconium cyclosilicate for hyperphosphatemia associated with chronic kidney disease, following any dietary restrictions or guidelines provided by the healthcare provider or registered dietitian is essential. Reducing dietary phosphate intake is often part of managing hyperphosphatemia.

• Take sodium zirconium cyclosilicate as the healthcare provider prescribes. It is typically taken with food, but the timing and instructions may vary. Follow the provider's guidance for the best results.

Missed Dose:

If people miss a dose of sodium zirconium cyclosilicate, take it as soon as people remember. However, if it is close to the time for the next scheduled dose, skip the missed dose and return to the regular dosing schedule. Do not take a double dose to make up for a missed one.

Overdose:

• If people suspect an overdose or have taken more sodium zirconium cyclosilicate than prescribed, seek immediate medical attention or contact a poison control center.

• Overdose symptoms may include severe diarrhea (loose motions), dehydration, electrolyte imbalances, or other severe side effects. Medical professionals can provide appropriate treatment for an overdose.

Storage

• Store sodium zirconium cyclosilicate according to the instructions on the medication's packaging. Typically, it should be stored at room temperature, away from excessive heat and moisture.

• Keep the medication out of the reach of children and pets.

• Do not use sodium zirconium cyclosilicate if it has expired, and always check the expiration date on the packaging.

• Follow any additional storage instructions provided by the healthcare provider or pharmacist.

For Doctors:

Indication:

Sodium zirconium cyclosilicate is indicated for treating hyperphosphatemia (high levels of phosphate in the blood) in adults with chronic kidney disease (CKD), including those on dialysis and those not on dialysis.

Dose:

The following is a general guideline:

• Initial Dose: The initial dose is often higher, 10g, and may be determined by the healthcare provider based on the specific condition. It is typically administered as a loading dose.

• Maintenance Dose: After the initial dose, the healthcare provider will adjust the maintenance dose to achieve and maintain target phosphate levels. The maintenance dose is usually lower than the initial loading dose.

• Frequency: Sodium zirconium cyclosilicate is typically taken orally once daily. However, the dosing frequency may vary based on the patient's needs and the healthcare provider's recommendations.

Dosing Considerations:

• Kidney function will play a significant role in determining the appropriate dose of sodium zirconium cyclosilicate. When prescribing the medication, the healthcare provider will consider the estimated glomerular filtration rate (eGFR).

• The healthcare provider will regularly monitor phosphate levels and adjust the dosage to maintain normal phosphate levels.

• Sodium zirconium cyclosilicate is often used in combination with dietary phosphate restriction. people may need to follow dietary guidelines provided by their healthcare provider or registered dietitian.

Pharmacological Aspects of Sodium Zirconium Cyclosilicate

Pharmacodynamics:

Pharmacodynamics refers to how a medication affects the body and its mechanisms of action.

• Phosphate Binding: Sodium zirconium cyclosilicate is a non-absorbed, non-absorbable cation exchange resin. When ingested orally, it enters the gastrointestinal tract.

• Ion Exchange: The medication undergoes ion exchange within the gastrointestinal tract. Sodium ions in sodium zirconium cyclosilicate are exchanged for phosphate ions.

• Phosphate Reduction: The bound phosphate forms a complex with sodium zirconium cyclosilicate, which is then excreted from the body through the feces. This process reduces phosphate absorption from food, helping lower phosphate levels in the bloodstream.

• Reduction of Serum Phosphate Levels: By reducing phosphate absorption in the gastrointestinal tract, sodium zirconium cyclosilicate helps lower and control elevated serum phosphate levels, which are common in individuals with chronic kidney disease (CKD).

Mechanism of Action:

Sodium zirconium cyclosilicate's mechanism of action is primarily through phosphate binding in the gastrointestinal tract. It does not get absorbed into the bloodstream but acts locally in the digestive system to reduce phosphate absorption.

Pharmacokinetics:

Pharmacokinetics involves the processes of drug absorption, distribution, metabolism, and elimination in the body.

• Absorption: Sodium zirconium cyclosilicate is not absorbed into the bloodstream. Instead, it remains in the gastrointestinal tract, where it binds to phosphate ions.

• Distribution: The medication does not distribute throughout the body but acts locally in the gastrointestinal tract.

• Metabolism: Sodium zirconium cyclosilicate is not metabolized by the body.

• Elimination: The medication is excreted primarily through the feces. It carries bound phosphate out of the body through the digestive system.

Toxicity:

Toxicity is a substance or medication's potential harm or adverse effects. Sodium zirconium cyclosilicate is generally considered safe when used as prescribed under the guidance of a healthcare provider. However, like any medication, it can have side effects, and toxicity is possible in cases of overdose or improper use.

Possible Toxic Effects:

• Electrolyte Imbalances: Too much sodium zirconium cyclosilicate can lead to electrolyte imbalances, particularly low potassium (hypokalemia) or magnesium (hypomagnesemia). Symptoms of these imbalances may include muscle weakness, irregular heartbeat, and fatigue.

• Gastrointestinal Symptoms: One of the most common side effects of sodium zirconium cyclosilicate is gastrointestinal symptoms, such as diarrhea, nausea, vomiting, abdominal discomfort, and flatulence. In severe cases, persistent diarrhea and dehydration could occur.

• Allergic Reactions: Although rare, allergic reactions to medications can happen. Signs of an allergic reaction may include hives, difficulty breathing, and swelling of the face, lips, tongue, or throat. Allergic reactions are considered serious and require immediate medical attention.

Clinical Studies:

A study in 2023 explored the challenge of hyperkalemia (increased potassium in the blood) in patients with advanced kidney disease, often limiting the Renin-Angiotensin-Aldosterone-System Inhibitors (RAASi).

Sodium polystyrene sulfonate, a traditional treatment, has limited evidence for chronic use. The review highlights sodium zirconium cyclosilicate (SZC) as a promising and safe alternative, demonstrating efficacy in one-year data. While head-to-head comparisons are lacking, SZC stands out for its rapid onset and effectiveness in potassium binding, offering a potential solution for optimizing RAAS inhibition in the context of kidney disease.

What Are the Contraindications of Sodium Zirconium Cyclosilicate?

• Hypersensitivity: Sodium zirconium cyclosilicate should not be used in individuals with known hypersensitivity or allergy to the medication or its components. Allergic reactions can be severe and require immediate medical attention.

• Severe Bowel Obstruction: The medication should not be used in individuals with severe bowel obstructions. It may exacerbate existing digestive issues.

Warnings and Precautions:

• Hypokalemia (Low Potassium): Sodium zirconium cyclosilicate can lead to low potassium levels (hypokalemia) in some individuals. This can be particularly concerning for individuals with a history of heart arrhythmias or other cardiac issues. the healthcare provider will monitor the potassium levels during treatment.

• Hypomagnesemia (Low Magnesium): In rare cases, the medication may cause low magnesium levels (hypomagnesemia). This can lead to muscle spasms and heart rhythm disturbances. the healthcare provider will monitor magnesium levels as well.

• Gastrointestinal Effects: Gastrointestinal side effects, such as diarrhea, nausea, vomiting, abdominal discomfort, and flatulence, are common. Severe or persistent gastrointestinal symptoms should be reported to the healthcare provider.

• Fluid Overload: Individuals at risk of fluid overload should be monitored closely while taking sodium zirconium cyclosilicate. This includes those with congestive heart failure and other conditions associated with fluid retention.

Drug Interactions of Sodium Zirconium Cyclosilicate

• Medications That Can Decrease Sodium Zirconium Cyclosilicate Absorption: Certain laxatives and stool softeners may increase gastrointestinal motility, potentially reducing the effectiveness of sodium zirconium cyclosilicate in binding to phosphate.

• Antacids: Some antacids contain aluminum, magnesium, or calcium, which can bind to sodium zirconium cyclosilicate and decrease absorption.

• Medications That May Increase the Risk of Hypokalemia (Low Potassium): Diuretics (water pills) can lead to potassium loss in the body. When combined with sodium zirconium cyclosilicate, there may be an increased risk of hypokalemia.

• Medications That May Increase the Risk of Hypomagnesemia (Low Magnesium): Some diuretics can also cause magnesium loss, and when taken concurrently with sodium zirconium cyclosilicate, there may be an increased risk of hypomagnesemia.

• Medications That May Affect Sodium Levels: Medications that affect sodium levels, such as sodium-containing medications or altering sodium balance in the body, may interact with sodium zirconium cyclosilicate. The healthcare provider will consider this when prescribing the medication.

• Medications That May Impact Gastrointestinal Motility: Medications that affect gastrointestinal motility, such as anticholinergic drugs or drugs that slow down the digestive system, may interact with sodium zirconium cyclosilicate by potentially altering its absorption or effectiveness.

• Medications That May Affect the Heart's Electrical Activity: Medications that affect the heart's electrical activity, such as certain antiarrhythmics, may interact with sodium zirconium cyclosilicate, especially in individuals at risk of heart rhythm disturbances.

Specific Considerations:

• Pregnancy and Breastfeeding: The safety of sodium zirconium cyclosilicate during pregnancy and breastfeeding is not well established. Discuss the risks and benefits with the healthcare provider if someone is pregnant, planning to become pregnant, or breastfeeding.

• Kidney Function: Adjustments to the dose of sodium zirconium cyclosilicate may be necessary for individuals with impaired kidney function. When prescribing the medication, the healthcare provider will consider the estimated glomerular filtration rate (eGFR).

• Children and Adolescents: The safety and effectiveness of sodium zirconium cyclosilicate in pediatric populations have not been established.

• Elderly: Elderly individuals may be more susceptible to electrolyte imbalances and other side effects. Close monitoring may be necessary.