Icodextrin for Peritoneal Dialysis - A Comprehensive Review

Overview

Icodextrin is commonly used in peritoneal dialysis solutions as a colloid osmotic agent. It helps to maintain an osmotic gradient in the peritoneal cavity, allowing excess fluid and waste materials to be removed from the body. Unlike other glucose-based solutions used in peritoneal dialysis, Icodextrin is absorbed slowly, allowing for a longer dwell time during the exchange procedure. Icodextrin was approved by the Food and Drug Administration (FDA) on 20th December 2022.

Drug Group

Icodextrin belongs to a pharmacological family known as "osmotic diuretics." Osmotic diuretics are drugs that enhance osmotic pressure within the renal tubules, promoting the removal of water and electrolytes from the body via urine. Icodextrin is used primarily in peritoneal dialysis solutions as an osmotic agent. While Icodextrin is classified as an osmotic diuretic, it should be noted that it is utilized specifically in peritoneal dialysis rather than as a typical diuretic for situations such as edema or elevated intracranial pressure.

Indications

Icodextrin is primarily used for peritoneal dialysis. Peritoneal dialysis is a renal replacement treatment for those who have kidney failure. Icodextrin is used as an osmotic agent in peritoneal dialysis solutions to help remove excess fluid and waste from the body via the peritoneal membrane.

• Ultrafiltration: Icodextrin contributes to the osmotic gradient required for peritoneal dialysis, which removes excess fluid from the body by ultrafiltration.

• Extended Dwell Time: Because of its sluggish absorption, Icodextrin allows for longer dwell times during peritoneal dialysis exchanges. This is especially beneficial for lengthy stay times, such as overnight exchanges in continuous ambulatory peritoneal dialysis (CAPD).

• Nocturnal Dialysis: Icodextrin is frequently used in overnight exchanges to offer extended ultrafiltration, which contributes to improved fluid balance in peritoneal dialysis patients.

• Reduced Glucose Absorption: Icodextrin is more slowly absorbed than typical glucose-based dialysis solutions. This delayed absorption may aid in minimizing glucose absorption in the body, thereby reducing consequences, including hyperglycemia (high blood sugar) and weight gain.

Contraindications of Icodextrin

The contraindications for Icodextrin in peritoneal dialysis are:

• Hypersensitivity: Individuals who have a known allergy or allergic response to Icodextrin or any of the peritoneal dialysis solution components should avoid using Icodextrin.

• Severe Lactic Acidosis: Icodextrin should not be used in individuals who have severe lactic acidosis, a condition in which lactic acid accumulates in the body.

• Hyperfibrinolysis: Patients with hyperfibrinolysis, a disorder characterized by excessive fibrin breakdown in the blood, should avoid using Icodextrin.

• Severe Anasarca: Anasarca is defined as significant global edema or swelling. Icodextrin may not be appropriate for people who have severe anasarca.

• Patients at Risk of Bleeding: Icodextrin should be taken with caution in patients at risk of bleeding or those taking drugs that enhance the risk of bleeding since it may impair coagulation.

• Severe Respiratory Failure: Icodextrin may not be appropriate for people who have severe respiratory failure.

Dosage Forms and Available Strengths

• Dosage Form: Injection or solution.

• Strength: Each 100 milliliters of the solution includes 7.5 grams of Icodextrin, along with additional electrolytes and osmotic agents.

Warnings and Precautions of Icodextrin

Healthcare professionals and patients who use Icodextrin should be aware of various warnings and precautions to ensure safe and effective therapy. Here are some general risks and precautions about Icodextrin in peritoneal dialysis:

• Hypersensitivity Reactions: Severe hypersensitivity responses, including anaphylaxis, have been documented with Icodextrin. Patients should be monitored for evidence of allergic reactions, and if any arise, the solution should be discontinued.

• Lactic Acidosis: Icodextrin metabolism can produce lactate. Patients with risk factors for lactic acidosis, such as liver disease or certain respiratory disorders, should be continuously monitored.

• Monitoring Electrolytes and Fluid Status: During Icodextrin-based peritoneal dialysis, electrolytes, fluid status, and acid-base balance must all be monitored regularly. Adjustments to the dialysis prescription may be required based on these characteristics.

• Infections: Peritonitis (inflammation of the tissue that covers the abdominal organs and lines the abdominal wall) is a common consequence of peritoneal dialysis. During exchanges, a strict aseptic technique should be used, and any indicators of infection, such as murky effluent, stomach discomfort, or fever, should be checked and treated right once.

• Concomitant Drugs: Some drugs may interact with Icodextrin or be influenced by fluid balance changes during peritoneal dialysis. Healthcare practitioners should be aware of any medications the patient is taking, including over-the-counter pharmaceuticals and vitamins.

• Cardiovascular Events: Patients with pre-existing cardiovascular illness should be closely monitored since Icodextrin may impair volume status and cardiovascular function.

• Pregnancy and Nursing: The safety of Icodextrin during pregnancy and nursing has not been determined. Individuals who are pregnant or nursing should carefully examine the possible advantages and hazards.

• Pediatric Use: Icodextrin's safety and efficacy in pediatric patients have not been thoroughly researched. Its usage in children should be based on a thorough assessment of the possible benefits and dangers.

For Patients

What Is the Clinical Condition for Using Icodextrin?

Icodextrin is primarily used in the therapeutic treatment of end-stage renal disease (ESRD) in patients undergoing peritoneal dialysis. Peritoneal dialysis is a renal replacement therapy in which the peritoneal membrane lining the abdominal cavity acts as a natural filter for waste elimination and fluid balance in people with kidney failure. Icodextrin is intended to treat the following clinical conditions:

• End-Stage Renal Disease (ESRD): ESRD is the end stage of chronic renal disease in which the kidneys are no longer able to function properly to support life. Peritoneal dialysis, which includes the use of Icodextrin solutions, is a method of eliminating waste products and excess fluid from the body when the kidneys are no longer able to operate.

Icodextrin is used to improve ultrafiltration during peritoneal dialysis, particularly during extended dwell times or overnight exchanges. Its sluggish absorption allows for a longer dwell period, which leads to more efficient fluid evacuation.

How Does the Icodextrin Work?

Icodextrin acts as an osmotic agent during peritoneal dialysis, a kind of renal replacement treatment for people with end-stage renal disease (ESRD). Its mode of action is based on its osmotic characteristics within the peritoneal cavity. This is how Icodextrin works.

• Osmotic Properties: Icodextrin is a high molecular weight glucose polymer that, when delivered into the peritoneal cavity as part of a peritoneal dialysis solution, produces an osmotic gradient.

• Ultrafiltration: Icodextrin's osmotic gradient causes water to flow from the circulation into the peritoneal cavity. The procedure is known as ultrafiltration. As water enters the peritoneal cavity, it transports waste products and excess solutes from the circulation.

• Extended Dwell Time: Icodextrin is absorbed more slowly than typical glucose-based dialysis solutions. This delayed absorption enables a longer stay duration during peritoneal dialysis exchange, particularly during nocturnal or long-dwell periods.

• Effective Fluid Elimination: The osmotic gradient, together with the increased dwell period, enables for more effective elimination of excess fluid from the body. This is critical in maintaining fluid balance in people with renal failure.

• Reduced Glucose Absorption: Icodextrin is absorbed more slowly than glucose, which may help to reduce systemic glucose absorption during peritoneal dialysis. This can assist in reducing issues related to glucose absorption, such as hyperglycemia and weight gain.

What Are the Clinical Uses of Icodextrin?

Icodextrin is therapeutically used in peritoneal dialysis solutions to treat end-stage renal disease (ESRD). Peritoneal dialysis is a renal replacement therapy in which the peritoneal membrane in the abdominal cavity acts as a natural filter, eliminating waste materials and excess fluid from the body. The clinical applications of Icodextrin in peritoneal dialysis include:

What Are the Side Effects of the Drug?

Icodextrin, a component of peritoneal dialysis solutions, may cause adverse effects. It is crucial to highlight that the negative effects are mostly related to the peritoneal dialysis method. Common adverse effects of peritoneal dialysis, including the usage of Icodextrin, might include:

• Fluid and Electrolyte Imbalance: Fluid and electrolyte imbalances can occur as a result of peritoneal dialysis, which includes Icodextrin exchanges. This can cause dehydration or excessive fluid retention, as well as fluctuations in sodium, potassium, and other electrolyte levels.

• Hypotension: Low blood pressure can develop during or after peritoneal dialysis, resulting in dizziness or fainting.

• Peritonitis: Peritonitis is a significant complication of peritoneal dialysis. Symptoms may include stomach discomfort, hazy dialysis fluid, and fever.

• Hypersensitivity Reactions: Although uncommon, hypersensitivity events, including anaphylaxis, have been observed with Icodextrin-containing solutions. If a person notices any of the symptoms of an allergic reaction, including rash, itching, swelling, severe dizziness, or difficulty breathing, they should get medical treatment immediately.

• High Blood Sugar Levels: Icodextrin includes carbs, which may lead to a rise in blood glucose levels. This impact is usually evaluated and treated as part of the overall peritoneal dialysis therapy regimen.

What Are the Things to Inform the Doctor Before Taking Icodextrin?

Before beginning Icodextrin or any peritoneal dialysis solution containing Icodextrin, one must notify the physician or healthcare provider about the medical history, current medicines, and any pre-existing health concerns. Here are some crucial points to mention to physicians:

• Allergies: Please share any allergies or hypersensitivity responses to Icodextrin or other components of the peritoneal dialysis solution.

• Medical History: Please provide a detailed medical history, including any history of cardiovascular illness, respiratory disorders, liver disease, or any serious medical problems.

• Current Medications: Provide a list of any medications the patient is presently taking, including prescription and over-the-counter medications, vitamins, and supplements. Some drugs may react with Icodextrin or be influenced by fluid balance changes during peritoneal dialysis.

• Pregnancy or Nursing: If the patient is pregnant, intends to become pregnant, or is nursing, consult with their healthcare professional. The safety of Icodextrin during pregnancy and nursing has not been proved, and the possible hazards and benefits must be carefully weighed.

• Fluid and Electrolyte Imbalance: Tell the doctor if the patient has a history of fluid and electrolyte imbalances or if he or she is taking any drugs that may influence fluid balance.

• Hypertension: If the patient has a history of hypertension (high blood pressure) or cardiovascular illness, the doctor may need to regularly monitor blood pressure throughout Icodextrin peritoneal dialysis treatment.

• Infection History: If one has a history of peritoneal infections or peritonitis, it is critical to address it with the healthcare practitioner because peritonitis is a possible consequence of peritoneal dialysis.

• Surgical History: Inform the doctor about any recent surgical operations or abdominal surgeries that may affect the feasibility or safety of peritoneal dialysis.

• Previous Dialysis Experience: Please describe any past dialysis experiences, including problems or difficulties.

Dietary Considerations:

When taking Icodextrin for peritoneal dialysis, patients should adhere to their healthcare team's dietary recommendations. Dietary limits on some nutrients, such as sodium, potassium, and phosphorus, may be necessary to maintain electrolyte balance. Additionally, healthcare practitioners may offer advice on protein consumption and hydration limitations. To maximize the efficacy of peritoneal dialysis, patients must follow the food plan prescribed by their healthcare providers.

Missed Dose:

Icodextrin is not delivered as a regular drug with missing doses. Peritoneal dialysis requires regular exchanges, and missing an exchange or not adhering to the specified dialysis schedule might result in insufficient waste clearance and fluid balance. Patients should follow the peritoneal dialysis protocol advised by their healthcare professional. If patients are concerned about missing exchanges or modifications from the specified timetable, they should immediately contact their healthcare team for assistance.

Overdose:

Icodextrin overdose is rare during peritoneal dialysis due to its mechanism of delivery. However, if the specified dialysis protocol is not followed correctly, excess fluid loss or fluid and electrolyte imbalances may result. Patients should strictly follow the specified exchange volumes and dwell periods to avoid problems. If patients are concerned about potential problems or overdose, they should seek medical assistance right once.

Storage of Icodextrin

Icodextrin solutions, like any other drug or medical solution, should be stored according to the manufacturer's recommendations and the product labeling. Here are some general principles for storing Icodextrin.

• Temperature: Icodextrin solutions are typically kept at a regulated room temperature. It is critical to review the individual product labeling for any temperature range specified by the manufacturer.

• Protection From Light: Some peritoneal dialysis solutions, notably those containing Icodextrin, may be light-sensitive. Make sure the solution is stored in a light-proof container.

• Expiration Date: Always check the expiration date on the Icodextrin solution package. Do not use the solution after its expiration date since it may have deteriorated and is no longer effective or safe.

• Manufacturer's Recommendations: Follow any extra storage recommendations supplied by the manufacturer. This may include particular information regarding the solution's storage and management.

For Doctors

What is the Pharmacodynamics of Icodextrin

Icodextrin's pharmacodynamics are largely focused on its use as an osmotic agent in peritoneal dialysis. The pharmacodynamic word relates to the drug's effects on the body and its methods of action. The following are the essential characteristics of the pharmacodynamics of Icodextrin:

• Osmotic Activity: Icodextrin is a high-molecular-weight glucose polymer. When Icodextrin is added to a peritoneal dialysis solution, it forms an osmotic gradient. This osmotic action promotes the flow of water from the circulation to the peritoneal cavity.

• Ultrafiltration: Icodextrin's osmotic gradient promotes ultrafiltration, which is the process by which water flows over the peritoneal membrane, transporting waste products and solutes. This is an important method for eliminating excess fluid from the body in people with end-stage renal disease who get peritoneal dialysis.

• Extended Dwell Time: Icodextrin absorbs more slowly than typical glucose-based dialysis solutions. This feature enables a longer stay duration during peritoneal dialysis exchanges, particularly for long-dwell periods or nocturnal exchanges. Slow absorption adds to longer ultrafiltration times and more effective fluid removal.

• Reduced Glucose Absorption: Compared to glucose-based dialysis solutions, Icodextrin absorbs more slowly. This feature may assist in limiting the systemic absorption of glucose during peritoneal dialysis, thereby reducing issues related to glucose absorption, such as hyperglycemia and weight gain.

• Maintenance of Osmotic Gradient: Icodextrin's sustained osmotic gradient allows for continuous fluid evacuation during peritoneal dialysis exchanges, which helps to control fluid balance in people with kidney failure.

Chemical Taxonomy

Icodextrin is a high-molecular-weight glucose polymer classified as a carbohydrate. It is a kind of dextrin, which is a carbohydrate formed by the partial hydrolysis of starch. Icodextrin is a complex branched-chain polysaccharide with a distinct structure that gives it osmotic characteristics, making it appropriate for use in peritoneal dialysis solutions.

In terms of chemical classification, Icodextrin belongs to the wider groups of carbohydrates, polysaccharides, and, more particularly, dextrins. Carbohydrates are organic molecules made up of carbon, hydrogen, and oxygen. They have the generic formula (CH2O)n, where "n" signifies the number of repeating units. Polysaccharides are big polymers composed of many sugar units. Icodextrin is made from amylopectin, a starch component, via a series of chemical steps. Its particular features, including delayed absorption and osmotic activity, make it ideal for peritoneal dialysis.

Mechanism of Action of Icodextrin

The mechanism of action of Icodextrin is directly related to its involvement in peritoneal dialysis. Peritoneal dialysis is a renal replacement therapy used to treat people with end-stage renal disease (ESRD), which occurs when the kidneys are no longer able to filter waste materials and excess fluid from the blood. Icodextrin is a component of the peritoneal dialysis solution that helps in the overall success of the therapy through the following mechanisms:

• Osmotic Gradient Creation: Icodextrin is a high molecular weight glucose polymer. Icodextrin, when delivered into the peritoneal cavity as part of the dialysis solution, causes an osmotic gradient to form. The gradient is produced between the peritoneal cavity and the bloodstream.

• Ultrafiltration: Icodextrin's osmotic gradient causes water to flow from the circulation into the peritoneal cavity. The procedure is known as ultrafiltration. As water flows over the peritoneal membrane, it transports waste products and excess solutes, eliminating them from the body.

• Extended Dwell Time: Icodextrin absorbs more slowly than typical glucose-based dialysis solutions. Because of the delayed absorption, the dialysis solution can stay in the peritoneal cavity for longer periods of time. During this extended stay, Icodextrin continues to contribute to the osmotic gradient and aids in continuous ultrafiltration.

• Reduced Glucose Absorption: Compared to glucose-based dialysis solutions, Icodextrin absorbs more slowly. This feature may assist limiting the systemic absorption of glucose during peritoneal dialysis, thereby reducing issues related to glucose absorption, such as hyperglycemia and weight gain.

• Continuous Fluid Removal: The prolonged osmotic gradient created by Icodextrin enables continuous fluid removal during peritoneal dialysis exchanges. This is critical for maintaining fluid balance in those with renal failure.

What is the Pharmacokinetics of Icodextrin

Icodextrin's pharmacokinetics in the context of peritoneal dialysis include its distribution, absorption, metabolism, and elimination within the body. It is vital to highlight that Icodextrin, unlike typical drugs, is not absorbed systemically; rather, its effects are predominantly limited to the peritoneal cavity during peritoneal dialysis. Here are important features of the pharmacokinetics of Icodextrin:

• Introduction Into the Peritoneal Cavity: Icodextrin is administered into the peritoneal cavity as part of a dialysis solution. The solution is introduced into the peritoneal cavity via a catheter and comes into touch with the peritoneal membrane.

• Osmotic Gradient and Ultrafiltration: Icodextrin's main pharmacodynamic impact is the formation of an osmotic gradient. This gradient causes water to migrate from the circulation into the peritoneal cavity, allowing for more efficient ultrafiltration. During this process, waste products and excess solutes are transported by the ultrafiltrate and successfully eliminated from the body.

• Slow Absorption: Icodextrin is absorbed more slowly than typical glucose-based dialysis solutions. This sluggish absorption adds to the dialysis solution's extended stay time in the peritoneal cavity, allowing for longer ultrafiltration.

• Metabolism: Icodextrin exhibits negligible metabolism in the peritoneal cavity. During peritoneal dialysis, it mainly stays intact as a high molecular weight glucose polymer.

• Elimination: Icodextrin is eliminated by draining the dialysis fluid at the end of the dwell period. The wasted dialysis solution, which contains waste products and excess fluid, is evacuated from the peritoneal cavity to complete the dialysis exchange.

Toxicity

Icodextrin is typically regarded as safe and well-tolerated in peritoneal dialysis solutions. However, like with any medical intervention, there are possible dangers and side effects. The fundamental problem with Icodextrin is its usage in the context of peritoneal dialysis, not its intrinsic toxicity.

• Hypersensitivity Events: Although uncommon, hypersensitivity events, including anaphylaxis, have been observed with Icodextrin-containing peritoneal dialysis solutions. Patients should be watched for indications of an allergic response, such as rash, itching, swelling, severe dizziness, or difficulty breathing.

• Peritonitis: Peritonitis is a documented complication of peritoneal dialysis. A strict aseptic procedure during exchanges is critical to avoiding peritonitis. The symptoms of peritonitis include stomach discomfort, murky dialysis fluid, and fever.

Drug Interactions

Because Icodextrin is primarily used for peritoneal dialysis, interactions are most likely connected to the patient's general health care, including any other drugs they may be taking. Below are some general considerations:

• Concomitant Medication: Patients receiving peritoneal dialysis may be administered additional drugs to treat comorbid diseases. Healthcare practitioners must be informed of the patient's whole pharmaceutical regimen, including prescription prescriptions, over-the-counter medications, vitamins, and supplements.

• Antibiotics: If a patient needs antibiotics to treat an infection, the drugs should be carefully chosen. Some antibiotics may be compatible with peritoneal dialysis, while others may need dose changes or alternate routes of delivery.

• Antifungal Drugs: Certain antifungal drugs may need to be adjusted in dose or administration for those undergoing peritoneal dialysis.

• Cardiovascular Drugs: Patients with cardiovascular disease may be receiving antihypertensive, diuretic, or heart failure drugs. The effects of peritoneal dialysis on fluid and electrolyte balance should be addressed while managing these drugs.

Use in Specific Populations

• Pregnancy: Icodextrin's safety during pregnancy has not been verified. Healthcare practitioners must balance the possible advantages of peritoneal dialysis with Icodextrin against the hazards to the growing fetus. Individual examinations and talks with pregnant women are critical for making educated decisions regarding its usage.

• Breastfeeding: It is uncertain if Icodextrin is secreted in breast milk. Due to a lack of evidence on the safety of Icodextrin during nursing, the choice to use it should be taken with the significance of breastfeeding and the potential dangers in mind.

• Pediatric Use: The safety and efficacy of Icodextrin in pediatric patients have not been thoroughly investigated. Healthcare practitioners may consider using it in children depending on the clinical circumstances, advantages, and possible hazards. Individualized evaluations are critical in pediatric populations.

• Geriatric Population: Elderly people may have age-related changes in renal function and other comorbidities. When prescribing Icodextrin for the elderly, healthcare practitioners should keep these things in mind. Close monitoring and changes to the peritoneal dialysis protocol may be required.

• Renal Impairment: Since Icodextrin is primarily used to treat end-stage renal illness, the people who take it usually have considerable kidney damage. However, the severity of renal impairment may alter the prescription and administration of Icodextrin, necessitating modifications.

• Hepatic Impairment: Patients with hepatic impairment may be at risk of developing lactic acidosis, a condition related to Icodextrin metabolism. Individuals with pre-existing hepatic disorders should exercise caution and pay great attention.

• Cardiovascular Diseases: Patients with pre-existing cardiovascular diseases should be closely monitored since the fluid and electrolyte changes caused by Icodextrin-based peritoneal dialysis can have an influence on the cardiovascular state.