icodextrin

Action and Spectrum

Actions and Spectrum: 

Mechanism of Action: 

During peritoneal dialysis, a dialysis solution is introduced into the peritoneal cavity through a catheter. This solution helps remove waste products and excess fluids from the body. Traditional dialysis solutions mainly use glucose as an osmotic agent to draw out fluid from the blood into the peritoneal cavity, allowing for the removal of toxins.  

However, glucose cannot draw out fluids, leading to lower ultrafiltration rates and potential complications like high glucose absorption and weight gain. 

On the other hand, icodextrin is a glucose polymer composed of glucose molecules linked together in a complex structure. Infusing icodextrin into the peritoneal cavity is not readily absorbed into the bloodstream like glucose. Instead, it remains in the peritoneal cavity for an extended period. 

Spectrum of Activity: 

The primary function of icodextrin is to enhance ultrafiltration during peritoneal dialysis, which helps remove excess fluid from the body more effectively than standard glucose-based solutions. By promoting better fluid removal, icodextrin can benefit patients with difficulty achieving adequate fluid removal with traditional dialysis solutions. 

Drug Interaction

Adverse Reaction

Frequency defined 

APD or CAPD 

>10% 

Upper respiratory infection (15%) 

Peritonitis 

Hypertension 

5% to 10% 

Chest pain 

Hypotension 

Hyperphosphatemia 

Hypoproteinemia 

Pain 

Weakness 

Flu syndrome 

Infection 

Edema 

Hyperglycemia 

Hypokalemia 

Arthralgia 

Accidental injury 

<5% 

CHF 

Orthostatic hypotension 

Laparoscopic surgery 

>10% 

Headache 

Dysmenorrhea 

Nausea 

Constipation 

1-10% 

Insomnia 

Pyrexia 

Urinary tract infection 

Dysuria  

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: icodextrin should not be used in patients with known hypersensitivity or allergy to icodextrin or its components. 
• Severe Renal Failure: icodextrin should not be used in patients with severe renal failure (anuria) or who cannot undergo peritoneal dialysis. 
• Lactate Dehydrogenase Deficiency: icodextrin should be used cautiously in patients with known lactate dehydrogenase (LDH) deficiency, as it may lead to falsely elevated glucose readings in specific glucose measurement systems. 

Caution: 

• Monitoring Blood Glucose: icodextrin is a glucose-based solution and can affect blood glucose levels. Patients with diabetes or impaired glucose tolerance may require more frequent monitoring of blood glucose levels during icodextrin use.  
• Lactate Dehydrogenase Deficiency: In patients with known lactate dehydrogenase (LDH) deficiency, icodextrin can lead to falsely elevated glucose readings in specific glucose measurement systems.  
• Peritoneal Membrane Function: icodextrin should be used cautiously in patients with significant alterations in peritoneal membrane function, as it may affect the ultrafiltration capacity during dialysis. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

icodextrin is a high molecular weight glucose polymer used as peritoneal dialysis (PD) solution. Its pharmacology closely relates to its role as an osmotic agent during PD exchanges. 

Pharmacodynamics:  

The pharmacodynamics of icodextrin focuses on its ability to generate osmotic pressure in the peritoneal cavity, leading to fluid movement and ultrafiltration during PD. By facilitating improved fluid removal and waste product clearance, icodextrin plays a vital role in maintaining fluid balance and managing fluid overload in patients undergoing peritoneal dialysis. 

Pharmacokinetics: 

Absorption 

During continuous ambulatory peritoneal dialysis (CAPD), icodextrin is absorbed into the bloodstream at a rate of 40% during a 12-hour dwell period.  

icodextrin is slowly transferred into the systemic circulation via peritoneal lymphatic drainage, which is different from typical glucose absorption. 

Distribution 

After peritoneal administration, it takes approximately 13 hours for icodextrin to reach its peak concentration in the plasma. This time to peak is relatively long compared to many other drugs, reflecting the slow and sustained absorption process of icodextrin.  

Metabolism 

The metabolism of icodextrin primarily occurs through the action of alpha-amylase. Alpha-amylase breaks down the glucose polymer into smaller oligosaccharides, including maltose (DP2), maltotriose (DP3), maltotetraose (DP4), and higher molecular weight species.   

Elimination and Excretion 

icodextrin is primarily excreted through the kidneys, and the amount excreted is proportional to the patient’s residual renal function. The more residual renal function a patient has, the more icodextrin will be cleared through urine. 

Adminstartion

Administration: 

Adept is administered intraperitoneally; Adept needs to be warmed to body temperature before use. Adept has an osmolarity of 278 mOsm/L. Extraneal can be warmed to 37°C (98.6°F) to increase patient comfort during administration using dry heat sources such as a heating pad or warming plate.

It is essential not to heat the solution above 40°C (104°F), and microwave ovens should not be used for warming. Extraneal has an osmolarity ranging from 282 to 286 mOsm/L. The osmolarity is maintained within a specific range to ensure safe and effective peritoneal dialysis. 

pH: Both Adept and Extraneal have a pH between 5.0 and 6.0.

Patient Information Leaflet

Patient information leaflet 

Generic Name: icodextrin 

Why do we use icodextrin? 

icodextrin is primarily used as a peritoneal dialysis (PD) solution. It is employed during PD exchanges to improve fluid removal and provide extended ultrafiltration. Here are the primary uses of icodextrin: 

• Peritoneal Dialysis (PD): It is used as a solution during peritoneal dialysis. It is typically utilized for long-dwell or overnight exchanges, as it remains in the peritoneal cavity for a more extended period without significant absorption into the bloodstream.  
• Improved Fluid Removal: The osmotic properties enable it to create an osmotic gradient in the peritoneal cavity, drawing fluid from the bloodstream into the peritoneal cavity. By facilitating increased fluid removal, icodextrin helps manage fluid overload and maintain fluid balance in patients with impaired kidney function. 
• Extended Ultrafiltration: Due to its prolonged dwell time, icodextrin provides extended ultrafiltration during PD exchanges. The ability to achieve extended ultrafiltration is particularly beneficial in patients who experience difficulties achieving adequate fluid removal with standard glucose-based PD solutions.