EXTRANEAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EXTRANEAL (EXTRANEAL).
Extraneal (icodextrin) is a glucose polymer that acts as an osmotic agent for peritoneal dialysis. It is absorbed from the peritoneal cavity into the bloodstream and metabolized to maltose and other oligosaccharides. Its primary mechanism is to create an osmotic gradient across the peritoneal membrane, facilitating ultrafiltration and removal of waste products.
| Metabolism | Icodextrin is absorbed from the peritoneal cavity and metabolized by circulating α-amylase to smaller oligosaccharides, primarily maltose, maltotriose, and maltotetraose. These metabolites are further metabolized or excreted renally. The metabolism does not involve cytochrome P450 enzymes. |
| Excretion | Icodextrin is metabolized to maltose, maltotriose, and other oligosaccharides. After intraperitoneal administration, approximately 40% of the administered dose is absorbed systemically; the absorbed icodextrin and its metabolites are primarily eliminated by renal excretion (via glomerular filtration). In patients with residual renal function, approximately 30-40% of the absorbed dose is excreted in urine over 14 days. Biliary/fecal excretion is negligible (<1%). |
| Half-life | The terminal elimination half-life of icodextrin in plasma is approximately 19 hours (range 12-22 hours) following intraperitoneal administration for a dwell of 8-12 hours. This long half-life reflects slow metabolism and clearance, particularly relevant in patients with impaired renal function, leading to accumulation of maltose and other oligosaccharides. |
| Protein binding | Icodextrin and its metabolites have negligible protein binding (<1%). They do not bind significantly to plasma proteins. |
| Volume of Distribution | The volume of distribution (Vd) of icodextrin is approximately 0.1 L/kg, indicating distribution primarily within the extracellular fluid compartment. This low Vd reflects its high molecular weight and limited tissue penetration. |
| Bioavailability | Intraperitoneal (IP) administration: The systemic absorption of icodextrin is approximately 40% of the intraperitoneally administered dose. No oral or other routes are clinically relevant. |
| Onset of Action | Intraperitoneal (IP) administration: Onset of ultrafiltration is rapid, with measurable net ultrafiltration occurring within 1-2 hours of instillation. The peak ultrafiltration effect is seen at 4-8 hours during a long dwell. |
| Duration of Action | Intraperitoneal administration: The ultrafiltration effect lasts for the entire dwell duration, typically 8-12 hours for a long exchange. For continuous ambulatory peritoneal dialysis (CAPD), a single exchange provides sustained ultrafiltration for the dwell period. Clinical note: Extraneal is indicated for a single long dwell per day in CAPD or automated peritoneal dialysis (APD). |
7.5% solution: 2 L intraperitoneally, dwell time 4–8 hours, up to 4 exchanges per day. For automated peritoneal dialysis: 2 L per cycle, typically 3–5 cycles overnight.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment; drug is used in patients with end-stage renal disease on peritoneal dialysis. Not recommended for GFR > 30 mL/min. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment due to potential accumulation of icodextrin metabolites. |
| Pediatric use | Weight-based: 500–1100 mL/m² body surface area per exchange, dwell time 8–12 hours continuous ambulatory peritoneal dialysis (CAPD); for automated peritoneal dialysis (APD), 600–800 mL/m² per cycle. Not recommended in children < 2 years. |
| Geriatric use | No specific dose adjustments; use standard adult dosing with careful monitoring of fluid and electrolyte balance due to age-related comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EXTRANEAL (EXTRANEAL).
| Breastfeeding | It is not known whether icodextrin or its metabolites are excreted in human milk. Due to limited data and potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. M/P ratio: not available. |
| Teratogenic Risk | Pregnancy Category C. Icodextrin and its metabolite maltose have been shown to cross the placenta in animal studies. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if potential benefit justifies potential risk to the fetus. First trimester: limited data, theoretical risk of hypoglycemia in fetus due to maltose accumulation if systemic absorption occurs. Second and third trimesters: risk of maternal and fetal hypoglycemia, potential for electrolyte disturbances. Avoid continuous exposure to high doses. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to icodextrin or any components of the product","Lactose intolerance or galactosemia (due to maltose metabolites)","Severe metabolic acidosis or uncompensated respiratory acidosis","Pre-existing severe hypertriglyceridemia","Patients with a history of severe cutaneous adverse reactions to icodextrin","Ineffective peritoneal dialysis (e.g., peritoneal fibrosis, adhesions)"]
| Precautions | ["Hypersensitivity reactions including severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome) and anaphylaxis","Peritoneal dialysis-related infections (e.g., peritonitis, exit-site infections)","Peritoneal membrane damage and ultrafiltration failure with long-term use","Electrolyte disturbances (e.g., hyponatremia, hypokalemia)","Metabolic acidosis due to lactate accumulation","Volume depletion or overload","Malnutrition due to protein loss","Hypoglycemia or hyperglycemia (icodextrin metabolites may interfere with glucose monitoring)"] |
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| Fetal Monitoring | Monitor maternal blood glucose levels frequently, as icodextrin can cause hypoglycemia via maltose accumulation. Monitor serum electrolytes (sodium, potassium, calcium, magnesium) and acid-base balance. Assess for signs of peritonitis (abdominal pain, cloudy dialysate). Fetal monitoring with ultrasound for growth and well-being if used during pregnancy. |
| Fertility Effects | Animal studies have not revealed evidence of impaired fertility at doses up to 2.7 g/kg/day in rats. There is no evidence of adverse effects on human fertility, but clinical data are limited. |