Extraneal (Solution) Instructions for Use

Marketing Authorization Holder

Baxter Healthcare, S.A. (Ireland)

ATC Code

B05D (Peritoneal dialysis solutions)

Dosage Form

Extraneal

Solution for peritoneal dialysis 7.5% (75 mg/1 ml): containers 1.5 L, 2 L or 2.5 L, packs of 1, 4 or 5 pcs.

Dosage Form, Packaging, and Composition

Solution for peritoneal dialysis transparent, light yellow in color.

Excipients: sodium hydroxide or hydrochloric acid – q.s. to adjust pH, water for injection – up to 1000 ml.

Theoretical osmolarity: 284 mOsm/L.

Ionic composition per 1000 ml of solution:
Sodium – 133 mmol/L, 133 mEq/L
Calcium – 1.75 mmol/L, 3.5 mEq/L
Magnesium – 0.25 mmol/L, 0.5 mEq/L
Chloride – 96 mmol/L, 96 mEq/L
Lactate – 40 mmol/L, 40 mEq/L
PH 5.0-6.0

1.5 L – plastic containers (1) – polyethylene bags.
1.5 L – plastic containers “Viaflex” (1) connected with a Y-shaped tube and an empty drainage container – “Twin Bag” system – polyethylene bags.
1.5 L – plastic containers “Viaflex” (1) connected with a Y-shaped tube and an empty drainage container – “Twin Bag” system – polyethylene bags (4) – cardboard boxes.
1.5 L – plastic containers “Viaflex” (1) connected with a Y-shaped tube and an empty drainage container – “Twin Bag” system – polyethylene bags (5) – cardboard boxes.
2 L – plastic containers (1) – polyethylene bags.
2 L – plastic containers (1) – plastic bags.
2 L – plastic containers “Viaflex” (1) connected with a Y-shaped tube and an empty drainage container – “Twin Bag” system – polyethylene bags.
2 L – plastic containers “Viaflex” (1) connected with a Y-shaped tube and an empty drainage container – “Twin Bag” system – polyethylene bags (4) – cardboard boxes.
2 L – plastic containers “Viaflex” (1) connected with a Y-shaped tube and an empty drainage container – “Twin Bag” system – polyethylene bags (5) – cardboard boxes.
2.5 L – plastic containers (1) – polyethylene bags.
2.5 L – plastic containers (1) – plastic bags.
2.5 L – plastic containers “Viaflex” (1) – polyethylene bags (4) – cardboard boxes.
2.5 L – plastic containers “Viaflex” (1) – polyethylene bags (5) – cardboard boxes.
2.5 L – plastic containers “Viaflex” (1) connected with a Y-shaped tube and an empty drainage container – “Twin Bag” system – polyethylene bags.
2.5 L – plastic containers “Viaflex” (1) connected with a Y-shaped tube and an empty drainage container – “Twin Bag” system – polyethylene bags (4) – cardboard boxes.
2.5 L – plastic containers “Viaflex” (1) connected with a Y-shaped tube and an empty drainage container – “Twin Bag” system – polyethylene bags (5) – cardboard boxes.

Clinical-Pharmacological Group

Solution for peritoneal dialysis

Pharmacotherapeutic Group

Peritoneal dialysis solution

Pharmacological Action

Icodextrin is a water-soluble polymer of dextrose, a starch derivative. It acts as an osmotic agent when administered intraperitoneally during continuous ambulatory peritoneal dialysis (CAPD). The 7.5% solution is approximately isoosmolar to blood serum but allows for ultrafiltration lasting up to 12 hours during CAPD. Caloric load is reduced compared to hyperosmolar glucose solutions. The ultrafiltration volume is comparable to that obtained with a 3.86% glucose solution during CAPD. It does not affect blood glucose and insulin concentrations. Ultrafiltration is maintained during episodes of peritonitis. The recommended dose is limited to a single exchange every 24 hours within the framework of CAPD or automated peritoneal dialysis (APD).

Pharmacokinetics

With daily use for nocturnal dialysis, the concentration of the carbohydrate polymer in the blood reaches C_ss in approximately 7-10 days. The polymer is hydrolyzed by amylase into smaller fragments, which are eliminated by peritoneal dialysis (PD). For glucose oligomers consisting of fewer than 9 subunits (G9), the reported C_ss in plasma was 1.8 mg/ml. An increase in serum maltose (G2) concentration to 1.1 mg/ml was also noted, but no significant changes in osmolality were observed. When this agent was used in APD with a long interval between dialysis procedures, the maltose concentration reached 1.4 mg/ml, but serum osmolality did not change significantly.

The long-term effects of increased concentrations of maltose and glucose polymers in plasma are unknown, but currently there is no reason to believe that they may be adverse.

Indications

Used as a replacement for one peritoneal exchange with a dextrose solution during CAPD or APD in chronic renal failure (CRF), especially for patients with impaired ultrafiltration when using dextrose solutions, as it can prolong the time of effective CAPD in this category of patients.

ICD codes

Dosage Regimen

This agent is recommended for use during the longest interval between CAPD or APD procedures.

The type of therapy, frequency of sessions, volume of solution for one exchange session, dwell time of the solution in the abdominal cavity, and duration of dialysis should be determined by the responsible physician managing the treatment of each specific patient.

Adult patients and elderly persons – the solution is used once daily.

Adverse Reactions

Infections and infestations uncommon – influenza.

Blood and lymphatic system disorders uncommon – anemia, leukocytosis, eosinophilia; frequency unknown – thrombocytopenia, leukopenia.

Immune system disorders frequency unknown – vasculitis, hypersensitivity, angioedema, generalized urticaria.

Endocrine disorders frequency unknown – parathyroid dysfunction.

Metabolism and nutrition disorders common – dehydration, hypovolemia; uncommon – hypoglycemia, hyponatremia, hypochloremia, hypomagnesemia, hypoproteinemia, weight increased, weight decreased; frequency unknown – hypoglycemic shock, fluid imbalance.

Psychiatric disorders uncommon – thought abnormality, anxiety, nervousness.

Nervous system disorders common – dizziness, headache; uncommon – hyperkinesia, paresthesia; frequency unknown – ageusia, hypoglycemic coma, burning sensation.

Eye disorders frequency unknown – blurred vision, periorbital edema.

Ear and labyrinth disorders common – tinnitus.

Cardiac disorders common – hypertension, hypotension; uncommon – tachycardia, orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders uncommon – pulmonary edema, dyspnea, cough, hiccups; frequency unknown – bronchospasm.

Gastrointestinal disorders common – abdominal pain; uncommon – intestinal obstruction, peritonitis, bloody peritoneal effluent, diarrhea, gastric ulcer, gastritis, gastrointestinal disorders, anorexia, vomiting, constipation, dyspepsia, nausea, dry mouth; frequency unknown – flatulence, ascites, inguinal hernia, stomach discomfort.

Skin and subcutaneous tissue disorders common – exfoliative dermatitis, rash (including macular, papular, erythematous), pruritus; uncommon – urticaria, bullous dermatitis, psoriasis, skin ulcer, eczema, nail disorder, dry skin, skin discoloration; frequency unknown – toxic epidermal necrolysis, erythema multiforme, toxic skin eruptions, dermatitis (including contact and allergic), blisters.

Musculoskeletal and connective tissue disorders uncommon – bone pain, muscle spasms, myalgia, neck pain; frequency unknown – arthralgia, back pain, musculoskeletal pain.

Renal and urinary disorders uncommon – kidney pain.

General disorders and administration site conditions common – peripheral edema, asthenia; uncommon – catheter placement complications, asthenia, chest pain, facial edema, edema, pain, pyrexia, chills, malaise, catheter site erythema, catheter site inflammation.

Investigations uncommon – increased ALT, increased AST, increased alkaline phosphatase.

Contraindications

Allergy to starch-based polymers (e.g., corn starch) and/or icodextrin; individual intolerance to maltose and isomaltose; glycogen storage diseases (glycogenoses); previous severe lactic acidosis; uncorrected mechanical defects that may interfere with effective PD or increase the risk of infection; documented loss of peritoneal function or extensive adhesions that impair peritoneal function;
Acute renal failure; children and adolescents under 18 years of age.

With caution

In conditions associated with impairments of peritoneal integrity, including rupture of the peritoneum or diaphragm due to surgery or trauma, until complete recovery, abdominal tumors, infections of the abdominal wall, hernias, fecal fistulas, colostomies or ileostomies, frequent episodes of diverticulitis, intestinal inflammation or ischemia, large polycystic kidneys and other conditions associated with impairments of peritoneal integrity or intraperitoneal cavities.

Recently undergone aortic valve transplantation and severe pulmonary diseases.

As with all PD solutions, this agent should be used with caution and after careful assessment of the potential risk and benefit in patients with impaired respiratory function, potassium deficiency, and digestive disorders.

Use in Pregnancy and Lactation

Data on use during pregnancy and breastfeeding are not available. Use during pregnancy and breastfeeding is possible only for emergency indications after a thorough assessment of the ratio of potential risk to the fetus and benefit to the mother.

It is not known whether this agent is excreted in human breast milk. Risk to newborns and infants cannot be excluded. The necessity to discontinue breastfeeding or to discontinue use of this agent should be assessed, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.

Use in Renal Impairment

Used in chronic renal failure.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

The drug is approved for use in elderly patients.

Special Precautions

In patients with diabetes mellitus, blood glucose concentration should be checked regularly, and doses of insulin and other drugs used for hyperglycemia should be adjusted after initiation of treatment. Blood glucose measurement should be performed using a glucose-specific method to exclude the influence of maltose on the result. GDH-PQQ or GDO-based methods should not be used. Furthermore, the use of some glucose meters and test strips using the GDH-FAD-based method also leads to falsely elevated glucose readings due to the presence of maltose. For information on the influence of icodextrin or maltose on results or on falsely elevated glucose determination results, consult the manufacturers of the glucose meters and test strips used. If GDH-PQQ, GDO, or GDH-FAD-based methods are used, then falsely negative hyperglycemia may be detected in patients receiving this agent, which may lead to the use of insulin in higher doses than necessary. This can cause hypoglycemia, which may result in loss of consciousness, coma, neurological impairment, and death. Furthermore, falsely negative hyperglycemia due to interaction with maltose may mask true hypoglycemia, allowing it to proceed without appropriate treatment provided for such conditions, which may lead to similar consequences. Falsely elevated glucose concentrations when using glucose meters and test strips for blood glucose determination based on GDH-PQQ, GDO, or GDH-FAD may be recorded for a period of up to two weeks after discontinuation of therapy with the drug. Since GDH-PQQ, GDO, or GDH-FAD-based glucose meters may be used in hospitals, it is important that healthcare professionals performing peritoneal dialysis with this agent carefully study the instructions for the blood glucose determination kit (including test strips) to ensure the kit’s compatibility with this agent. To avoid the administration of incorrect insulin doses, all patients undergoing therapy with this agent should be instructed that in case of hospitalization, they should notify doctors about the possibility of the mentioned interaction.

Sclerosing encapsulating peritonitis (SEP) is considered a known rare complication of PD therapy. SEP has been observed in patients who used PD solutions, including this agent. Occasionally, fatal SEP has been reported during therapy with this agent.

Patients with severe lactic acidosis should not be prescribed lactate-based PD solution therapy. In patients with conditions known to increase the risk of lactic acidosis (e.g., severe arterial hypotension or sepsis, which may be associated with acute renal failure; congenital metabolic disorders; treatment with drugs such as metformin and nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)), the occurrence of lactic acidosis must be monitored before initiation and during therapy with lactate-based PD solutions.

When individually prescribing, potential interaction between dialysis treatment and therapy aimed at other existing diseases should be taken into account. Serum potassium concentrations should be carefully monitored in patients taking cardiac glycosides.

In case of peritonitis development, the choice and dose of antibiotics should, if possible, be based on the results of identification studies and sensitivity testing of the isolated microorganism(s). Before the microorganism(s) is identified, broad-spectrum antibiotics may be prescribed.

If a hypersensitivity reaction is suspected, administration of the solution should be stopped immediately and the solution should be removed from the abdominal cavity, and countermeasures should be taken according to clinical indications.

Fluid balance should be carefully controlled and the patient’s body weight should be constantly monitored to avoid hyper- or hypohydration; indicators of general and biochemical blood tests and electrolyte concentrations, including magnesium and bicarbonate, should be monitored.

In case of low serum magnesium concentrations, oral magnesium supplements or PD solutions containing high magnesium concentrations may be used. Significant losses of protein, amino acids, water-soluble vitamins, and other drugs may occur during PD, which may require replacement therapy.

Effect on ability to drive and operate machinery

During PD, patients with end-stage renal failure may experience adverse effects that may affect the ability to drive vehicles and perform other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

Drug Interactions

Measurement of blood glucose concentration should be performed using a glucose-specific method to prevent maltose-induced distortion of the result. Methods based on pyrroloquinoline quinone-dependent glucose dehydrogenase or glucose-dye oxidoreductase should not be used. For some glucose meters and test strips whose action is based on the use of flavin adenine dinucleotide-glucose dehydrogenase, cases of falsely elevated blood glucose values due to the presence of maltose in the analyzed solution have been described.

A noticeable decrease in serum amylase activity has been observed in patients receiving this agent.
Some added drugs may be incompatible with this agent.

Potassium is not added to the solutions of this agent because dialysis may be performed to correct hyperkalemia. With normal serum potassium levels or with hypokalemia, the addition of potassium chloride in concentrations up to 4 mEq/L may be indicated to prevent severe hypokalemia, which should be done only under the guidance of a physician and after accurate determination of serum and total body potassium concentration.

Appropriate monitoring of blood glucose concentration should be performed when this agent is initiated in patients with diabetes mellitus, and the insulin dose should be adjusted if necessary.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.