Extraneal is recommended as a once daily replacement for a single glucose
exchange as part of a continuous ambulatory peritoneal dialysis (CAPD) or
automated peritoneal dialysis (APD) regimen for the treatment of chronic renal
failure, particularly for patients who have lost ultrafiltration on glucose solutions,
because it can extend time on CAPD therapy in such patients.

Posology:
Extraneal is recommended for use during the longest dwell period, i.e. in CAPD
usually overnight and in APD for the long daytime dwell.
• The mode of therapy, frequency of treatment, exchange volume,
duration of dwell and length of dialysis should be initiated and
supervised by the physician.
Adults
By intraperitoneal administration limited to a single exchange in each 24 hourperiod,
as part of a CAPD or APD regimen.
The volume to be instilled should be given over a period of approximately
10 to 20 minutes at a rate which the patient finds comfortable. For adult patients
of normal body size the instilled volume should not exceed 2.0 L. For larger
patients (more than 70-75 kg), a fill volume of 2.5L may be used.
If the instilled volume causes discomfort due to abdominal tension the instilled
volume should be reduced. The recommended dwell time is between 6 and
12 hours in CAPD and 14-16 hours in APD. Drainage of the fluid is by gravity at a
rate comfortable for the patient.
Older people
As for Adults.
Paediatric population
The safety and efficacy of Extraneal in children aged less than 18 years has not
been established. No data are available.

Administration:
Precautions to be taken before handling or administering the medicinal product
• EXTRANEAL is intended for intraperitoneal administration only. Not for
intravenous injection.
• Peritoneal dialysis solutions may be warmed in the overpouch to 37°C
to enhance patient comfort. However, only dry heat (for example,
heating pad, warming plate) should be used. Solutions should not be
heated in water or in a microwave oven due to the potential for patient
injury or discomfort.
• Aseptic technique should be employed throughout the peritoneal
dialysis procedure.
• Do not administer if the solution is discoloured, cloudy, contains
particulate matter or shows evidence of leakage, or if seals are not
intact.
• The drained fluid should be inspected for the presence of fibrin or
cloudiness, which may indicate the presence of infection or aseptic
peritonitis (see Section 4.4).
• For single use only

• Patients with diabetes mellitus often need additional insulin in order
to maintain glycaemic control during Peritoneal Dialysis (PD). Transfer
from glucose based PD solution to Extraneal may necessitate an
adjustment of the usual insulin dosage. Insulin can be administered
intraperitoneally.
• Blood glucose measurement must be done with a glucose specific
method to prevent maltose interference. Glucose dehydrogenase
pyrroloquinolinequinone (GDH- PQQ) or glucose-dye-oxidoreductase
(GDO)-based methods should not be used. Also, the use of some
glucose monitors and test strips using glucose dehydrogenase
flavin- adenine dinucleotide (GDH-FAD) methodology has resulted in
falsely elevated glucose readings due to the presence of maltose. The
manufacturer(s) of the monitor and test strips should be contacted
to determine if icodextrin or maltose causes interference or falsely
elevated glucose results.
• If GDH-PQQ, GDO, or GDH-FAD-based methods are used, using
Extraneal may cause a falsely high glucose reading, which could result
in the administration of more insulin than needed. Administration
of more insulin than needed has caused hypoglycaemia, which has
resulted in loss of consciousness, coma, neurological damage and
death. Additionally, falsely elevated blood glucose measurements due
to maltose interference may mask true hypoglycaemia and allow it
to go untreated with similar consequences. Falsely elevated glucose
levels may be measured up to two weeks following cessation of
EXTRANEAL (icodextrin) therapy when GDH-PQQ, GDO or GDH-FADbased
blood glucose monitors and test strips are used.
Because GDH-PQQ, GDO, or GDH-FAD-based blood glucose monitors
may be used in hospital settings, it is important that the health care
providers of peritoneal dialysis patients using EXTRANEAL (icodextrin)
carefully review the product information of the blood glucose testing
system, including that of test strips, to determine if the system is
appropriate for use with EXTRANEAL (icodextrin).

To avoid improper insulin administration, educate patients to alert
healthcare providers of this interaction whenever they are admitted to
the hospital.
• Peritoneal dialysis should be done with caution in patients with: 1)
abdominal conditions, including disruption of the peritoneal membrane
and diaphragm by surgery, from congenital anomalies or trauma until
healing is complete, abdominal tumours, abdominal wall infection,
hernias, faecal fistula, colostomy or iliostomy, frequent episodes of
diverticulitis, inflammatory or ischemic bowel disease, large polycystic
kidneys, or other conditions that compromise the integrity of the
abdominal wall, abdominal surface, or intra-abdominal cavity; and 2)
other conditions including recent aortic graft replacement and severe
pulmonary disease.
• Encapsulating peritoneal sclerosis (EPS) is considered to be a known,
rare complication of peritoneal dialysis therapy. EPS has been reported
in patients using peritoneal dialysis solutions including some patients
using EXTRANEAL as part of their PD therapy. Infrequently, fatal
outcomes have been reported with EXTRANEAL.
• Patients with conditions known to increase the risk of lactic acidosis
[e.g., severe hypotension, sepsis, acute renal failure, inborn errors
of metabolism, treatment with drugs such as metformin and
nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)] should
be monitored for occurrence of lactic acidosis before the start of
treatment and during treatment with lactate-based peritoneal dialysis
solutions.
• When prescribing the solution to be used for an individual patient,
consideration should be given to the potential interaction between
the dialysis treatment and therapy directed at other existing illnesses.
Serum potassium levels should be monitored carefully in patients
treated with cardiac glycosides.
• Peritoneal reactions, including abdominal pain, cloudy effluents with
or without bacteria (aseptic peritonitis) have been associated with
Extraneal (see section 4.8). In case of peritoneal reactions, the patient
should keep the icodextrin drained fluid bag along with its batch
number, and contact the medical team for analysis of the drained fluid
bag.
The drained fluid should be inspected for the presence of fibrin or
cloudiness, which may indicate the presence of infection or aseptic
peritonitis. Patients should be asked to inform their physician if this
occurs and appropriate microbiological samples should be drawn. The
initiation of antibiotic treatment should be a clinical decision based
on whether or not infection is suspected. If other possible reasons for
cloudy fluid have been excluded, Extraneal should be stopped and the
result of this action evaluated. If Extraneal is stopped and the fluid
becomes clear afterwards, Extraneal should not be reintroduced unless
under close supervision. If by re-challenging with Extraneal, the cloudy
fluid recurs then this patient should not be prescribed Extraneal again.
Alternative peritoneal dialysis therapy should be initiated and the
patient should be kept under close supervision.
• If peritonitis occurs, the choice and dosage of antibiotics should be
based upon the results of identification and sensitivity studies of
the isolated organism(s) when possible. Prior to identification of the
involved organism(s), broadspectrum antibiotics may be indicated.
• Rarely, serious hypersensitivity reactions to Extraneal have
been reported such as toxic epidermal necrolysis, angioedema,
erythema multiforme and vasculitis. Anaphylactic/anaphylactoid
reactions may occur. Stop the infusion immediately and drain the
solution from the peritoneal cavity if any signs or symptoms of a
suspected hypersensitivity reaction develop. Appropriate therapeutic
countermeasures must be instituted as clinically indicated.
• Extraneal is not recommended in patients with acute renal failure.
• Protein, amino acids, water-soluble vitamins and other medicines may
be lost during peritoneal dialysis and may require replacement.
• Patients should be carefully monitored to avoid over or under
hydration. Enhanced ultra-filtration, particularly in elderly patients, may
lead to dehydration, resulting in hypotension and possibly neurological
symptoms. An accurate fluid balance record should be kept and the
patient’s body weight monitored.
• Overinfusion of an EXTRANEAL volume into the peritoneal cavity may
be characterised by abdominal distension, feeling of fullness and/or
shortness of breath.
• Treatment of EXTRANEAL overinfusion is to release the EXTRANEAL
from the peritoneal cavity by drainage of the EXTRANEAL volume
contained within the peritoneal cavity.

• In common with other peritoneal dialysis fluids, Icodextrin should be
used with caution, after careful evaluation of its potential risks and
benefits, in patients with conditions which preclude normal nutrition,
with impaired respiratory function or with potassium deficiency.
• Fluid, haematology, blood chemistry, and electrolyte concentrations
should be monitored periodically, including magnesium and
bicarbonate. If serum magnesium levels are low, oral magnesium
supplements or peritoneal dialysis solutions containing higher
magnesium concentrations may be used.
• A decrease in the serum sodium and chloride level has been observed
in some patients. Though these decreases have been regarded as
clinically non-significant, it is recommended that serum electrolyte
levels are monitored regularly.
• A decrease in serum amylase levels has also been noticed as a
common finding in PD patients on long term treatment. The decrease
has not been reported to be accompanied with any side effects.
However, it is not known whether subnormal amylase level may mask
the rise in serum amylase, commonly seen during acute pancreatitis.
An increase in serum alkaline phosphatase of approximately 20 IU/L
was seen during clinical trials. There were individual cases where
increased alkaline phosphatase was associated with elevated SGOT
levels.
Paediatric population
• Extraneal is not recommended in children

forms of Interaction
No interaction studies have been conducted with EXTRANEAL. The blood
concentrations of dialysable drugs may be reduced by dialysis. Corrective
therapy should be instituted if necessary.
Blood glucose measurement must be done with a glucose-specific method to
prevent maltose interference. Glucose dehydrogenase pyrroloquinolinequinone
(GDH-PQQ)- or glucose-dye- oxidoreductase–based methods must not be
used. Also, the use of some glucose monitors and test strips using glucose
dehydrogenase flavin-adenine dinucleotide (GDH-FAD) methodology has resulted
in falsel

Pregnancy
There are no or limited amount of data from the use of Extraneal in pregnant
women.
Animal studies are insufficient with respect to reproductive toxicity (see section
5.3).
Extraneal is not recommended during pregnancy and in women of childbearing
potential not using contraception.
Breastfeeding
It is unknown whether Extraneal metabolites are excreted in human milk.
A risk to the newborns/infants cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to
discontinue/abstain from Extraneal therapy taking into account the benefit of
breast feeding for the child and the benefit of therapy for the woman.
Fertility
There are no clinical data on fertility.

End stage renal disease (ESRD) patients undergoing peritoneal dialysis may
experience undesirable effects, which could affect the ability to drive or use
machines.

Undesirable effects which occurred in patients treated with Extraneal from the
clinical trials and post marketing are listed below.
Extraneal associated skin reactions, including rash and pruritus, are generally
mild or moderate in severity. Occasionally, these rashes have been associated
with exfoliation. In the event of this occurring and depending on the severity,
Extraneal should be withdrawn at least temporarily.
Frequency is based upon the following scale: Very Common (≥1/10); Common
(≥1/100-<1/10), Uncommon (≥1/1,000-<1/100), Rare (≥1/10,000-<1/1,000),
Very Rare (<1/10,000), not known (cannot be estimated from the available data).

*Icodextrin interferes with blood glucose measurement devices (see section
4.4).

** Hypersensitivity-type reactions have been reported in patients using Extraneal
including bronchospasm, hypotension, rash, pruritus and urticaria
Other undesirable effects of peritoneal dialysis related to the procedure: fungal
peritonitis, bacterial peritonitis, catheter site infection, catheter related infection
and catheter related complication.

Enhanced ultrafiltration, particularly in the elderly patients, may lead to
dehydration, resulting in hypotension, dizziness and possibly neurological
symptoms (see section 4.4).
Hypoglycaemic episodes in diabetic patients (see section 4.4).
Increase in serum alkaline phosphatases (see section 4.4) and electrolyte
disturbances (e.g. hypokalaemia, hypocalcaemia and hypercalcaemia).
Peritoneal reactions, including abdominal pain, cloudy effluents with or without
bacteria, aseptic peritonitis (see section 4.4).
Fatigue was often reported spontaneously and in literature as an undesirable
effect related to the procedure.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk balance
of the medicinal product. Healthcare professionals are asked to report any
suspected adverse reactions

No data are available on the effects of overdosage. However, continuous
administration of more than one bag of Extraneal in 24 hours would increase
plasma levels of carbohydrate metabolites and maltose. The effects of
such an increase are unknown but an increase in plasma osmolality may
occur. Treatment could be managed by Icodextrin-free peritoneal dialysis or
haemodialysis.

Icodextrin is a starch-derived glucose polymer which acts as an osmotic agent
when administered intraperitoneally for continuous ambulatory peritoneal
dialysis. A 7.5% solution is approximately iso-osmolar to serum but produces
sustained ultrafiltration over a period up to 12 hours in CAPD. There is a
reduction in calorie load compared to hyperosmolar glucose solutions.
The volume of ultrafiltrate produced is comparable to that with 3.86% glucose
when used in
CAPD. Blood glucose and insulin levels remain unaffected.
Ultrafiltration is maintained during episodes of peritonitis.
The recommended posology is limited to a single exchange in each 24 hourperiod,
as part of a CAPD or APD regimen.

Carbohydrate polymer levels in blood reach steady state after about 7-10 days
when used on a daily basis for overnight dialysis. The polymer is hydrolysed by
amylase to smaller fragments which are cleared by peritoneal dialysis. Steady
state plasma levels of 1.8 mg/ml have been measured for oligomers of glucose
units greater than 9 (G9) and there is a rise in serum maltose (G2) to 1.1 mg/ml
but there is no significant change in serum osmolality. When used for the long
day time dwell in APD maltose levels of 1.4 mg/ml have been measured but with
no significant change in serum osmolality.
The long-term effects of raised plasma levels of maltose and glucose polymer
are unknown, but there is no reason to suppose these to be harmful.

Acute toxicity
Acute i.v. and i.p. studies in mice and rats have demonstrated no effects at
doses up to
2000mg/kg.
Subchronic toxicity
Twice daily i.p. administration of 20% Icodextrin solution for 28 days to rats and
dogs revealed no target organ or tissue toxicity. The major effect was upon the
dynamics of fluid balance.
Mutagenic and tumorigenic potential
In vitro and in vivo studies on mutagenicity gave negative results.
Carcinogenicity studies with the product are not feasible but carcinogenic
effects are unlikely given the chemical nature of the molecule, its lack of
pharmacological effect, lack of target organ toxicity and negative results in
mutagenicity studies.
Reproductive toxicity
A reproduction toxicity study in rats demonstrated no effect on fertility or
embryofetal development.

Water for Injections
Sodium Hydroxide or
Hydrochloric acid q.s. to required pH.

None known.
Drug compatibility must be checked before admixture. In addition, the pH and
salts of the solution must be taken into account.

store below 30°C
Do not use unless the solution is clear and the container undamaged.

Flexible PVC container holding 1.5, 2.0 or 2.5 litres.
The lineo connector that may equip the Y transfer line of the twin bag, contains
10.5% of
Povidone iodine ointment
1.5 L 8 units per box Single bag Sy II (luer connector)
1.5 L 8 units per box Single bag Sy III (spike connector)
1.5 L 8 units per box Twin bag Sy II (luer connector)
1.5 L 8 units per box Twin bag Sy III (spike connector)
1.5 L 6 units per box Single bag Sy II (luer connector)
1.5 L 6 units per box Single bag Sy III (spike connector)
1.5 L 6 units per box Twin bag Sy II (luer connector)
1.5 L 6 units per box Twin bag Sy III (spike connector)
1.5 L 6 units per box Twin bag (lineo connector)
2.0 L 8 units per box Single bag Sy II (luer connector)
2.0 L 8 units per box Single bag Sy III (spike connector)
2.0 L 8 units per box Twin bag Sy II (luer connector)
2.0 L 8 units per box Twin bag Sy III (spike connector)
2.0 L 6 units per box Single bag Sy II (luer connector)
2.0 L 6 units per box Single bag Sy III (spike connector)
2.0 L 6 units per box Twin bag Sy II (luer connector)
2.0 L 6 units per box Twin bag Sy III (spike connector)
2.0 L 5 units per box Single bag Sy II (luer connector)
2.0 L 5 units per box Single bag Sy III (spike connector)
2.0 L 5 units per box Twin bag Sy II (luer connector)
2.0 L 5 units per box Twin bag Sy III (spike connector)
2.0 L 5 units per box Twin bag (lineo connector)
2.5 L 5 units per box Single bag Sy II (luer connector)
2.5 L 5 units per box Single bag Sy III (spike connector)
2.5 L 5 units per box Twin bag Sy II (luer connector)
2.5 L 5 units per box Twin bag Sy III (spike connector)
2.5 L 4 units per box Single bag Sy II (luer connector)
2.5 L 4 units per box Single bag Sy III (spike connector)
2.5 L 4 units per box Twin bag Sy II (luer connector)
2.5 L 4 units per box Twin bag Sy III (spike connector)
Not all pack sizes may be marketed.

For details see section 4.2
A range of antibiotics including vancomycin, cephazolin, ampicillin/flucloxacillin,
ceftazidime, gentamycin, amphotericin and insulin have shown no evidence of
incompatibility with Extraneal. However aminoglycosides should not be mixed
with penicillins due to chemical incompatibility.
The product should be used immediately after adding any drug. Discard any
unused remaining solution.