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NIKKISO

PACKAGE LEAFLET: INFORMATION FOR THE USER CENG^

MONOSOL, Solution for haemofiltration, haemodialysis

and haemodiafiltration

Read all of this leaflet carefully before you start using this medicine.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor.

•    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

In this leaflet:

1.    What MONOSOL is and what it is used for

2.    Before MONOSOL is given

3.    How MONOSOL is given

4.    Possible side effects

5 How to store MONOSOL 6. Further information

1. WHAT MONOSOL IS AND WHAT IT IS USED FOR

MONOSOL is a solution for haemofiltration, haemodialysis and haemodiafiltration.

MONOSOL is prescribed to you if you have kidney failure.

It purifies your blood of waste products; it corrects the acidity or alkalinity and the level of salts in your blood. As a replacement fluid in haemodiafiltration and haemofiltration, it can also be used as a source of salts and water for hydration.

MONOSOL solutions must only be used by or under the direction of a doctor.

2. BEFORE MONOSOL IS GIVEN

Before starting the therapy, your doctor will ensure that you have a good access to your vein and artery. He will also ensure that you do not present a high risk of bleeding.

MONOSOL solutions are available in different potassium concentrations. Your blood level of potassium will be monitored very closely to ensure that the most appropriate MONOSOL formulation is used.

Do not take MONOSOL solution and tell your doctor if you

•    do not have good access to the veins and/or arteries.

•    have an excessive risk of bleeding during therapy.

•    have a potassium blood level too low, unless you are simultaneously receiving potassium supplementation.

•    have a clinical condition in which your body is not able to metabolise lactate normally.

•    If your doctor has not prescribed treatment by haemofiltration, haemodialysis or haemodiafiltration.

Take special care with MONOSOL

MONOSOL can only be used by or under the direction of a doctor who has experience with the haemofiltration, haemodialysis and haemodiafiltration techniques.

Your doctor will

•    measure the acidity, different salts and waste product levels in your blood.

•    ensure that their levels are correct and closely monitored during your treatment.

•    ensure that the fluid balance of your body is well maintained. Your weight will be recorded regularly to ensure that you receive the right quantity of fluid.

•    measure the lactate level in your blood before prescribing to you MONOSOL solutions.

•    check the level of potassium in your blood to ensure that you receive the correct strength of MONOSOL.

•    check the acidity or alkalinity of your blood especially if you have liver and heart problems.

•    check your blood glucose very carefully, especially if you are diabetic.

Taking other medicines

Inform your doctor if you are taking other medicines, even those not prescribed.

Taking MONOSOL may affect and interact with other medicines.

•    If you are diabetic your glucose level will be carefully measured.

Your insulin dose will be adjusted as needed as this solution contains glucose.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant or breast-feeding. He will determine the

benefit versus the risk of using MONOSOL.

3. HOW MONOSOL IS GIVEN

Depending on your therapy, your doctor will administer MONOSOL solution by way of the tubing from the dialysis machine

The treatment by haemofiltration, haemodialysis or haemodiafiltration that you receive will depend upon your clinical diagnosis, physical examination findings, laboratory results and response to treatment.

Your doctor will determine the right formulation and amount of MONOSOL solutions for your clinical condition.

How much and how often?

Your doctor will decide and adjust the flow rate and volume of the solution to be administered.

The amount of fluid required depends upon how MONOSOL is being used. MONOSOL should be used as indicated and needed until your doctor decides to stop the treatment.

4. POSSIBLE SIDE EFFECTS

Like all medicines MONOSOL solutions can cause side effects, but not everyone gets them.

You may experience possible side effects. They may not all be due to the solutions or treatment. The potential undesirable effects that may occur are:

•    Disturbance in the different salts level in your blood (e.g. disturbance in sodium, potassium, calcium in your blood).

•    Disturbance in the fluid balance in your body

•    Reduction (hypovolaemia) or increase (hypervolaemia) in body fluid volume

•    Reduction (hypotension) or increase (hypertension) in blood pressure

•    Muscle cramps.

If you experience any of the side effects listed above, or any other side effects, please inform your doctor.

5. HOW TO STORE MONOSOL

Keep out of the reach and sight of children.

Do not store above 25°C.

Do not keep in a refrigerator or in a freezer.

Do not use MONOSOL after the expiry date stated on the label and carton after Exp. The expiry date refers to the last day of that month.

The doctor will check if the solution is clear and the container undamaged.

6. FURTHER INFORMATION

Name of the Medicinal Product

MONOSOL, Solution for haemofiltration, haemodialysis and haemodiafiltration

The composition of the solution MONOSOL is:

Ingredients	MONOSOL solution
Calcium chloride dihydrate	0.257 g/l
Magnesium chloride hexahydrate	0.152 g/l
Sodium chloride	6.43 g/l
Sodium lactate	3.36 g/l
Glucose monohydrate	1.1 g/l

The other Ingredient is Water for Injections.

What MONOSOL looks like and Contents of the pack

MONOSOL is supplied in a carton box containing two units of 5 litres PVC bags. Each bag is over-wrapped in its overpouch.

The solution in the bag is sterile, clear and colourless.

Marketing Authorisation Holder:

Nikkiso Belgium bvba

Industriepark, 6 3300 Tienen Belgium

Phone (Belgium): +32 (0)16 781770 Phone (United Kingdom): +44 (0)1483 212151

Manufacturer:

Baxter Healthcare S.A.

Moneen Road Castlebar

County Mayo - Ireland

This leaflet was last approved in:

Monosol is a trademark of Nikkiso Co., Ltd.

The following information is intended for Medical or Healthcare professionals only INFORMATION FOR THE HEALTHCARE PROFESSIONAL

MONOSOL, Solution for haemofiltration, haemodialysis and haemodiafiltration

1. NAME OF THE MEDICINAL PRODUCT_

MONOSOL

Solution for haemofiltration, haemodialysis and haemodiafiltration

For a full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM_

Solution for haemofiltration, haemodialysis and haemodiafiltration.

MONOSOL is a sterile, non-pyrogenic, clear solution.

4.    CLINICAL PARTICULARS_

4.1.    Therapeutic Indications

As substitution solution in continuous hemofiltration and hemodiafiltration and as dialysis solution in continuous hemodialysis and hemodiafiltration for acute renal failure.

4.2.    Posology and Method of Administration

Substitution fluid may be infused either in pre or post-dilutional mode, according to the physicians prescription. The amount of substitution fluid is determined so as to ensure a proper negative balance, according to each individual case, between the fluids infused and the fluids lost by ultrafiltration.

The solution can be used as a dialysate fluid with any type of dialysis membrane or fluid with any type of dialysis membrane or hemofilter. Dialysate fluid must be properly circulated from dialysate inlet to dialysate outlet, as in conventional haemodialysis. The usual dialysate flow rate in CAVHD or CVVHD is much lower than in conventional dialysis, ranging from 15 ml/min to 30 ml/min.

Administration

•    Haemodialysis: via the dialysis compartment of the dialyser

•    Haemofiltration: via the arterial or venous blood line

4.3.    Contraindications

Solution dependent contra-indications

•    Hypokalaemia,

•    Severe metabolic acidosis,

•    Impaired metabolism of lactate.

Haemofiltration / haemodialysis dependent contra-indications

•    Inadequate blood flow from vascular access,

•    All states with elevated risk of haemorrhage on account of systemic anticoagulation.

4.4.    Special Warnings and Special Precautions for Use

•    These solutions are to be used only by or under the direction of a physician who should have a sound experience of intensive care nursing and/or haemofiltration and haemodiafiltration techniques.

•    When using, high volumes of fluid, either as a replacement fluid or dialysate, consideration should be given to the fact that the lactate uptake to blood may exceed the metabolic capabilities to convert it into bicarbonate.

•    Very special care must be devoted to ensuring proper fluid balance.

An accurate fluid balance record must be kept and the weight of the patient must be closely monitored to avoid fluid balance problems which may lead to life-threatening complications such as congestive heart failure or hypovolaemic shock due to excessive volume depletion.

•    Close monitoring of kalaemia must be performed to enable selection of the appropriate potassium concentration and thus avoid hyperkalaemia or hypokalaemia.

•    Special attention must be paid to acid-base equilibium, especially in those patients with liver impairment and cardiogenic shock. Serum lactate and pH must be closely monitored.

•    Glycaemia, phosphataemia, calcaemia and magnesaemia should also be frequently monitored, together with the levels of urea and other waste products.

•    Care should be taken when the solution is used in patients with hypercatabolism associated with acute renal failure, hepatic insufficiency with lactate acidosis and serious cardiac insufficiency.

•    Due to the fact that the solution may be infused into the blood path of the extracorporeal circuit, special care must be devoted to keeping the infusion path sterile. The dialysate circuit must also be kept sterile, since backfiltration may easily occur in CAVHD, CVVHD, CAVHDF and CWHDF.

4.5.    Interactions with Other Medicinal Products and Other Forms of

Interaction

When prescribing the solution to be used for an individual patient, consideration should be given to the potential interaction between treatment with MONOSOL and therapy directed at other existing illnesses. For example: rapid potassium removal may create arrhythmias in cardiac patients using digitalis or similar drugs; digitalis toxicity may be asked by elevated potassium or magnesium, and by hypocalcaemia. Correction of electrolytes may precipitate signs and symptoms of digitalis excess. Conversely, toxicity may occur at suboptimal doses of digitalis if potassium is low or calcium is high.

Chloride plasma levels should be monitored as the chloride concentration in the solution is higher than in normal plasma.

Diabetics require careful monitoring of insulin requirements during and following treatment with glucose containing solutions.

4.6.    Pregnancy and Lactation

The safety of these solutions for use in human pregnancy has not been established. These solutions should only be administered to pregnancy women if clearly needed.

4.7.    Effects on Ability to Drive and Use Machines Not applicable.

4.8. Undesirable Effects

The undesirable effects below listed reflect the type of undesirable effects that may be reported with haemofiltration or haemodialysis solutions.

4.9. Overdose

The infusion rate of the substitution fluid should be properly prescribed in order to obtain an appropriate fluid, electrolyte and acid/ base balance and to avoid fluid overload.

5. PHARMACOLOGICAL PROPERTIES_

5.1.    Pharmacodynamic Properties Haemodialytics and Haemofiltrates (B05Z)

As dialysates, the solutions remove metabolic waste products and help to manage serum electrolyte and / or fluid imbalances during continuous renal replacement therapies in the treatment of acute renal failure. As a replacement fluid the solution serves as an alkalinising agent and provides a continuous source of water for hydration, electrolytes and calories.

5.2.    Pharmacokinetic Properties

Insignificant amounts of the solutions are absorbed by patients utilising them as dialysates. There is only an exchange between the dialysate and the patient’s serum resulting in the removal of excess body fluid, electrolytes and metabolic waste products.

Solution used to adjust blood volume is absorbed directly into the blood stream where each component of the solution is essential in the maintenance of homeostasis.

Most of the components of the solution are excreted predominantly in the urine; consequently, during acute renal failure, normal extracellular fluid levels of each product component must be maintained trough the use of continuous renal replacement therapies. Lactate is a biological precursor of bicarbonate.

5.3.    Preclinical Safety Data

All ingredients are physiological components in animal and human plasma. Within the therapeutic dosage range toxic effects are not to be expected under the condition of clinical application.

6.    PHARMACEUTICAL PARTICULARS_

6.1.    List of Excipients Water for Injections

6.2.    Incompatibilities

•    Additives should not be added to the solution when acting as a dialysate fluid.

•    Additives may be added to the solution when acting as a substitution fluid, but only those additives for which compatibility has been documented should been used.

•    Never add bicarbonate to the solution as precipitation of calcium and magnesium carbonate will occur.

•    Bicarbonate solutions, if required, must be infused separately.

6.3.    Shelf Life

The shelf life is 2 years in the overpouch. The product, once removed from its individual overpouch, should be used immediately.

6.4.    Special Precautions for Storage

Do not store above 25°C. Do not refrigerate or freeze.

6.5.    Nature and Contents of Container

The solution is packaged in flexible plasticised (poly vinyl chloride) bags of 5000 ml size, containing 5000 ml of solution. Each unit is sealed inside a high density polyethylene overpouch.

Pack size: Each box contains two single 5L bags.

6.6.    Special Precautions for Disposal

•    Follow directions of attending physician and package leaflet accompanying the product.

•    Remove the container from the overwrap.

•    Check for minute leaks by squeezing the bag firmly. If leaks are found discard the solution as sterility may be impaired. Occasionally condensation does occur between the overpouch and the bag due to the manufacturing process and is not necessarily indicative of a leak. In addition, do not use the solution if the fluid is cloudy or the blue tip protector is missing.

•    If the resealable rubber plug on the medication port is missing or partially removed, do not use product if medication is to be added.

•    Once the bag has been removed from the overpouch, it should be used immediately.

•    Remove the blue tip protector from the port, hang the bag onto either a drip stand or weighing scales (if using an automated machine) and insert the giving set into the bag.

•    The product is for single use only.

•    Discard any damaged or partially used container.

7.    MARKETING AUTHORISATION HOLDER_

Nikkiso Belgium bvba

Industriepark, 6 3300 Tienen Belgium

Phone (Belgium): +32 (0)16 781770 Phone (United Kingdom): +44 (0)1483 212151

8.    MARKETING AUTHORISATION NUMBER_

PL 44204/0004

Monosol is a trademark of Nikkiso Co., Ltd.

CB-30-02-083

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