SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

KIBOUsol potassium-free, solution for haemofiltration

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

BEFORE RECONSTITUTION:

Composition of the separate compartments	Per 1000 ml
Small compartment ml 500
Glucose monohydrate	11.000 g
Calcium chloride dihydrate	2.573 g
Magnesium chloride hexahydrate	1.017 g
Large compartment 4500ml
Sodium hydrogen carbonate	3.547 g
Sodium chloride	6.623 g

AFTER RECONSITUTION:

The 500 ml solution of the small compartment and the 4500 ml solution of the large comparments are mixed to give 5000 ml final reconsituted solution, whose composition is:

Composition of final solution	Per 1000 ml
Glucose monohydrate	1.100 g
Calcium chloride dihydrate	0.257 g
Magnesium chloride hexahydrate	0.102 g
Sodium hydrogen carbonate	3.192 g
Sodium chloride	5.961 g

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Solution for haemofiltration.

KIBOUsol potassium-free solution for haemofiltration is a sterile, non-pyrogenic, clear and colourless or almost colourless solution.

Theoretical osmolarity: 292,3 mosm/l pH ~ 7.0-8.5

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

KIBOUsol potassium-free solution for haemofiltration is indicated for the treatment of acute and chronic renal failure, as substitution solution in haemofiltration.

Posology and method of administration

The amount of substitution solution to be administered in adults is determined by the ultrafiltration rate and is set for each individual case to ensure an adequate electrolyte fluid balance.

The filtration rate is prescribed by the attending physician depending on the clinical status and the body weight of the patient. Unless otherwise prescribed a total filtration rate of 800 to 1400 mL/h is appropriate in adults to remove metabolic waste products depending on the metabolic status of the patient.

There is no clinical experience on the use and dosing of this product in children.

KIBOUsol Potassium-free, solution for haemofiltration can be administered into the extra corporeal blood circuit either in pre- and/or post- dilution mode according to the physician’s prescription.

Administration: via the arterial or venous blood line.

The ready-to-use solution for haemofiltration is obtained by mixing the solution contained in the large chamber (4500 ml) with the solution contained in the small chamber (500 ml). For instructions for use and handling, please refer to section 6.6.

4.3 Contraindications

Solution dependent contraindications:

-    Hypokalaemia, if no simultaneous adapted potassium supplementation.

-    Metabolic alkalosis.

Haemofiltration dependent contraindication due to the technical procedure itself:

-    Renal failure with increased hypercatabolism in cases where uraemic symptoms can no longer be relieved by haemofiltration.

-    Inadequate blood flow from vascular access.

-    If there is a high risk of haemorrhage on account of systemic anticoagulation

4.4 Special warnings and precautions for use

•    KIBOUsol potassium-free solution for haemofiltration must only be used by or under the direction of a physician experienced in haemofiltration techniques,

•    White particulate formation of calcium carbonate could be observed in the predilution and post-dilution CRRT lines in association with the use of solution for haemofiltration. Therefore every 30 minutes during CRRT with solution for haemofiltration, pre- and post-dilution lines should be closely inspected to verify that the solution in the tubing is clear and without particles. In some cases precipitation may not appear until several hours after the start of therapy. If precipitate is observed, the solution for haemofiltration and CRRT tubing lines must be replaced immediately and the patient carefully monitored.

•    The haemofiltration solution should be warmed prior to infusion with appropriate equipment to approximately body temperature and should not be infused under any circumstances below room temperature.

The warming of this solution to approximately body temperature must be carefully

•    controlled verifying that the solution is clear and without particles.

•    Fluid balance must be carefully monitored,

•    Acid-base balance must be carefully monitored,

•    Similarly, electrolyte balance (chloraemia, phosphataemia, calcaemia, magnesaemia and natraemia) should be monitored regularly to detect any potential imbalance,

•    Kalaemia must be monitored regularly before and during treatment. If hypokalaemia is present or starts to develop, supplementation of potassium and/or changing to a substitution solution with higher potassium concentration may be required. If hyperkalaemia starts to develop, an increase in the filtration rate and/or changing to a substitution solution with a lower potassium concentration may be indicated as well as usual measures of intensive care medicine,

•    Blood glucose levels must be monitored closely, especially in diabetic patients.

•    In case the inter-chamber seal is not opened and the solution of the small chamber (500 ml) is given, alkalosis may arise. Most common clinical signs / symptoms of alkalosis are nausea, lethargy, headache, arrhythmia, respiratory depression.

•    Prior to use the solution, bag must be carefully inspected as described in detail in Section 6.6 “Special precautions for disposal and other handling”.

•    Do not use before mixing the two solutions.

4.5 Interaction with other medicinal products and other forms of interaction

When prescribing KIBOUsol potassium-free, solution for haemofiltration, consideration should be given to the potential interactions between this treatment and other concomitant therapies related to other pre-existing conditions.

-    Blood concentration of other medicinal products may be altered during haemofiltration, especially of drugs with a low protein binding capacity. An appropriate revision of the dose of such concomitants drugs may be required.

-    Plasma levels of potassium in patients using cardiac glycosides must be carefully monitored due to an increased risk of hypokalaemia associated arrhythmias.

4.6 Fertility, pregnancy and lactation

There are no preclinical or clinical data on the use of solutions for haemofiltration during pregnancy and lactation. KIBOUsol potassium-free, solution for haemofiltration should only be administered to pregnant and lactating women if clearly needed.

Not relevant.

4.8 Undesirable effects

The undesirable effects reported are based on literature review. Frequency is not available

Undesirable effects that may occur with KIBOUsol potassium-free, solution for haemofiltration, can result from the procedure of treatment (related to fluid removal) or from the product (especially when the electrolyte and fluid balance of the patient is not carefully monitored).

System Organ Class	Adverse Drug Reaction	Procedure related	Product related
Nervous system disorders	Dizziness	Yes (related to fluid removal during the treatment)	/
Gastro-intestinal disorders	Nausea, vomiting	Yes (related to fluid removal during the treatment)	/
Muscoloskeletal and connective tissue disorders	Muscle cramps	Yes (related to fluid removal during the treatment)	/
Vascular disorders	Hypotension	Yes (related to fluid removal during the treatment)	/
	Hypo- and hypertension		Yes
	Bleeding, air embolism (thrombosis)	Yes (related to repeated and prolonged vascular access)	/

Blood and lymphatic system disorders	Clotting	Yes (related to repeated and prolonged vascular access)	/
Infections and infestations	Vascular access realated infection	Yes (related to repeated and prolonged vascular access)	/
Metabolism and nutritional disorders	Hypophosphataemia, hypoglycaemia hypervolaemia, metabolic alkalosis		Yes

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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9 Overdose

Overdose should not occur if the fluid and electrolyte balances are monitored regularly as recommended in section 4.4.

Overdose may lead to hypervolaemia and electrolyte disturbances. These symptoms can be corrected by adjusting the ultrafiltration rate and the volume of solution administered.

Electrolyte imbalances should be managed according to the specific electrolyte disturbance.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Haemofiltrates, ATC code: B05Z B

KIBOUsol potassium-free, solution for haemofiltration is pharmacologically inactive. The solution consists of ions that are present at concentrations similar to physiological level in plasma.

During continuous haemofiltration water and solutes such as uremic toxins, electrolytes, and bicarbonate are removed from the blood by ultrafiltration. The ultrafiltrate is replaced by a substitution solution (a solution for haemofiltration), with

a balanced electrolyte and buffer composition. The ready-to-use haemofiltration solution is a bicarbonate-buffered substitution solution for intravenous administration for the treatment of acute renal failure of any origin by continuous haemofiltration. The electrolytes Na+, K+, Mg²+, Ca²+, Cl^-, and bicarbonate are essential for the maintenance and correction of fluids and electrolyte homeostasis (blood volume, osmotic equilibrium, acid-base balance).

5.2 Pharmacokinetic properties

The active ingredients of KIBOUsol potassium-free, solution for haemofiltration are pharmacologically inactive and near to physiological plasma concentrations.

The distribution of electrolytes and bicarbonate is regulated in accordance with requirements and the metabolic status and residual renal function. The active substances of the substitution solution are not metabolized except for glucose. The elimination of water and electrolytes depends on cellular requirements, the metabolic status, and the residual renal function and on other routes of fluid losses (e.g., gut, lung, and skin).

5.3 Preclinical safety data

There are no preclinical data considered relevant to clinical safety beyond data included in other sections of the SPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Hydrochloric acid, water for injection.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. If an addition to the substitution solution is done, it should be done only after evaluating the compatibility with the substitution solution and only after the two chambers of the substitution solution have been thoroughly mixed. See also section 4.5 for interactions.

6.3 Shelf life

Shelflife 18 months.

Shelf life after opening of the container

Not applicabale, since KIBOUsol potassium-free solution for haemofiltration, should be used immediately after mixing.

6.4 Special precautions for storage

Do not store below +4°C

6.5 Nature and contents of container

Pre-printed two-chamber bag (4500 ml +500ml ), with an injection point and a double luer lock Bag is composed by three different layers: a polyester outer layer, a polyethylene core, an inner layer of propylene copolymer .

Big chamber (4500 ml) contains basic solution, while small chamber (500 ml) contains acid solution.

The two-chamber bag is wrapped into a polyamide/polypropylene film and packed in cardboard boxes

6.6 Special precautions for disposal

•    Check the integrity of the product. If the seal is opened prematurely, do not use the bag. In case of damage, discard the container.

•    The two-compartments bag are mixed immediately before use to obtain a solution ready-for use. The mixed solution is clear and colourless. Do not administer unless the solution is clear.

•    Aseptic technique should be observed throughout the whole procedure.

•    After removal of the overwrapping film immediately before use, the chambers should be connected to mix the two solutions, in the following way: apply pressure with hands on the acid compartment squashing the external edges and pushing until the seal of separation between both compartments has opened and the solutions from both compartments are mixed. Discard any unused remaining solution.

•    For single use only.