Hemosol B0 Solution For Haemofiltration And Haemodialysis

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Hemosol B0 solution for haemodialysis/haemofiltration

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Hemosol B0 consists of a two compartment PVC or polyolefine bag containing the electrolyte solution in the small compartment (compartment A) and the buffer solution in the large compartment (compartment B).

BEFORE RECONSTITUTION

1 000 ml of electrolyte solution (small compartment A) contains:

active substances:

Calcium chloride, 2H₂O Magnesium chloride, 6H₂O Lactic acid	5,145 g 2,033 g 5,4 g
1 000 ml of buffer solution (large compartment B) contains:
active substances:
Sodium hydrogen carbonate	3,09 g
Sodium chloride	6,45 g

AFTER RECONSTITUTION

The small and the large compartments are mixed to give one reconstituted solution whose ionic composition is:

		in mmol/l	in mEq/l
Calcium	Ca²+	1,75	3,50
Magnesium	_Mg2+	0,5	1,0
Sodium	Na+	140	140
Chloride	Cl^-	109,5	109,5
Lactate		3	3
Hydrogen carbonate	HCO3^-	32	32

For the full list of excipients, see section 6.1

3. PHARMACEUTICAL FORM

Solution for haemodialysis/haemofiltration Clear and colourless reconstituted solution.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

As substitution solution in continuous haemofiltration and haemodiafiltration and as dialysis solution in continuous haemodialysis for acute renal failure in adult and children of all ages.

4.2 Posology and method of administration Posology:

The volume of substitution solution to be administered will depend on the intensity of the treatment performed and on the amount of solution, which has to be replaced in order to achieve the target fluid balance. The dose volume is therefore at the discretion of the responsible physician.

Commonly used flow rates for the substitution solution in haemofiltration and haemodiafiltration are:

Adult: 500 - 1500 ml/hour

Commonly used flow rates for the dialysis solution (dialysate) in continuous haemodialysis are:

Adult: 500 - 2000 ml/hour

Special population:

Elderly population

Evidence from clinical studies and experience suggests that use in the elderly population is not associated with differences in safety or effectiveness.

Paediatric population:

Commonly used flow rates for the substitution solution in haemofiltration and haemodiafiltration are:

Adolescents (12-18 years of age): 500 - 1500 ml/hour

Neonates, infants, children (0-12 years of age): 15 - 20 ml/kg/hour

Commonly used flow rates for the dialysis solution (dialysate) in continuous haemodialysis are:

Adolescents (12-18 years of age): 500 - 2000 ml/hour

Neonates, infants, children (0-12 years of age): 15 - 20 ml/kg/hour

Method of administration:

Hemosol B0, when used as a substitution solution is administered into the circuit before (pre-dilution) or after the haemofilter (post-dilution).

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

4.3. Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

4.4. Special Warnings and Precautions for Use Warnings:

The substitution solution Hemosol B0 is potassium-free.

Check that the solutions are clear and that all seals are intact before mixing. Carefully follow the instructions for use.

The electrolyte solution must be mixed with the buffer solution before use to obtain the final solution suitable for

haemofiltration/haemodiafiltration/continuous haemodialysis.

Do not administer the solution unless it is clear. Aseptic technique must be used during connection / disconnection of the line sets.

When used with a monitor, only monitors for Continuous Renal Replacement Therapies must be used. Do not use with a haemodialysis monitor.

Precautions for use:

The heating of this substitution solution to body temperature (37°C) must be carefully controlled.

Before and during treatment, haemodynamic status, fluid balance, electrolyte and acid-base balance should be closely monitored throughout the procedure.

Special attention should be given to potassium levels. Phosphate substitution and potassium supplement might be necessary.

The use of contaminated haemofiltration solution may cause sepsis, shock and fatal conditions.

Paediatric population:

There are no specific warnings and precautions when using this medicine for children.

4.5. Interaction with other medical products and other forms of interaction

The blood concentration of filterable/dialysable drugs may be reduced during treatment. Corresponding corrective therapy should be instituted if necessary. Interactions with other medications due to electrolyte and/or acid-base imbalances can be avoided by correct dosage of the solution for haemodialysis/haemofiltration and precise monitoring.

However, the following interactions are conceivable:

• The risk of digitalis-induced cardiac arrhythmia is increased during hypokalaemia;

• Vitamin D and medicinal products containing calcium, e.g. calcium carbonate as phosphate binder, can increase the risk of hypercalcaemia;

• Additional sodium bicarbonate substitution may increase the risk of metabolic alkalosis.

4.6. Fertility, pregnancy and lactation

No effects on fertility or during pregnancy or on the breast-fed newborn/infant are anticipated. There is no report on Hemosol B0 during pregnancy or lactation but literature on renal replacement therapy during acute kidney injury does not suggest risks associated with solutions. The prescriber should consider the benefit/risk relationship before administering Hemosol B0 to pregnant or breast feeding women.

4.7. Effects on Ability to Drive and Use Machines

Not relevant

4.8 Undesirable effects

Some undesirable effects related to the dialysis treatment can occur, such as nausea, vomiting, muscle cramps and hypotension.

Electrolyte disturbances may occur. Special attention must be taken for patients with hypokalaemia as this solution is potassium-free (see section 4.4).

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 Yellow Card Scheme.

Website: www.mhra.gov.uk/yellowcard

4.9. Overdose

Overdose with Hemosol B0 substitution fluid should not occur if the procedure is carried out correctly and the fluid balance, electrolyte and acid-base balance of the patient are carefully monitored.

However, overdose will result in fluid overload in patients with renal failure. Continued application of haemofiltration will remove excess fluid and electrolytes. In case of hyperhydration, the ultrafiltration must be increased and the rate of administration of the solution for haemofiltration reduced. In the case of a severe dehydration it is necessary to cease ultrafiltration and to increase the inflow of solution for haemofiltration appropriately.

Overdose could lead to severe consequences, such as congestive heart failure, electrolyte or acid-base disturbances.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Hemofiltrates:

ATC code: B05ZB

Hemosol B0 is pharmacologically inactive. The sodium, calcium, magnesium and chloride ions are present at concentrations similar to physiological levels in plasma. The solution is used to replace water and electrolytes removed during haemofiltration or to serve as a suitable exchange medium for use during haemodiafiltration or continuous haemodialysis.

Bicarbonate is used as an alkalising buffer.

5.2. Pharmacokinetic Properties

Not relevant. The active ingredients are pharmacologically inactive and are present at concentrations similar to physiological plasma levels.

5.3.

Preclinical Safety Data

Not relevant. The active ingredients are pharmacologically inactive and are present at concentrations similar to physiological plasma levels.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

In the small compartment A: Water for injections

In the large compartment B: Water for injections, Carbon dioxide

6.2. Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

It is the responsibility of the physician to judge the incompatibility of an additive medication with the Hemosol B0 solution by checking for eventual colour change and/or eventual precipitation, insoluble complexes or crystals. The Instructions for Use of the medication to be added must be consulted.

Before adding a drug, verify it is soluble and stable in water at the pH of Hemosol B0 (pH of reconstituted solution is 7.0 to 8.5).

The compatible medication must be added to the reconstituted solution and the solution must be administered immediately.

6.3 Shelf life

PVC: 1 year as packaged for sale.

Polyolefin: 18 months as packaged for sale.

Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 24 hours at 22° C. From a microbiological point of view, once opened (i.e. connected to the line), and as hydrogen carbonate is present, the reconstituted solution should be used immediately. Other in-use storage times and conditions prior to use are the responsibility of the user and would not normally be longer than 24 hours, including the duration of the treatment.

6.4. Special Precautions for Storage

Do not store below +4°C.

For storage conditions after reconstitution of the medicinal product, see section

6.3.

6.5 Nature and contents of container

The container made in Polyvinyl chloride (PVC) or polyolefin is a two-compartment bag. The 5000 ml bag is comprised of a small compartment (250 ml) and a large compartment (4750 ml). The two compartments are separated by a frangible pin or a peel seal.

The large compartment B is fitted with an injection connector (or spike connector) made of polycarbonate (PC), which is closed with a rubber disc covered by a cap as well as a luer connector (PC) with a frangible pin (PC) or a valve made of silicone rubber for the connection of the bag with a suitable replacement solution line or dialysis line.

The bag is over wrapped with a transparent overwrap made of multilayer polymer film.

Each two-compartment bag contains 5000 ml.

Package size: 2 x 5000 ml in a box.

6.6 Special precautions for disposal and other handling

The electrolyte solution is added to the buffer solution after breaking the frangible pin or opening the peel seal and before administration to the patient.

A patient information leaflet with detailed instruction for use is enclosed in the box.

Aseptic technique should be used throughout administration to the patient:

If a frangible pin separates the two compartments of the bag and a frangible pin is located in the luer connector the following instructions for use should be followed:

I Remove the over-wrap from the bag immediately before use and discard any other packaging materials.

Open the seal by breaking the frangible-pin between the two compartments of the bag. The frangible-pin will remain in the bag.

II Make sure all the fluid from the small compartment A is transferred into the large compartment B.

III Rinse the small compartment A twice by pressing the mixed solution back into the small compartment and then back into the large compartment B.

IV When the small compartment is empty: shake the large compartment B so that the contents mix completely.

The solution is now ready for use and the bag can be hung on the equipment.

V The dialysis or replacement line may be connected to either of the two access ports.

V.a If the luer connector is used, remove the cap and connect the male luer lock on the dialysis or replacement line to the female luer receptor on the bag; tighten. Using thumb and fingers, break the coloured frangible pin at its base, and move it back and forth. Do not use a tool. Verify that the pin is completely separated and that the fluid is flowing freely. The pin will remain in the luer port during the treatment.

V.b If the injection port is used, first remove the snap-off cap. Then introduce the spike through the rubber septum. Verify that the fluid is flowing freely.

The solution should be used immediately after removal of the over wrap and after addition of solution A to solution B. If not used immediately, the reconstituted solution should be used within 24 hours after addition of the electrolyte solution to the buffer solution.

The reconstituted solution is for single use only.

Do not use if container is damaged or if solution is not clear.

Discard any unused solution.

If a frangible pin separates the two compartments of the bag and a valve is located in the luer connector, the following instructions for use shall be followed:

I Remove the over wrap from the bag immediately before use and discard any other packaging materials. Open the seal by breaking the frangible pin between the two compartments of the bag. The frangible pin will remain in the bag.

II Make sure all the fluid from the small compartment A is transferred into the large compartment B.

III Rinse the small compartment A twice by pressing the mixed solution back into the small compartment A and then back into the large compartment B.

IV When the small compartment A is empty: shake the large compartment B so that the contents mix completely. The solution is now ready for use and the bag can be hung on the equipment.

V The dialysis or replacement line may be connected to either of the two access ports.

Va If the luer access is used, remove the cap with a twist and pull motion, and connect the male luer lock on the dialysis or replacement line to the female luer receptor on the bag using a push and twist motion. Ensure that the connection is fully seated and tighten. The connector is now open. Verify that the fluid is flowing freely.

When the dialysis or replacement line is disconnected from the luer connector, the connector will close and the flow of the solution will stop. The luer port is a needle-less and swabbable port.

Vb If the injection port is used, first remove the snap-off cap. Then introduce the spike through the rubber septum. Verify that the fluid is flowing freely.

The reconstituted solution is for single use only.

Do not use if container is damaged or if solution is not clear.

Discard any unused solution.

If a peel seal separates the two compartments of the bag and a frangible pin is located in the luer connector the following instructions for use should be followed:

I Immediately before use remove the overwrap from the bag and mix the solutions in the two different compartments. Hold the small compartment with both hands and squeeze it until an opening is created in the peel seal between the two compartments.

II Push with both hands on the large compartment until the peel seal between the two compartments is entirely open.

III Secure complete mixing of the solution by shaking the bag gently. The solution is now ready for use, and can be hung on the equipment.

IV The dialysis or replacement line may be connected to either of the two access ports.

IVa If the luer access is used, remove the cap and connect the male luer lock on the dialysis or replacement line to the female luer receptor on the bag; tighten. Using thumb and fingers, break the coloured frangible pin at its base, and move it back and forth. Do not use a tool. Verify that the pin is completely separated and that the fluid is flowing freely. The pin will remain in the luer port during the treatment.

IVb If the injection port is used, first remove the snap-off cap. Then introduce the spike through the rubber septum. Verify that the fluid is flowing freely.

The reconstituted solution is for single use only. Do not use if container is damaged or if solution is not clear. Discard any unused portion immediately after use.

If a peel seal separates the two compartments of the bag and a valve is located in the luer connector the following instructions for use should be followed:

II Push with both hands on the large compartment until the peel seal between the two compartments is entirely open.

III Secure complete mixing of the solution by shaking the bag gently. The solution is now ready for use, and can be hung on the equipment.

IV The dialysis or replacement line may be connected to either of the two access ports.

IVa If the luer access is used, remove the cap with a twist and pull motion, and connect the male luer lock on the dialysis or replacement line to the female luer receptor on the bag using a push and twist motion. Ensure that the connection is fully seated and tighten. The connector is now open. Verify that the fluid is flowing freely.

When the dialysis or replacement line is disconnected from the luer connector, the connector will close and the flow of the solution will stop. The luer port is a needle-less and swabbable port.

IVb If the injection port is used, first remove the snap-off cap. Then introduce the spike through the rubber septum. Verify that the fluid is flowing freely.

The reconstituted solution is for single use only. Do not use if container is damaged or if solution is not clear. Discard any unused portion immediately after use.

No special requirements for disposal.

7 MARKETING AUTHORISATION HOLDER

Gambro Lundia AB Magistratsvagen 16 SE-226 43 Lund SWEDEN

8. MARKETING AUTHORISATION NUMBER

PL 14983/0012

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

15/10/2014

10 DATE OF REVISION OF THE TEXT

15/10/2014