BICAVERA 2.3% GLUCOSE 1.25 MMOL/L CALCIUM SOLUTION FOR PERITONEAL DIALYSIS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

bicaVera 2.3 % Glucose, 1.25 mmol/l Calcium

Solution for peritoneal dialysis

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

bicaVera 2.3 % Glucose, 1.25 mmol/l Calcium is delivered in a double chamber bag. One chamber contains the alkaline hydrogen carbonate solution, the other chamber contains the acidic glucose-based electrolyte solution. Mixing of both solutions by opening the median seam between the two chambers results in the ready-to-use solution.

BEFORE RECONSTITUTION

1 litre of acidic glucose based electrolyte solution contains:

active substances:

Calcium chloride dihydrate 0.3675 g

Sodium chloride 11.57 g

Magnesium chloride hexahydrate 0.2033 g

Glucose monohydrate 50.0 g

(equivalent to glucose) (45.46 g)

This corresponds to

Ca2+   2.5 mmol/l

Na+   198 mmol/l

Mg2+ 1.0 mmol/l

Cl-    207 mmol/l

1 litre of alkaline hydrogen carbonate solution contains:

active substances:

Sodium hydrogen carbonate 5.88 g

This corresponds to

Na+   70 mmol/l

HCO3– 70 mmol/l

AFTER RECONSTITUTION

1 litre of the ready-to-use solution contains:

active substances:

Calcium chloride dihydrate 0.1838 g

Sodium chloride

5.786 g

Sodium hydrogen carbonate 2.940 g

Magnesium chloride hexahydrate

0.1017 g

Glucose monohydrate 25.0 g

(equivalent to glucose) (22.73 g)

This corresponds to

Ca2+   1.25 mmol/l

Na+   134 mmol/l

Mg2+ 0.5 mmol/l

Cl-     103.5 mmol/l

HCO3– 34 mmol/l

Glucose 126.1 mmol/l

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Solution for peritoneal dialysis

Clear and colourless solution

Theoretical osmolarity: 399 mOsm/l pH – 7.4

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

End-stage (decompensated) chronic renal failure of any origin treated with peritoneal dialysis.

4.2 Posology and method of administration

Posology

bicaVera 2.3 % Glucose, 1.25 mmol/l Calcium is exclusively indicated for the intraperitone­al use.

The mode of therapy, frequency of administration, and dwell time required will be specified by the attending physician.

Continuous ambulatory peritoneal dialysis (CAPD)

Adults:

Unless otherwise advised, patients will receive an infusion of 2000 ml solution per exchange four times a day. After a dwell time between 2 and 10 hours the solution will be drained.

Adjustment of dosage, volume and number of exchanges will be necessary for individual patients.

If dilation pain occurs at the commencement of peritoneal dialysis treatment, the solution volume per exchange should be temporarily reduced to 500–1500 ml.

In large patients, and if residual renal function is lost, an increased volume of dialysis solution will be necessary. In these patients, or patients who tolerate larger volumes, a dose of 2500 ml solution per exchange may be given.

Children:

In children the solution volume per exchange should be prescribed according to age and body surface area (BSA).

For initial prescription, the volume per exchange should be 600–800 ml/m2 BSA with 4 (sometimes 3 or 5) exchanges per day. It can be increased up to 1000–1200 ml/m2 BSA depending on tolerance, age and residual renal function.

Automated peritoneal dialysis (APD)

If a machine (sleep safe cycler) is used for intermittent or continuous cyclic peritoneal dialysis larger volume bags (3000 or 5000 ml) providing more than one solution exchange are used. The cycler performs the solution exchanges according to the medical prescription stored in the sleep safe cycler.

Adults:

Typically patients spend 8–10 hours a night cycling. Dwell volumes range from 1500 to 3000 ml and the number of cycles usually varies from 3 to 10 per night. The amount of fluid used is typically between 10 and 18 l but can range from 6 to 30 l. The cycler therapy at night is usually combined with 1 or 2 exchanges during the daytime.

Children:

The volume per exchange should be 800–1000 ml/m2 BSA with 5–10 exchanges overnight. It can be increased up to 1400 ml/m2 BSA depending on tolerance, age and residual renal function.

There are no special dosage recommendations for elderly patients.

Depending on the required osmotic pressure, bicaVera 2.3 % Glucose, 1.25 mmol/l Calcium can be used sequentially with other peritoneal dialysis solutions with lower or higher glucose content (i.e. with lower or higher osmolarity).

Peritoneal dialysis solutions with a high glucose concentration (2.3 % or 4.25 %) are used when the body weight is above the desired dry weight. The withdrawal of fluid from the body increases in relation to the glucose concentration of the peritoneal dialysis solution. These solutions should be used cautiously to protect the peritoneal membrane and to prevent dehydration and in order to keep the glucose burden as low as possible.

bicaVera 2.3 % Glucose, 1.25 mmol/l Calcium contains 22.73 g glucose in 1000 ml solution. According to the dosage instruction up to 30 g glucose are supplied to the body with each bag.

Peritoneal dialysis is a long-term therapy involving repeated administrations of single solutions.

Method and duration of administration

Patients should proficient at performing peritoneal dialysis before performing it at home. The training should be performed by qualified personnel. The attending physician must ensure that the patient masters the handling techniques sufficiently before the patient performs peritoneal dialysis at home. In case of any problems or uncertainty the attending physician should be contacted.

Dialysis using the prescribed doses should be performed daily.

Peritoneal dialysis should be continued for as long as renal function substitution therapy is required.

For the step-by-step instruction for use please be referred to section 6.6.

Continuous ambulatory peritoneal dialysis (CAPD)

The solution bag is first warmed up to body temperature.

The heating will be performed with a heating plate. The time for heating is about 120 minutes for a 2000 ml bag at a temperature of 22° C. Details can be read in the instruction manual of the heating plate. A microwave oven must not be used due to the risk of local overheating.

Depending on physician's in­structions, the dose should dwell in the peritoneal cavity for 2 to 10 hours (equilibrium time), and then be drained.

Automated peritoneal dialysis (APD)

The connectors of the prescribed sleep safe solution bags are inserted in the free sleep safe tray ports and then automatically connected to the sleep safe tubing set by the cycler. The cycler checks the bar codes of the solution bags and gives an alarm when the bags do not comply with the prescription stored in the cycler. After this check the tubing set can be connected to the patient’s catheter extension and the treatment be started. The sleep safe solution is automatically warmed up to body temperature by the sleep safe cycler during the inflow into the abdominal cavity. Dwell times and selection of glucose concentrations are carried out according to the medical prescription stored in the cycler (for more details please refer to the operating instructions of the sleep safe cycler).

4.3 Contraindications

For this specific peritoneal dialysis solution

bicaVera 2.3 % Glucose, 1.25 mmol/l Calcium must not be used in patients with severe hypokalaemia, severe hypocalcaemia, hypovolaemia and hypotension.

This peritoneal dialysis solution must not be used for intravenous infusion.

For peritoneal dialysis in general

Peritoneal dialysis should not be commenced in case of

– recent abdominal surgery or injury, a history of abdominal operations with fibrous adhesions, severe abdominal burns, bowel perforation,

– extensive inflammatory conditions of the abdominal skin (dermatitis),

– inflammatory bowel diseases (Crohn's disease, ulcerative colitis, diverticulitis),

– localized peritonitis,

– internal or external abdominal fistula,

– umbilical, inguinal or other abdominal hernia,

– intra-abdominal tumours,

– ileus,

– pulmonary disease (especially pneumonia),

– sepsis,

– extreme hyperlipidaemia,

– in rare cases of uraemia, which cannot be managed by peritoneal dialysis,

– cachexia and severe weight loss, particularly in cases in which the ingestion of adequate protein is not guaranteed,

– patients who are physically or mentally incapable of performing peritoneal dialysis as instructed by the physician.

If any of the above mentioned disorders develops during the peritoneal dialysis treatment, the attending physician has to decide on how to proceed.

4.4 Special warnings and precautions for use

bicaVera 2.3 % Glucose, 1.25 mmol/l Calcium may only be administered after careful benefit-risk assessment in:

– patients with loss of electrolytes due to vomiting and/or diarrhoea.

– patients with hypocalcaemia: It may be necessary to use a peritoneal dialysis solution with a higher calcium concentration either temporarily or permanently, in case an adequate enteral supply of calcium, by calcium-containing phosphate binders and/or vitamin D, is not possible.

– patients with hyperparathyro­idism: The administration of calcium-containing phosphate binders and/or vitamin D may be considered to ensure adequate enteral calcium supply.

– patients receiving digitalis therapy: Regular monitoring of the serum potassium level is mandatory. Severe hypokalaemia may necessitate the use of a potassium-containing dialysis solution besides dietary counselling.

– patients with large polycystic kidneys.

The natural metabolic acidosis due to renal failure might not be totally compensated by the 34 mmol/l bicarbonate level of the final solution. Acidosis might be associated with undesirable effects e.g. malnutrition.

A loss of proteins, amino acids, and water-soluble vitamins occurs during peritoneal dialysis. To avoid deficiencies an adequate diet or supplementation should be ensured.

The transport characteristics of the peritoneal membrane may change during long-term peritoneal dialysis primarily indicated by a loss of ultrafiltration. In severe cases peritoneal dialysis must be stopped and haemodialysis commenced.

The monitoring of the following parameters is recommended:

– body weight for the early recognition of over- and dehydration,

– serum sodium, potassium, calcium, magnesium, phosphate, acid base status and blood proteins

– serum creatinine and urea,

– parathormone and other indicators of bone metabolism,

– blood sugar,

– residual renal function in order to adapt the peritoneal dialysis

Encapsulating peritoneal sclerosis is considered to be a known, rare complication of peritoneal dialysis therapy which can infrequently lead to fatal outcome.

Elderly patients

The increased incidence of hernia should be considered in elderly patients prior to the start of peritoneal dialysis.

4.5 Interaction with other medicinal products and other forms of interaction

The use of this peritoneal dialysis solution can lead to a loss of efficacy of other medicinal products if these are dialysable through the peritoneal membrane. A dose adjustment might become necessary.

A distinct reduction of the serum potassium level can increase the frequency of digitalis-associated adverse reactions. Potassium levels must be monitored particularly closely during concurrent digitalis therapy.

Special attention and monitoring is required in the case of secondary hyperparathyro­idism. The therapy with calcium-containing phosphate binders and/or vitamin D may be required.

The use of diuretic agents may help maintain residual diuresis, but may also result in water and electrolyte imbalances.

In diabetic patients the daily dose of blood sugar reducing medication must be adjusted to the increased glucose load.

4.6 Fertility, pregnancy and lactation

Fertility

No data available.

Pregnancy

There are no clinical data available from use of bicaVera solutions in pregnant women. Animal studies are insufficient with respect to reproductive and developmental toxicity (see section 5.3). bicaVera solution should only be used during pregnancy when the benefit to the mother clearly outweighs the potential risks to the fetus (see section 4.4).

Lactation

It is not known whether bicaVera solution ingredients are excreted in human milk.

bicaVera solution should only be used in lactating women, when the benefit to the mother clearly outweighs the potential risks to the infant.

4.7 Effects on ability to drive and use machines

bicaVera has no or negligible influence on the ability to drive and to use machines.

4.8 Undesirable effects

bicaVera 2.3 % Glucose, 1.25 mmol/l Calcium is an electrolyte solution which composition is similar to blood.

In addition the physiological buffer bicarbonate is used.

Possible adverse reactions may result from the peritoneal dialysis itself or may be induced by the peritoneal dialysis solution.

The adverse drug reactions are ranked under the headings of reporting frequency, using the following convention:

Potential adverse reactions of the peritoneal dialysis solution:

Potential adverse reactions of the treatment mode

Peritonitis

is indicated by a cloudy effluent. Later abdominal pain, fever, and general malaise may develop or, in very rare cases, sepsis. The patient should seek medical advice immediately. The bag with the cloudy effluent should be closed with a sterile cap and assessed for microbiological contamination and white blood cell count.

Skin exit site and tunnel infections

are indicated by redness, oedema, exudations, crusts and pain at the catheter exit site. In case of skin exit site and tunnel infections the attending physician should be consulted as soon as possible.

Disturbances in hydration

is indicated by a rapid decrease (dehydration) or increase (overhydration) in body weight.

Severe dehydration might occur when using solutions of higher glucose concentration.

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 at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Any excess of dialysis solution infused in the peritoneal cavity can easily be drained in the drainage bag. In case of too frequent exchanges dehydration and/or electrolyte disturbances might result which necessitate immediate medical attention.

If one or more of the daily exchanges are missed or a too small solution volume has been administered, overhydration and electrolyte disturbances may develop.

Interruption or discontinuation of treatment may result in life-threatening overhydration and uraemia.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Peritoneal dialytics, hypertonic solutions

ATC code:   B05D B

The electrolyte profile of the solution is basically the same as that of physiological serum. It has been adapted for use in uraemic patients, to enable renal replacement therapy by means of intraperitoneal substance and fluid exchange. Substances which are normally eliminated with the urine, such as urea, creatinine, and water, are removed from the body into the dialysis solution. It should be borne in mind that therapeutic substances may also be eliminated during dialysis, and that a dose adjustment may be necessary.

Individual parameters (patient size and body weight, laboratory parameters, residual renal function, ultrafiltration, required dialysis dose) must be considered to determine the adequate dose and the combination of solutions with differing osmolarity (glucose concentration), and sodium, and calcium concentrations. The efficacy of therapy should be regularly monitored on the basis of these parameters.

The calcium concentration of this dialysis solution is 1.25 mmol/l, which has been shown to reduce the risk of hypercalcaemia during concomitant treatment with calcium containing phosphate binders and/or vitamin D.

bicaVera 2.3 % Glucose, 1.25 mmol/l Calcium contains bicarbonate – the physiological buffer – instead of lactate or acetate.

5.2 Pharmacokinetic properties

No animal studies have been performed with the intraperitoneal application of bicarbonate-containing bicaVera solutions. Clinical studies in patients on bicaVera have shown that dialysate bicarbonate equilibrates with blood bicarbonate within a two-hour dwell time.

5.3 Preclinical safety data

6   PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Hydrochloric acid

Sodium hydroxide

Carbon dioxide

Water for injections

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3 Shelf life

Shelf life within the container: 2 years

Shelf life of the ready-to-use solution prepared as described in section 6.6 and without any additional drugs: 24 hours

6.4 Special precautions for storage

bicaVera stay safe/sleep safe: Do not store below 4°C.

bicaVera sleep safe combo: Store at 5°C – 30°C.

6.5 Nature and contents of container

Double-chamber bag:

One chamber contains the alkaline hydrogen carbonate solution; the other chamber contains the acidic glucose-based electrolyte solution. Mixing of both solutions (ratio 1:1) by opening the median seam between the two chambers results in the ready-to-use solution.

stay safe:

The stay safe system is provided as a double bag system consisting of a doublechamber solution bag and a drainage bag, both with injection units, a transfer tubing system and a system connector. All components are based on polypropylene. The bags and tubings also contain synthetic elastomers. The solution bag is laminated in addition by polyester. The stay safe system is wrapped up in an outer bag made of polyolefins.

sleep safe:

The sleep safe system is provided as a single bag system consisting of a doublechamber solution bag with an injection unit, a transfer tubing system and a bag connector. All components are based on polypropylene. The bags and tubings also contain synthetic elastomers. Further materials of the solution bag are polyester and polyamide. The sleep safe system is wrapped up in an outer bag made of polyolefines.

sleep safe combo:

The sleep safe combo system is bicaVera sleep safe additionally provided with a disinfection cap and a sleep safe Set Plus for the application to the patient.

Pack sizes:

stay safe:

4 bags of 2000 ml

4 bags of 2500 ml

sleep safe:

4 bags of 3000 ml

2 bags of 5000 ml

sleep safe combo:

2 bags of 5000 ml + disinfection cap + sleep safe Set Plus

Not all pack sizes may be marketed.

6.6

Disposal

No special requirements for disposal.

Handling

Plastic containers may occasionally be damaged during transport or storage. This can result in a contamination with growth of microorganisms in the dialysis solution. Thus all containers should be carefully inspected for damage prior to connection of the bag and prior to use of the peritoneal dialysis solution. Any damage, even minor, to connectors, at the closure, container welds and corners must be noted because of possible contamination.

Damaged bags or bags with cloudy content should never be used!

Only use the peritoneal dialysis solution if container and seal are undamaged. In case of doubt the attending physician should decide on the use of the solution.

The overwrap should only be removed before administration.

Do not use before the two solutions have been mixed.

Aseptic conditions must be maintained during dialysate exchange in order to reduce the risk of infection.

Instruction for use of the stay safe system:

The solution bag is first warmed to body temperature. This should be done by using an appropriate bag warmer. The heating time for a 2000 ml bag with a starting temperature of 22 °C is approximately 120 min. More detailed information can be obtained from the operating instructions of the bag warmer. A microwave oven must not be used to warm the solution due to the risk of local overheating. After warming the solution you can start with the exchange of the bags.

1. Preparation of the solution

» Check the warmed solution bag (label, expiry date, clearness of the solution, bag and overwrap not damaged, peel seams intact). » Place the bag on a solid surface. » Open the overwrap of the bag and the packaging of the disinfection cap. » Wash your hands with an antimicrobial washing lotion. » Roll up the bag, which is lying on the overwrap, from one of the side edges until the middle seam opens. The solutions in the two chambers are mixed automatically. » Now roll up the bag from the upper edge until the peel seam of the lower triangle is completely open. » Check that all peel seams are completely open. » Check that the solution is clear and that the bag is not leaking.

2. Preparation of the bag exchange

» Hang the solution bag in the upper hole of the infusion pole, unroll the tubing line of the solution bag, and place the DISC into the organizer. After unrolling the tubing line to the drainage bag, hang the drainage bag in the lower hole of the infusion pole. » Place catheter connector into one of the two inserts of the organizer. » Place the new disinfection cap into the other free insert. » Disinfect your hands and remove the protection cap of the DISC. » Connect catheter connector to the DISC.

3. Outflow

» Open the clamp on the extension. The outflow starts. » Position (

4. Flush

» After completion of outflow flush fresh solution into the drainage bag (approx.

5 seconds). » Position

5. Inflow

» Start inflow by turning the control switch to » Position

6. Safety step

» Close the catheter extension by introducing the PIN into the catheter connector. » Position.

» Close the clamp on catheter extension.

7. Disconnection

» Remove protection cap from the new disinfection cap and screw it onto the old one. » Screw the catheter connector off the DISC and screw the catheter connector to the new disinfection cap.

8. Closure of the DISC

» Close the DISC with the open end of the used disinfection cap, which has remained in the right hole of the organizer.

9. Check the drained dialysate for clarity and weight and if the effluent is clear discard it.

Instruction for use of the sleep safe system:

During automated peritoneal dialysis (APD) the solution is warmed automatically by the cycler.

3000 ml sleep safe system

1. Preparation of the solution: see stay safe system

2. Unroll tubing of bag.

3. Remove the protection cap.

4. Insert bag connector in free tray port of the sleep safe cycler.

5. The bag is now ready for use with the sleep safe set.

5000 ml sleep safe system

1. Preparation of the solution

» Check the solution bag (label, expiry date, clearness of the solution, bag, and overwrap not damaged, peel seams intact). » Place the bag on a solid surface. » Open the overwrap of the bag. » Wash your hands with an antimicrobial washing lotion. » Unfold middle peel seam and bag connector. » Roll up the bag, which is lying on the overwrap, from the diagonal end towards the bag connector. The middle peel seam will open. » Continue until the peel seam of the small chamber opens as well. » Check that all peel seams are completely open. » Check that the solution is clear and that the bag is not leaking.

2 – 5.: see 3000 ml sleep safe system

Medicinal products must be added under aseptic conditions only when medically prescribed.

Because of the risk of incompatibility between the dialysis solution and the added medicinal products only the following medicinal products may be added up to the mentioned concentration if indicated by the attending physician: heparin 1000 I.U./l, insulin 20 I.U./l, vancomycin 1000 mg/l, teicoplanin 400 mg/l, cefazolin 500 mg/l, ceftazidime 250 mg/l, gentamycin 8 mg/l. After thorough mixing and checking for the absence of any turbidity the peritoneal dialysis solution must be used immediately (no storage).

7 MARKETING AUTHORISATION HOLDER

Fresenius Medical Care Deutschland GmbH

Else-Kröner-Straße 1 61352 Bad Homburg Germany

8 MARKETING AUTHORISATION NUMBER(S)

PL 13689/0022

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

31/05/2021