Accusol 35

Package Leaflet: Information for the User

ACCUSOL 35, solution for hemofiltration, hemodialysis, and hemodiafiltration

Please read carefully the contents of this leaflet before using the medicine, as it contains

important information for the patient.

• Please keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor. See section 4.

Table of Contents of the Leaflet:

• 1. What Accusol 35 is and what it is used for
• 2. Important information before using Accusol 35
• 3. How to use Accusol 35
• 4. Possible side effects
• 5. How to store Accusol 35
• 6. Contents of the pack and other information

1. What Accusol 35 is and what it is used for

Accusol 35 is a solution for hemofiltration, hemodialysis, and hemodiafiltration.
Accusol 35 is prescribed to patients with acute or chronic renal failure.
It cleans the patient's blood of unnecessary metabolic products; corrects acidity or alkalinity and the concentration of salts in the patient's blood. As a replacement fluid in hemodiafiltration and hemofiltration, it can also be used as a source of salts and water for hydration.
Accusol 35 solutions are supplied in a two-chamber bag (not containing PVC). Both chambers are separated by a long weld (weld between chambers). Before use, both chambers of the Accusol 35 solution must be mixed by opening the long weld (weld between chambers), and then the short 'SafetyMoon' weld near the access port.
Accusol 35 can be used especially in cases of high potassium levels.
Accusol 35 solutions can only be used by a doctor or under their supervision.

2. Important information before using Accusol 35

Before starting treatment, the doctor will ensure that the patient's vein and artery access is correct.
They will also ensure that the patient does not have a high risk of bleeding.
Accusol 35 solutions with different potassium and glucose concentrations are available. The potassium and glucose levels in the patient's blood will be closely monitored to ensure that the most suitable Accusol 35 composition is used.
The doctor will not administer Accusol 35 to the patient:

• if access to the veins and/or arteries is incorrect.
• if there is an increased risk of bleeding.
• if there is a high level of bicarbonate in the blood.
• if the potassium level in the blood is too low, unless potassium supplementation is also administered.
• in a clinical condition where the acidity or alkalinity of the blood may worsen.
• if, due to renal failure, metabolic products cannot be removed from the blood by hemofiltration.

Warnings and Precautions

Accusol 35 can only be used by a doctor or under the supervision of a doctor experienced in hemofiltration, hemodialysis, or hemodiafiltration techniques.

The attending physician:

• will control the acidity, salt concentration, and unnecessary metabolic products in the blood;
• will ensure that these values are correct and closely monitored during treatment;
• will ensure the maintenance of proper fluid balance in the body;
• will carefully check the glucose level in the blood, especially if the patient has diabetes;
• will ensure regular monitoring of potassium levels in the blood;
• will ensure that, immediately before administration, the contents of both chambers have been mixed by opening the long weld (weld between chambers), and then the short 'SafetyMoon' weld near the access port. If unmixed solutions are administered, the bicarbonate concentration in the blood may increase. This can cause side effects such as nausea, drowsiness, headache, irregular heartbeat, and breathing difficulties.

Accusol 35 and Other Medicines

Please tell your doctor about all medicines you are taking or have recently taken, as well as any medicines you plan to take.
Taking Accusol 35 may affect other medicines and interact with them.

• If the patient is taking vitamin D or calcium-containing medicines, the calcium level in the blood may change.
• If the patient is also taking sodium bicarbonate, there is an increased risk of abnormal salt and base levels (alkalosis) in the blood.
• If the patient is taking heart medicines, known as cardiac glycosides, additional potassium administration may be necessary. The attending physician will closely monitor the patient during treatment.

Pregnancy and Breastfeeding

The patient should inform the attending physician if she is pregnant or breastfeeding.
The doctor will assess the benefit-risk balance of using Accusol 35.

3. How to Use Accusol 35

Depending on the treatment method, the doctor will administer Accusol 35 using the dialysis device tubes.

Treatment with hemofiltration, hemodialysis, or hemodiafiltration used in the patient will depend on
the clinical diagnosis, medical examination, laboratory results, and response to treatment.
The doctor will determine the appropriate composition and amount of Accusol 35 solutions according to the patient's clinical condition.

In What Doses and How Often to Use?

The attending physician will determine and adjust the flow rate and volume of the solution to be administered.
The required amount of fluid depends on the method of Accusol 35 administration.
If the patient is an adult or elderly and

• is being treated for chronic renal failure with Accusol 35 as a replacement fluid, they should receive 7 to 35 ml/kg body weight/hour or more;
• is being treated for acute renal failure with Accusol 35 as a replacement fluid, they should receive 20 to 35 ml/kg body weight/hour or more;
• is being treated for chronic or acute renal failure with Accusol 35 as a dialysis solution, the amount of solution will depend on the frequency and duration of treatment.

4. Possible Side Effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Possible rare side effects (occurring in less than 1 in 1000 patients) of Accusol 35 may include:

• low glucose level (hypoglycemia).

Other side effects may occur. Not all of them have to be a result of the solution or treatment. Potential side effects that may occur include:

• decrease (hypovolemia) or increase (hypervolemia) in body fluid volume;
• decrease (hypotension) or increase (hypertension) in blood pressure;
• very low phosphate level in the blood (hypophosphatemia);
• disturbances in base levels in the blood (alkalosis);
• feeling of nausea;
• vomiting;
• muscle cramps;
• bleeding;
• infection;
• shortness of breath, irregular breathing (caused by air bubbles entering the blood);
• disturbances in the levels of various salts in the blood (e.g., disturbances related to sodium, potassium, calcium in the blood);
• increased tendency to form blood clots.

Reporting Side Effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor. Side effects can be reported directly to
the Department of Medicinal Product Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
PL-02 222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to Store Accusol 35

Store the medicine out of sight and reach of children.
Do not store in the refrigerator or freeze.
Do not use this medicine after the expiry date stated on the label and carton after the words 'Expiry Date'. The expiry date refers to the last day of the month.
The doctor will not use Accusol 35 if the solution is not clear or the container is damaged.

6. Contents of the Pack and Other Information

Medicinal Product Name

Accusol 35, solution for hemofiltration, hemodialysis, and hemodiafiltration
The composition of Accusol 35 solution:

5000 ml of the final solution is obtained by mixing 3750 ml of solution "A" with 1250 ml of solution "B".

Ion Composition of the Final Solution:

Other ingredients are: water for injection, hydrochloric acid, sodium hydroxide, and disodium phosphate dihydrate.

What Accusol 35 Looks Like and Contents of the Pack

Accusol 35 is supplied in a cardboard box containing two 5-liter two-chamber bags not containing PVC.
Each bag is packaged in an outer protective bag.
The solution in the bag is clear and colorless.

Marketing Authorization Holder:

Nikkiso Belgium
Industriepark 6
3300 Tienen
Belgium
Phone (Belgium): +32 (0)16 781770
Phone (Poland): +48 (00)800 1211465

Manufacturers:

Serumwerk Bernburg AG
Hallesche Landstrasse 105b
06406 Bernburg
Germany

Date of Last Revision of the Leaflet: 19.09.2021

ACCUSOL is a trademark of Nikkiso Co., Ltd .
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The Following Information is Intended for Healthcare Professionals Only

LEAFLET FOR HEALTHCARE PROFESSIONALS

Accusol 35, solution for hemofiltration, hemodialysis, and hemodiafiltration

1. MEDICINAL PRODUCT NAME

Accusol 35,
solution for hemofiltration, hemodialysis, and hemodiafiltration

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Corresponding to the following ionic composition:

5000 ml of the final solution is obtained by mixing 3750 ml of solution "A" with 1250 ml of solution "B".
The pH of the final solution is between 7.0-7.5.
The number "35" in the name indicates the buffer concentration in the solution (bicarbonate = 35 mmol/l).

3. PHARMACEUTICAL FORM

Solution for hemofiltration, hemodialysis, and hemodiafiltration.
Accusol 35 is a sterile, clear, and colorless solution.

4. CLINICAL PARTICULARS

4.1. Therapeutic Indications

Accusol 35 is indicated for the treatment of acute and chronic renal failure, as a replacement solution in hemofiltration and hemodiafiltration, and as a dialysis solution in hemodialysis and hemodiafiltration.
Accusol 35 is intended for use primarily in patients with hyperkalemia.

4.2. Dosage and Administration

For hemofiltration, hemodialysis, and hemodiafiltration.
Accusol 35 as a replacement solution
The volume of the replacement solution administered to adult patients is determined by the ultrafiltration coefficient and is individualized to ensure adequate fluid and electrolyte balance.
Adults:

• chronic renal failure: 7 to 35 ml/kg body weight/hour or more,
• acute renal failure: 20 to 35 ml/kg body weight/hour or more, Elderly: as for adults.

The above volume recommendations may be adjusted by the attending physician according to the patient's clinical condition.
Accusol 35 can be administered into the extracorporeal circuit before or after dilution of the fluid, as recommended by the doctor.

Accusol 35 as a dialysis solution
The type and volume of the prescribed dialysis solution depend on the treatment method, its frequency, and duration; the choice is made by the doctor according to the patient's clinical condition.
Administration:
Hemodialysis: through the dialyzer's dialysate compartment.
Hemofiltration: through the arterial or venous blood line.
After removing the outer protective bag, immediately open the long weld (weld between chambers) to mix both solutions, and then open the short 'SafetyMoon' weld (weld near the access port) to allow administration of the mixed solution. The bag should be connected to the patient's line and the access port opened. The solution should be used within 24 hours of mixing.

4.3. Contraindications

Contraindications related to the solution:

• hypokalemia, unless potassium supplementation is also administered;
• metabolic alkalosis.

Contraindications related to hemofiltration, hemodialysis, or hemodiafiltration, related to the technical procedure itself:

• renal failure accompanied by severe catabolism in patients with uremic symptoms that do not respond to hemofiltration;
• inadequate blood flow at the vascular access site;
• if there is a high risk of bleeding due to anticoagulant therapy.

4.4. Special Warnings and Precautions for Use

• Accusol 35 can only be used by or under the supervision of a doctor experienced in hemofiltration, hemodialysis, or hemodiafiltration techniques. Rarely, precipitation may occur after a few hours of treatment. In such a case, the Accusol 35 bag and the line set should be replaced immediately, and the patient should be closely monitored.
• Fluid balance should be carefully controlled.
• Acid-base balance parameters should be carefully controlled.
• Similarly, electrolyte balance parameters (chloride, phosphate, calcium, magnesium, and sodium levels) should be regularly monitored to detect any possible disturbances.
• Accusol 35 does not contain potassium. Before and during treatment, potassium levels in the blood should be regularly monitored. In case of hypokalemia or a gradual decrease in serum potassium levels, potassium supplementation should be initiated and/or a replacement fluid containing a higher potassium concentration should be used. In case of hyperkalemia, consideration should be given to increasing the filtration coefficient and implementing appropriate measures in an intensive care setting.
• Accusol 35 does not contain glucose. Close monitoring of blood glucose levels is necessary, especially in diabetic patients.
• In case the long weld (weld between chambers) is not opened (i.e., only the short 'SafetyMoon' weld near the access port is opened) and the solution from the small chamber "B" is administered, alkalosis may occur. The most common subjective and objective clinical symptoms of alkalosis include: nausea, coma, headache, arrhythmia, respiratory failure.

4.5. Interactions with Other Medicinal Products and Other Forms of Interaction

When prescribing Accusol 35, possible interactions between this treatment and other ongoing treatments should be considered.

• The blood concentration of other medicinal products may change during hemodialysis, hemofiltration, and hemodiafiltration.
• In patients taking cardiac glycosides, serum potassium levels should be closely monitored due to the increased risk of arrhythmia due to hypokalemia.
• The use of vitamin D and calcium-containing medicines may increase the risk of hypercalcemia (e.g., the use of calcium carbonate as a potassium-chelating agent).
• Additional sodium bicarbonate supplementation may increase the risk of metabolic alkalosis.

4.6. Fertility, Pregnancy, and Lactation

There are no clinical or preclinical data on the use of Accusol 35 during pregnancy and lactation. Accusol 35 can be used in pregnant and breastfeeding women only if necessary.

4.7. Ability to Drive and Use Machines

Not applicable.

4.8. Undesirable Effects

The following undesirable effects come from reports of adverse events that occurred during clinical trials (see point (1) below) and were considered by the investigator to be related to Accusol, as well as from literature data (see point (2) below).
Frequency of occurrence was determined using the following criteria: very common (>1/10), common (> 1/100 to <1>1/1,000 to <1>1/10,000 to <1>

• 1) Clinical Trials

• 2) Literature Data

The following undesirable effects reflect the types of undesirable effects that may occur during the use of hemofiltration and hemodialysis solutions.

• Possible undesirable effects related to treatment may include nausea, vomiting, muscle cramps, hypotension, bleeding, clotting, infection, and air embolism.
• Possible undesirable effects related to the product may include metabolic alkalosis, electrolyte disturbances, and/or fluid balance disturbances: hypophosphatemia, hypoglycemia, hypovolemia, hypervolemia, hypotension, or hypertension.

Reporting Suspected Adverse Reactions
After authorization of the medicinal product, it is important to report any suspected adverse reactions. Healthcare professionals are asked to report any suspected adverse reactions via
the Department of Medicinal Product Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
PL-02 222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl

4.9. Overdose

Overdose should not occur if fluid and electrolyte balance is regularly monitored as recommended in section 4.4. Overdose may lead to hypervolemia and electrolyte disturbances. These symptoms can be corrected by adjusting the ultrafiltration coefficient and the volume of the administered solution.
Electrolyte balance disturbances should be corrected according to their type.

5. PHARMACEUTICAL PARTICULARS

5.1. Incompatibilities

This medicinal product must not be mixed with other medicinal products, except for those mentioned in section 5.5.

5.2. Shelf-Life

Shelf-life
24 months if the product is stored in the outer protective bag.
Shelf-life after mixing
After removal from the outer protective bag and mixing, Accusol 35 should be used within 24 hours.

5.3. Special Precautions for Storage

Do not store in the refrigerator or freeze.

5.4. Nature and Contents of Container

Accusol 35 is stored in a two-chamber bag not containing PVC, made of a multi-layered film of polypropylene, polyamide, and a mixture of polypropylene, SEBS, and polyethylene (Clear-Flex). The two chambers are separated by a long weld (weld between chambers).
The large chamber "A" has a port for adding drugs, while the small chamber "B" has an access port for connecting to the appropriate administration set.
The two-chamber bag is supplied in an outer transparent protective bag.
The volume of the container after mixing is 5000 ml (3750 ml in the large chamber and 1250 ml in the small chamber).
Accusol 35 is available in boxes containing 2 packs of 5000 ml.

5.5. Special Precautions for Disposal and Preparation of the Medicinal Product for Administration

• Check if the product is damaged. Do not use if one of the bag's welds has been prematurely opened. If damaged, the container should be discarded.
• Do not administer if the solution is not clear.
• During the entire procedure, aseptic principles should be maintained.
• Concomitantly administered drugs can be added to the solution through the drug addition port in the large chamber. Before mixing, the compatibility of the solution with the added drugs should be checked. After adding a drug, the long weld (weld between chambers of the bag) should be opened immediately. After adding any drug, the product should be used immediately.
• After removing the outer protective bag, immediately tear the long weld (weld between chambers) to mix both solutions. Ensure that the long weld (weld between chambers) is fully opened and both solutions are completely mixed. Then, open the short 'SafetyMoon' weld (weld near the access port) to allow administration of the mixed solution. The bag should be connected to the patient's line and the access port opened. The solution should be used within 24 hours of mixing.
• Any unused solution should be discarded.
• For single use only. Accusol 35 should only be used with appropriate equipment that allows control of the treatment process.

6. MARKETING AUTHORIZATION HOLDER WITH MARKETING AUTHORIZATION

Nikkiso Belgium
Industriepark 6
3300 Tienen
Belgium
Phone (Belgium): +32 (0)16 781770
Phone (Poland): +48 (00)800 1211465

7. MARKETING AUTHORIZATION NUMBER

12260