Prismasol 2

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PRISMASOL 2

Composition:

Before mixing:

Electrolyte solution (small compartment A):

Active substances: calcium chloride dihydrate, magnesium chloride hexahydrate, anhydrous glucose, (S)-lactic acid;

1000 ml of electrolyte solution contain: calcium chloride dihydrate – 5.145 g, magnesium chloride hexahydrate – 2.033 g, anhydrous glucose – 22.0 g, (S)-lactic acid – 5.4 g;

Excipient: water for injections.

Buffer solution (large compartment B):

Active substances: sodium chloride, potassium chloride, sodium bicarbonate;

1000 ml of buffer solution contain: sodium chloride – 6.45 g, potassium chloride – 0.157 g, sodium bicarbonate – 3.09 g;

Excipients: carbon dioxide, water for injections.

After mixing:

The solution from compartment A (250 ml) and the solution from compartment B (4750 ml) are mixed to obtain a mixed solution (5000 ml).

Ion composition after mixing: 1000 ml of mixed solution contain:

Theoretical osmolarity: 297 mOsm/L;

pH of the mixed solution: 7.0 – 8.5.

Pharmaceutical form. Solution for hemofiltration and hemodialysis.

Main physico-chemical properties: the solution should be clear and not more intense than Y7.

Pharmacotherapeutic group.

Plasma substitutes and perfusion solutions. Agents for hemodialysis and hemofiltration.

ATC code B05ZB.

Pharmacological properties.

Pharmacodynamics.

Prismsol 2, a solution for hemofiltration and hemodialysis, is pharmacologically inactive. It contains sodium, calcium, magnesium, potassium, chloride ions, and glucose at concentrations corresponding to physiological plasma concentrations. This solution is used to replace water and electrolytes lost during hemofiltration and hemodiafiltration. It also serves as a replacement fluid during prolonged hemodiafiltration or prolonged hemodialysis.

Bicarbonates are used as an alkalizing buffer.

Pharmacokinetics.

Not applicable.

The active ingredients of the drug are pharmacologically inactive and present in concentrations similar to the physiological composition of blood plasma.

Clinical characteristics.

Indications.

• Treatment of renal failure – as a replacement solution in hemofiltration and hemodiafiltration, and as a dialysis solution in prolonged hemodialysis and prolonged hemodiafiltration;
• drug intoxications with substances that are filtered and dialyzed;
• hyperkalemia.

Contraindications.

Hypersensitivity to the active substances or to any of the excipients. Contraindications for the use of the solution:

• hypokalemia;
• metabolic alkalosis.

Contraindications for hemofiltration/hemodialysis procedures:

• severe renal failure associated with increased hypercatabolism, when uremic symptoms cannot be corrected by hemofiltration;
• low blood pressure;
• systemic coagulation disorders (high risk of hemorrhage).

Interaction with other medicinal products and other forms of interaction.

During therapy, the blood concentration of substances that are filtered and dialyzed may decrease. If necessary, appropriate replacement therapy should be administered to achieve the desired blood concentration of drugs removed during treatment. Interactions with other medicinal products can be avoided by precise dosing of hemofiltration and hemodialysis solutions and careful monitoring. However, the following interactions are possible:

• in hypokalemia, the risk of digoxin-induced cardiac arrhythmia is increased;
• vitamin D and its analogs, as well as calcium-containing medicinal products (e.g., calcium chloride or calcium gluconate used to maintain calcium homeostasis in patients undergoing continuous renal replacement therapy (CRRT) who receive citrate anticoagulation, and calcium carbonate used as a phosphate binder), may increase the risk of hypercalcemia;
• additional administration of sodium bicarbonate (or another buffer source) contained in fluids for prolonged renal replacement therapy or other fluids administered during treatment may increase the risk of metabolic alkalosis;
• when citrate is used as an anticoagulant, it contributes to the total buffer load and may reduce plasma calcium levels.

Special precautions for use

This solution should be administered either by a physician experienced in the treatment of renal failure using haemofiltration, haemodiafiltration, and prolonged haemodialysis methods, or under his/her direct supervision.

Warning

To obtain the ready-to-use solution suitable for haemofiltration (haemodiafiltration, prolonged haemodialysis), the electrolyte solution must be mixed with the buffer solution immediately before administration.

The medicinal product should only be used when appropriate equipment for extracorporeal procedures is available.

This solution contains potassium. Serum potassium concentration should be monitored before and during haemofiltration and/or haemodialysis. Depending on the serum potassium concentration prior to treatment, hypokalaemia or hyperkalaemia may develop.

If hypokalaemia occurs, potassium supplementation and/or dialysate with a higher potassium concentration may be required.

If hyperkalaemia develops after initiation of treatment, additional sources of potassium affecting its blood concentration should be evaluated. When the solution is used as a replacement fluid, the infusion rate should be reduced and it should be ensured that the desired potassium concentration is achieved. If hyperkalaemia persists, infusion should be stopped immediately.

If hyperkalaemia develops when the solution is used as dialysate, potassium-free dialysate may be required to increase the rate of potassium removal.

Despite the absence of severe hypersensitivity reactions to corn during the use of Prismasol 2, solutions containing glucose derived from hydrolysed corn starch should not be administered to patients with a history of allergy to corn or corn products.

Administration should be stopped immediately if signs of hypersensitivity reactions occur. Appropriate therapeutic measures should be initiated as clinically indicated.

Since the solution contains glucose and lactate, hyperglycaemia may develop, especially in patients with diabetes mellitus. Blood glucose levels should be monitored regularly. If hyperglycaemia develops, administration of a glucose-free replacement solution/dialysate may be required. Other corrective measures may also be necessary to maintain desired glycaemic control.

Prismasol 2 contains bicarbonate and lactate (a precursor of bicarbonate), which may affect the acid-base balance in the patient. If metabolic alkalosis develops or worsens during therapy with this solution, the infusion rate may need to be reduced or infusion discontinued.

Administration of a contaminated solution for haemofiltration and haemodialysis may lead to sepsis, shock, and death.

Special precautions for use

Prismasol 2 may be warmed to 37°C to increase patient comfort during administration. Warming of the solution before use should only be performed with dry heat and only before reconstitution. Solutions should not be heated in water or in a microwave oven. The solution should be visually inspected for the presence of particulate matter and discoloration before administration, if the solution and container permit. Do not use if the solution is cloudy or if the seal between the two compartments of the bag is damaged.

Electrolyte and acid-base balance should be carefully monitored before and during treatment throughout the entire procedure.

Up to 1.2 mmol/L of phosphate may be added to the solution. If potassium phosphate is added, the total potassium concentration should not exceed 4 mEq/L (4 mmol/L). Inorganic phosphate should be added in cases of hypophosphataemia.

The patient's haemodynamic status and fluid balance should be monitored throughout the procedure and adjusted as needed.

Children

There are no specific warnings or precautions when this product is used in children.

Use during pregnancy or breastfeeding

Pregnancy and breastfeeding

There are insufficient data on the use of Prismasol 2 in pregnant women or women who are breastfeeding. Before prescribing Prismasol 2 to pregnant women or breastfeeding mothers, the physician must carefully assess the benefit-risk ratio.

Fertility

Data on the effect on fertility are not available.

Ability to affect reaction speed when driving or operating machinery

No effect.

Method of Administration and Dosage

Dosing

The infusion rate of PrismaSol 2 depends on the patient's serum electrolyte concentrations, acid-base balance, fluid balance, and overall clinical condition. The volume of replacement solution and/or dialysate administered also depends on the desired intensity (dose) of therapy. The solution must be prescribed and administered (including dosage, infusion rate, and total volume) only by a physician experienced in managing critical care (resuscitation) and performing prolonged renal replacement therapy (CRRT).

The flow rate when using the product as a replacement solution during hemofiltration and hemodiafiltration in adults is 500–3000 mL/hour.

The flow rate for dialysis solution (dialysate) during prolonged hemodialysis and prolonged hemodiafiltration in adults is 500–2500 mL/hour.

Typically, the flow rate for adult patients is approximately 2000–2500 mL/hour, corresponding to a daily fluid volume of 48–60 L.

Special Populations

Elderly Patients

Clinical study results and usage experience indicate that administration in elderly patients is not associated with differences in safety or efficacy.

Children

The flow rate when using the product as a replacement solution during hemofiltration and hemodiafiltration, as well as a dialysis solution (dialysate) during prolonged hemodialysis in children (from newborns to adolescents up to 18 years of age), is 1000–2000 mL/hour/1.73 m².

A flow rate of up to 4000 mL/hour/1.73 m² may be required, especially when used in younger children (body weight ≤ 10 kg). The absolute flow rate (mL/hour) in the pediatric population generally should not exceed the maximum flow rate for adults.

Method of Administration

Administer intravenously and for hemodialysis.

When used as a replacement solution, PrismaSol 2 is infused into the bloodstream before the hemofilter (predilution) or after the hemofilter or hemodiafilter (postdilution).

PrismaSol 2 is packaged in a dual-compartment bag: small compartment A containing the electrolyte solution, and large compartment B containing the buffer solution. Immediately before use, the electrolyte solution (small compartment A) is mixed with the buffer solution (large compartment B) by breaking the frangible spike between the compartments.

Strict aseptic technique must be observed. Remove the bag from its outer wrapper only when fully prepared to perform the procedure.

Use only if the outer wrapper and all seals are intact, the frangible spike is not broken, and the solution is clear. To check for leakage, firmly squeeze the bag. If leakage is detected, discard the solution immediately, as sterility can no longer be assured.

Large compartment B has an injection port allowing for the addition of required medications after solution mixing. After checking the solution for possible color change and/or the presence of precipitate, insoluble components, or crystals, the physician, under their own responsibility, determines the compatibility or incompatibility of additional medications with PrismaSol 2 solution. Refer to the instructions for use of any medications intended for addition.

Before adding any drug, ensure that it is water-soluble and stable at the pH level of PrismaSol 2 (the pH of the prepared solution ranges from 7.0 to 8.5). Added drugs may be incompatible.

Medications are added to the solution as follows: remove any liquid from the injection port, hold the bag upside down, inject the medication through the injection port, and thoroughly mix with the solution. Administration and mixing with other medicinal products must always be performed before connecting the solution bag to the extracorporeal circuit. The solution must be used immediately.

If the two compartments of the bag are separated by a frangible spike and the Luer connector contains a valve, follow these instructions:

1. Immediately before use, remove the bag from the outer wrapper and any other packaging material. Break the frangible spike on the partition separating the compartments. Leave the broken spike remnants inside the bag (see Fig. I).
2. Ensure that all liquid from small compartment A has completely transferred into large compartment B (see Fig. II).
3. Twice, rinse small compartment A by moving the mixed solution into compartment A and returning it to compartment B (see Fig. III).
4. After completely emptying compartment A, thoroughly mix the solution in compartment B to ensure complete homogenization. The solution is now ready for use and may be hung on equipment (see Fig. IV).
5. The dialysate or replacement solution line may be connected to either of the two available inlets.

5a. If using the Luer port, unscrew and remove the cap, then connect by unscrewing and pulling the corresponding (male) Luer lock of the dialysate or replacement solution line to the corresponding (female) Luer connector on the bag. Ensure the connection is fully seated and tighten. The connector is now open. Check that fluid flows freely and without obstruction (see Fig. V.a).

When the dialysate or replacement solution line is disconnected from the Luer connector, the connector will close automatically, and solution flow will stop. The Luer port is a positive-pressure port and does not require a needle.

5b. If using the injection port, first remove the broken cap. The injection port may be disinfected. Then insert the needle through the rubber membrane. Check that fluid flows freely and without obstruction (see Fig. V.b).

The solution should be used immediately after mixing. If delayed, the solution must be used within 24 hours of mixing the electrolyte solution with the buffer solution, including the duration of therapy.

The mixed solution is for single use only.

The product must not be used if the bag is damaged or if the solution is cloudy.

Any unused medicinal product or waste material must be disposed of in accordance with local requirements.

Children.

The medicinal product PrismaSol 2 is administered to children according to the information provided in the section "Method of Administration and Dosage."

Overdose.

Under conditions of proper procedure performance and careful monitoring of fluid, electrolyte, and acid-base balance in patients, overdose of PrismaSol 2 is unlikely.

However, overdose may lead to serious consequences such as congestive heart failure and disturbances in electrolyte or acid-base balance.

Hypervolemia or hypovolemia, if they occur, should be corrected immediately.

If disturbances in electrolyte and acid-base balance are observed (e.g., metabolic alkalosis, hypophosphatemia, hypokalemia, etc.), administration should be stopped immediately. There is no specific antidote for overdose. Risk can be minimized by careful monitoring of electrolyte and acid-base balance and appropriate correction during treatment (see section "Special Precautions for Use").

Adverse Reactions

The adverse effects listed below have been reported during post-marketing use. The adverse reactions are presented by MedDRA system organ classes and preferred terms; frequency is unknown (cannot be estimated from available data).

Metabolism and nutrition disorders – electrolyte imbalance (e.g. hypophosphatemia, hypokalemia), acid-base imbalance (e.g. metabolic alkalosis), fluid imbalance (e.g. fluid retention, dehydration), hyperglycemia.

Cardiac disorders – hypotension.

Gastrointestinal disorders – nausea, vomiting.

Musculoskeletal and connective tissue disorders – muscle cramps.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after registration of the medicinal product is important. This allows continued monitoring of the benefit-risk balance. Healthcare professionals are requested to report any suspected adverse reactions via the national reporting system.

Shelf life

For dual-chamber bags made of polyvinyl chloride – 1 year.

After mixing, the solution is stable for 24 hours.

Storage conditions

Keep out of reach and sight of children. Store at a temperature between 4 °C and 30 °C.

Incompatibilities

Due to lack of scientific data on compatibility, this medicinal product should not be mixed with other medicinal products. After visually inspecting the solution for possible color change and/or presence of precipitate, insoluble complexes, or crystals, the physician may, at his or her own discretion, determine compatibility or incompatibility of additional medications with PrismaSol 2 solution. Reference should be made to the package leaflet of any medicinal product intended for addition.

Before adding any drug, ensure that it is water-soluble and stable at the pH value characteristic of PrismaSol 2 (the pH of the prepared solution ranges from 7.0 to 8.5). Compatible drugs may then be added to the prepared solution. The solution should be used immediately after addition.

Packaging

Inner packaging:

Dual-chamber bag made of polyvinyl chloride with a total volume of 5000 ml (small chamber 250 ml and large chamber 4750 ml, separated by a frangible stem, with a Luer lock connector equipped with a valve).

Outer packaging:

Transparent multilayer film. Two bags per cardboard box.

Prescription category

Prescription only.

Manufacturer

B. BRAUN MEDICAL S.P.A.

Manufacturer's address and location of operations

VIA STELVIO, 94 - 23035 SONDRIO (SO), ITALY.

INSTRUCTIONS FOR USE

for medical use of the medicinal product

PRISMASOL 2

Composition:

Before mixing:

Electrolyte solution (small compartment A):

active substances: calcium chloride dihydrate, magnesium chloride hexahydrate, anhydrous glucose, (S)-lactic acid;

1000 ml of electrolyte solution contain: calcium chloride dihydrate – 5.145 g, magnesium chloride hexahydrate – 2.033 g, anhydrous glucose – 22.0 g, (S)-lactic acid – 5.4 g;

excipient: water for injections.

Buffer solution (large compartment B):

active substances: sodium chloride, potassium chloride, sodium bicarbonate;

1000 ml of buffer solution contain: sodium chloride – 6.45 g, potassium chloride – 0.157 g, sodium bicarbonate – 3.09 g;

excipients: carbon dioxide, water for injections.

After mixing:

Solution from compartment A (250 ml) and solution from compartment B (4750 ml) are mixed to obtain a mixed solution (5000 ml).

Ion composition after mixing: 1000 ml of the mixed solution contain:

Theoretical osmolarity: 297 mOsm/L;

pH of the mixed solution: 7.0 – 8.5.

Pharmaceutical form. Solution for hemofiltration and hemodialysis.

Main physicochemical properties: the solution should be clear and not more intense than Y7.

Pharmacotherapeutic group.

Plasma substitutes and perfusion solutions. Agents for hemodialysis and hemofiltration.

ATC code B05ZB.

Pharmacological properties.

Pharmacodynamics.

Prismasol 2, a solution for hemofiltration and hemodialysis, is pharmacologically inactive. It contains sodium, calcium, magnesium, potassium, chloride ions, and glucose at concentrations corresponding to physiological plasma concentrations. This solution is used to replace water and electrolytes lost during hemofiltration and hemodiafiltration. It also serves as a replacement fluid during prolonged hemodiafiltration or prolonged hemodialysis.

Hydrogencarbonates are used as a buffering alkalizing agent.

Pharmacokinetics.

Not applicable.

The active ingredients of the drug are pharmacologically inactive and are present in concentrations similar to the physiological composition of blood plasma.

Clinical Characteristics.

Indications.

• Treatment of renal failure – as a replacement solution in hemofiltration and hemodiafiltration, as well as a dialysis solution in prolonged hemodialysis and prolonged hemodiafiltration;
• drug intoxications with substances that are filterable and dialyzable;
• hyperkalemia.

Contraindications.

Hypersensitivity to the active substances or to any of the excipients. Contraindications for the use of the solution:

• hypokalemia;
• metabolic alkalosis.

Contraindications for hemofiltration/hemodialysis procedures:

• severe renal failure associated with increased hypercatabolism, when uremic symptoms cannot be corrected by hemofiltration;
• low blood pressure;
• systemic coagulation disorders (high risk of hemorrhage).

Interaction with other medicinal products and other forms of interaction.

During therapy, blood concentrations of substances that are filterable and dialyzable may decrease. If necessary, appropriate replacement therapy should be administered to compensate for losses and achieve the desired blood concentration of drugs removed during treatment. Interactions with other medicinal products can be avoided by accurate dosing of hemofiltration and hemodialysis solutions and careful monitoring. However, the following interactions are possible:

• in hypokalemia, the risk of digitalis-induced cardiac arrhythmia is increased;
• vitamin D and its analogs, as well as calcium-containing medicinal products (e.g., calcium chloride or calcium gluconate used to maintain calcium homeostasis in patients undergoing continuous renal replacement therapy (CRRT) who receive citrate anticoagulation, and calcium carbonate used as a phosphate binder), may increase the risk of hypercalcemia;
• additional administration of sodium bicarbonate (or another buffer source) contained in fluids for continuous renal replacement therapy or other fluids administered during treatment may increase the risk of metabolic alkalosis;
• when citrate is used as an anticoagulant, it contributes to the total buffer load and may reduce plasma calcium levels.

Special precautions for use

This solution must be administered either by a physician experienced in the treatment of renal failure using hemofiltration, hemodiafiltration, and prolonged hemodialysis, or under his/her direct supervision.

Warning

To obtain a ready-to-use solution suitable for hemofiltration (hemodiafiltration, prolonged hemodialysis), the electrolyte solution must be mixed with the buffer solution immediately before administration.

The medicinal product should be used only if appropriate equipment for extracorporeal procedures is available.

This solution contains potassium. Serum potassium concentration should be monitored before and during hemofiltration and/or hemodialysis. Depending on the serum potassium concentration prior to treatment, hypokalemia or hyperkalemia may develop.

If hypokalemia occurs, potassium supplementation and/or dialysate with a higher potassium concentration may be required.

If hyperkalemia develops after initiation of treatment, additional sources of potassium affecting its blood concentration should be evaluated. When the solution is used as a replacement fluid, the infusion rate should be reduced and it should be ensured that the desired potassium concentration is achieved. If hyperkalemia persists, infusion should be stopped immediately.

If hyperkalemia develops when the solution is used as dialysate, potassium-free dialysate may be required to increase the rate of potassium removal.

Despite the absence of severe hypersensitivity reactions to corn associated with the use of Prismasol 2, solutions containing glucose derived from hydrolyzed corn starch should not be administered to patients with a history of allergy to corn or corn products.

Administration should be discontinued immediately if signs of hypersensitivity reactions appear. Appropriate therapeutic measures should be initiated as clinically indicated.

Since the solution contains glucose and lactate, hyperglycemia may occur, especially in patients with diabetes mellitus. Blood glucose levels should be monitored regularly. If hyperglycemia develops, administration of a glucose-free replacement solution/dialysate may be required. Other corrective measures may also be necessary to maintain desired glycemic control.

Prismasol 2 contains bicarbonate and lactate (a precursor of bicarbonate), which may affect the patient's acid-base balance. If metabolic alkalosis develops or worsens during therapy with this solution, the infusion rate may need to be reduced or infusion discontinued.

Use of a contaminated solution for hemofiltration or hemodialysis may result in sepsis, shock, and death.

Special precautions for use

Prismasol 2 may be warmed to 37°C to increase patient comfort during administration. Warming of the solution before use should be performed with dry heat only and prior to reconstitution. Solutions should not be heated in water or in a microwave oven. The solution should be visually inspected for the presence of particulate matter and discoloration before administration, whenever the solution and container permit. Do not use if the solution is cloudy or if the seal between the two compartments of the bag is damaged.

Electrolyte and acid-base balance should be carefully monitored before and during treatment throughout the entire procedure.

Up to 1.2 mmol/L of phosphate may be added to the solution. If potassium phosphate is added, the total potassium concentration should not exceed 4 mmol/L (4 mEq/L). Inorganic phosphate should be added in cases of hypophosphatemia.

The patient's hemodynamic status and fluid balance should be monitored throughout the procedure and adjusted as necessary.

Children

There are no specific warnings or precautions when using this product in children.

Use during pregnancy or breastfeeding

Pregnancy and breastfeeding

There are insufficient data on the use of Prismasol 2 in pregnant or breastfeeding women. Before prescribing Prismasol 2 to pregnant women or mothers who are breastfeeding, the physician must carefully assess the benefit-risk ratio.

Fertility

Data on effects on fertility are lacking.

Ability to affect reaction speed when driving or operating machinery

Has no effect.

Method of Administration and Dosage.

Dosing

The infusion rate of PrismaSol 2 depends on the patient's serum electrolyte concentrations, acid-base balance, fluid balance, and overall clinical condition. The volume of replacement solution and/or dialysate administered also depends on the desired intensity (dose) of therapy. The solution must be prescribed and administered (dose, infusion rate, and total volume) only by a physician experienced in managing critical conditions (resuscitation) and in performing continuous renal replacement therapy (CRRT).

The flow rate when using the drug as a replacement solution in hemofiltration and hemodiafiltration in adults is 500–3000 mL/hour.

The flow rate for dialysate solution during prolonged hemodialysis and prolonged hemodiafiltration in adults is 500–2500 mL/hour.

Typically, the flow rate for adult patients is approximately 2000–2500 mL/hour, corresponding to a daily fluid volume of 48–60 L.

Special Populations

Elderly Patients

Clinical study results and usage experience indicate that use in elderly patients is not associated with differences in safety or efficacy.

Children

The flow rate when using the drug as a replacement solution in hemofiltration and hemodiafiltration, as well as a dialysate solution during prolonged hemodialysis in children (from newborns to adolescents up to 18 years of age), is 1000–2000 mL/hour/1.73 m².

A flow rate of up to 4000 mL/hour/1.73 m² may be required, especially when used in younger children (body weight ≤ 10 kg). The absolute flow rate (mL/hour) in the pediatric population generally should not exceed the maximum rate for adults.

Method of Administration

Administer intravenously and for hemodialysis.

When used as a replacement solution, PrismaSol 2 is administered into the bloodstream before the hemofilter (predilution) or after the hemofilter or hemodiafilter (postdilution).

PrismaSol 2 is packaged in a dual-compartment bag: small compartment A containing the electrolyte solution and large compartment B containing the buffer solution. Immediately before use, the electrolyte solution (small compartment A) must be mixed with the buffer solution (large compartment B) by breaking the frangible spike between the compartments.

Strict aseptic technique must be observed. Remove the bag from its outer wrapper only when fully prepared to perform the procedure.

Use only if the outer wrapper and all seals are intact, the frangible spike is not broken, and the solution is clear. To check for leakage, firmly squeeze the bag. If leakage is detected, discard the solution immediately, as sterility can no longer be assured.

The large compartment B has an injection port to allow addition of necessary medications after mixing the solutions. After checking the solution for possible color change and/or presence of precipitate, insoluble components, or crystals, the physician, under their own responsibility, must determine the compatibility or incompatibility of additional medications with PrismaSol 2 solution. Always refer to the instructions for use of any medications intended for addition.

Before adding any medication, ensure that it is water-soluble and stable at the pH level of PrismaSol 2 (the pH of the prepared solution ranges from 7.0 to 8.5). Added medications may be incompatible.

Medications are added to the solution as follows: remove any liquid from the injection port, hold the bag upside down, inject the medication through the injection port, and thoroughly mix it with the solution. Administration and mixing with other medicinal products must always be performed before connecting the solution bag to the extracorporeal circuit. The solution must be used immediately.

If the compartments of the bag are separated by a frangible spike and the Luer connector also contains a frangible spike, follow these instructions:

1. Remove the bag from its outer wrapper and any other packaging material and remove the insert. Break the frangible spike on the partition separating the compartments. Leave the broken spike remnants inside the bag (see Fig. I).
2. Ensure that all liquid from small compartment A has completely flowed into large compartment B (see Fig. II).
3. Twice, rinse small compartment A by moving the mixed solution into compartment A and returning it to compartment B (see Fig. III).
4. After completely emptying compartment A, thoroughly mix the solution in compartment B to ensure complete homogenization. The solution is now ready for use and can be hung on the equipment (see Fig. IV).
5. The dialysate or replacement solution line can be connected to either of the two available inlets.

5a. If using the Luer port, remove the cap and connect the appropriate (male) Luer lock of the dialysate or replacement solution line to the corresponding (female) Luer connector on the bag, then tighten. Using the thumb and fingers of one hand, break the blue frangible pin at its base and move it backward and outward. Do not use auxiliary tools (instruments, etc.). Check that the pin is completely detached and that fluid flows freely and unimpeded. The pin will remain in the Luer port during the treatment procedure (see Fig. V.a).

5b. If using the injection port, first remove the broken cap. The injection port may be disinfected. Then insert the needle through the rubber membrane. Check that fluid flows freely and without obstruction (see Fig. V.b).

The mixed solution should be used immediately. In case of delay, this solution must be used within 24 hours of adding the electrolyte solution to the buffer solution, including the duration of therapy.

The mixed solution is for single use only.

The drug must not be used if the bag is compromised or if the solution is cloudy.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Children.

The medicinal product PrismaSol 2 is administered to children according to the information provided in the section "Method of Administration and Dosage."

Overdose.

When the procedure is properly conducted and fluid balance, electrolyte balance, and acid-base balance are carefully monitored, overdose of PrismaSol 2 is unlikely.

However, overdose may lead to serious consequences such as congestive heart failure and disturbances in electrolyte or acid-base balance.

Hypervolemia or hypovolemia, if they occur, should be corrected immediately.

If disturbances in electrolyte and acid-base balance (e.g., metabolic alkalosis, hypophosphatemia, hypokalemia, etc.) are observed, administration should be stopped immediately. There is no specific antidote for overdose. The risk can be minimized by careful monitoring of electrolyte and acid-base balance and appropriate correction during treatment (see section "Special Warnings and Precautions for Use").

Side effects

The following adverse effects have been reported during post-marketing use. The side effects are presented by MedDRA system organ classes and preferred terms; frequency is unknown (cannot be estimated from available data).

Metabolism and nutrition disorders – electrolyte imbalance (e.g. hypophosphatemia, hypokalemia), acid-base imbalance (e.g. metabolic alkalosis), fluid balance disturbances (e.g. fluid retention, dehydration), hyperglycemia.

Cardiac disorders – hypotension.

Gastrointestinal disorders – nausea, vomiting.

Musculoskeletal and connective tissue disorders – muscle cramps.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance. Healthcare professionals are encouraged to report suspected adverse reactions through the national reporting system.

Shelf life

For dual-chamber bags made of polyvinyl chloride – 1 year.

After mixing, the solution is stable for 24 hours.

Storage conditions

Keep out of reach of children. Store at a temperature between 4 °C and 30 °C.

Incompatibilities

Due to lack of scientific data on compatibility, this medicinal product should not be mixed with other medicinal products. After checking the solution for possible changes in color and/or the presence of precipitate, insoluble complexes, or crystals, the physician may, at their own discretion, determine compatibility or incompatibility of additional medications with PrismaSol 2 solution. It is necessary to consult the instructions for use of any medicinal products intended for addition.

Before adding any drug, ensure that it is water-soluble and stable at the pH value characteristic of PrismaSol 2 (the pH of the prepared solution ranges from 7.0 to 8.5). Compatible drugs may then be added to the prepared solution. The solution should be used immediately after preparation.

Packaging

Inner packaging

Dual-chamber polyvinyl chloride bag with a total volume of 5000 ml (small chamber 250 ml and large chamber 4750 ml, separated by a frangible plug; the Luer connector also contains a frangible plug).

Outer packaging

Transparent multilayer film. Two bags per cardboard box.

Prescription status

Prescription only.

Manufacturer

B. BRAUN MEDICAL S.P.A.

Manufacturer's address and location of operations

VIA STELVIO, 94 - 23035 SONDRIO (SO), ITALY.

INSTRUCTION

for medical use of the medicinal product

PRISMASOL 2

Composition:

Before mixing:

Electrolyte solution (small compartment A):

Active substances: calcium chloride dihydrate, magnesium chloride hexahydrate, anhydrous glucose, (S)-lactic acid;

1000 ml of electrolyte solution contain: calcium chloride dihydrate – 5.145 g, magnesium chloride hexahydrate – 2.033 g, anhydrous glucose – 22.0 g, (S)-lactic acid – 5.4 g;

Excipient: water for injections.

Buffer solution (large compartment B):

Active substances: sodium chloride, potassium chloride, sodium bicarbonate;

1000 ml of buffer solution contain: sodium chloride – 6.45 g, potassium chloride – 0.157 g, sodium bicarbonate – 3.09 g;

Excipients: carbon dioxide, water for injections.

After mixing:

Solution from compartment A (250 ml) and solution from compartment B (4750 ml) are mixed to obtain a mixed solution (5000 ml).

Ionic composition after mixing: 1000 ml of the mixed solution contain:

Theoretical osmolarity: 297 mOsm/L;

pH of the mixed solution: 7.0 – 8.5.

Pharmaceutical form. Solution for hemofiltration and hemodialysis.

Main physicochemical characteristics: the solution should be clear and not more intense than Y7.

Pharmacotherapeutic group.
Plasma substitutes and perfusion solutions. Agents for hemodialysis and hemofiltration.
ATC code B05Z B.

Pharmacological properties.

Pharmacodynamics.

Prismasol 2, a solution for hemofiltration and hemodialysis, is pharmacologically inactive. It contains sodium, calcium, magnesium, potassium, chloride ions, and glucose at concentrations corresponding to physiological plasma concentrations. This solution is used to replace water and electrolytes lost during hemofiltration and hemodiafiltration. It also serves as a replacement fluid during prolonged hemodiafiltration or prolonged hemodialysis.

Bicarbonates are used as a buffering alkalizing agent.

Pharmacokinetics.

Not applicable.

The active ingredients of the drug are pharmacologically inactive and are present in concentrations similar to the physiological composition of blood plasma.

Clinical characteristics.

Indications.

• Treatment of renal failure – as a replacement solution in hemofiltration and hemodiafiltration, and as a dialysis solution in prolonged hemodialysis and prolonged hemodiafiltration;
• drug intoxications with substances that are filtered and dialyzed;
• hyperkalemia.

Contraindications.

Hypersensitivity to the active substances or to any of the excipients. Contraindications for the use of the solution:

• hypokalemia;
• metabolic alkalosis.

Contraindications for hemofiltration/hemodialysis procedures:

• severe renal failure associated with increased hypercatabolism when uremic symptoms cannot be corrected by hemofiltration;
• low arterial pressure;
• systemic coagulation disorders (high risk of hemorrhage).

Interaction with other medicinal products and other forms of interaction.

During therapy, the blood concentration of substances that are filtered and dialyzed may decrease. If necessary, appropriate replacement therapy should be administered to maintain desired blood concentrations of drugs removed during treatment. Interactions with other medicinal products can be avoided by precise dosing of hemofiltration and hemodialysis solutions and careful monitoring. However, the following interactions are possible:

• in hypokalemia, the risk of digoxin-induced cardiac arrhythmia is increased;
• vitamin D and its analogs, as well as calcium-containing medicinal products (e.g., calcium chloride or calcium gluconate used to maintain calcium homeostasis in patients on continuous renal replacement therapy (CRRT) receiving citrate anticoagulation, and calcium carbonate used as a phosphate binder), may increase the risk of hypercalcemia;
• additional administration of sodium bicarbonate (or another buffer source) contained in fluids for prolonged renal replacement therapy or other fluids administered during treatment may increase the risk of metabolic alkalosis;
• when citrate is used as an anticoagulant, it contributes to the total buffer load and may reduce plasma calcium levels.

Special precautions for use

The use of this solution must be carried out either by a physician experienced in managing renal failure with hemofiltration, hemodiafiltration, and prolonged hemodialysis techniques, or under direct supervision of such a physician.

Warning

To obtain a ready-to-use solution suitable for hemofiltration (hemodiafiltration, prolonged hemodialysis), the electrolyte solution must be mixed with the buffer solution immediately before administration.

The medicinal product should only be used when appropriate equipment for extracorporeal procedures is available.

This solution contains potassium. Serum potassium concentration should be monitored before and during hemofiltration and/or hemodialysis. Depending on the serum potassium concentration prior to treatment, hypokalemia or hyperkalemia may develop.

If hypokalemia occurs, potassium supplementation and/or use of a dialysate with a higher potassium concentration may be required.

If hyperkalemia develops after initiation of treatment, additional sources of potassium affecting blood potassium concentration should be evaluated. When the solution is used as a replacement fluid, the infusion rate should be reduced and it should be ensured that the desired potassium concentration is achieved. If hyperkalemia persists, infusion should be stopped immediately.

If hyperkalemia develops when the solution is used as dialysate, a potassium-free dialysate may be required to increase the rate of potassium removal.

Despite the absence of cases of severe hypersensitivity reactions to corn with the use of Prismasol 2, solutions containing glucose derived from hydrolyzed corn starch should not be administered to patients with a history of allergy to corn and corn products.

Administration should be stopped immediately if signs of hypersensitivity reactions appear. Appropriate therapeutic measures should be initiated as clinically indicated.

Since the solution contains glucose and lactate, hyperglycemia may develop, particularly in patients with diabetes mellitus. Blood glucose levels should be monitored regularly. If hyperglycemia develops, administration of a glucose-free replacement solution/dialysate may be required. Other corrective measures may also be necessary to maintain desired glycemic control.

Prismasol 2 contains bicarbonate and lactate (a precursor of bicarbonate), which may affect the acid-base balance in the patient. If metabolic alkalosis develops or worsens during therapy with this solution, reduction or discontinuation of the infusion rate may be necessary.

Use of a contaminated solution for hemofiltration and hemodialysis may result in sepsis, shock, and death.

Special precautions for use

Prismasol 2 may be warmed to 37°C to increase patient comfort during administration. Warming of the solution before use should be performed with dry heat only and prior to reconstitution. Solutions should not be heated in water or in a microwave oven. The solution should be visually inspected for presence of particulate matter and discoloration before administration, whenever the solution and container permit. Do not use if the solution is cloudy or if the seal between the two compartments of the bag is damaged.

Electrolyte and acid-base balance should be closely monitored before and during treatment throughout the entire procedure.

Up to 1.2 mmol/L of phosphate may be added to the solution. If potassium phosphate is added, the total potassium concentration should not exceed 4 mEq/L (4 mmol/L). Inorganic phosphate should be added in cases of hypophosphatemia.

The patient's hemodynamic status and fluid balance should be monitored throughout the procedure and adjusted as necessary.

Children

There are no specific warnings or precautions when using this product in children.

Use during pregnancy or breastfeeding

Pregnancy and breastfeeding

There are insufficient data on the use of Prismasol 2 in pregnant or breastfeeding women. Before prescribing Prismasol 2 to pregnant women or nursing mothers, the physician must carefully assess the benefit-risk ratio.

Fertility

Data on the effect on fertility are lacking.

Ability to affect reaction speed when driving or operating machinery

No effect.

Method of Administration and Dosage.

Dosing

The infusion rate of PrismaSol 2 depends on the patient's serum electrolyte concentrations, acid-base balance, fluid balance, and overall clinical condition. The volume of replacement solution and/or dialysate administered also depends on the desired intensity (dose) of treatment. The solution must be prescribed and administered (dose, infusion rate, and total volume) only by a physician experienced in managing critical care (resuscitation) and performing continuous renal replacement therapy (CRRT).

The flow rate when using the drug as a replacement solution during hemofiltration and hemodiafiltration in adults is 500–3000 mL/h.

The flow rate for dialysate solution during prolonged hemodialysis and prolonged hemodiafiltration in adults is 500–2500 mL/h.

Typically, the flow rate for adult patients is approximately 2000–2500 mL/h, corresponding to a daily fluid volume of 48–60 L.

Special Populations

Elderly Patients

Clinical study results and usage experience indicate that administration in elderly patients is not associated with differences in safety or efficacy.

Children

The flow rate when using the drug as a replacement solution during hemofiltration and hemodiafiltration, as well as a dialysate solution during prolonged hemodialysis in children (from newborns to adolescents up to 18 years of age), is 1000–2000 mL/h/1.73 m².

A flow rate of up to 4000 mL/h/1.73 m² may be required, especially when used in younger children (body weight ≤ 10 kg). The absolute flow rate (mL/h) for the pediatric population generally should not exceed the maximum adult rate.

Method of Administration

Administered intravenously and for hemodialysis.

PrismaSol 2, when used as a replacement solution, is infused into the bloodstream before the hemofilter (predilution) or after the hemofilter or hemodiafilter (postdilution).

PrismaSol 2 is packaged in a dual-compartment bag: small compartment A containing the electrolyte solution and large compartment B containing the buffer solution. Immediately before use, the electrolyte solution (small compartment A) must be mixed with the buffer solution (large compartment B) by breaking the seal between the compartments.

Strict aseptic conditions must be maintained. The bag should be removed from the outer wrapper only immediately before the procedure.

Use only if the outer wrapper and all seals are intact, the breakable seal is unbroken, and the solution is clear. To check for leakage, firmly squeeze the bag. If leakage is detected, discard the solution immediately, as sterility can no longer be guaranteed.

The large compartment B has an injection port allowing addition of necessary medications after mixing the solutions. After checking the solution for possible color change and/or presence of precipitate, insoluble components, or crystals, the physician, under their own responsibility, must determine the compatibility or incompatibility of additional medications with PrismaSol 2 solution. Always refer to the instructions for use of the medications intended for addition.

Before adding any medication, ensure that it is water-soluble and stable at the pH value characteristic of PrismaSol 2 (the pH of the prepared solution ranges from 7.0 to 8.5). Added medications may be incompatible.

Medications are added to the solution as follows: remove any liquid from the injection port, hold the bag upside down, inject the medication through the injection port, and thoroughly mix it with the solution. Administration and mixing with other medicinal products should always be performed before connecting the solution bag to the extracorporeal circuit. The solution must be used immediately.

If the two compartments of the bag are separated by a breakable seal and the Luer connector has a valve, follow these instructions:

1. Immediately before use, remove the bag from the outer wrapper and shake the solutions in both compartments. Squeeze the small compartment with both hands until an opening forms in the breakable seal between the two compartments (see Fig. I).
2. Press both hands against the large compartment until the breakable seal between the two compartments opens completely (see Fig. II).
3. Carefully complete the mixing by gently shaking the bag contents. The solution is now ready for use and can be hung on the equipment (see Fig. III).
4. The dialysate or replacement solution line can be connected to either of the two available inlets.

4a. If using the Luer port, unscrew and pull off the cap, then connect by unscrewing and pulling the corresponding (male) Luer lock of the dialysate or replacement solution line to the corresponding (female) Luer connector on the bag. Ensure the connection is fully seated and tighten it. The connector is open. Check that fluid flows freely and without obstruction (see Fig. IV.a).

When the dialysate line or replacement solution line is disconnected from the Luer connector, the connector will close and the solution flow will stop. The Luer port is a valve-type port and does not require the use of a needle.

4b. If using the injection port, first remove the break-off cap. The injection port can be disinfected. Then insert the needle through the rubber membrane. Check that fluid flows freely and without obstruction (see Fig. IV.b).

The solution should be used immediately after mixing. If delayed, this solution must be used within 24 hours of adding the electrolyte solution to the buffer solution, including the duration of therapy.

The mixed solution is for single use only.

The product must not be used if the bag is damaged or if the solution is cloudy.

Any unused medicinal product or waste material must be disposed of in accordance with local requirements.

Children.

The medicinal product PrismaSol 2 is administered to children according to the information provided in the section "Method of Administration and Dosage."

Overdose.

Under conditions of proper procedure performance and careful monitoring of fluid, electrolyte, and acid-base balance in patients, overdose of PrismaSol 2 is unlikely.

However, overdose may lead to serious consequences such as congestive heart failure and disturbances in electrolyte or acid-base balance.

Hypervolemia or hypovolemia, if they occur, should be corrected immediately.

If disturbances in electrolyte and acid-base balance (e.g., metabolic alkalosis, hypophosphatemia, hypokalemia, etc.) are observed, administration should be stopped immediately. There is no specific antidote for overdose. The risk can be minimized by careful monitoring of electrolyte and acid-base balance and appropriate correction during treatment (see section "Special Warnings and Precautions for Use").

Adverse reactions.

The undesirable effects listed below have been reported during post-marketing use. Adverse reactions are presented by MedDRA system organ classes and preferred terms; frequency is unknown (cannot be estimated from available data).

Metabolism and nutrition disorders – electrolyte imbalance (e.g. hypophosphatemia, hypokalemia), acid-base balance disturbances (e.g. metabolic alkalosis), fluid balance disturbances (e.g. fluid retention, dehydration), hyperglycemia.

Cardiac disorders – hypotension.

Gastrointestinal disorders – nausea, vomiting.

Musculoskeletal and connective tissue disorders – muscle cramps.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals are encouraged to report suspected adverse reactions through the national reporting system.

Shelf life.

For polyolefin dual-compartment bags – 1.5 years.

After mixing, the solution is stable for 24 hours.

Storage conditions.

Store out of the reach of children, at a temperature between 4 °C and 30 °C.

Incompatibilities.

Since scientific data on compatibility are lacking, this medicinal product should not be mixed with other medicinal products. After visually inspecting the solution for possible changes in color and/or for the presence of precipitate, insoluble complexes or crystals, the physician may, at his or her own responsibility, determine compatibility or incompatibility of additional medications with Prismsol 2 solution. Reference should be made to the instructions for use of the medicinal products intended for addition.

Prior to adding any drug, ensure that it is water-soluble and stable at the pH value characteristic of Prismsol 2 (the pH of the prepared solution ranges from 7.0 to 8.5). Compatible drugs may then be added to the prepared solution. The solution should be used immediately after addition.

Packaging.

Inner.

Dual-compartment polyolefin bag with a total volume of 5000 ml (small compartment 250 ml and large compartment 4750 ml, separated by a sealing and equipped with a Luer connector valve).

Outer.

Transparent multilayer film. Two bags per cardboard box.

Prescription category.

Prescription only.

Manufacturer.

BIEFFE MEDITAL S.P.A.

Manufacturer's location and address of its business premises.

VIA STELVIO, 94 - 23035 SONDRIO (SO), ITALY.