Multibic 2 mmol/l potassium

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT multiBic 2 mmol/l potassium

Composition:

Active substances: potassium chloride, sodium chloride, sodium hydrogencarbonate, calcium chloride dihydrate, magnesium chloride hexahydrate, glucose monohydrate (glucose).

"multiBic 2 mmol/l potassium" is supplied in a dual-chamber bag: 4750 ml of alkaline hydrogencarbonate solution in one chamber and 250 ml of acidic electrolyte solution based on glucose in the other chamber.

Before mixing:

1000 ml of solution contains:

in the acidic electrolyte solution based on glucose (small chamber):

in an alkaline solution of bicarbonate (large chamber):

After mixing:

1000 ml of ready-to-use solution contains:

Excipients: carbon dioxide, hydrochloric acid 25 %, water for injections, sodium dihydrogen phosphate dihydrate.

Pharmaceutical form. Solution for hemodialysis/hemofiltration.

Basic physicochemical properties: ready-to-use solution, clear and colorless.

Theoretical osmolarity — 296 mOsm/L, pH ≈ 7.4.

Pharmacotherapeutic group. Blood substitutes and perfusion solutions. Agents for hemodialysis and hemofiltration.

ATC code B05Z B.

Pharmacological Properties

Pharmacodynamics

Mechanism of action

Basic principles of hemodialysis, hemofiltration, and hemodiafiltration. During hemofiltration, water and dissolved substances such as uremic toxins, electrolytes, and bicarbonates are removed from the blood by ultrafiltration. The ultrafiltrate is replaced with a hemofiltration solution having a balanced electrolyte and buffer composition.

During hemodialysis, exchange of water and dissolved substances such as uremic toxins, electrolytes, bicarbonate, and other small molecules occurs between the patient's blood and the hemodialysis solution via diffusion. The direction and extent of the diffusion process depend on the respective concentration gradients between blood and the hemodialysis solution.

Hemodiafiltration combines the basic principles of hemofiltration and hemodialysis.

This medicinal product is a bicarbonate-buffered solution for intravenous administration or for use as a hemodialysis solution to balance the removal of water and electrolytes during continuous renal replacement therapy, which is applied, for example, in the treatment of acute kidney injury.

The electrolytes Na+, K+, Mg2+, Ca2+, Cl–, and bicarbonate are necessary for maintaining and correcting fluid and electrolyte homeostasis (blood volume, osmotic equilibrium, acid-base balance).

Pharmacokinetics

This medicinal product is administered only intravenously or as a hemodialysis solution.

Distribution / Biotransformation / Elimination

Distribution of electrolytes and bicarbonates is regulated according to the patient's needs, metabolic status, and residual kidney function. The active substances of this medicinal product are not metabolized, except for glucose. Removal of water and electrolytes depends on cellular requirements, metabolic status, residual kidney function, and other routes of fluid loss (e.g., gastrointestinal tract, lungs, and skin).

Safety Preclinical Data

There are no preclinical data of relevance to the prescribing physician.

Clinical characteristics

Indications

"multiBic 2 mmol/l potassium" is intended for intravenous use as a replacement solution in hemofiltration and hemodiafiltration, and as a dialysis solution in hemodialysis and hemodiafiltration.

It should be administered to patients:

• with acute renal failure requiring continuous renal replacement therapy: continuous hemodialysis, hemofiltration, or hemodiafiltration treatment;
• with chronic kidney disease who are receiving temporary treatment with the solution, for example, during admission to the intensive care unit;
• for whom continuous renal replacement therapy is part of the management of intoxication with water-soluble, filterable/dialyzable toxins.

"multiBic 2 mmol/l potassium" is intended for adults.

Contraindications

Contraindications for the use of the solution:

• hypersensitivity to the active substances or to any of the excipients contained in the medicinal product;
• hypokalemia;
• metabolic alkalosis.

Contraindications related to the procedure technique:

• insufficient blood flow from the vascular access;
• high risk of bleeding due to systemic anticoagulation.

Interaction with other medicinal products and other types of interactions

Interaction studies have not been conducted.

Appropriate selection of the dose of "multiBic 2 mmol/l potassium" and strict monitoring of clinical-chemical parameters and vital signs will help avoid risks associated with interactions with other medicinal products.

Possible reactions:

• toxic effects of digitalis may be masked by hyperkalemia, hypermagnesemia, and hypocalcemia. Correction of the levels of these electrolytes via continuous renal replacement therapy may provoke the appearance of signs and symptoms of digitalis toxicity, including cardiac arrhythmias;
• electrolyte replacement, parenteral nutrition, and other types of infusions usually administered during intensive therapy affect serum laboratory values and the patient's fluid balance. This should be taken into account during continuous renal replacement therapy;
• continuous renal replacement therapy may reduce blood concentrations of medicinal substances, particularly those with low protein binding, low volume of distribution, molecular weight lower than the hemofilter cutoff, and substances adsorbed by the hemofilter. Dose adjustment of such medicinal products may be required.

Special precautions for use

The medicinal product is used only after mixing two solutions.

"multiBic 2 mmol/l potassium" must be warmed before administration using appropriate equipment to approximately body temperature and under no circumstances should be used if the solution temperature is below room temperature.

Careful monitoring of the warming of the ready-to-use solution to approximately body temperature is required, checking that the solution is clear and free from particles.

During administration of the ready-to-use solution, formation of a white precipitate of calcium carbonate in the tubing system has been observed rarely, particularly near the pump system of the machine and the heating block. The precipitate may occur primarily if the temperature of the ready-to-use solution exceeds 30°C before it enters the pump system of the machine.

Therefore, the ready-to-use solution in the tubing systems must be carefully inspected every 30 minutes during continuous renal replacement therapy to ensure that the solution in the tubing system is clear and free from precipitate. Precipitation may also occur with a significant delay after the start of therapy.

If precipitate formation is observed, the ready-to-use solution and the tubing systems used for continuous renal replacement therapy must be replaced immediately, and the patient must be closely monitored.

Serum potassium concentration must be regularly monitored before and during continuous renal replacement therapy. The patient's potassium level and its dynamics during therapy should be taken into account. In case of hypokalemia, potassium supplementation and/or switching to a hemodialysis/hemofiltration solution with a higher potassium concentration may be necessary. In case of hyperkalemia, increasing the administered dose and/or switching to a hemodialysis/hemofiltration solution with a lower potassium concentration may be indicated, along with standard intensive care measures.

Serum sodium concentration must be regularly monitored before and during use of this hemodialysis/hemofiltration solution to control risks associated with hypo-/hypernatremia. The hemodialysis/hemofiltration solution may be diluted with an adequate amount of water for injections or, if necessary, concentrated sodium chloride solution may be added. The rate of desired normalization should be carefully planned to avoid adverse reactions due to rapid changes in serum sodium concentration.

In addition, the following parameters should be monitored before and during continuous renal replacement therapy: serum calcium, serum magnesium, serum phosphate, serum glucose, acid-base balance, urea and creatinine levels, body weight, and fluid balance (for early detection of hyperhydration and dehydration).

Clinically important substances may be removed by hemodialysis, hemofiltration, and hemodiafiltration treatments and are not replenished by this medicinal product. This loss of essential nutrients should be compensated by adequate nutrition, dietary supplements, or adapted parenteral nutrition.

Use during pregnancy or breastfeeding

Pregnancy

There is no or very limited information available on the use of the medicinal product "multiBic 2 mmol/l potassium" in pregnant women.

Reproductive toxicity studies in animals have been conducted in insufficient numbers.

"multiBic 2 mmol/l potassium" should not be used during pregnancy except when the woman's clinical condition requires continuous renal replacement therapy.

Breastfeeding

Interaction studies of the active substances/metabolites of the medicinal product "multiBic 2 mmol/l potassium" with breast milk have been conducted in insufficient (minimal) numbers.

Women are not recommended to breastfeed during treatment with "multiBic 2 mmol/l potassium".

Fertility

There are no clinical data on the effect of the medicinal product on fertility.

Ability to influence the speed of reactions when driving or operating machinery. "multiBic 2 mmol/l potassium" does not affect the ability to drive or operate machinery.

Method of Administration and Dosage

Continuous renal replacement therapy, including administration of this medicinal product, must be supervised by a physician experienced in such treatment.

Doses

In acute renal failure, continuous treatment with the medicinal product "multiBic 2 mmol/l potassium" is recommended for adults with a body weight of 70 kg at a dose of 2000 ml/hour, allowing for the removal of metabolic waste products depending on the patient's metabolic status. The dose should be adjusted according to the patient's body weight.

For patients with chronic kidney disease, unless otherwise clinically indicated, the dose of the medicinal product "multiBic 2 mmol/l potassium" should be at least one-third of the body weight per session, administered in three sessions per week. It may be necessary to increase the weekly volume or distribute the weekly volume over more than three procedures per week.

The dose and duration of hemodialysis, hemofiltration, or hemodiafiltration required to treat acute intoxication states depend on the toxin, its concentration, and the severity of clinical symptoms, and must be clinically determined according to the individual patient's condition.

The recommended maximum dose is 75 liters per day.

The safety and efficacy of the medicinal product "multiBic 2 mmol/l potassium" in children have not been established.

Only clear, colorless, ready-to-use solution in an undamaged bag with intact connectors should be used.

The medicinal product is intended for single use only. Any unused solution must be discarded.

The medicinal product must be administered using dosing pumps.

The hemodialysis/hemofiltration solution should be prepared in three steps:

1. Removal of the protective film and careful inspection of the bag.

Remove the protective film only immediately before use. Plastic containers may occasionally be damaged during transport from the manufacturer to the clinic or within the clinic. This may lead to contamination and microbial or fungal growth in the solutions. Therefore, careful visual inspection of the bag and solutions is required before mixing. Particular attention should be paid to even the smallest damage to the closure site, connecting seam, and corners of the bag due to possible contamination.

2. Mixing the contents of the two chambers.

The contents of the dual-chamber bag — the bicarbonate chamber and the glucose-based electrolyte chamber — should be mixed immediately before use to obtain a ready-to-use solution (see Fig. 1).

Fig. 1

After mixing the contents of both chambers of the bag, it is necessary to check whether the central seam is fully open, whether the mixed solution is clear and colorless, and whether the bag is leaking.

1. Use of the ready-to-use solution.

The ready-to-use solution should be used immediately, but no later than within 48 hours after mixing.

Any additives to the ready-to-use solution may be introduced only after the ready-to-use solution has been thoroughly mixed. After such addition, the ready-to-use solution must be thoroughly mixed again before administration.

Sodium chloride solution (concentration from 3% to 30% sodium chloride; up to 250 mmol sodium chloride per 5 L of "multiBic 2 mmol/L potassium" solution) and water for injections (up to 1250 mL per 5 L of "multiBic 2 mmol/L potassium" solution) are compatible with this medicinal product.

Unless otherwise indicated, the ready-to-use solution should be warmed immediately before administration to a temperature of 36.5–38.0 °C. The exact temperature is determined according to clinical parameters and the type of technical equipment used.

There are no special requirements for the disposal of the medicinal product.

Children

There is no clinical experience with the use of this medicinal product in children. "multiBic 2 mmol/L potassium" is not recommended for use in children until additional data are available.

Overdose

No emergencies occurred after administration of the medicinal product at recommended doses; furthermore, administration of this medicinal product can be stopped at any time. If fluid balance is not accurately calculated and monitored, hyperhydration or dehydration with associated circulatory reactions may occur. These may manifest as changes in arterial pressure, central venous pressure, heart rate, and pulmonary arterial pressure. In case of hyperhydration, congestive heart failure and/or pulmonary congestion may develop.

In case of hyperhydration, the removal of pure fluid should be increased on the continuous renal replacement therapy device. In case of acute severe dehydration, the removal of pure fluid on the continuous renal replacement therapy device should be reduced or interrupted; alternatively, fluid resuscitation may be used to restore hydration balance.

Administration of an excessively large volume may cause disturbances in electrolyte concentrations and acid-base balance. For example, bicarbonate overdose may occur if an inappropriately large volume of hemodialysis/hemofiltration solution is infused. This may lead to metabolic alkalosis, decreased ionized calcium levels, or tetany.

Side effects

The following adverse reactions may be due to the treatment method itself or may be caused by this medicinal product:

Gastrointestinal disorders — nausea, vomiting;

Vascular disorders — hypertension, hypotension;

Musculoskeletal and connective tissue disorders — muscle cramps.

Potential adverse reactions associated with the treatment method:

Metabolism and nutrition disorders — hyper- or hypohydration, electrolyte disturbances (e.g., hypokalemia), hypophosphatemia, hyperglycemia, and metabolic alkalosis.

The exact frequency of these events is unknown (cannot be estimated from the available data).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. The shelf life of the medicinal product in the original retail packaging is 2 years.

Storage conditions

Store at a temperature not below +4 °C.

After mixing the contents of the two chambers of the bag (ready-to-use solution): chemical and physical stability of the ready-to-use solution is maintained for 48 hours at 30 °C.

It is not recommended to store the ready-to-use solution for longer than 48 hours, including the duration of the procedure, or at temperatures above 30 °C prior to administration via the apparatus pump system.

From a microbiological standpoint, and due to the presence of bicarbonate, the medicinal product should be used immediately after connection to the hemodialysis, hemofiltration, or hemodiafiltration system. Keep out of reach of children.

Incompatibilities. This medicinal product must not be mixed with other medicinal products except as specified in this leaflet.

Packaging. 5000 ml in a dual-chamber bag system; 2 bags per cardboard box labeled in Ukrainian and other languages.

Dual-chamber bag: 4750 ml alkaline bicarbonate solution + 250 ml acidic glucose-based electrolyte solution = 5000 ml ready-to-use solution.

The film used for the bag is made of polyethylene terephthalate, SiOx, polyamide, and polyolefin.

Each bag is equipped with an HF connector, a Luer-lock connector, and an injection port, and is covered with a protective film.

Prescription status. Prescription only.

Manufacturer. Fresenius Medical Care Deutschland GmbH

Manufacturer's address. Frankfurter Strasse 6-8, 66606 St. Wendel, Germany

Marketing Authorization Holder. Fresenius Medical Care Deutschland GmbH

Address of the Marketing Authorization Holder. Else-Kroener-Str. 1, 61352 Bad Homburg v.d.H., Germany

Local representative of the Marketing Authorization Holder. LLC "Fresenius Medical Care Ukraine", 9 Borysplilska St., Kyiv, 02099, Ukraine