Multibik (Solution) Instructions for Use

Marketing Authorization Holder

Fresenius Medical Care Deutschland, GmbH (Germany)

ATC Code

B05ZB (Hemofiltration solutions)

Dosage Forms

	Multibik	Hemofiltration solution 2 mmol/L: 5 L bags
		Hemofiltration solution 4 mmol/L: 5 L bags

Dosage Form, Packaging, and Composition

Hemofiltration solution 2 mmol/L potassium, transparent, colorless.

Excipients: hydrochloric acid 25%, carbon dioxide, water for injections up to 1000 ml.

5 L – plastic bags (2) dual-chamber (with a 250 ml chamber for solution A and a 4750 ml chamber for solution B) with connecting tubes – plastic bags – cardboard boxes.

Hemofiltration solution 4 mmol/L potassium, transparent, colorless.

Excipients: hydrochloric acid 25%, carbon dioxide, water for injections up to 1000 ml.

5 L – plastic bags (2) dual-chamber (with a 250 ml chamber for solution A and a 4750 ml chamber for solution B) with connecting tubes – plastic bags – cardboard boxes.

Clinical-Pharmacological Group

Solution for hemofiltration

Pharmacotherapeutic Group

Solution for hemofiltration

Pharmacological Action

Basic principles of hemofiltration

During the procedure, water and substances dissolved in it, such as uremic toxins, electrolytes, and bicarbonate, are removed from the blood by ultrafiltration.

The ultrafiltrate is replaced by a substitution solution (hemofiltration solution), which has a balanced electrolyte composition and contains a buffer.

The ready-to-use substitution solutions contain a bicarbonate buffer and can be used for intravenous infusion in the treatment of acute renal failure by continuous hemofiltration.

Electrolytes Na⁺, K⁺, Mg²⁺, Ca²⁺, Cl^–, as well as bicarbonate, are essential elements for maintaining and correcting fluid and electrolyte homeostasis (circulating blood volume, osmotic equilibrium, acid-base balance).

Pharmacokinetics

Ready-to-use hemofiltration solutions should only be used intravenously. The distribution of electrolytes and bicarbonate is regulated according to the patient’s needs and metabolic status, as well as residual renal function. The active substances of the substitution solution are not metabolized, with the exception of glucose. The elimination of water and electrolytes depends on cellular needs, metabolic status, residual renal function, and other routes of fluid excretion (e.g., through the intestines, lungs, skin).

Indications

• For use in patients with acute renal failure requiring prolonged hemofiltration.

ICD codes

Dosage Regimen

Multibik is intended for intravenous administration only.

Infusion of the ready-to-use solution into the extracorporeal circulation system is carried out using a roller pump.

During the hemofiltration procedure, the filtered volume of blood serum must be replaced by the hemofiltration solution, minus the volume of fluid removed if additional ultrafiltration was performed.

The filtration rate is prescribed by the attending physician depending on the clinical condition and body weight of the patient. If not otherwise prescribed, a total filtration rate from 800 to 1400 ml/h is acceptable for adults, ensuring the removal of end products of metabolism, depending on the patient’s metabolism. The recommended maximum filtration rate is 75 L per day.

Preparation of hemofiltration solutions for use should be carried out in accordance with the following steps.

1. Removal of the outer packaging and thorough inspection of the hemofiltration solution bag.

The outer packaging must be removed immediately before the procedure. Plastic containers may be accidentally damaged during transportation from the manufacturer to the procedure site. This may lead to a breach of sterility of the hemofiltration solution. A thorough visual inspection of the container before connection to the system, as well as the solution before use, must be performed. Particular attention should be paid to even minor damage to the protective cap, seams, and corners of the container to detect possible leakage/contamination.

This solution should be used only if it is clear and transparent, and only if the container and connectors are intact.

In doubtful cases, the decision on the use of this hemofiltration solution should be made by the attending physician.

2. Mixing the contents of the two sections.

The dual-chamber bag containing bicarbonate, electrolytes, and in a separate chamber – glucose, is mixed immediately before use to obtain the ready-to-use solution.

After mixing the contents of both chambers, it is necessary to check that the connecting seam is completely open, that the solution is clear and transparent, and that the container is not leaking.

3. Ready-to-use solution.

The ready-to-use solution must be used immediately, maximum within 48 hours after mixing.

If not otherwise prescribed, the ready-to-use substitution solution must be warmed immediately before infusion to a temperature of 36.5-38°C (97.7-100.4°F). The exact temperature should be selected depending on clinical recommendations and the equipment used. The hemofiltration solution is intended for single use. Partially used and damaged containers are discarded as waste.

Adverse Reactions

During the procedure, adverse reactions such as nausea, vomiting, muscle cramps, hypotension, or hypertension may develop, which may be associated with the administration of the substitution solution.

Features of the use of Multibik solution are: increased buffer capacity, better correction of metabolic acidosis, significantly fewer episodes of hypotension, fewer cardiovascular complications. Therefore, solutions with a bicarbonate buffer can be used in all patients with acute renal failure.

The following side effects of treatment are also likely: Hyperhydration or hypohydration, electrolyte disturbances (e.g., hypokalemia), hypophosphatemia, hyperglycemia, and metabolic alkalosis.

Contraindications

• Metabolic alkalosis;
• Pediatric age.

Multibik 2 mmol/L potassium

• Hypokalemia.

Multibik 4 mmol/L potassium

• Hyperkalemia.

Contraindications arising during the hemofiltration procedure

• Renal failure with increasing hypercatabolism, in cases where uremic symptoms can no longer be alleviated by hemofiltration;
• Inadequate vascular access that does not provide sufficient blood flow;
• High risk of bleeding as a result of systemic anticoagulation.

Use in Pregnancy and Lactation

There is no clinical experience to date. The substitution solution containing a bicarbonate buffer should be used only after assessing the potential risk and benefit for the mother and child.

Use in Renal Impairment

For use in patients with acute renal failure requiring prolonged hemofiltration.

Contraindication arising during the hemofiltration procedure: renal failure with increasing hypercatabolism, in cases where uremic symptoms can no longer be alleviated by hemofiltration.

Pediatric Use

Contraindicated in children.

Special Precautions

It is necessary to monitor the serum potassium concentration before the start of hemofiltration and its changes during the procedure. In the presence of hypokalemia or tendencies to its development, the addition of potassium and/or changing the substitution solution to a solution with a higher potassium content may be required.

Hemofiltration in patients with acute renal failure, the selection and prescription of substitution solutions, should be controlled by a physician experienced in performing such procedures.

In acute renal failure, treatment is carried out for a limited time and stopped after complete recovery of kidney function.

In the presence of a tendency to develop hyperkalemia, an increase in the filtration rate and/or replacement of the substitution solution with a solution with a lower potassium concentration is indicated, as well as basic intensive care measures.

In addition, before the start of hemofiltration and during the procedure, it is necessary to monitor the following parameters: Serum sodium, Serum calcium, Serum magnesium, Serum phosphate, Serum glucose, acid-base balance, urea and creatinine levels, body weight and fluid balance (for early diagnosis of hyperhydration and dehydration).

Before use, a thorough inspection of the solution bag must be carried out, as described in the “Dosage Regimen” section.

The hemofiltration solution must be warmed before administration using appropriate equipment, approximately to body temperature. Infusion of a substitution solution with a temperature below room temperature is strictly prohibited.

For this product, there is no experience with clinical studies on use and dosing in children.

Never use solutions without first mixing the chamber contents!

Given the lack of incompatibility studies, this medicinal product should not be mixed with other medical products.

During the use of the drug, in rare cases, white precipitates of calcium carbonate were observed in the system of connecting tubes, especially close to the pump unit and the heating element warming the solution.

Precipitation can occur especially if the temperature of the Multibik solution at the inlet of the pump unit is already higher than 25°C (77°F).

Therefore, the solution in the system of connecting tubes must be carefully visually inspected every 30 min during the procedure to ensure that the solution in the system of connecting tubes is clear and does not contain precipitate. Precipitation can also occur with a significant delay after the start of treatment.

If precipitate appears, the drug and the system of connecting tubes for this procedure must be replaced immediately, and the patient’s condition should be carefully monitored.

Effect on the ability to drive vehicles and operate machinery

Not applicable.

Overdose

No emergency situations have been reported after the use of recommended doses; moreover, the administration of this solution can be stopped at any time. If fluid balance is not calculated and monitored properly, hyperhydration or dehydration may develop, causing corresponding circulatory disturbances. This may manifest as changes in blood pressure, central venous pressure, heart rate, and pulmonary pressure. In cases of hyperhydration, congestive heart failure and/or pulmonary edema may develop.

In cases of hyperhydration, it is necessary to increase ultrafiltration, as well as reduce the rate and volume of the administered substitution solution. In cases of severe dehydration, it is necessary to reduce or stop ultrafiltration, as well as appropriately increase the volume of the substitution solution.

Overdose can lead to electrolyte disturbances and acid-base balance disorders, for example, bicarbonate overdose can occur if an inadequately large volume of substitution solution is administered. This can cause metabolic alkalosis, decreased ionized calcium, or seizures.

Drug Interactions

Proper dosing of substitution solutions and strict monitoring of biochemical parameters and clinical symptoms can avoid the negative consequences of interaction with other drugs.

The following interactions are possible.

The administration of electrolytes, parenteral nutrition, and other infusions usually carried out during intensive care alter the patient’s serum composition and water-electrolyte balance. This must be taken into account when performing the hemofiltration procedure.

The hemofiltration procedure can reduce the concentration of drugs in the blood, especially drugs with low protein binding capacity, low volume of distribution, molecular weight below the hemofilter membrane cutoff threshold – due to their filtration, as well as adsorption of some drugs on the hemofilter membrane. An increase in the dose of such drugs during the procedure may be required.

The toxic effects of digitalis may be masked in the presence of hyperkalemia, hypermagnesemia, and hypocalcemia. Correction of these electrolyte disturbances during hemofiltration may enhance the manifestations of digitalis toxicity, for example, cardiac arrhythmia.

Storage Conditions

Store at a temperature not lower than 4°C (39.2°F). Do not freeze. Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.