Consumer medicine information

Multibic

Calcium chloride dihydrate; Glucose; Magnesium chloride hexahydrate; Potassium chloride; Sodium chloride; Sodium bicarbonate

BRAND INFORMATION

Brand name

Multibic

Active ingredient

Calcium chloride dihydrate; Glucose; Magnesium chloride hexahydrate; Potassium chloride; Sodium chloride; Sodium bicarbonate

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Multibic.

SUMMARY CMI

MULTIBIC potassium-free and MULTIBIC 4 mmol/L potassium solutions for haemofiltration

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using MULTIBIC?

MULTIBIC solutions contain the active ingredients Potassium chloride (MULTIBIC 4 mmol/L potassium only), Sodium chloride, Sodium bicarbonate, Calcium chloride dihydrate, Magnesium chloride hexahydrate and Glucose monohydrate. MULTIBIC is used as a substitution solution in haemofiltration therapy.

For more information, see Section 1. Why am I using MULTIBIC? in the full CMI.

2. What should I know before I use MULTIBIC?

Do not use if you have ever had an allergic reaction to MULTIBIC or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use MULTIBIC? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with MULTIBIC and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use MULTIBIC?

Your doctor, nurse or pharmacist will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines. Do not stop taking your medicine or change your dosage without first checking with your doctor. More instructions can be found in Section 4. How do I use MULTIBIC? in the full CMI.

5. What should I know while using MULTIBIC?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using MULTIBIC.
Things you should not do
  • Give this medicine to anyone else, even if their symptoms seem similar to yours
  • Take your medicine to treat any other condition unless your doctor, nurse or pharmacist tells you to
  • Stop taking your medicine, or change the dosage, without first checking with your doctor.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how MULTIBIC affects you.
Drinking alcohol
  • Tell your doctor if you drink alcohol
Looking after your medicine
  • Follow the instructions in the carton on how to take care of your medicine properly
  • Store it in a cool dry place away from moisture, heat or sunlight.

For more information, see Section 5. What should I know while using MULTIBIC? in the full CMI.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

MULTIBIC potassium-free and MULTIBIC 4 mmol/L potassium solutions for haemofiltration

Active ingredient(s): Potassium chloride (MULTIBIC 4 mmol/L potassium only), Sodium chloride, Sodium bicarbonate, Calcium chloride dihydrate, Magnesium chloride hexahydrate and Glucose monohydrate


Consumer Medicine Information (CMI)

This leaflet provides important information about using MULTIBIC potassium-free and MULTIBIC 4 mmol/L potassium solutions. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using MULTIBIC potassium-free and 4 mmol/L potassium solutions.

Where to find information in this leaflet:

1. Why am I using MULTIBIC?
2. What should I know before I use MULTIBIC?
3. What if I am taking other medicines?
4. How do I use MULTIBIC?
5. What should I know while using MULTIBIC?
6. Are there any side effects?
7. Product details

1. Why am I using MULTIBIC?

MULTIBIC solutions contain the active ingredients Sodium chloride, Sodium bicarbonate, Calcium chloride dihydrate, Magnesium chloride hexahydrate and Glucose monohydrate. In addition, MULTIBIC 4mmol/L potassium solution also contains Potassium chloride.

MULTIBIC potassium-free and MULTIBIC 4 mmol/L potassium are solutions for haemofiltration. This is a process where the blood is cleaned and replaced in the body. It is used for patients whose kidneys do not function as well as they should. MULTIBIC is a (high risk) registered medicine which is used only in hospitals.

MULTIBIC potassium-free and MULTIBIC 4mmol/L potassium solutions are used to treat patients with acute kidney (renal) failure requiring continuous haemofiltration. It is administered intravenously in ICU units of a hospital

2. What should I know before I use MULTIBIC?

Warnings

Do not use MULTIBIC potassium-free and MULTIBIC 4 mmol/L potassium if:

  • You are allergic to Potassium chloride (MULTIBIC 4 mmol/L potassium only), Sodium chloride, Sodium bicarbonate, Calcium chloride dihydrate, Magnesium chloride hexahydrate and Glucose monohydrate or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
  • You have or have had any of the following:
    - You suffer from high (for MULTIBIC 4 mmol/L potassium) or low (for MULTIBIC potassium-free mmol/L potassium) levels of potassium
    - if you have metabolic alkalosis (a condition where there is too much bicarbonate in the blood)
    - if haemofiltration is in general the wrong treatment in your situation for the following reasons:
    -- excessive protein metabolism (hypercatabolism)
    -- an impossibility to achieve a sufficient blood flow through the haemofilter
    -- a high risk of bleeding related to medications required to prevent clotting in the haemofilter
  • If your laboratory results show that your serum levels of sodium, calcium, magnesium, phosphate, glucose, acid-base balance, urea and creatinine, body weight and fluid balance are outside of safe levels, you must stop taking this medicine immediately.

Check with your doctor if:

  • You have allergies to:
    - any other medicines
    - any other substances, such as foods, preservatives or dyes.
  • You have or have had any medical conditions, especially the following:
    - End Stage Renal Disease
    - Chronic Kidney Disease
    - Hypertension
    - Cardiovascular disease
  • You are planning to have surgery or an anaesthetic.
  • You are currently receiving or are planning to receive dental treatment.
  • You are taking or are planning to take any other medicines, this includes vitamins and supplements that are available from your pharmacy, supermarket or health food shop.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant. Do not take this medicine whilst pregnant until you and your doctor have discussed the risks and benefits involved.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Do not take this medicine whilst breast-feeding until you and your doctor have discussed the risks and benefits involved.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with MULTIBIC potassium-free and MULTIBIC 4 mmol/L potassium solutions and affect how they work.

These include:

  • Electrolyte substitution solutions
  • Parenteral nutrition and other infusions

If you are taking any of these you may need a different dose or you may need to take different medicines.

Other medicines not listed above may also interact with this medicine.

Haemofiltration treatments like MULTIBIC may reduce the blood concentration of certain medicines. Your doctor may need to revise the dose of these medicines.

Toxic effects of digitalis (a medication for certain heart conditions) may be masked by high levels of electrolytes, particularly potassium, magnesium or calcium. The correction of these electrolytes by haemofiltration with MULTIBIC may initiate signs and symptoms of digitalis toxicity e.g. cardiac arrhythmia

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect MULTIBIC potassium-free and 4 mmol/L potassium solutions or if MULTIBIC affects the waythese medicines work.

4. How do I use MULTIBIC?

How much to take / use

  • MULTIBIC solutions are given as IV infusions and will be administered to you by your doctor or nurse while you are in hospital. They will determine how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

When to take / use MULTIBIC solutions

  • MULTIBIC potassium-free and MULTIBIC 4mmol/L potassium are given as IV infusions using a special pump so can only be given while you are in hospital.
  • Your doctor will tell you when you should attend the ICU unit for administration of the solutions

If you forget to use MULTIBIC solutions

Your doctor will tell you when these solutions are required. This solution is administered only by healthcare professionals in a hospital. You must make sure you keep all your appointments.

If you use too much MULTIBIC solutions

As MULTIBIC is given to you by your doctor it is unlikely that you will be given too much. If you think that you have used too much MULTIBIC solution you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using MULTIBIC?

Things you should do

Tell your doctor that you are taking this medicine if:

  • you are about to be started on any new medicine
  • you are pregnant or are planning to become pregnant
  • you are breast-feeding or are planning to breast-feed
  • you are about to have any blood tests
  • you are going to have surgery or an anaesthetic or are going into hospital.

Your doctor will check your hydration status (the amount of water in your body), the levels of potassium, other salts, certain waste products, and your blood sugar levels. Your doctor also might advise you about your diet.

Call your doctor straight away if you:

  • Experience any adverse reactions such as nausea, vomiting, muscle cramps, low blood pressure and high blood pressure.
  • Experience serious side-effects, including seizures, breathlessness and swelling of ankles and legs.

Remind any doctor, nurses, dentist or pharmacist you visit that you are using MULTIBIC potassium-free or MULTIBIC 4 mmol/L potassium solution.

Things you should not do

  • Give this medicine to anyone else, even if their symptoms seem similar to yours
  • Take your medicine to treat any other condition unless your doctor, nurse or pharmacist tells you to
  • Stop taking your medicine, or change the dosage, without first checking with your doctor.

The following parameters should be monitored before and during haemofiltration:

Serum potassium, serum sodium, serum calcium, serum magnesium, serum phosphate, serum glucose, acid-base status, levels of urea and creatinine, body weight and fluid balance (for the early recognition of hyper- and dehydration).

The correct dosing of substitution solutions and strict monitoring of clinical chemistry parameters and vital signs will avoid interactions with other drugs.

Go to your doctor regularly for a check-up.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how MULTIBIC affects you.

Your doctor will tell you whether to be careful when driving or operating machinery until you know how this medicine affects you.

MULTIBIC potassium-free and MULTIBIC 4 mmol/L potassium solutions may cause dizziness in some people

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

Storage

As your medicine will be administered to you while you are in hospital, the hospital pharmacist will be responsible for ensuring the product is stored correctly.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do

Common side effects:

  • nausea (feeling sick)
  • muscle cramps
  • changes in blood pressure

Fluid-related side effects:

  • shortness of breath
  • swelling of the ankles and legs
  • dehydration (e.g. dizziness, muscle cramps, feeling thirsty)
  • blood disorders (e.g. abnormal salt concentrations in your blood)
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do

Rare side-effects

  • Vomiting

Very serious side-effects:

  • Seizures
  • Breathlessness
  • Swelling of ankles and legs
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects that you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What MULTIBIC potassium-free and MULTIBIC 4 mmol/L potassium contains

Active ingredient
(main ingredient)
1000 mL of the mixed solution contain: 6.136 g of Sodium chloride, 0 or 0.2982 g of Potassium chloride, 2.940 g of Sodium bicarbonate, 0.2205g of Calcium chloride, 0.1017 g of Magnesium chloride; 1.100 g of Glucose monohydrate (as 1.000g of Glucose anhydrous) as the active ingredients.
Other ingredients
(inactive ingredients)
  • Water for injections
  • Hydrochloric acid 25%
  • Carbon dioxide
  • Monobasic sodium phosphate dihydrate
Potential allergensThis medicine is gluten-free, lactose-free, tartrazine-free and free of other azo dyes

Do not take this medicine if you are allergic to any of these ingredients.

What MULTIBIC potassium-free and MULTIBIC 4 mmol/L potassium looks like

MULTIBIC potassium-free and MULTIBIC 4 mmol/L potassium are provided in a two-compartment bag with 4.75 L of an alkaline hydrogen carbonate solution in one compartment and 0.25 L of an acidic electrolyte, glucose solution in the other compartment.

The clear and colourless solutions are intended for haemofiltration administration.

MULTIBIC potassium-free Solution for Haemofiltration

AUST R 357591

MULTIBIC 4 mmol/L potassium Solution for Haemofiltration

AUST R 357590

Who distributes MULTIBIC potassium-free and MULTIBIC 4 mmol/L potassium

MULTIBIC is supplied in Australia by:

Fresenius Medical Care Australia Pty. Ltd.
305 Woodpark Road
Smithfield NSW 2164

Australian Sponsor:

Fresenius Medical Care Pty Ltd
Level 27, 100 Miller Street
North Sydney NSW 2060
Phone: (02) 9466 8000
Website: www.fmc-au.com

This leaflet was prepared in September 2021

Published by MIMS October 2021

BRAND INFORMATION

Brand name

Multibic

Active ingredient

Calcium chloride dihydrate; Glucose; Magnesium chloride hexahydrate; Potassium chloride; Sodium chloride; Sodium bicarbonate

Schedule

Unscheduled

 

1 Name of Medicine

Potassium chloride (Multibic 4 mmol/L potassium only), sodium chloride, sodium bicarbonate, calcium chloride dihydrate, magnesium chloride hexahydrate, glucose monohydrate.

2 Qualitative and Quantitative Composition

Multibic haemofiltration (HF) solution is a solution comprised of electrolytes needed for continuous renal replacement therapies (CRRT). It is used as a substitution solution in haemofiltration therapy.
Multibic HF solution is provided in a two compartment bag with 4.75 L of an alkaline bicarbonate solution in one compartment (compartment B) and 0.25 L of an acidic electrolyte, glucose solution in the other compartment (compartment A) to give a total volume of 5 L after mixing.
Before mixing, each 1000 mL Multibic solution contains the following. See Tables 1 and 2.
See Table 3.
Theoretical osmolarity: Multibic potassium free: 292 mOsm/L; Multibic 4 mmol/L potassium: 300 mOsm/L.
For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution, dialysis (Solution for Haemofiltration).
Clear colourless solution, pH 7.4.

4 Clinical Particulars

4.1 Therapeutic Indications

Replacement fluid, which is administered intravenously in patients with acute renal failure in intensive care units.

4.2 Dose and Method of Administration

Haemofiltration in patients with acute renal failure including the prescription of Multibic solutions should be under the direction of a physician with experience in this treatment.
In acute renal failure treatment is carried out for a limited period and is discontinued when renal function is fully restored.
Multibic solutions containing 0 and 4 mmol/L potassium are exclusively indicated for intravenous use.
Infuse the ready to use Multibic solution into the extracorporeal circulation by means of a metering pump.
As blood serum is filtered off in haemofiltration, the filtered volume, minus the necessary ultrafiltration fluid, must be substituted in the form of Multibic solution.
The filtration rate is prescribed by the attending physician depending on the clinical status and the body weight of the patient. Unless otherwise prescribed a total filtration rate of 20-25 mL/kg/h is appropriate in adults to remove metabolic waste products depending on the metabolic status of the patient. A maximum filtration rate of 75 L per day is recommended.
There is no clinical experience on the use and dosing of this product in children.

Instructions on use of the product.

Do not use unless the ready-to-use solution is clear and colourless, and the bag and connectors are undamaged.
For single use only. In case of doubt, the treating physician should decide about the use of the haemofiltration solution.
The haemofiltration solution should be administered in three steps:

1. Removal of the protective foil and careful inspection of the haemofiltration bag.

The protective foil should only be removed immediately before administration.
Plastic containers may occasionally be damaged during transport from the manufacturer to the dialysis clinic or within the clinic itself. This can lead to contamination and microbiological or fungal growth in the haemofiltration solution. Therefore, careful visual inspection of the bag and the solutions before mixing is necessary. Particular attention should be paid to even the slightest damage to the closure, the welded seam and the corners of the bag in view of a possible contamination.

2. Mixing of the two compartments.

The two-compartment-bag - the bicarbonate and the electrolytes including glucose compartments - are mixed immediately before use to obtain a ready-for-use solution. After mixing both compartments, it must be checked, that the peel seam is completely open, that the solution is clear and colourless and that the bag is not leaking.
Unfold the small compartment; roll up the solution bag starting from the corner opposite the small compartment until the peel seam between both compartments has opened along its entire length and the solutions from both compartments are mixed.

3. Application of the ready-to-use solution.

The ready-to-use solution must be used immediately, but within a maximum of 48 hours after mixing. Any admixture to the ready-to-use solution must only be done after the ready-to-use solution has been thoroughly mixed. After such an admixture, the ready-to-use solution should again be thoroughly mixed prior to use.
If not otherwise prescribed, the ready-to-use solution should be warmed immediately before use to 36.5°C - 38.0°C. The exact temperature must be selected depending on clinical requirements and the technical equipment used.

4.3 Contraindications

Contraindications are dependent on the solutions used in patients.
Multibic potassium free solution should not be used in patients suffering from:
1. Hypokalaemia.
2. Metabolic alkalosis.
Multibic solution containing 4 mmol/L potassium should not be used in patients suffering from:
1. Hyperkalaemia.
2. Metabolic alkalosis.
Haemofiltration dependent contraindications that are due to the technical procedure itself:
1. Renal failure with increased hypercatabolism in cases where uraemic symptoms can no longer be relieved by haemofiltration.
2. Inadequate blood flow from vascular access.
3. If there is a high risk of haemorrhage on account of systemic anticoagulation.

4.4 Special Warnings and Precautions for Use

The haemofiltration solution should be warmed prior to infusion with appropriate equipment to approximately body temperature and must not be infused under any circumstances below room temperature. The warming of the ready-to-use solution to approximately body temperature must be carefully controlled verifying that the ready-to-use solution is clear and without particles.
During application of Multibic in CRRT, white calcium carbonate precipitation has been observed in the tubing lines in rare cases, particularly close to the pump unit and the heating unit warming Multibic. Precipitations particularly can occur if the temperature of the ready-to-use solution at the inlet of the pump unit is already higher than 30°C. Therefore, the Multibic solution in the tubing lines should be closely visually inspected every 30 min during CRRT in order to ensure, that the solution in the tubing system is clear and free from precipitate.
Precipitations may occur also with substantial delay after start of treatment.
If precipitate is observed, the ready-to-use solution and CRRT tubing lines must be replaced immediately and the patient carefully monitored.
The serum potassium concentration must be checked regularly before and during haemofiltration. The potassium status of the patient and its trend during haemofiltration must be considered. If hypokalaemia is present or tends to develop, supplementation of potassium and/or changing to a Multibic solution with higher potassium concentration may be required.

For Multibic potassium free solution.

If hyperkalaemia tends to develop, an increase in the filtration rate may be indicated as well as usual measures of intensive care medicine.

For Multibic solution containing 4 mmol/L potassium.

If hyperkalaemia tends to develop, an increase in the filtration rate and/or changing to a substitution solution with a lower potassium concentration may be indicated as well as usual measures of intensive care medicine.
In addition, the following parameters should be monitored before and during haemofiltration: serum sodium, serum calcium, serum magnesium, serum phosphate, serum glucose, acid/ base status, levels of urea and creatinine, body weight and fluid balance (for the early recognition of hyper- and hypohydration).
Prior to use the solution bag must be carefully inspected as described in detail in Dose and Method of Administration.
Do not use before mixing the two compartment solutions.

Special populations.

No studies have been conducted on special target patient groups.

Use in the elderly.

At present no clinical experience of use of this medicine with patients in this target group is available.

Paediatric use.

There is no clinical experience on the use of this product in children.

Effect on laboratory tests.

The effect on laboratory tests of this medicine has not been established.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The correct dosing of substitution solutions and strict monitoring of clinical chemistry parameters and vital signs will limit interactions with other drugs.
The following interactions could occur:
1. Electrolyte substitution solutions, parenteral nutrition and other infusions, which are usually given in intensive care medicine, could interact with the serum composition and the fluid status of the patient. This must be considered when prescribing haemofiltration treatments.
2. Haemofiltration treatments may reduce the blood concentration of drugs, especially of drugs with a low protein binding capacity, with a small distribution volume, with molecular weight below the cut off of the haemofilter and of drugs adsorbed to the haemofilter. An appropriate revision of the dose of such drugs may be required.
3. Toxic effects of digitalis may be masked by hyperkalaemia, hypermagnesaemia and hypocalcaemia. The correction of these electrolytes by haemofiltration may precipitate signs and symptoms of digitalis toxicity, e.g. cardiac arrhythmia.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No studies have been conducted to assess the effects of Multibic on fertility.
(Category Exempt)
There are no adequate and well controlled studies in pregnant women with Multibic. The bicarbonate buffered substitution solution must only be used after assessment of the potential risks and benefits for the mother and child.
At present no clinical experience of use of this medicine with patients in this target group is available. The bicarbonate buffered substitution solution must only be used after assessment of the potential risks and benefits for the mother and child.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions may result from the treatment mode itself or may be induced by this medicinal product:

Gastrointestinal disorders.

Nausea, vomiting.

Vascular disorders.

Hypotension and hypertension.

Musculoskeletal and connective tissue disorders.

Muscle cramps.
In general, the tolerability of bicarbonate buffered haemofiltration solution is good. However, the following potential side effects of the treatment can be anticipated: hyper- or hypohydration; electrolyte disturbances (e.g. hypokalaemia); hypophosphataemia, hyperglycaemia; and metabolic alkalosis.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

No reports of emergency situations have arisen after using recommended doses. Moreover, the administration of the solution can be discontinued at any time. If the fluid balance is not accurately calculated and monitored, hyperhydration or hypohydration may occur resulting in associated circulatory reactions. These may be manifest through changes in blood pressure, central venous pressure, heart rate, and pulmonary arterial pressure. In cases of hyperhydration congestive cardiac failure and/or pulmonary congestion may be induced.
In cases of hyperhydration, ultrafiltration should be increased, and the rate and volume of substitution solution infused reduced. In cases of marked hypohydration, ultrafiltration should be decreased or discontinued, and the volume of substitution solution infused increased as appropriate.
Overdosage may result in disturbances of electrolyte concentrations and the acid-base-balance, e.g. an overdose of bicarbonate may occur if an inappropriate large volume of substitution solution is infused/administered. This could possibly lead to metabolic alkalosis, decrease of ionized calcium, or tetany.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Solution for haemofiltration.
ATC Code: B05Z B - Haemofiltrates.

Mechanism of action.

During continuous haemofiltration water and solutes such as uremic toxins, electrolytes, and bicarbonate are removed from the blood by ultrafiltration. The ultrafiltrate is replaced by a substitution solution (Multibic), with a balanced electrolyte and buffer composition.
It is used to help remove uraemic toxins and correct the patient's fluid balance; Multibic HF solution also corrects the patient's acid-base-balance. Renal failure leads to the buffer systems being exhausted which causes metabolic acidosis, and so administration of buffer base is required. Bicarbonate-buffered hemofiltration solutions result in a direct increase of the buffer capacity in blood.
The ready to use Multibic solution is a bicarbonate buffered substitution solution for intravenous administration for the treatment of acute renal failure, of any origin, by continuous haemofiltration.
The electrolytes Na+, K+, Mg2+, Ca2+, Cl-, and bicarbonate are essential for the maintenance and correction of fluids and electrolyte homeostasis (blood volume, osmotic equilibrium, acid/ base balance). The pharmacodynamic effects of the haemofiltration solution result from the additive physiological effects of the well balanced single components.

Clinical trials.

Multibic solution is a replacement fluid, which is administered intravenously in patients with acute renal failure in intensive care units.
The clinical trial program showed that Multibic solution is effective for the target population of patients.
An open randomised multicentre trial was conducted which compared the bicarbonate buffered haemofiltration solution with a lactate solution in the continuous venovenous haemofiltration (CVVH) therapy of patients with acute renal failure. Patients were treated in parallel groups with bicarbonate (n = 61) or lactate (n = 56) buffered haemofiltration solution. The bicarbonate buffered solutions contained 0 or 2 mmol potassium depending on the serum potassium values of individual patients. The normal dosage rate was 1000 mL/h (range 600-1200 mL/h).
Both solutions produced statistically equivalent serum bicarbonate concentrations. The lactate buffered solution resulted in serum bicarbonate and base excess levels below the optimum with a trend towards acidosis. The bicarbonate buffered solution resulted in statistically higher serum bicarbonate and base excess levels but still below alkolotic values. The lactate buffered solution produced a trend towards higher serum lactate concentrations (see Table 4).
No adverse events or side effects specifically related to the bicarbonate buffered solutions were recorded.
Both solutions were adequate and therapeutically equivalent with respect to the treatment of acute renal failure.
An open label multicentre trial was conducted using bicarbonate buffered haemofiltration solution in continuous haemofiltration therapy of patients with acute renal failure and lactacidemia (N = 25). Patients were treated with bicarbonate buffered haemofiltration solution until either renal function was restored or the patient was removed from the study. The bicarbonate buffered solutions contained 0 or 2 mmol potassium depending on the serum potassium values of individual patients. The normal dosage rate was 1000 mL/h (range 600-1200 mL/h).
The solution produced physiological serum bicarbonate concentrations and acidosis was balanced within the first day of treatment. The bicarbonate buffered solution did not produce any shift to alkolotic serum bicarbonate and base excess levels. Serum bicarbonate was at optimum levels (approx. 24 mmol/L) from day 2 of treatment (see Table 5).
Haemofiltration mean duration of treatment was 5.8 ± 0.91 days (range 1 to 17 days). On day 5, mean daily ultrafiltration volume was 28.9 ± 3.17 L (range 18.7 to 55.0 L). The corresponding mean substitution volume was 26.9 ± 2.98 L (range 16.0 to 52.0 L).
No adverse events or side effects specifically related to the bicarbonate buffered solutions were recorded. The reported adverse events were complications of the severe underlying disease.
The solutions were adequate with respect to the treatment of acute renal failure and the bicarbonate buffered solution normalised the acidosis without risk for alkalosis or side effects.

5.2 Pharmacokinetic Properties

The ready to use Multibic solutions must only be administered intravenously.
The distribution of electrolytes and bicarbonate is regulated in accordance with requirements and the metabolic status and residual renal function. The active substances of the substitution solution are not metabolized except for glucose. The elimination of water and electrolytes depends on cellular requirements, metabolic status, residual renal function, and on other routes of fluid losses (e.g. gut, lung, and skin).
No pharmacokinetic interactions between the individual ingredients of Multibic are known.

Absorption.

Bioavailability of substitution solutions is 100% as they are administered intravenously.

Distribution.

The distribution of substitution solutions depends on the osmotic gradient between extra- and intracellular space, whereas the distribution of dissolved electrolytes is regulated according to their intra- and extracellular concentration gradients. Glucose freely distributes in the extracellular space and subsequently enters the cells under the assistance of insulin.

Metabolism.

The active substances of Multibic are not metabolized except for glucose.

5.3 Preclinical Safety Data

Genotoxicity.

Given the nature of its components, Multibic is not considered to pose a genotoxic hazard.

Carcinogenicity.

Given the nature of its components, Multibic is not considered to pose a carcinogenic hazard.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each bag with haemofiltration solution contains the following excipients, see Table 6.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. If an addition to the substitution solution is done, it should be done only after evaluating the compatibility with the substitution solution and only after the two compartments of the substitution solution have been thoroughly mixed.

6.3 Shelf Life

In Australia information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C. Do not store below 4°C.
Product is for single use in one patient only. Discard any residue.

Storage conditions after mixing of the two compartments (ready-to-use solution).

Chemical and physical in-use stability of the ready-to-use solution has been demonstrated for 48 hours at 30°C. It is not recommended to store the ready-to-use solution longer than 48 h including duration of treatment or at a temperature higher than 30°C prior to the inlet of the pump unit.
From a microbiological point of view, once connected to the haemofiltration circuit, and as bicarbonate is present, the product shall be used immediately.

6.5 Nature and Contents of Container

Multibic potassium-free solution for haemofiltration. AUST R Number 357591.
Multibic 4 mmol/L potassium Solution for Haemofiltration. AUST R Number 357590.
The container consists of a double chamber bag. The contents of this bag are 4.75 L (alkaline bicarbonate solution) + 0.25 L (acidic electrolyte, glucose solution) = 5.0 L (ready-to-use solution).
The film used for the bag is made of polyethylene terephthalate (PET), which is coated with SiOx as a gas barrier, polyamide and a polypropylene-synthetic elastomer blend.
The double chamber bag is wrapped in a film made of a polyolefine-synthetic elastomer and/or plastomer blend.
Each bag is equipped with a HF-connector, a Luer-lock-connector and an injection port and is covered by a protective foil.

Pack size.

Carton containing 2 x 5000 mL double chamber bags.

6.6 Special Precautions for Disposal

In Australia any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

See Table 7.

7 Medicine Schedule (Poisons Standard)

Unscheduled.

Summary Table of Changes