Phoxilium

Package leaflet: Information for the user

PHOXILIUM 1.2 mmol/l phosphates
Solution for hemodialysis and hemofiltration
Calcium chloride dihydrate, magnesium chloride hexahydrate, sodium chloride, sodium bicarbonate, potassium chloride, disodium phosphate anhydrous
Please read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet:

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

1. What Phoxilium is and what it is used for

Phoxilium is a solution for hemofiltration containing calcium chloride dihydrate, magnesium chloride hexahydrate, sodium chloride, sodium bicarbonate, potassium chloride, and disodium phosphate anhydrous.
Phoxilium is used in hospitals under intensive medical care to restore blood chemical balance in patients with kidney damage.
Continuous renal replacement therapy aims to remove accumulated metabolic waste products from the blood when the kidneys are not functioning.
Phoxilium solution is used to treat critically ill patients with acute kidney injury who have:

• normal blood potassium levels (normokalemia) or
• normal or low blood phosphate levels (normo- or hypophosphatemia).

This medicine may also be used in cases of poisoning with drugs containing substances that are dialyzable or filterable.

2. Information before using Phoxilium

Do not use Phoxilium in the following three cases:

• if the patient has high potassium levels in the blood (hyperkalemia);
• if the patient has high bicarbonate levels in the blood (metabolic alkalosis);
• if the patient has high phosphate levels in the blood (hyperphosphatemia).

1/8
Do not use hemodialysis or hemofiltration in the following three cases:

• if symptoms caused by high urea levels in the blood (uremic symptoms), resulting from kidney damage with marked hypercatabolism (abnormal increase in breakdown processes), cannot be alleviated by hemofiltration;
• insufficient arterial pressure in the vascular access;
• reduced blood coagulation (systemic anticoagulation) when there is an existing risk of bleeding.

Warnings and precautions
Before starting treatment with Phoxilium, discuss this with your doctor, pharmacist, or nurse.
Before and during treatment, blood tests will be performed to monitor acid-base balance and electrolyte levels, including the volume of infused intravenous fluids and fluids removed (urine output), even if these are not directly related to the treatment.

Phoxilium and other medicines
Inform your doctor or pharmacist about all medicines currently used or recently used, as well as any medicines you plan to take. This is important because the levels of other medicines may influence Phoxilium treatment. Your doctor will decide whether any adjustments to your other medications are necessary.
In particular, inform your doctor about the use of:

• phosphates from additional sources (e.g. nutritional fluids), as they may increase the risk of high phosphate levels in the blood (hyperphosphatemia);
• vitamin D and medications containing calcium chloride or calcium gluconate, due to the possible increased risk of high calcium levels in the blood (hypercalcemia);
• sodium bicarbonate, as it may increase the risk of excess bicarbonate in the blood (metabolic alkalosis);
• citrate as an anticoagulant, as it may reduce serum calcium levels.

Pregnancy, breastfeeding, and effects on fertility
Pregnancy and breastfeeding:
There are no documented clinical data on the use of this medicine during pregnancy and lactation. This medicine should be administered to pregnant and breastfeeding women only if clearly needed.

Fertility:
Phoxilium is not expected to affect fertility, as calcium, sodium, potassium, magnesium, chlorides, dihydrogen phosphates, and bicarbonates are normal components of the human body.

Driving and operating machinery
Phoxilium has no effect on the ability to drive or operate machinery.

3. How to use Phoxilium

Phoxilium is a product used in hospitals and is administered exclusively by medical personnel.
The volume of Phoxilium and thus the dose depends on the patient's condition. The treating physician will determine the dose volume.
Phoxilium may be administered directly into the bloodstream (intravenously) via a CRRT device or during hemodialysis, when the solution passes on one side of the dialysis membrane and blood on the other side.
2/8
This medicine should always be used exactly as directed by the doctor, pharmacist, or nurse. If in doubt, consult the doctor, pharmacist, or nurse.
Instructions for use are provided in the section "The following information is intended exclusively for healthcare professionals".
Use of a higher than recommended dose of Phoxilium
Phoxilium is intended for hospital use and must be administered only by physicians under careful monitoring of fluid balance and blood chemistry.
Therefore, administration of a higher than recommended dose of Phoxilium is unlikely.
In the unlikely event of overdose, the treating physician will take all necessary corrective actions and adjust the dose accordingly.
Overdose may lead to fluid overload, decreased plasma bicarbonate concentration (metabolic acidosis), and/or elevated phosphate levels (hyperphosphatemia) in patients with kidney impairment.
It may also lead to serious consequences such as congestive heart failure and disturbances in blood chemistry.
If there are any doubts regarding the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Three adverse reactions may occur related to the use of Phoxilium:

• abnormal water content in the body (overhydration or dehydration),
• changes in blood mineral salt levels (electrolyte imbalance, such as hyperphosphatemia), and
• increased bicarbonate concentration in plasma (metabolic alkalosis) or decreased bicarbonate concentration in plasma (metabolic acidosis).

There are also certain adverse reactions that may be caused by dialysis treatment:

• nausea, vomiting, muscle cramps, and low blood pressure (hypotension).

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed
in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions
can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Aleje Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 4921301
Fax: +48 22 4921309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions allows more information on the safety of the medicine to be collected.
3/8

5. How to store Phoxilium

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and on the packaging.
The expiry date refers to the last day of the specified month.
Store between +4°C and +30°C. Do not store in a refrigerator or freeze.
Chemical and physical stability of the reconstituted solution has been demonstrated for 24 hours at +22 ºC. If the solution is not used immediately, the user is responsible for the storage conditions and duration prior to use, which should not exceed 24 hours in total, including the duration of the procedure.
Do not use this medicine if the solution appears cloudy or if the outer protective packaging is damaged. All seals must be intact.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the packaging and other information

What Phoxilium contains
The active substances before mixing and after mixing (reconstitution) are listed below.
Active substances before mixing:
1000 ml of solution in small chamber A contains:
Calcium chloride dihydrate 3.68 g
Magnesium chloride hexahydrate 2.44 g
1000 ml of solution in large chamber B contains:
Sodium chloride 6.44 g
Sodium bicarbonate 2.92 g
Potassium chloride 0.314 g
Disodium phosphate anhydrous 0.225 g
Active substances after mixing:
Solutions in chambers A (250 ml) and B (4750 ml) are mixed to obtain one reconstituted
solution (5000 ml) containing:
mmol/l
calcium, Ca 1.25
magnesium, Mg 0.6
sodium, Na 140
chloride, Cl - 115.9
hydrogen phosphate, HPO 1.2
bicarbonate, HCO 30
potassium, K 4
Theoretical osmolarity: 293 mOsm/l
Other ingredients:

• carbon dioxide (for pH adjustment), E290;
• hydrochloric acid (for pH adjustment), E507;
• water for injections.

4/8
What Phoxilium looks like and contents of the pack
Phoxilium is a solution for hemodialysis and hemofiltration supplied in dual-chamber bags.
The final reconstituted solution is obtained by breaking the seal and mixing both solutions.
The reconstituted solution is clear and colourless. Each bag (A+B) contains 5000 ml of solution
for hemofiltration and hemodialysis. Each bag is placed in a transparent outer packaging.
Each pack contains two bags and a package leaflet.
Marketing Authorisation Holder:
Vantive Belgium SRL
Boulevard d’Angleterre 2
1420 Braine-l’Alleud
Belgium
Manufacturer:
Bieffe Medital S.p.A., Via Stelvio 94, 23035 Sondalo (SO), ITALY
Vantive Manufacturing Limited, Moneen Road, Castlebar, County Mayo, F23 XR63, Ireland
This medicinal product is authorised in the European Economic Area and Great Britain (Northern Ireland) under the following names:
Austria, Belgium, Bulgaria, Cyprus, Denmark, Estonia, Finland, France, Greece, Spain, the Netherlands,
Ireland, Iceland, Lithuania, Luxembourg, Latvia, Malta, Germany, Norway, Poland, Portugal, Romania,
Slovakia, Slovenia, Sweden, United Kingdom (Northern Ireland), Italy: Phoxilium
Hungary: Phoxil

The following information is intended exclusively for healthcare professionals:

Phoxilium 1.2 mmol/l phosphates
Solution for hemodialysis and hemofiltration
Precautions
Strictly follow the instructions for use / handling of the medicinal product Phoxilium.
The solutions from both chambers must be mixed before use.
Administration of a contaminated solution may cause sepsis and shock.
To increase patient comfort, Phoxilium may be warmed to +37°C. Warming
the solution before use must be performed before reconstitution and only using a dry heat source.
Solutions must not be warmed in a water bath or microwave oven. Before administration,
Phoxilium should be visually inspected for the presence of particulate matter and discoloration.
Do not administer if the solution is not clear or if the seal is damaged.
Serum inorganic phosphate levels should be monitored regularly. Inorganic phosphates
should be supplemented in cases of low blood phosphate concentration.
Additional substitution of sodium bicarbonate may increase the risk of metabolic alkalosis.
In case of fluid imbalance, the clinical status should be carefully monitored and fluid balance restored:

• In case of hypervolemia, the net ultrafiltration rate in the CRRT machine may be increased and (or) the infusion rate of fluids other than replacement fluid and (or) dialysate may be reduced.

5/8

• In case of hypovolemia, the net ultrafiltration rate in the CRRT machine may be reduced and (or) the infusion rate of fluids other than replacement fluid and (or) dialysate may be increased.

Warnings:
Phoxilium should not be used in patients with hyperkalemia. Serum potassium
concentration must be monitored before and during hemofiltration and (or) hemodialysis.
Since Phoxilium is a potassium-containing solution, transient hyperkalemia may occur
after initiation of treatment. The infusion rate should be reduced until appropriate potassium
concentration is achieved. If hyperkalemia persists, administration of the medicinal product should be discontinued immediately.
If hyperkalemia occurs during use of Phoxilium as dialysate, it may be necessary to administer a potassium-free dialysate to increase potassium removal rate.
Since Phoxilium is a phosphate-containing solution, transient hyperphosphatemia may occur
after initiation of treatment. The infusion rate should be reduced until appropriate phosphate
concentration is achieved. If hyperphosphatemia persists, administration of the medicinal product should be discontinued immediately.
Patients receiving Phoxilium should have regular monitoring of electrolytes and blood acid-base status. Phoxilium contains phosphoric acid, a weak acid, which may affect the patient's acid-base balance. If metabolic acidosis develops or worsens during treatment with Phoxilium, it may be necessary to reduce the infusion rate or discontinue administration of the medicinal product.
Since Phoxilium does not contain glucose, its administration may lead to hypoglycemia. Blood glucose levels should be monitored regularly in diabetic patients (especially those receiving insulin or other glucose-lowering agents); this should also be considered in non-diabetic patients, for example due to the risk of asymptomatic hypoglycemia during treatment. In case of hypoglycemia, use of a glucose-containing solution should be considered. Other corrective measures may also be necessary to maintain appropriate blood glucose concentration.

Dosage:
The volume and rate of administration of the medicinal product Phoxilium depend on serum phosphate and other electrolyte concentrations, acid-base balance, fluid balance, and the patient's overall clinical condition. The volume of replacement fluid and (or) dialysate to be administered will also depend on the desired treatment intensity (dose). The method of administration (dose, infusion rate, and total volume) of Phoxilium should be determined solely by a physician experienced in intensive care and continuous renal replacement therapy (CRRT).
Therefore, the dose volume depends on the physician's decision and recommendations.
Flow rate ranges for replacement fluid in hemofiltration and hemodiafiltration are:
Adults: 500 to 3000 ml/hour
Flow rate ranges for dialysate in continuous hemodialysis and continuous hemodiafiltration are:
Adults: 500 to 2500 ml/hour
In adults, the usual total CRRT flow rate (dialysate and replacement fluids) is typically 2000 to 2500 ml/hour, corresponding to a daily fluid volume of approximately 48 to 60 liters.
6/8
Children and adolescents:
In children, from neonates to adolescents up to 18 years of age, the flow rate range when used as replacement fluid in hemofiltration and hemodiafiltration, or as dialysis solution (dialysate) in continuous hemodialysis and continuous hemodiafiltration, is 1000 to 4000 ml/hour/1.73 m².
When the calculated pediatric dose exceeds the maximum adult dose in adolescents (12–18 years), the adult dose should be applied.

Instructions for use/handling
The solution from the small chamber A is added to the solution in the large chamber B by breaking the frangible seal or tearing the seal immediately before use. The reconstituted solution should be clear and colorless.
Aseptic technique must be used during handling and administration of the medicinal product to the patient.
Use only if the outer protective packaging is intact, all seals are undamaged, the peelable seal is not damaged, and the solution is clear. Squeeze the bag firmly to check for leaks. If leakage is observed, the solution must be discarded immediately, as sterility cannot be guaranteed.
The large chamber B is equipped with an injection port, which allows addition of other necessary medicinal products after reconstitution. The user is responsible for assessing compatibility of the added medicinal product with Phoxilium by checking for any discoloration and (or) precipitation, presence of insoluble complexes or crystals.
Before adding another medicinal product, verify that it is soluble and stable in Phoxilium and that the pH range of Phoxilium is suitable (pH of the reconstituted solution is 7.0–8.5). Additional components may be incompatible with the solution. Refer to the instructions for use of the added medicinal product.
Remove fluid from the injection port, hold the inverted bag ("upside down"), inject the medicinal product through the injection port, and mix thoroughly. Introduction and mixing of additional components must always be performed before connecting the bag to the extracorporeal circuit. The solution should be administered immediately.
I Remove the outer packaging immediately before use, discard all remaining packaging. Open the seal by holding the small chamber with both hands and squeezing until the peelable seal separating the two chambers breaks (see Figure I below).
II Press the large chamber with both hands until the peelable seal between the two chambers is completely opened (see Figure II below).
III Thorough mixing is ensured by gently agitating the bag. The solution is now ready for use and the bag can be hung on an IV pole (see Figure III below).
IV Each of the two access ports can be connected to a dialysis or replacement line.
IVa If using a luer-type connector, remove the cap by twisting and pulling, then connect the male luer-lock end of the dialysis or replacement line to the female luer-lock receptor on the bag by pushing and twisting. Ensure the connection is fully seated and secure. The connection is now open. Check that fluid flows freely (see Figure IV.a below).
When dialysis or replacement lines are disconnected from the luer connector, the connection will close and fluid flow will stop. The luer port is needle-free and can be wiped with disinfectants.
IVb When using the injection port, first remove the cap by breaking it off. The injection port can be wiped with disinfectants. Then puncture the rubber septum with a needle. Check that fluid flows freely (see Figure IV.b below).
7/8
The reconstituted solution should be used immediately. If not used immediately, the reconstituted solution should be used within 24 hours after adding solution A to solution B, including treatment time.
The reconstituted solution is for single use only. Unused solution must be discarded immediately after use.
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

8/8

Package leaflet: Information for the user

PHOXILIUM 1.2 mmol/l phosphates
Solution for hemodialysis and hemofiltration
Calcium chloride dihydrate, magnesium chloride hexahydrate, sodium chloride, sodium bicarbonate, potassium
chloride, disodium phosphate anhydrous
Please read this leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor, pharmacist, or nurse.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

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

1. What is Phoxilium and what is it used for

Phoxilium is a medicinal product belonging to the group of haemofiltration solutions and contains calcium chloride dihydrate,
magnesium bicarbonate hexahydrate, sodium chloride, sodium bicarbonate, potassium chloride and disodium phosphate anhydrous.
Phoxilium is used in hospitals under intensive medical care conditions to restore blood chemical balance in patients with kidney impairment.
Continuous renal replacement therapy aims to remove accumulated metabolic waste products from the blood when the kidneys are not functioning.
Phoxilium solution is used to treat critically ill patients with acute kidney injury who have:

• normal blood potassium levels (normokalemia) or
• normal or low blood phosphate levels (normo- or hypophosphatemia).

This medicinal product may also be used in cases of poisoning with drugs containing substances that are dialysable or filterable.

2. Important information before using Phoxilium

Do not use Phoxilium in the following three cases:

• if the patient has high potassium levels in the blood (hyperkalemia);
• if the patient has high bicarbonate levels in the blood (metabolic alkalosis);
• if the patient has high phosphate levels in the blood (hyperphosphatemia).

1/8
Do not use hemodialysis or hemofiltration in the following three cases:

• if hemofiltration cannot alleviate symptoms caused by high urea levels in the blood (uremic symptoms) resulting from kidney damage with marked hypercatabolism (abnormal increase in substance breakdown processes);
• insufficient arterial pressure in the vascular access;
• reduced blood coagulation (systemic anticoagulation) when there is an existing risk of bleeding.

Warnings and precautions
Before starting treatment with Phoxilium, discuss this with your doctor, pharmacist,
or nurse.
Before and during treatment, blood tests will be performed to monitor acid-base balance and electrolyte concentrations, including volumes of infused intravenous fluids and excreted fluids (urine), even those not directly related to the treatment.
Phoxilium and other medicines
You must inform your doctor or pharmacist about all medicines currently used or recently used, as well as any medicines you plan to take. This is important because the levels of other medicines may affect Phoxilium treatment. Your doctor will decide whether any changes to your other medications are necessary.
In particular, inform your doctor about taking:

• phosphates from additional sources (e.g. nutritional fluids), as they may increase the risk of high phosphate levels in the blood (hyperphosphatemia);
• vitamin D and medications containing calcium chloride or calcium gluconate, due to the possible increased risk of high calcium levels in the blood (hypercalcemia);
• sodium bicarbonate, as it may increase the risk of excess bicarbonate in the blood (metabolic alkalosis);
• citrate as an anticoagulant, as it may reduce serum calcium levels.

Pregnancy, breastfeeding, and effects on fertility
Pregnancy and breastfeeding:
There are no documented clinical data on the use of this medicine during pregnancy and lactation. This medicine should be administered to pregnant and breastfeeding women only if clearly necessary.
Fertility:
An effect of the medicine on fertility is not expected, since calcium, sodium, potassium, magnesium, chlorides, dihydrogen phosphates, and bicarbonates are normal components of the human body.
Driving and operating machinery
Phoxilium has no effect on the ability to drive or operate machinery.

3. How to use Phoxilium

Phoxilium is a hospital product administered exclusively by medical personnel.
The volume of Phoxilium and thus the dose depends on the patient's condition. The treating physician will determine the dose volume.
Phoxilium may be administered directly into the bloodstream (intravenously) via a CRRT machine or during hemodialysis, when the solution passes on one side of the dialysis membrane and blood on the other side.
2/8
This medicine should always be used exactly as directed by the physician, pharmacist, or nurse. If in doubt, consult the physician, pharmacist, or nurse.
Instructions for use are provided in the section "The following information is intended exclusively for healthcare professionals".
Use of a higher than recommended dose of Phoxilium
Phoxilium is intended for hospital use and must be administered only by physicians under careful monitoring of fluid balance and blood chemical composition.
Therefore, administration of a higher than recommended dose of Phoxilium is unlikely.
In the unlikely event of overdose, the treating physician will take all necessary corrective actions and adjust the dose accordingly.
Overdose may lead to fluid overload, decreased plasma bicarbonate concentration (metabolic acidosis), and/or elevated phosphate levels (hyperphosphatemia) in patients with kidney impairment.
It may also lead to serious consequences such as congestive heart failure and disturbances in blood chemical composition.
If there are any doubts regarding the use of this medicine, consult the physician or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will experience them.
Three adverse reactions may be related to the use of Phoxilium:

• abnormal fluid levels in the body (overhydration or dehydration),
• changes in blood mineral salt levels (electrolyte imbalance, such as hyperphosphatemia), and
• increased bicarbonate concentration in plasma (metabolic alkalosis) or decreased bicarbonate concentration in plasma (metabolic acidosis).

There are also certain adverse reactions that may be caused by dialysis therapy:

• nausea, vomiting, muscle cramps, and low blood pressure (hypotension).

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed
in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions
can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Aleje Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 4921301
Fax: +48 22 4921309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.
3/8

5. How to store Phoxilium

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and on the packaging.
The expiry date refers to the last day of the specified month.
Store between +4°C and +30°C. Do not store in the refrigerator or freeze.
Chemical and physical stability of the reconstituted solution has been demonstrated for 24 hours at +22 ºC. If the solution is not used immediately, the user is responsible for the storage conditions and duration prior to use, which should not exceed 24 hours, including the duration of the procedure.
Do not use this medicine if the solution appears cloudy or if the outer protective packaging is damaged. All seals must be intact.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Phoxilium contains
The active substances before mixing and after mixing ( reconstitution ) are listed below.
Active substances before mixing:
1000 ml of solution in small chamber A contains:
Calcium chloride dihydrate 3.68 g
Magnesium chloride hexahydrate 2.44 g
1000 ml of solution in large chamber B contains:
Sodium chloride 6.44 g
Sodium hydrogen carbonate 2.92 g
Potassium chloride 0.314 g
Disodium phosphate anhydrous 0.225 g
Active substances after mixing:
The solutions in chambers A (250 ml) and B (4750 ml) are mixed to obtain one reconstituted
solution (5000 ml) containing:
mmol/l
calcium, Ca 1.25
magnesium, Mg 0.6
sodium, Na 140
chloride, Cl - 115.9
hydrogen phosphate, HPO 1.2
bicarbonate, HCO 30
potassium, K 4
Theoretical osmolarity: 293 mOsm/l
Other components:

• carbon dioxide (for pH adjustment), E290;
• hydrochloric acid (for pH adjustment), E507;
• water for injections.

4/8
What Phoxilium looks like and contents of the pack
Phoxilium is a solution for hemodialysis and hemofiltration, supplied in dual-chamber bags.
The final reconstituted solution is obtained by breaking the breakable seal and mixing both
solutions. The reconstituted solution is clear and colourless. Each bag (A+B) contains 5000 ml
of solution for hemofiltration and hemodialysis. Each bag is placed in a transparent outer
packaging.
Each package contains two bags and a patient information leaflet.
Marketing Authorisation Holder:
Vantive Belgium SRL
Boulevard d’Angleterre 2
1420 Braine-l’Alleud
Belgium
Manufacturer:
Bieffe Medital S.p.A., Via Stelvio 94, 23035 Sondalo (SO), ITALY
Vantive Manufacturing Limited, Moneen Road, Castlebar, County Mayo, F23 XR63, Ireland
This medicinal product is authorised in the European Economic Area and Great Britain (Northern Ireland) under the following names:
Austria, Belgium, Bulgaria, Cyprus, Denmark, Estonia, Finland, France, Greece, Spain, Netherlands,
Ireland, Iceland, Lithuania, Luxembourg, Latvia, Malta, Germany, Norway, Poland, Portugal, Romania,
Slovakia, Slovenia, Sweden, United Kingdom (Northern Ireland), Italy: Phoxilium
Hungary: Phoxil

The following information is intended exclusively for healthcare professionals:

Phoxilium 1.2 mmol/l phosphates
Solution for hemodialysis and hemofiltration
Precautions
Strictly follow the instructions for use / handling of the medicinal product Phoxilium.
The solutions from both chambers must be mixed before use.
Administration of a contaminated solution may cause sepsis and shock.
To increase patient comfort, Phoxilium may be warmed to +37°C. Warming the solution before use must be performed prior to reconstitution and only using a dry heat source. Do not warm solutions in a water bath or microwave oven. Before administration, visually inspect Phoxilium for the presence of particulate matter or discoloration. Do not administer if the solution is not clear or if the seal is damaged.
Serum inorganic phosphate levels should be monitored regularly. Inorganic phosphates must be supplemented in cases of low blood phosphate concentration.
Additional substitution of sodium bicarbonate may increase the risk of metabolic alkalosis.
In cases of fluid imbalance, the clinical status should be carefully monitored and fluid balance restored:

• In hypervolemia, the net ultrafiltration rate in the CRRT machine may be increased and (or) the infusion rate of fluids other than replacement fluid and (or) dialysate may be reduced.

5/8

• In hypovolemia, the net ultrafiltration rate in the CRRT machine may be reduced and (or) the infusion rate of fluids other than replacement fluid and (or) dialysate may be increased.

Warnings:
Phoxilium should not be used in patients with hyperkalemia. Serum potassium levels must be monitored before and during hemofiltration and (or) hemodialysis.
Since Phoxilium is a potassium-containing solution, transient hyperkalemia may occur after initiating treatment. The infusion rate should be reduced until the appropriate potassium concentration is achieved. If hyperkalemia persists, administration of the medicinal product must be immediately discontinued.
If hyperkalemia occurs during the use of Phoxilium as a dialysate, it may be necessary to administer a potassium-free dialysate to enhance potassium removal.
Since Phoxilium is a phosphate-containing solution, transient hyperphosphatemia may occur after initiating treatment. The infusion rate should be reduced until the appropriate phosphate concentration is achieved. If hyperphosphatemia persists, administration of the medicinal product must be immediately discontinued.
Patients receiving Phoxilium should have regular monitoring of electrolytes and blood acid-base status. Phoxilium contains monohydrogen phosphate, a weak acid, which may affect the patient's acid-base balance. If metabolic acidosis develops or worsens during treatment with Phoxilium, it may be necessary to reduce the infusion rate or discontinue administration of the medicinal product.
Since Phoxilium does not contain glucose, its administration may lead to hypoglycemia. Blood glucose levels should be regularly monitored in diabetic patients (especially those receiving insulin or other glucose-lowering medications); this should also be considered in non-diabetic patients due to the risk of asymptomatic hypoglycemia during treatment. In case of hypoglycemia, use of a glucose-containing solution should be considered. Other corrective measures may also be necessary to maintain appropriate blood glucose levels.
Dosage:
The volume and rate of administration of Phoxilium depend on serum phosphate and other electrolyte concentrations, acid-base balance, fluid balance, and the patient's overall clinical condition. The volume of replacement fluid and (or) dialysate to be administered will also depend on the desired treatment intensity (dose). The method of administration (dose, infusion rate, and total volume) of Phoxilium should be determined solely by a physician experienced in intensive care and continuous renal replacement therapy (CRRT).
Therefore, the dosage volume is subject to the physician's decision and recommendations.
Flow rate ranges for replacement fluid in hemofiltration and hemodiafiltration are:
Adults: 500 to 3000 ml/hour.
Flow rate ranges for dialysate in continuous hemodialysis and continuous hemodiafiltration are:
Adults: 500 to 2500 ml/hour.
In adults, the usual total flow rate for CRRT (dialysate and replacement fluids) is typically between 2000 and 2500 ml/hour, corresponding to a daily fluid volume of approximately 48 to 60 liters.
6/8
Children and adolescents:
In children, from neonates to adolescents up to 18 years of age, the flow rate range when used as replacement fluid in hemofiltration and hemodiafiltration, or as dialysis solution (dialysate) in continuous hemodialysis and continuous hemodiafiltration, is 1000 to 4000 ml/hour/1.73 m².
In adolescents (12–18 years), if the calculated pediatric dose exceeds the maximum adult dose, the adult dose should be applied.
Instructions for use/handling
The solution from the small chamber A is added to the solution in the large chamber B by breaking the frangible seal or tearing the seal immediately before use. The reconstituted solution should be clear and colorless.
Aseptic technique must be used during handling and administration of the medicinal product to the patient.
Use only if the outer protective packaging is intact, all seals are undamaged, the frangible seal is not broken, and the solution is clear. Squeeze the bag firmly to check for leaks. If leakage is observed, the solution must be immediately discarded, as sterility cannot be guaranteed.
The large chamber B is equipped with an injection port, which allows the addition of other necessary medicinal products after reconstitution. The user is responsible for assessing compatibility with Phoxilium by checking for any discoloration and (or) precipitation, presence of insoluble complexes, or crystals.
Before adding another medicinal product, verify whether it is soluble and stable in Phoxilium and whether the pH range of Phoxilium is suitable (pH of the reconstituted solution is 7.0–8.5). Additional components may be incompatible with the solution. Refer to the instructions for use of the added medicinal product.
Remove fluid from the injection port, hold the bag inverted (upside down), inject the medicinal product through the injection port, and mix thoroughly. Introduction and mixing of additional components must always be performed before connecting the solution bag to the extracorporeal circuit. The solution must be administered immediately.
I Remove the outer packaging immediately before use and discard all remaining packaging. Open the seals between both chambers of the bag by breaking the frangible seal. The frangible seal will remain in the bag (See Figure I below).
II Ensure that all fluid from the small chamber A has been transferred into the large chamber B (See Figure II below).
III Rinse the small chamber A twice by squeezing the mixed solution back into the small chamber A, then back into the large chamber B (See Figure III below).
IV If the small chamber A is empty: shake the large chamber B to ensure complete mixing of its contents. The solution is now ready for use and the bag may be hung on an IV pole (See Figure IV below).
V Dialysis or replacement lines can be connected to each of the two access ports.
V.a If using a luer-type access, use aseptic technique, remove the cap, and connect the male luer-lock end of the dialysis or replacement line to the female luer receptor on the bag; tighten. Using both hands, break the blue frangible seal at the base and move it back and forth. Do not use tools. Check that the seal is completely separated and that fluid flows freely. During treatment, the seal will remain in the luer port (See Figure V.a below).
V.b When using the injection port, first remove the cap by snapping it off. The injection port may be wiped with disinfectants. Then puncture the rubber septum with a spike. Check that fluid flows freely (See Figure V.b below).
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The reconstituted solution should be used immediately. If the reconstituted solution is not used immediately, it should be used within 24 hours after mixing solution A with solution B, including the duration of the procedure.
The reconstituted solution is for single use only.
Any unused solution must be discarded immediately after use.
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.

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Package leaflet: Information for the user

PHOXILIUM 1.2 mmol/l phosphates
Solution for hemodialysis and hemofiltration
Calcium chloride dihydrate, magnesium chloride hexahydrate, sodium chloride, sodium bicarbonate, potassium chloride, disodium phosphate anhydrous
Please read all of this leaflet carefully before using this medicine because it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If any adverse reactions occur in the patient, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

1. What Phoxilium is and what it is used for
2. What you need to know before using Phoxilium
3. How to use Phoxilium
4. Possible side effects
5. How to store Phoxilium
6. Contents of the pack and other information

1. What is Phoxilium and what is it used for

Phoxilium is a medicinal product belonging to the group of haemofiltration solutions. It contains calcium chloride dihydrate,
magnesium bicarbonate hexahydrate, sodium chloride, sodium bicarbonate, potassium chloride and disodium phosphate anhydrous.
Phoxilium is used in hospitals under intensive medical care conditions to restore blood chemical balance in patients with kidney impairment.
Continuous renal replacement therapy aims to remove accumulated metabolic waste products from the blood when the kidneys are not functioning.
Phoxilium solution is used to treat critically ill patients with acute kidney injury who have:

• normal blood potassium levels (normokalemia) or
• normal or low blood phosphate levels (normo- or hypophosphatemia).

This medicinal product may also be used in cases of poisoning with drugs containing substances that are dialysable or filterable.

2. Important information before using Phoxilium

Do not use Phoxilium in the following three cases:

• if the patient has high potassium levels in the blood (hyperkalaemia);
• if the patient has high bicarbonate levels in the blood (metabolic alkalosis);
• if the patient has high phosphate levels in the blood (hyperphosphataemia).

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Do not use hemodialysis or hemofiltration in the following three cases:

• if symptoms caused by high urea levels in the blood (uraemic symptoms) due to kidney damage with marked hypercatabolism (abnormal increase in breakdown processes) cannot be alleviated by hemofiltration;
• insufficient arterial pressure in the vascular access;
• reduced blood coagulation (systemic anticoagulation) when there is an existing risk of bleeding.

Warnings and precautions
Before starting treatment with Phoxilium, discuss this with your doctor, pharmacist, or nurse.
Blood tests will be performed before and during treatment to monitor acid-base balance and electrolyte concentrations, as well as the volume of infused fluids (intravenous infusions) and fluids removed (urine output), even those not directly related to CRRT.
Phoxilium and other medicines
You must inform your doctor or pharmacist about all medicines currently or recently used by the patient, as well as any medicines the patient plans to use. This is necessary because the levels of other concomitant medicines may influence Phoxilium treatment. Your doctor will decide whether any adjustments to other medications are required.
In particular, inform your doctor about the use of:

• phosphates from additional sources (e.g. nutritional fluids), as they may increase the risk of high phosphate levels in the blood (hyperphosphataemia);
• vitamin D and drugs containing calcium chloride or calcium gluconate, due to the possible increased risk of high calcium levels in the blood (hypercalcaemia);
• sodium bicarbonate, as it may increase the risk of excess bicarbonate in the blood (metabolic alkalosis);
• citrate as an anticoagulant, as it may reduce serum calcium levels.

Pregnancy, breastfeeding, and fertility
Pregnancy and breastfeeding:
There are no documented clinical data on the use of this medicine during pregnancy and lactation. This medicine should be administered to pregnant and breastfeeding women only if clearly needed.
Fertility:
An effect of the medicine on fertility is not expected, as calcium, sodium, potassium, magnesium, chlorides, hydrogen phosphates, and hydrogen carbonates are normal constituents of the human body.
Driving and operating machinery
Phoxilium has no influence on the ability to drive or operate machinery.

3. How to use Phoxilium

Phoxilium is a hospital product administered exclusively by medical personnel.
The volume of Phoxilium and thus the dose depends on the patient's condition. The treating physician will determine the dose volume.
Phoxilium may be administered directly into the bloodstream (intravenously) via a CRRT machine or via hemodialysis, where the solution flows on one side of the dialysis membrane and blood on the other side.
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This medicine should always be used exactly as directed by the doctor, pharmacist, or nurse. If in doubt, consult the doctor, pharmacist, or nurse.
Instructions for use are provided in the section "The following information is intended exclusively for healthcare professionals".
Use of a higher than recommended dose of Phoxilium
Phoxilium is intended for hospital use and must be administered only by physicians under careful monitoring of fluid balance and blood chemistry.
Therefore, administration of a higher than recommended dose of Phoxilium is unlikely.
In the unlikely event of overdose, the treating physician will take all necessary corrective actions and adjust the dose accordingly.
Overdose may lead to fluid overload, decreased plasma bicarbonate concentration (metabolic acidosis), and/or elevated phosphate levels (hyperphosphatemia) in patients with kidney impairment.
It may also lead to serious consequences such as congestive heart failure and disturbances in blood chemistry.
If there are any doubts regarding the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Three adverse reactions may occur related to the use of Phoxilium:

• abnormal water content in the body (overhydration or dehydration),
• changes in mineral salt levels in the blood (electrolyte imbalance, such as hyperphosphatemia), and
• increased bicarbonate concentration in plasma (metabolic alkalosis) or decreased bicarbonate concentration in plasma (metabolic acidosis).

There are also certain adverse reactions that may be caused by dialysis treatment:

• nausea, vomiting, muscle cramps, and low blood pressure (hypotension).

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed
in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions
can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Aleje Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 4921301
Fax: +48 22 4921309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.
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5. How to store Phoxilium

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and on the packaging.
The expiry date refers to the last day of the specified month.
Store between +4ºC and +30ºC. Do not store in a refrigerator or freeze.
Chemical and physical stability of the reconstituted solution has been demonstrated for 24 hours at +22ºC.
If the solution is not used immediately, the user is responsible for the storage conditions and duration prior to use,
which must not exceed 24 hours in total, including the duration of the procedure.
Do not use this medicine if the solution appears cloudy or if the outer protective packaging is damaged.
All seals must be intact.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required.
This will help protect the environment.

6. Contents of the pack and other information

What Phoxilium contains
The active substances before mixing and after mixing (reconstitution) are listed below.
Active substances before mixing:
1000 ml of solution in small chamber A contains:
Calcium chloride dihydrate 3.68 g
Magnesium chloride hexahydrate 2.44 g
1000 ml of solution in large chamber B contains:
Sodium chloride 6.44 g
Sodium bicarbonate 2.92 g
Potassium chloride 0.314 g
Disodium phosphate anhydrous 0.225 g
Active substances after mixing:
Solutions from chamber A (250 ml) and chamber B (4750 ml) are mixed to obtain one reconstituted
solution (5000 ml) containing:
mmol/l
calcium, Ca 1.25
magnesium, Mg 0.6
sodium, Na 140
chloride, Cl - 115.9
hydrogen phosphate, HPO 1.2
bicarbonate, HCO 30
potassium, K 4
Theoretical osmolarity: 293 mOsm/l
Other components:

• carbon dioxide (for pH adjustment), E290;
• hydrochloric acid (for pH adjustment), E507;
• water for injections.

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What Phoxilium looks like and contents of the pack
Phoxilium is a solution for hemodialysis and hemofiltration supplied in dual-chamber bags.
The final reconstituted solution is obtained by breaking the frangible closure and mixing both
solutions. The reconstituted solution is clear and colourless. Each bag (A+B) contains 5000 ml
of solution for hemofiltration and hemodialysis. Each bag is placed in a transparent outer
packaging.
Each pack contains two bags and a patient information leaflet.
Marketing Authorisation Holder:
Vantive Belgium SRL
Boulevard d’Angleterre 2
1420 Braine-l’Alleud
Belgium
Manufacturer:
Bieffe Medital S.p.A., Via Stelvio 94, 23035 Sondalo (SO), ITALY
Vantive Manufacturing Limited, Moneen Road, Castlebar, County Mayo, F23 XR63, Ireland
This medicinal product is authorised in the European Economic Area and in Great Britain (Northern Ireland) under the following names:
Austria, Belgium, Bulgaria, Cyprus, Denmark, Estonia, Finland, France, Greece, Spain, the Netherlands,
Ireland, Iceland, Lithuania, Luxembourg, Latvia, Malta, Germany, Norway, Poland, Portugal, Romania,
Slovakia, Slovenia, Sweden, Great Britain (Northern Ireland), Italy: Phoxilium
Hungary: Phoxil

The following information is intended exclusively for healthcare professionals:

Phoxilium 1.2 mmol/l phosphate
Solution for haemodialysis and haemofiltration

Precautions
Strictly follow the instructions for use / handling of the medicinal product Phoxilium.
The solutions from both chambers must be mixed before use.
Administration of a contaminated solution may cause sepsis and shock.
To increase patient comfort, Phoxilium may be warmed to +37°C. Warming the solution should be performed before reconstitution and only using a dry heat source. Do not warm solutions in a water bath or microwave oven. Visually inspect Phoxilium before administration to detect the presence of particulate matter or discoloration. Do not administer if the solution is not clear or if the seal is damaged.
Regularly monitor inorganic phosphate levels. Inorganic phosphates should be supplemented in cases of low blood phosphate concentration.
Additional substitution with sodium bicarbonate may increase the risk of metabolic alkalosis.
In case of fluid imbalance, carefully monitor the clinical status and restore fluid balance as follows:

• In hypervolemia, increase the net ultrafiltration rate in the CRRT machine and/or reduce the infusion rate of fluids other than replacement fluid and/or dialysate.
• In hypovolemia, reduce the net ultrafiltration rate in the CRRT machine and/or increase the infusion rate of fluids other than replacement fluid and/or dialysate.

Warnings:
Phoxilium should not be used in patients with hyperkalemia. Serum potassium levels must be monitored before and during haemofiltration and/or haemodialysis.
Since Phoxilium is a potassium-containing solution, transient hyperkalemia may occur after initiating treatment. Reduce the infusion rate until appropriate potassium levels are achieved. If hyperkalemia persists, discontinue administration of the medicinal product immediately.
If hyperkalemia occurs during use of Phoxilium as dialysate, it may be necessary to switch to a potassium-free dialysate to enhance potassium removal.
Since Phoxilium is a phosphate-containing solution, transient hyperphosphatemia may occur after initiating treatment. Reduce the infusion rate until appropriate phosphate levels are achieved. If hyperphosphatemia persists, discontinue administration of the medicinal product immediately.
In patients receiving Phoxilium, regularly monitor blood electrolytes and acid-base balance. Phoxilium contains hydrogen phosphate, a weak acid, which may affect the patient's acid-base balance. If metabolic acidosis develops or worsens during treatment with Phoxilium, consider reducing the infusion rate or discontinuing administration of the medicinal product.
Since Phoxilium does not contain glucose, its administration may lead to hypoglycemia. Regularly monitor blood glucose levels in diabetic patients (especially those receiving insulin or other glucose-lowering agents); also consider this in non-diabetic patients due to the risk of asymptomatic hypoglycemia during treatment. In case of hypoglycemia, consider using a glucose-containing solution. Other corrective measures may also be necessary to maintain appropriate blood glucose levels.

Dosage:
The volume and rate of administration of Phoxilium depend on blood phosphate and other electrolyte concentrations, acid-base balance, fluid balance, and the patient’s overall clinical condition. The volume of replacement and/or dialysate solution required will also depend on the desired treatment intensity (dose). The method of administration (dose, infusion rate, and total volume) of Phoxilium should be determined solely by a physician experienced in intensive care and continuous renal replacement therapy (CRRT).
Therefore, the dose volume depends on the physician's decision and recommendations.

Flow rate ranges for replacement fluid in haemofiltration and haemodiafiltration:
Adults: 500 to 3000 ml/hour

Flow rate ranges for dialysate in continuous haemodialysis and continuous haemodiafiltration:
Adults: 500 to 2500 ml/hour

In adults, the usual total flow rate during CRRT (dialysate and replacement fluids) is typically between 2000 and 2500 ml/hour, corresponding to a daily fluid volume of approximately 48 to 60 liters.

Children and adolescents:
In children, from neonates to adolescents up to 18 years of age, the flow rate range when used as replacement fluid in haemofiltration and haemodiafiltration, or as dialysis solution (dialysate) in continuous haemodialysis and continuous haemodiafiltration, is 1000 to 4000 ml/hour/1.73 m².
When the calculated pediatric dose exceeds the maximum adult dose in adolescents (12–18 years), the adult dose should be applied.

Instructions for use/handling
The solution from the small chamber A is added to the solution in the large chamber B by breaking the frangible seal or tearing the seal immediately before use. The reconstituted solution should be clear and colorless.
Maintain aseptic technique during handling and administration of the medicinal product to the patient.
Use only if the outer protective packaging is intact, all seals are undamaged, the frangible seal is not broken, and the solution is clear. Squeeze the bag firmly to check for leaks. If leakage is observed, discard the solution immediately, as sterility cannot be guaranteed.

The large chamber B is equipped with an injection port, which allows addition of other necessary medicinal products after reconstitution. The user is responsible for assessing compatibility of the added medicinal product with Phoxilium by checking for any change in color and/or precipitation, presence of insoluble complexes, or crystals. Before adding another medicinal product, verify that it is soluble and stable in Phoxilium and that the pH range of Phoxilium is suitable (the pH of the reconstituted solution is 7.0–8.5). Additional components may be incompatible with the solution. Refer to the instructions for use of the added medicinal product.
Remove fluid from the injection port, hold the bag inverted ("upside down"), inject the medicinal product through the injection port, and mix thoroughly. Introduction and mixing of additional components must always be performed before connecting the solution bag to the extracorporeal circuit. The solution should be administered immediately.

I Remove the outer packaging immediately before use and discard all additional packaging. Open the seal between both chambers of the bag by breaking the frangible seal. The frangible seal remains in the bag (see Figure I below).
II Ensure that all fluid from the small chamber A has been transferred into the large chamber B (see Figure II below).
III Rinse the small chamber A twice by squeezing the mixed solution back into chamber A and then back into chamber B (see Figure III below).
IV If the small chamber A is empty: shake the large chamber B to ensure complete mixing of its contents. The solution is now ready for use and the bag may be hung on an IV stand (see Figure IV below).
V Connect dialysis or replacement lines to each of the two access ports.
V.a If using a luer-type access, remove the cap by twisting and pulling, then connect the male luer-lock end of the dialysis or replacement line to the female luer-receptor connector on the bag by pushing and twisting. Ensure the connection is fully seated and secure. The connection is now open. Check that fluid flows freely (see Figure V.a below).
When dialysis or replacement lines are disconnected from the luer connector, the connection will close and fluid flow will stop. The luer port is needle-free and can be wiped with disinfectants.
V.b When using the injection port, first remove the cap by breaking it off. The injection port can be wiped with disinfectants. Then puncture the rubber septum with a spike. Check that fluid flows freely (see Figure V.b below).

The reconstituted solution should be used immediately. If not used immediately, the reconstituted solution must be used within 24 hours after mixing solution A with solution B, including treatment time.
The reconstituted solution is for single use only.
Immediately discard any unused solution after administration.
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.