Phoxilium

Package leaflet: Information for the user

PHOXILIUM 1.2 mmol/l phosphate

Solution for haemodialysis and haemofiltration
Calcium chloride dihydrate, magnesium chloride hexahydrate, sodium chloride, sodium bicarbonate, potassium chloride, disodium phosphate dihydrate
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What Phoxilium is and what it is used for
2. What you need to know before Phoxilium is administered
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, which belongs to the group of haemofiltration solutions, contains calcium chloride dihydrate,
magnesium chloride hexahydrate, sodium chloride, sodium bicarbonate, potassium chloride and disodium phosphate
dihydrate.
Phoxilium is used in hospital settings within intensive care therapies to correct disturbances in blood electrolyte balance caused by kidney damage.
Treatments using continuous renal replacement therapy are designed to remove waste products from the blood that accumulate when the kidneys are not functioning properly.
The Phoxilium solution is particularly used to treat critically ill patients with acute kidney injury who have:

• normal blood potassium levels (normal kaliemia) or
• normal or low blood phosphate levels (hypophosphatemia or normal phosphatemia).

This medicine may also be used in cases of drug poisoning or intoxication with dialysable or filterable substances.

2. What you need to know before using Phoxilium

Do not use Phoxilium in the following three cases:

• high potassium levels in the blood ( hyperkalemia)
• high bicarbonate levels in the blood (metabolic alkalosis)
• high phosphate levels in the blood ( hyperphosphatemia)

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

• when hemofiltration is unable to correct symptoms caused by high levels of urea in the blood (uremic symptoms), resulting from kidney damage with marked hypercatabolism (an abnormal increase in the breakdown process of substances)
• insufficient arterial pressure at the vascular access site
• reduced blood coagulation ( systemic anticoagulation), if there is a high risk of bleeding.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Phoxilium.
Before and during treatment, your blood parameters will be monitored, for example, acid-base balance and blood electrolyte levels, including all fluid inputs (intravenous infusions) and outputs (urine excretion), even those not directly related to the therapy.

Other medicines and Phoxilium
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. The levels of other medicines may affect treatment with Phoxilium. Your doctor will decide whether it is necessary to adjust the dosage of your medicines.
In particular, inform your doctor if you are taking any of the following products:

• Other sources of phosphate (e.g., nutritional fluids), as they may increase the risk of high phosphate levels in the blood (hyperphosphatemia).
• Vitamin D and other medicinal products containing calcium chloride or calcium gluconate, as they may increase the 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 used as an anticoagulant, as it may reduce plasma calcium levels.

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

Fertility:
No effects on fertility are expected, as calcium, sodium, potassium, magnesium, chloride, hydrogen phosphate, and bicarbonate are normal components of the body.

Driving and using machines
Phoxilium does not affect the ability to drive or operate machinery.

3. How to use Phoxilium

Phoxilium is a product intended for use in hospital settings and must be administered exclusively by medical personnel. The volume of Phoxilium, and therefore the dose, will depend on your clinical condition. The dose volume will be determined by the physician in charge of your treatment.
Phoxilium can be administered directly into the bloodstream (intravenous use) via a CRRT machine or through haemodialysis, where the solution flows on one side of a dialysis membrane while blood flows on the other side.
Use this medicine exactly as instructed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
For instructions for use, see the section "The following information is intended exclusively for healthcare professionals".

If you use more Phoxilium than you should
Phoxilium is a product intended for use in hospital settings and is administered exclusively by medical personnel under close monitoring of fluid balance, electrolyte balance, and acid-base balance of the blood.
Therefore, it is unlikely that you will receive more Phoxilium than required.
In the unlikely event of an overdose, the doctor will take all necessary corrective measures and adjust the dose accordingly.
An overdose may cause fluid overload, decreased plasma bicarbonate concentration (metabolic acidosis) and/or elevated phosphate concentration (hyperphosphataemia), particularly if you have kidney impairment.
This could lead to serious consequences such as congestive heart failure or alterations in blood chemical parameters.
If you have any questions about the use of this product, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following three side effects are possible related to the use of Phoxilium:

• abnormal increase or decrease in body water volume (hypervolemia or hypovolemia),
• changes in blood salt levels (electrolyte imbalances, such as hyperphosphatemia), and
• increased plasma bicarbonate concentration (metabolic alkalosis) or reduced plasma bicarbonate concentration (metabolic acidosis).

Other side effects may also occur, which could be caused by dialysis treatments, for example:

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

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 packaging.
The expiry date refers to the last day of that month.
Store at a temperature between +4 °C and +30 °C. Do not refrigerate or freeze.
The reconstituted solution has been shown to be chemically and physically stable for 24 hours at 22 °C.
If the reconstituted solution is not used immediately, the storage times and conditions are the responsibility of the user and must not exceed 24 hours, including the duration of treatment.
Do not use this medicine if the solution is cloudy or if the outer packaging is damaged. All seals must be intact.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Phoxilium contains
The active substances before and after mixing (reconstitution) are listed below.
Active substances before mixing:
1000 ml of solution in the small compartment (A) contains:
Calcium chloride, 2 H₂O 3.68 g
Magnesium chloride, 6 H₂O 2.44 g
1000 ml of solution in the large compartment (B) contains:
Sodium chloride 6.44 g
Sodium bicarbonate 2.92 g
Potassium chloride 0.314 g
Disodium phosphate, 2 H₂O 0.225 g
Active substances after mixing:
The solutions in compartments A (250 ml) and B (4750 ml) are mixed to obtain a reconstituted solution (5000 ml) with the following composition:
mmol/l
Calcium, Ca 1.25
Magnesium, Mg 0.6
Sodium, Na 140
Chloride, Cl 115.9
Hydrogen phosphate, HPO₄²⁻ 1.2
Bicarbonate, HCO₃⁻ 30
Potassium, K 4
Theoretical osmolarity: 293 mOsm/l
Other components are:

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

Description of the appearance of Phoxilium and package contents
Phoxilium is a solution for haemodialysis and haemofiltration contained in a two-compartment bag.
The final reconstituted solution is obtained after breaking the breakable cone and mixing the two solutions. The reconstituted solution is clear and colourless. Each bag (A+B) contains 5000 ml of solution for haemodialysis and haemofiltration. The bag is wrapped in a transparent film.
Each carton contains two bags and a leaflet.
Marketing Authorization 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
or
Vantive Manufacturing Limited, Moneen Road, Castlebar, County Mayo, F23 XR63, Ireland
This medicinal product is authorized in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Austria, Belgium, Bulgaria, Cyprus, Denmark, Estonia, Finland, France, Germany, Greece, Ireland, Iceland, Italy, Latvia, Lithuania, Luxembourg, Malta, Norway, Netherlands, Poland, Portugal, United Kingdom (Northern Ireland), Romania, Slovakia, Slovenia, Spain, Sweden:
Phoxilium
Hungary: Phoxil

The following information is intended exclusively for healthcare professionals

Phoxilium 1.2 mmol/l phosphate
Solution for hemodialysis and hemofiltration

Precautions
The instructions for use/handling of Phoxilium must be strictly followed.
The solutions contained in the two compartments must be mixed before use.
Administration of a contaminated solution may cause sepsis and shock.
Phoxilium may be warmed to 37°C to improve patient comfort. Warming the solution before use must be performed before reconstitution and only with dry heat.
Solutions must not be heated in water or in a microwave oven. Before administration, Phoxilium must 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 not intact.
Measure serum inorganic phosphate concentration regularly. Replace inorganic phosphate in case of low blood phosphate levels.
Additional supplementation of sodium bicarbonate may increase the risk of metabolic alkalosis.
In case of disturbances in fluid balance, closely monitor the clinical condition and restore fluid balance.

• In case of hypervolemia, the prescribed net ultrafiltration rate for the CRRT device may be increased and the administration rate of solutions other than replacement fluid and/or dialysate may be reduced.
• In case of hypovolemia, the prescribed net ultrafiltration rate for the CRRT device may be reduced and/or the administration rate of solutions other than replacement fluid and/or dialysate may be increased.

Warnings:
Phoxilium must 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 develop after the start of treatment. The infusion rate must be reduced until the desired potassium concentration is achieved. If hyperkalemia does not resolve, administration must be promptly discontinued.
If hyperkalemia develops when Phoxilium is used as dialysate, administration of a potassium-free dialysate may be required to increase potassium elimination rate.
Since Phoxilium is a phosphate-containing solution, transient hyperphosphatemia may develop after the start of treatment. The infusion rate must be reduced until the desired phosphate concentration is achieved. If hyperphosphatemia does not resolve, administration must be promptly discontinued.
Electrolyte and acid-base balance parameters in blood must be regularly monitored in patients treated with Phoxilium. Phoxilium contains hydrogen phosphate, a weak acid, which may affect the patient's acid-base balance. If metabolic acidosis develops or worsens during therapy with Phoxilium, the infusion rate may need to be reduced or administration may need to be interrupted.
Since Phoxilium does not contain glucose, administration may cause hypoglycemia. Blood glucose levels must be regularly monitored in diabetic patients (with particular attention to patients treated with insulin or other hypoglycemic agents), but also in non-diabetic patients, for example due to the risk of silent hypoglycemia during the procedure. If hypoglycemia develops, consider using a glucose-containing solution. Additional corrective measures may be necessary to maintain desired glycemic control.

Dosage:
The volume and rate at which Phoxilium is administered depend on the concentration of phosphate and other electrolytes in the blood, acid-base balance, fluid balance, and the patient's general clinical condition. The volume of replacement and/or dialysate solution to be administered will also depend on the desired treatment intensity (dose). The administration (dose, infusion rate, and total volume) of Phoxilium must be determined exclusively by a physician experienced in intensive care and continuous renal replacement therapy (CRRT).
The dose volume is therefore at the discretion of the responsible physician and must be prescribed by them.
The flow rate ranges for replacement solution in hemofiltration and hemodiafiltration are:
Adults: 500–3000 ml/hour
The flow rate ranges for dialysis solution (dialysate) in continuous hemodialysis and continuous hemodiafiltration are:
Adults: 500–2500 ml/hour
Commonly used total flow rates for CRRT (dialysate and replacement solutions) in adults are approximately 2000–2500 ml/hour, corresponding to a daily fluid volume of approximately 48–60 liters.

Pediatric population:
In children, from neonates to adolescents up to 18 years of age, the flow rate range for use as replacement solution in hemofiltration and hemodiafiltration and as dialysis solution (dialysate) in continuous hemodialysis and continuous hemodiafiltration is 1000–4000 ml/hour/1.73 m².
For adolescents (12–18 years), the adult dose should be used when the calculated pediatric dose exceeds the maximum adult dose.

Instructions for use/handling
The solution in the small compartment A is added to the solution in the large compartment B after breaking the frangible cone immediately before use. The reconstituted solution must be clear and colorless.
Use aseptic techniques throughout the handling and administration to the patient.
Use only if the outer wrapper is intact, all seals are undamaged, the frangible cone is not broken, and the solution is clear. Press firmly on the bag to check for leaks. If leaks are detected, discard the solution immediately, as sterility can no longer be assured.
The large compartment B is equipped with an injection port for the possible addition of other necessary medications after solution reconstitution.
It is the user’s responsibility to assess the compatibility of an added medicinal product by checking for any changes in color and/or formation of precipitates, crystals, or insoluble complexes.
Before adding a medicinal product, verify that it is soluble and stable in this solution and that the pH of Phoxilium is appropriate (the pH of the reconstituted solution is between 7.0 and 8.0). Added products may not be compatible. Consult the instructions for use of the medicinal product to be added.
Remove any liquid from the injection port, invert the bag, insert the drug through the injection port, and mix thoroughly. The introduction and mixing of additives must always be performed before connecting the solution bag to the extracorporeal circuit. Administer the solution immediately.

I Remove the outer wrapper from the bag immediately before use and discard any other packaging material. Open the seal by breaking the frangible cone between the two compartments of the bag. The frangible cone will remain inside the bag (see figure I below).

II Ensure that all liquid from the small compartment A is transferred into the large compartment B (see figure II below).

III Rinse the small compartment A twice by pressing the mixed solution back into compartment A and then into compartment B (see figure III below).

IV Once the small compartment A is emptied: shake the large compartment B to ensure complete mixing of the contents. The solution is now ready for use and the bag can be hung on the equipment (see figure IV below).

V The dialysis or replacement line can be connected to either of the two access ports.

V.a If using a luer access, using an aseptic technique, remove the cap and connect the male luer lock of the dialysis or replacement line to the female luer connector on the bag, then tighten. Using both hands, break the blue frangible cone at the base and move it back and forth. Do not use any tools. Ensure that the cone has completely separated and that fluid flows freely. During treatment, the cone will remain in the luer port (see figure V.a below).

V.b If using the injection port, first remove the snap cap. Then insert the spike through the rubber septum. Ensure that fluid flows freely (see figure V.b below).

Use the reconstituted solution immediately. If not used immediately, the reconstituted solution must be used within 24 hours, including the duration of treatment, from the time solution A is added to solution B.
The reconstituted solution is for single use only. Discard any unused solution immediately after use.
Unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local regulations.

Package leaflet: information for the user

PHOXILIUM 1.2 mmol/l phosphate

Solution for haemodialysis and haemofiltration
Calcium chloride dihydrate, magnesium chloride hexahydrate, sodium chloride, sodium bicarbonate, potassium chloride, disodium phosphate dihydrate
Please read this leaflet carefully before using this medicine as it contains
important information for you.

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

Contents of this leaflet:

1. What Phoxilium is and what it is used for
2. What you need to know before administration of 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, which belongs to the group of haemofiltration solutions, contains calcium chloride dihydrate,
magnesium chloride hexahydrate, sodium chloride, sodium bicarbonate, potassium chloride and disodium phosphate
dihydrate.
Phoxilium is used in hospital settings within intensive care therapies to correct disturbances in the blood electrolyte balance caused by kidney injury.
Treatments using continuous renal replacement therapy are designed to remove waste products that accumulate in the blood when the kidneys are not functioning properly.
The Phoxilium solution is specifically used to treat critically ill patients with acute kidney injury who have:

• normal blood potassium levels (normal kaliemia) or
• normal or low blood phosphate levels (hypophosphatemia or normal phosphatemia).

This medicine may also be used in cases of drug poisoning or intoxication with dialysable or filterable substances.

2. What you need to know before using Phoxilium

Do not use Phoxilium in the following three cases:

• high potassium levels in the blood (hyperkalaemia)
• high bicarbonate levels in the blood (metabolic alkalosis)
• high phosphate levels in the blood (hyperphosphataemia)

Do not use haemodialysis or haemofiltration in any of the following three cases:

• when haemofiltration is unable to correct symptoms caused by high urea levels in the blood (uraemic symptoms), resulting from kidney damage with marked hypercatabolism (an abnormal increase in the breakdown process of substances)
• insufficient blood pressure in the vascular access
• reduced blood coagulation (systemic anticoagulation), if there is a high risk of bleeding.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Phoxilium.
Before and during treatment, your blood parameters will be monitored, such as acid-base balance and electrolyte levels in the blood, including all fluid inputs (intravenous infusions) and outputs (urine output), even those not directly related to CRRT.

Other medicines and Phoxilium
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. The concentration of other medicines may influence treatment with Phoxilium. Your doctor will decide whether it is necessary to adjust the dosage of your medicines.
In particular, inform your doctor if you are taking any of the following products:

• Other sources of phosphate (e.g. nutritional fluids), as they may increase the risk of high phosphate levels in the blood (hyperphosphataemia).
• Vitamin D and other medicinal products containing calcium chloride or calcium gluconate, as they may increase the 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 used as an anticoagulant, as it may reduce calcium levels in plasma.

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

Fertility:
No effects on fertility are expected, since calcium, sodium, potassium, magnesium, chloride, hydrogen phosphate, and bicarbonate are normal components of the body.

Driving and using machines
Phoxilium has no influence on the ability to drive or operate machinery.

3. How to use Phoxilium

Phoxilium is a product intended for use in hospital settings and must be administered exclusively by medical personnel. The volume of Phoxilium, and therefore the dose, will depend on your clinical condition. The dose volume will be determined by the physician in charge of treatment.
Phoxilium can be administered directly into the bloodstream (intravenous use) via a CRRT machine or through hemodialysis, where the solution flows on one side of a dialysis membrane while blood flows on the other side.
Use this medicine exactly as instructed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
For instructions for use, see the section "The following information is intended exclusively for doctors or healthcare professionals".

If you use more Phoxilium than you should
Phoxilium is a product intended for use in hospital settings, administered exclusively by medical staff under careful monitoring of fluid balance, electrolyte balance, and acid-base balance of the blood.
Therefore, it is unlikely that you will receive more Phoxilium than required.
In the unlikely event of an overdose, the doctor will take all necessary corrective measures and adjust the dose accordingly.
An overdose may cause fluid overload, decreased plasma bicarbonate concentration (metabolic acidosis) and/or elevated phosphate concentration (hyperphosphatemia), especially if you have kidney impairment.
This could lead to serious consequences, such as congestive heart failure or alterations in blood chemical parameters.
If you have any questions about the use of this product, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following three side effects are possible related to the use of Phoxilium:

• abnormal increase or decrease in the body's water volume (hypervolemia or hypovolemia),
• changes in blood salt levels (electrolyte imbalances, such as hyperphosphatemia), and
• increased plasma bicarbonate concentration (metabolic alkalosis) or reduced plasma bicarbonate concentration (metabolic acidosis).

Other side effects may also occur, which could be caused by dialysis treatments, for example:

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system at the following website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

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 that month.
Store between +4 °C and +30 °C. Do not refrigerate or freeze.
The reconstituted solution has been shown to be chemically and physically stable for 24 hours at 22 °C.
If the reconstituted solution is not used immediately, the storage times and conditions are the responsibility of the user and must not exceed 24 hours, including the duration of treatment.
Do not use this medicine if the solution is cloudy or if the outer packaging is damaged. All seals must be intact.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Phoxilium contains
The active substances before and after mixing (reconstitution) are listed below.
Active substances before mixing:
1000 ml of solution in the small compartment (A) contains:
Calcium chloride, 2 H₂O 3.68 g
Magnesium chloride, 6 H₂O 2.44 g
1000 ml of solution in the large compartment (B) contains:
Sodium chloride 6.44 g
Sodium bicarbonate 2.92 g
Potassium chloride 0.314 g
Disodium phosphate, 2 H₂O 0.225 g
Active substances after mixing:
The solutions in compartments A (250 ml) and B (4750 ml) are mixed to obtain a reconstituted solution (5000 ml) with the following composition:
mmol/l
Calcium, Ca 1.25
Magnesium, Mg 0.6
Sodium, Na 140
Chloride, Cl 115.9
Hydrogen phosphate, HPO₄²⁻ 1.2
Bicarbonate, HCO₃⁻ 30
Potassium, K 4
Theoretical osmolarity: 293 mOsm/l
Other components are:

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

Description of the appearance of Phoxilium and contents of the pack
Phoxilium is a solution for haemodialysis and haemofiltration contained in a two-compartment bag.
The final reconstituted solution is obtained after breaking the frangible cone and mixing the two solutions. The reconstituted solution is clear and colourless. Each bag (A+B) contains 5000 ml of solution for haemodialysis and haemofiltration. The bag is wrapped in a transparent film.
Each carton contains two bags and a package leaflet.
Marketing Authorization 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
or
Vantive Manufacturing Limited, Moneen Road, Castlebar, County Mayo, F23 XR63, Ireland
This medicinal product is authorized in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Austria, Belgium, Bulgaria, Cyprus, Denmark, Estonia, Finland, France, Germany, Greece, Ireland, Iceland, Italy, Latvia, Lithuania, Luxembourg, Malta, Norway, Netherlands, Poland, Portugal, United Kingdom (Northern Ireland), Romania, Slovakia, Slovenia, Spain, Sweden:
Phoxilium
Hungary: Phoxil

The following information is intended exclusively for healthcare professionals

Phoxilium 1.2 mmol/l phosphate
Solution for hemodialysis and hemofiltration
Precautions
The instructions for use/handling of Phoxilium must be strictly followed.
The solutions contained in the two compartments must be mixed before use.
The use of a contaminated solution may cause sepsis and shock.
Phoxilium may be warmed to 37 °C to improve patient comfort. Warming of the solution before use must be performed prior to reconstitution and only with dry heat.
Solutions must not be heated in water or in a microwave oven. Before administration, Phoxilium must be inspected visually for particulate matter and discoloration. Do not administer if the solution is not clear or if the seal is not intact.
Measure serum inorganic phosphate concentration regularly. Replace inorganic phosphate in case of low blood phosphate levels.
Additional replacement of sodium bicarbonate may increase the risk of metabolic alkalosis.
In case of disturbances in fluid balance, monitor the patient’s clinical condition carefully and restore fluid balance.

• In case of hypervolemia, the prescribed net ultrafiltration rate for the CRRT device may be increased and/or the administration rate of solutions other than replacement fluid and/or dialysate may be reduced.
• In case of hypovolemia, the prescribed net ultrafiltration rate for the CRRT device may be reduced and/or the administration rate of solutions other than replacement fluid and/or dialysate may be increased.

Warnings:
Phoxilium must 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 develop after the start of treatment. The infusion rate must be reduced until the desired potassium concentration is achieved. If hyperkalemia does not resolve, administration must be promptly discontinued.
If hyperkalemia develops when Phoxilium is used as dialysate, administration of a potassium-free dialysate may be necessary to increase potassium removal rate.
Since Phoxilium is a phosphate-containing solution, transient hyperphosphatemia may develop after the start of treatment. The infusion rate must be reduced until the desired phosphate concentration is achieved. If hyperphosphatemia does not resolve, administration must be promptly discontinued.
Electrolyte and acid-base balance parameters in blood must be monitored regularly in patients treated with Phoxilium. Phoxilium contains hydrogen phosphate, a weak acid, which may affect the patient’s acid-base balance. If metabolic acidosis develops or worsens during Phoxilium therapy, the infusion rate may need to be reduced or administration may need to be interrupted.
Since Phoxilium does not contain glucose, administration may cause hypoglycemia. Blood glucose levels must be monitored regularly in diabetic patients (with particular attention to patients receiving insulin or other hypoglycemic agents), but also considered in non-diabetic patients, for example due to the risk of silent hypoglycemia during the procedure. If hypoglycemia develops, consider using a glucose-containing solution. Other corrective measures may be necessary to maintain desired glycemic control.

Dosage:
The volume and rate at which Phoxilium is administered depend on serum 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 to be administered will also depend on the desired treatment intensity (dose). The administration (dose, infusion rate, and total volume) of Phoxilium must be determined exclusively by a physician experienced in intensive care and continuous renal replacement therapy (CRRT).
Therefore, the dose volume is at the discretion of the responsible physician, based on prescription.
The flow rate ranges for replacement solution in hemofiltration and hemodiafiltration are:
Adults: 500–3000 ml/hour
The flow rate ranges for dialysate solution in continuous hemodialysis and continuous hemodiafiltration are:
Adults: 500–2500 ml/hour
Commonly used total combined flow rates for CRRT (dialysate and replacement solutions) in adults are approximately 2000–2500 ml/hour, corresponding to a daily fluid volume of about 48–60 liters.

Pediatric population:
In children, from neonates to adolescents up to 18 years of age, the flow rate ranges for use as replacement solution in hemofiltration and hemodiafiltration and as dialysis solution (dialysate) in continuous hemodialysis and continuous hemodiafiltration are 1000–4000 ml/hour/1.73 m².
For adolescents (12–18 years), the recommended adult dose should be used when the calculated pediatric dose exceeds the maximum adult dose.

Instructions for use/handling
The solution in the small compartment A is added to the solution in the large compartment B after breaking the frangible cone immediately before use. The reconstituted solution must be clear and colorless.
Use aseptic techniques throughout handling and administration to the patient.
Use only if the outer wrapper is intact, all seals are intact, the frangible cone is not broken, and the solution is clear. Press the bag firmly to check for leaks. If leaks are detected, discard the solution immediately, as sterility can no longer be assured.
The large compartment B is equipped with an injection port for the possible addition of other required medications after solution reconstitution.
It is the user’s responsibility to assess the compatibility of any additional medication with Phoxilium by checking for any color changes and/or formation of precipitates, crystals, or insoluble complexes.
Before adding a medication, verify that it is soluble and stable in this solution and that the pH of Phoxilium is appropriate (the pH of the reconstituted solution ranges between 7.0 and 8.0). Added products may be incompatible. Consult the instructions for use of the medication to be added.
Remove any liquid from the injection port, invert the bag, insert the medication through the injection port, and mix thoroughly. The introduction and mixing of additives must always be performed before connecting the solution bag to the extracorporeal circuit. Administer the solution immediately.

I Remove the outer wrapper from the bag immediately before use and discard any other packaging materials. Open the seal by breaking the frangible cone between the two compartments of the bag. The frangible cone will remain inside the bag (see figure I below).
II Ensure that all liquid from the small compartment A is transferred into the large compartment B (see figure II below).
III Rinse the small compartment A twice by pressing the mixed solution back into the small compartment A and then into the large compartment B (see figure III below).
IV Once the small compartment A is emptied: shake the large compartment B to ensure complete mixing of the contents. The solution is now ready for use and the bag can be hung on the equipment (see figure IV below).
V The dialysis or replacement line can be connected to either of the two access ports.
V.a If using a luer access, remove the cap with a twisting and pulling motion and connect the male luer lock of the dialysis or replacement line to the female luer connector on the bag with a twisting and pulling motion. Ensure the connection is correct and secure. The connector is now open. Check that fluid flows freely (see figure V.a below).
When the dialysis or replacement line is disconnected from the luer connector, the connector closes and solution flow stops. The luer port is a needle-free, cleanable port.
V.b If using the injection port, first remove the snap-off cap. Then insert the spike through the rubber septum. Check that fluid flows freely (see figure V.b below).
Use the reconstituted solution immediately. If not used immediately, the reconstituted solution must be used within 24 hours, including treatment duration, from the time solution A is added to solution B.
The reconstituted solution is for single use only. Discard any unused solution immediately after use.
Unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.

Package leaflet: information for the user

PHOXILIUM 1.2 mmol/l phosphate

Solution for hemodialysis and hemofiltration
Calcium chloride dihydrate, magnesium chloride hexahydrate, sodium chloride, sodium bicarbonate, potassium chloride, disodium phosphate dihydrate
Please read this leaflet carefully before using this medicine because it contains important information for you.

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

Contents of this leaflet:

1. What Phoxilium is and what it is used for
2. What you need to know before administration of 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, which belongs to the group of haemofiltration solutions, contains calcium chloride dihydrate,
magnesium chloride hexahydrate, sodium chloride, sodium bicarbonate, potassium chloride and disodium phosphate
dihydrate.
Phoxilium is used in hospital settings within intensive care therapies to correct disturbances in the blood electrolyte balance caused by kidney injury.
Treatments using continuous renal replacement therapy are designed to remove accumulated waste products from the blood when the kidneys are not functioning.
The Phoxilium solution is specifically used to treat critically ill patients with acute kidney injury who have:

• normal blood potassium concentration (normal kaliemia) or
• normal or low blood phosphate concentration (hypophosphatemia or normal phosphatemia).

This medicine may also be used in cases of drug poisoning or intoxication with dialysable or filterable substances.

2. What you need to know before using Phoxilium

Do not use Phoxilium in the following three cases:

• high potassium levels in the blood (hyperkalemia)
• high bicarbonate levels in the blood (metabolic alkalosis)
• high phosphate levels in the blood (hyperphosphatemia)

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

• when hemofiltration is unable to correct symptoms caused by high urea levels in the blood (uremic symptoms), resulting from kidney damage with marked hypercatabolism (an abnormal increase in the breakdown process of substances)
• insufficient blood pressure in the vascular access
• reduced blood coagulation (systemic anticoagulation), if there is a high risk of bleeding.

Warnings and precautions
Consult your doctor, pharmacist, or nurse before using Phoxilium.
Before and during treatment, your blood parameters will be monitored, such as acid-base balance and blood electrolyte concentrations, including all fluid inputs (intravenous infusion) and outputs (urine excretion), even those not directly related to therapy.

Other medicines and Phoxilium
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. The levels of other medicines may influence treatment with Phoxilium. Your doctor will decide whether a dosage adjustment is necessary.
In particular, inform your doctor if you are taking any of the following products:

• Other sources of phosphate (e.g. nutritional fluids), as they may increase the risk of high phosphate levels in the blood (hyperphosphatemia).
• Vitamin D and other medicinal products containing calcium chloride or calcium gluconate, as they may increase the 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 used as an anticoagulant, as it may reduce plasma calcium levels.

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

Fertility:
No effects on fertility are expected, since calcium, sodium, potassium, magnesium, chloride, hydrogen phosphate, and bicarbonate are normal components of the body.

Driving and using machines
Phoxilium does not affect the ability to drive or operate machinery.

3. How to use Phoxilium

Phoxilium is a product intended for use in hospital settings and must be administered exclusively by medical personnel. The volume of Phoxilium, and therefore the dose, will depend on your clinical condition. The dose volume will be determined by the physician in charge of treatment.
Phoxilium can be administered directly into the bloodstream (intravenous use) via a CRRT machine or through hemodialysis, where the solution flows on one side of a dialysis membrane while blood flows on the other side.
Use this medicine exactly as instructed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
For instructions on use, see the section "The following information is intended exclusively for healthcare professionals."
If you use more Phoxilium than you should
Phoxilium is a product intended for use in hospital settings and is administered exclusively by medical personnel under careful monitoring of fluid balance, electrolyte balance, and acid-base balance of the blood.
Therefore, it is unlikely that you will receive more Phoxilium than required.
In the unlikely event of an overdose, the doctor will take all necessary corrective measures and adjust the dose accordingly.
An overdose may cause fluid overload, decreased plasma bicarbonate concentration (metabolic acidosis), and/or elevated phosphate concentration (hyperphosphatemia), especially if you have renal impairment.
This could lead to serious consequences such as congestive heart failure or alterations in blood chemical parameters.
If you have any questions about the use of this product, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following three side effects are possible related to the use of Phoxilium:

• abnormal increase or decrease in body water volume (hypervolemia or hypovolemia),
• changes in blood salt levels (electrolyte imbalances, such as hyperphosphatemia), and
• increased plasma bicarbonate concentration (metabolic alkalosis) or reduced plasma bicarbonate concentration (metabolic acidosis).

Some side effects may also occur that could be caused by dialysis treatments, for example:

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

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 packaging.
The expiry date refers to the last day of that month.
Store between +4 °C and +30 °C. Do not refrigerate or freeze.
The reconstituted solution has been shown to be chemically and physically stable for 24 hours at
22 °C. If the reconstituted solution is not used immediately, the storage times and conditions prior
to use are the responsibility of the user and must not exceed 24 hours, including the duration of
treatment.
Do not use this medicine if the solution is cloudy or if the outer packaging is damaged. All seals must
be intact.
Do not dispose of any medicine 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 and after mixing (reconstitution) are listed below.
Active substances before mixing:
1000 ml of solution in the small compartment (A) contains:
Calcium chloride, 2 H₂O 3.68 g
Magnesium chloride, 6 H₂O 2.44 g
1000 ml of solution in the large compartment (B) contains:
Sodium chloride 6.44 g
Sodium bicarbonate 2.92 g
Potassium chloride 0.314 g
Disodium phosphate, 2 H₂O 0.225 g
Active substances after mixing:
The solutions in compartments A (250 ml) and B (4750 ml) are mixed to obtain a reconstituted solution (5000 ml) with the following composition:
mmol/l
Calcium, Ca 1.25
Magnesium, Mg 0.6
Sodium, Na 140
Chloride, Cl 115.9
Hydrogen phosphate, HPO₄ 1.2
Bicarbonate, HCO₃ 30
Potassium, K 4
Theoretical osmolarity: 293 mOsm/l
Other components are:

• Carbon dioxide (for pH adjustment) E290,
• Hydrochloric acid (for pH adjustment) E507 and
• Water for injections.

Description of the appearance of Phoxilium and contents of the pack
Phoxilium is a solution for haemodialysis and haemofiltration contained in a two-compartment bag.
The final reconstituted solution is obtained after breaking the peel seal and mixing the two solutions. The reconstituted solution is clear and colourless. Each bag (A+B) contains 5000 ml of solution for haemodialysis and haemofiltration. The bag is wrapped in a transparent film.
Each carton contains two bags and a package leaflet.
Marketing Authorization 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
or
Vantive Manufacturing Limited, Moneen Road, Castlebar, County Mayo, F23 XR63, Ireland
This medicinal product is authorized in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Austria, Belgium, Bulgaria, Cyprus, Denmark, Estonia, Finland, France, Germany, Greece, Ireland, Iceland, Italy, Latvia, Lithuania, Luxembourg, Malta, Norway, the Netherlands, Poland, Portugal, United Kingdom (Northern Ireland), Romania, Slovakia, Slovenia, Spain, Sweden:
Phoxilium
Hungary: Phoxil

The following information is intended exclusively for healthcare professionals

Phoxilium 1.2 mmol/l phosphate
Solution for hemodialysis and hemofiltration

Precautions
The instructions for use/handling of Phoxilium must be strictly followed.
The solutions contained in the two compartments must be mixed before use.
The use of a contaminated solution may cause sepsis and shock.
Phoxilium may be warmed to 37°C to improve patient comfort. Warming the solution prior to use must be performed before reconstitution and only with dry heat.
Solutions must not be heated in water or in a microwave oven. Before administration, Phoxilium must 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 not intact.
Measure the inorganic phosphate concentration regularly. Replace inorganic phosphate in case of low blood phosphate levels.
Additional replacement with sodium bicarbonate may increase the risk of metabolic alkalosis.
In case of disturbances in fluid balance, closely monitor the clinical condition and restore fluid balance.

• In case of hypervolemia, the prescribed net ultrafiltration rate for the CRRT device may be increased and/or the administration rate of solutions other than replacement fluid and/or dialysate may be reduced.
• In case of hypovolemia, the prescribed net ultrafiltration rate for the CRRT device may be reduced and/or the administration rate of solutions other than replacement fluid and/or dialysate may be increased.

Warnings:
Phoxilium must 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 develop after the start of treatment. The infusion rate must be reduced until the desired potassium concentration is achieved. If hyperkalemia does not resolve, administration must be promptly discontinued.
If hyperkalemia develops when Phoxilium is used as dialysate, administration of a potassium-free dialysate may be necessary to increase the rate of potassium removal.
Since Phoxilium is a phosphate-containing solution, transient hyperphosphatemia may develop after the start of treatment. The infusion rate must be reduced until the desired phosphate concentration is achieved. If hyperphosphatemia does not resolve, administration must be promptly discontinued.
Electrolyte and acid-base balance parameters in blood must be regularly monitored in patients treated with Phoxilium. Phoxilium contains hydrogen phosphate, a weak acid, which may affect the patient's acid-base balance. If metabolic acidosis develops or worsens during Phoxilium therapy, the infusion rate may need to be reduced or administration may need to be interrupted.
Since Phoxilium does not contain glucose, administration may cause hypoglycemia. Blood glucose levels must be regularly monitored in diabetic patients (with careful consideration also for patients treated with insulin or other hypoglycemic agents), but also in non-diabetic patients, for example due to the risk of silent hypoglycemia during the procedure. If hypoglycemia develops, consider using a glucose-containing solution. Additional corrective measures may be necessary to maintain desired glycemic control.

Dosage:
The volume and rate at which Phoxilium is administered depend on the concentration of phosphate and other electrolytes in the blood, acid-base balance, fluid balance, and the patient's overall clinical condition. The volume of replacement and/or dialysate solution to be administered will also depend on the desired intensity (dose) of treatment. The administration (dose, infusion rate, and total volume) of Phoxilium must be determined exclusively by a physician experienced in intensive care and continuous renal replacement therapy (CRRT).
Therefore, the dose volume is at the discretion of the responsible physician, based on their prescription.
The flow rate ranges for replacement solution in hemofiltration and hemodiafiltration are:
Adults: 500–3000 ml/hour
The flow rate ranges for dialysate in continuous hemodialysis and continuous hemodiafiltration are:
Adults: 500–2500 ml/hour
The total combined flow rates commonly used for CRRT (dialysate and replacement solutions) in adults are approximately 2000–2500 ml/hour, corresponding to a daily fluid volume of approximately 48–60 liters.

Pediatric population:
In children, from neonates to adolescents up to 18 years of age, the flow rate range for use as replacement solution in hemofiltration and hemodiafiltration, and as dialysis solution (dialysate) in continuous hemodialysis and continuous hemodiafiltration, is 1000–4000 ml/hour/1.73 m².
For adolescents (12–18 years), the adult dose should be used when the calculated pediatric dose exceeds the maximum adult dose.

Instructions for use/handling
The solution in the small compartment A is added to the solution in the large compartment B after tearing the peel seal immediately before use. The reconstituted solution must be clear and colorless.
Use aseptic techniques throughout the handling and administration to the patient.
Use only if the outer packaging is intact, all seals are intact, the peel seal is unbroken, and the solution is clear. Press firmly on the bag to check for leaks. If leaks are detected, immediately discard the solution as sterility can no longer be assured.
The large compartment B is equipped with an injection port for the possible addition of other required medications after solution reconstitution.
It is the user’s responsibility to assess the compatibility of an additional medicinal product with Phoxilium by checking for any changes in color and/or formation of precipitates, crystals, or insoluble complexes. Before adding a medicinal product, verify that it is soluble and stable in this solution and that the pH of Phoxilium is appropriate (the pH of the reconstituted solution ranges between 7.0 and 8.0). Added products may be incompatible. Consult the instructions for use of the medicinal product to be added.
Remove any liquid from the injection port, invert the bag, insert the drug through the injection port, and mix thoroughly. The addition and mixing of additives must always be performed before connecting the solution bag to the extracorporeal circuit. Administer the solution immediately.

I Remove the outer bag wrapper immediately before use and discard any other packaging materials. Open the seal by holding the small compartment with both hands and pressing until an opening is created in the seal between the two compartments (see Figure I below).

II Press with both hands on the large compartment until the seal between the two compartments opens completely (see Figure II below).

III Mix the solution thoroughly by gently agitating the bag. The solution is now ready for use and can be hung on the equipment (see Figure III below).

IV The dialysis or replacement line may be connected to either of the two access ports.

IV.a If using a luer access, remove the cap with a twisting and pulling motion and connect the male luer lock of the dialysis or replacement line to the female luer connector on the bag with a twisting and pulling motion. Ensure the connection is correct and secure. The connector is now open. Check that fluid flows freely (see Figure IV.a below).
When the dialysis or replacement line is disconnected from the luer connector, the connector closes and the solution flow stops. The luer port is an aseptic, needle-free access port.

IV.b If using the injection port, first remove the snap-off cap. Then insert the spike through the rubber septum. Verify that fluid flows freely (see Figure IV.b below).
Use the reconstituted solution immediately. If not used immediately, the reconstituted solution must be used within 24 hours, including the duration of treatment, from the time solution A is added to solution B.
The reconstituted solution is for single use only. Discard any unused solution immediately after use.
Unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.