BIPHOZYL Solution for haemodialysis Ref.[28147] Active ingredients: Magnesium chloride Potassium chloride Sodium bicarbonate Sodium chloride Sodium phosphate

The solution should be used only by, or under the direction of, a physician competent in CRRT treatments using haemofiltration, haemodiafiltration and haemodialysis.

Warnings

Biphozyl should not be used in patients with hyperkalemia (see section 4.3). The serum potassium concentration must be monitored before and during haemofiltration and/or haemodialysis.

Because Biphozyl is a potassium-containing solution, hyperkalaemia may occur transiently after treatment is initiated. Decrease the infusion rate and confirm that the desired potassium concentration is achieved. If hyperkalaemia does not resolve, stop administration promptly.

If hyperkalaemia develops when Biphozyl is used as a dialysate, administration of a potassium-free dialysate may be necessary to increase the rate of potassium removal.

Because Biphozyl is a phosphate-containing solution, hyperphosphatemia may occur transiently after treatment is initiated. Decrease the infusion rate and confirm that the desired phosphate concentration is achieved. If hyperphosphatemia does not resolve, stop administration promptly (See Section 4.3).

Electrolyte and blood acid–base parameters should be monitored regularly in patients treated with Biphozyl. Biphozyl contains hydrogen phosphate, a weak acid that can influence the patient’s acid-base balance. If metabolic acidosis develops or worsens during therapy with Biphozyl, the infusion rate may need to be decreased or its administration stopped.

Because Biphozyl contains no glucose, administration may lead to hypoglycaemia. Blood glucose levels should be monitored regularly in diabetic patients (including careful consideration of patients receiving insulin or other glucose lowering medications), but also considered in non-diabetic patients, e.g. risk for silent hypoglycemia during the procedure. If hypoglycaemia develops, use of a glucose-containing solution should be considered. Other corrective measures may be necessary to maintain desired glycaemic control.

The instructions for use (see section 6.6) must be strictly followed. The solutions in the two compartments must be mixed before use. Use of a contaminated solution may cause sepsis and shock.

Use only with an appropriate extracorporal renal replacement equipment.

Special precautions for use

Biphozyl is calcium free and could cause hypocalcaemia (see section 4.8). Infusion of calcium might be necessary.

Biphozyl may be warmed to 37°C to enhance patient comfort. Warming of the solution prior to use should be done before reconstitution with dry heat only. Solutions should not be heated in water or in a microwave oven. Biphozyl should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer unless the solution is clear and the seal is intact.

Haemodynamic status, fluid balance, electrolyte and acid-base balance should be closely monitored throughout the procedure including all fluid inputs and outputs, even those not directly related to CRRT. The content of hydrogen carbonate in Biphozyl is at the lower end of the normal range for blood concentration. Biphozyl is appropriate when using citrate anticoagulation, as citrate is metabolized to hydrogen carbonate, or when CRRT has been able to restore normal pH values. Assessment of buffer needs through measurement of repeated blood acid/base parameters and review of the overall therapy is mandatory. A solution with higher hydrogen carbonate content may be required.

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

In case of hypovolaemia, the net ultrafiltration rate prescribed for the CRRT device can be reduced and/or the rate of administration of solutions other than replacement fluid and/or dialysate can be increased. (see section 4.9)

For general therapy related precautions/contraindications see section 4.3.

The blood concentration of filterable/dialysable drugs may be reduced during the treatment due to their removal by the haemodialyser, haemofilter or haemodiafilter. Corresponding corrective therapy should be instituted if necessary to establish the desired blood concentrations for drugs removed during treatment.

Additional sources of phosphate (e.g., hyperalimentation fluid) may influence serum phosphate concentration and may increase the risk of hyperphosphatemia.

Additional sodium bicarbonate (or buffer source) contained in the CRRT fluids or in other fluids may increase the risk of metabolic alkalosis.

When citrate is used as an anticoagulant, it contributes to the overall buffer load and can reduce plasma calcium levels.

Fertility

No effects on fertility are anticipated, since sodium, potassium, magnesium, chloride, hydrogen phosphate and hydrogen carbonate are normal constituents of the body.

Pregnancy and lactation

There are no documented clinical data on the use of Biphozyl during pregnancy and lactation. Biphozyl should only be administered to pregnant and lactating women if clearly needed.

Biphozyl is not known to affect the ability to drive or use machines.

Undesirable effects can result from the Biphozyl solution used or the dialysis treatment. Special precautions for use have been described in section 4.4.

The following undesirable effects are reported from post-marketing experience. Hydrogen carbonatebuffered haemofiltration and haemodialysis solutions are generally well tolerated. The table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level). Frequencies cannot be estimated from the available data.

^* undesirable effects related generally to dialysis treatments

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.