Phoxillum Drug Information

• PRISMASOL and PHOXILLUM solutions are indicated in pediatric and adult patients for use as a replacement solution in Continuous Renal Replacement Therapy (CRRT) to replace plasma volume removed by ultrafiltration and to correct electrolyte and acid-base imbalances. They may also be used in case of drug poisoning when CRRT is used to remove dialyzable substances. PRISMASOL and PHOXILLUM solutions are indicated:
• As a replacement solution in Continuous Renal Replacement Therapy (CRRT) and in case of drug poisoning when CRRT is used to remove dialyzable substances

Administration Instructions

Visually inspect PRISMASOL and PHOXILLUM for particulate matter and discoloration prior to administration. Administration should only be under the direction of a physician competent in intensive care treatment including CRRT. Use only with extracorporeal dialysis equipment appropriate for CRRT.

The prepared solution is for single patient use only. Aseptic technique should be used throughout administration to the patient. Discard any unused solution.

Dosing Considerations

PRISMASOL replacement solutions contain 4 different combinations of active ingredients (7 different products with varying ingredient amounts). PHOXILLUM replacement solutions contain 2 different combinations of active ingredients (2 different products with varying ingredient amounts). PRISMASOL and PHOXILLUM are supplied in a two-compartment bag that must be mixed immediately prior to use: • Small compartment A (250 mL) containing an electrolyte solution, and • Large compartment B (4750 mL) containing the buffer solution.

See Table 1 for the concentrations of the active ingredients (after mixing) in these 9 different replacement solutions (total volume is 5 Liters). Table 1: Concentrations of Active Ingredients in the 7 PRISMASOL and 2 The mode of therapy, solute formulation, flow rates, and length of PRISMASOL and PHOXILLUM replacement therapy in CRRT should be established by a physician based on the patient’s clinical condition, blood concentration of phosphate and other electrolytes, acid-base and glucose balance. Administer either PRISMASOL or PHOXILLUM into the extracorporeal circuit: • Before (pre-dilution) the hemofilter or hemodiafilter, • After (post-dilution) the hemofilter or hemodiafilter, or • Before and after the hemofilter or hemodiafilter.

Preparing the Solution

Use only if the overwrap is not damaged, all seals are intact, peel seal is not broken, and the solution is clear. The solution may be warmed to 37°C/98.6°F prior to removing the overwrap to enhance patient comfort. However, only dry heat should be used.

Solutions should not be heated in water or in a microwave oven. After heating, verify that the solution remains clear and contains no particulate matter. The solutions are supplied in two different two-compartment bags made of polyolefin with a peel seal separating compartment A and B (see Figure 1 ).

Follow the instructions below when connecting the solution bags for correct use of the access ports. Instructions for preparing solutions supplied in a two-compartment, polyolefin bag with a peel seal: Figure 1 Figure 1

Adding Drugs to the Solutions

After mixing, additional drugs may be added to the bag via injection connector (spike connector) in large compartment B. In general, administer drugs other than phosphate through a different access line. When introducing drugs, use aseptic techniques and mix thoroughly prior to connecting the solution bag to the extracorporeal circuit.

Do not use if there is a color change and/or the appearance of precipitates, insoluble complexes or crystals after addition of medication. Phosphate: Up to 1.2 mmol/L of phosphate can be added to the bag as potassium phosphate or sodium phosphate. The total potassium concentration of PRISMASOL solution should not exceed 4 mEq/L.

Use sodium phosphate to add phosphate if the total potassium concentration in PRISMASOL solution is 4 mEq/L. PHOXILLUM Solutions: Phosphate: Phosphate up to 0.2 mmol/L may be added to the solution. Use sodium phosphate if adding phosphate to bag.

The total phosphate concentration should not exceed 1.2 mmol/L.

• The following adverse reactions have been identified during postapproval use with these or other similar products and therefore may occur with use of PHOXILLUM or PRISMASOL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• Metabolic acidosis
• Hypotension
• Acid-base disorders
• Electrolyte imbalance including calcium ionized increased (reported in PRISMASOL solutions containing calcium), hyperphosphatemia, and hypophosphatemia
• Fluid imbalance

Citrate

When used as an anticoagulant, citrate contributes to the overall buffer load and can reduce plasma calcium levels. Select the PRISMASOL/PHOXILLUM formulation(s) accordingly.

Pregnancy Risk Summary PRISMASOL and PHOXILLUM are pharmacologically inactive solutions. While there are no adequate and well controlled studies in pregnant women, appropriate administration of PRISMASOL and PHOXILLUM solutions with monitoring of fluid, electrolyte, acid-base and glucose balance, is not expected to cause fetal harm. Animal reproduction studies have not been conducted with PRISMASOL and PHOXILLUM solutions.

The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Clinical Considerations Maintenance of normal acid-base balance is important for fetal well-being.

Pediatric Use Safety and effectiveness have been established based on published clinical data of CRRT replacement solutions with compositions similar to PRISMASOL and PHOXILLUM used in adults and two hemofiltration studies in pediatric patients, including a study of newborns to 17 years old.

PHOXILLUM and PRISMASOL replacement solutions are contraindicated in patients with known hypersensitivities to these products. Known hypersensitivities to PRISMASOL and PHOXILLUM solutions