Phoxillum Prescribing Information

2.1 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.

2.2 Dosing Considerations

PRISMASOL replacement solutions contain 4 different combinations of active ingredients (8 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 [see Dosage and Administration (2.3)]:

• 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 10 different replacement solutions (total volume is 5 Liters).

Select the mode of therapy, solute formulation, flow rates, and length of PRISMASOL and PHOXILLIUM replacement therapy in CRRT based on the patient's clinical condition, and fluid, electrolyte, acid-base, 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.

2.3 Preparing the Solution

Use only if the overwrap is not damaged, all seals are intact, and the solution is clear. Press bag firmly to test for any leakage. Do not use if container is damaged or leaking.

The solution may be heated to no more than 40°C/104°F inside of the overwrap. After heating, verify that the solution remains clear and contains no particulate matter.

Follow the instructions below when connecting the solution bags for correct use of the access ports

Figure 1

Figure 2	Step 1 Immediately before use, remove the overwrap from the bag and mix the solutions in the two different compartments. As soon as the overwrap is removed, the reconstitution of compartments A and B should be done and the mixed solution should be used immediately. After removal of the overwrap, the solution is stable for 24 hours including the duration of the treatment. Open the seal by breaking the red frangible pin between the two compartments of the bag. The frangible pin will remain in the bag. (See Figure 2 beside)
Figure 3	Step 2 Make sure all the fluid from the small compartment A is transferred into the large compartment B. (See Figure 3 beside)
	Step 3 Rinse the small compartment A twice by pressing the mixed solution back into the small compartment A and then back into the large compartment B. (See Figure 3 beside)
Figure 4	Step 4 When the small compartment A is empty, shake the large compartment B so that the contents mix completely. (See Figure 4 beside) The solution is now ready to use and the bag can be hung on the equipment.
Figure 5a	Step 5 The replacement line may be connected to the bag through either the luer connector or the injection connector (spike connector). Step 5a The luer connector is a needle-less and swabbable connector. Remove the cap with a twist and pull motion, and connect the male luer lock on the replacement line to the female luer receptor on the bag. (See Figure 5a beside) Ensure that the connection is fully seated and tighten. The connector is now open. Verify that the fluid is flowing freely during use. When the replacement line is disconnected from the luer connector, the connector will close and the flow of the solution will stop.
Figure 5b	Step 5b If the injection connector (spike connector) is used, first remove the snap-off cap. Then introduce the replacement line spike through the rubber septum of the bag connector. (See Figure 5b beside) Ensure that the spike is fully inserted and verify that the fluid is flowing freely during use.

2.4 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, drugs other than phosphate should be administered through a different access line. When introducing additives, use aseptic techniques.

5.1 Electrolyte and Volume Abnormalities

Monitor hemodynamic status and fluid, electrolyte and acid-base balance throughout the procedure. During hemofiltration or hemodiafiltration using PRISMASOL or PHOXILLUM replacement solutions, abnormalities in the plasma concentration of potassium, calcium, magnesium, and phosphate may develop. These abnormalities may be corrected by changing the formulations of replacement solution or by supplementation [see Dosage and Administration (2)].

5.2 Hyperglycemia with Dextrose Containing Solutions

The use of PRISMASOL replacement solutions containing dextrose may increase the risk for hyperglycemia in patients with impaired glucose tolerance. Patients may require initiation of or modification of antidiabetic therapy during treatment with PRISMASOL solutions containing dextrose. Monitor blood glucose.

7.1 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.

8.1 Pregnancy

8.3 Nursing Mothers

The components of PRISMASOL and PHOXILLUM solutions are excreted in human milk. Appropriate administration of PRISMASOL and PHOXILLUM solutions with monitoring of fluid, electrolyte, acid-base and glucose balance, is not expected to harm a nursing infant.

8.4 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.

8.5 Geriatric Use

The experience with PRISMASOL and PHOXILLUM solutions in geriatric patients has not identified novel concerns.

12.1 Mechanism of Action

PRISMASOL and PHOXILLUM solutions are pharmacologically inactive. The electrolyte concentrations in the solutions are chosen to restore plasma levels to clinically desired concentrations or maintain plasma levels at the desired concentrations.

PRISMASOL and PHOXILLUM solutions are used as replacement solution to replace water and electrolytes removed during hemofiltration and hemodiafiltration. Bicarbonate (or precursor lactate) in the solution is used as an alkalinizing buffer to restore acid-base balance to a clinically desirable level.

12.3 Pharmacokinetics

The distribution of electrolytes, bicarbonate, and dextrose is determined by the patient's clinical condition, metabolic status, and residual renal function.

The elimination and replacement of water, electrolytes and buffer depend on the patient's electrolyte and acid-base balance, metabolic status, residual renal function and ongoing physiologic losses through intestinal, respiratory and cutaneous routes.

Storage conditions

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15º-30ºC (59º-86ºF). [See USP Controlled Room Temperature]

Do not freeze or expose to excessive heat. Do not use if precipitate has formed or if container seals have been damaged.