These Highlights Do Not Include All The Information Needed To Use Delflex ®

Risk Summary

DELFLEX solutions consist of electrolytes, lactate, and bicarbonate at physiological levels, and glucose to facilitate ultrafiltration. While there are no adequate and well controlled studies in pregnant women, appropriate administration of DELFLEX 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 DELFLEX.

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 2 to 4% and 15 to 20%, respectively.

Principal Display Panel – 1.5% Dextrose 3000 mL Bag Label

DELFLEX ^®

PERITONEAL DIALYSIS SOLUTION

With

1.5% DEXTROSE

LOW MAGNESIUM / LOW CALCIUM

and attached

stay•safe ^®Exchange Set

CAT. NO. 054-30321

NDC 46163-206-95

3000 mL

(Approx. 60 mL excess)

The DELFLEX® peritoneal dialysis solutions (low magnesium/low calcium) are sterile, non-pyrogenic formulations of dextrose and electrolytes in water for injection, USP, for use in peritoneal dialysis. These solutions do not contain antimicrobial agents or additional buffers. The stay•safe exchange set utilizes an easy to use dial designed to eliminate the use of clamps and to prevent touch contamination of internal connection components. Composition, calculated osmolarity, pH, and ionic concentrations are shown in Table 2.

Dextrose, USP, is chemically designated D-glucose monohydrate (C ₆H ₁₂O ₆•H ₂O) a hexose sugar freely soluble in water. The structural formula is shown here:

Calcium chloride, USP, is chemically designated calcium chloride dihydrate (CaCl ₂•2H ₂O) white fragments or granules freely soluble in water.

Magnesium chloride, USP, is chemically designated magnesium chloride hexahydrate (MgCl ₂•6H ₂O) colorless flakes or crystals very soluble in water.

Sodium lactate solution, USP, is chemically designated (CH ₃CH(OH)COONa), a 60% aqueous solution miscible in water.

Sodium chloride, USP, is chemically designated (NaCl), a white, crystalline compound freely soluble in water.

Water for injection, USP, is chemically designated (H ₂O).

Hydrochloric Acid or Sodium Hydroxide may be added for pH adjustment. pH is 5.5 ± 0.5.

Exposure to temperatures above 25°C (77°F) during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period. Since the inner bag is compounded from a specific polyvinyl chloride, water may permeate from the inner bag into the overwrap in quantities insufficient to affect the solution significantly. Solutions in contact with the plastic inner bag can cause certain chemical components of the bag to leach out in very small amounts; however, the safety of the plastic formulation is supported by biological tests for plastic containers.

Over infusion of peritoneal dialysis solution volume into the peritoneal cavity may be characterized by abdominal distention, feeling of fullness and/or shortness of breath. Drain the peritoneal dialysis solution from the peritoneal cavity to treat over infusion.

Safety and effectiveness in pediatric patients have not been established.

Monitor patients with conditions known to increase the risk of lactic acidosis [e.g., severe hypotension or sepsis that can be associated with acute kidney failure, inborn errors of metabolism, treatment with drugs such as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)] for lactic acidosis before the start of treatment and during treatment with DELFLEX.

Solutions containing the lactate ion should be used with great care in patients with metabolic or respiratory alkalosis. Lactate should be administered with great care in those conditions in which there is an increased level or an impaired utilization of this ion, such as severe hepatic insufficiency.

None.

Solution related adverse reactions may include peritonitis, catheter site infection, electrolyte and fluid imbalances, hypovolemia, hypervolemia, hypertension, hypotension, disequilibrium syndrome, muscle cramping, abdominal pain, abdominal distension, and abdominal discomfort.

DELFLEX® is indicated in the treatment of chronic kidney failure patients being maintained on peritoneal dialysis

DELFLEX peritoneal dialysis solutions are hypertonic peritoneal dialysis solutions containing dextrose, a monosaccharide, as the primary osmotic agent. An osmotic gradient must be created between the peritoneal membrane and the dialysis solution in order for ultrafiltration to occur. The hypertonic concentration of glucose in DELFLEX solutions exert an osmotic pressure across the peritoneal membrane resulting in transcapillary ultrafiltration. Like other peritoneal dialysis solutions, DELFLEX solutions contain electrolytes to facilitate the correction of acid-base and electrolyte abnormalities. DELFLEX solutions contain a buffer, lactate, to help normalize acid-base abnormalities.

Compatible medications can be added via the medication port [ see Dosage and Administration ( 2.2) ]. The following medications have demonstrated stability with DELFLEX solutions: cefazolin, ceftazidime, gentamicin, and vancomycin [ see Clinical Pharmacology ( 12.3) ].

• Monitor patient for electrolyte, fluid, and nutrition imbalances. ( 5.1)
• Encapsulating Peritoneal Sclerosis (EPS) ( 5.2)
• Peritonitis: Initiate appropriate antimicrobial therapy ( 5.2)
• Monitor for Lactic Acidosis in patients at risk. ( 5.3)

For intraperitoneal dialysis only. ( 2)

DELFLEX® is intended for intraperitoneal administration only. Not for intravenous or intra-arterial administration.

The mode of therapy, frequency of treatment, formulation, exchange volume, duration of dwell, and length of dialysis should be selected by the physician responsible for the treatment of the individual patient.

Utilize the peritoneal dialysis solution with lowest level of osmolarity consistent with the fluid removal requirements for that exchange.

Do not store solutions containing additives.

DELFLEX peritoneal dialysis solutions are available in transparent single-dose flexible bags. The solution is clear with color being slightly yellow to colorless. All DELFLEX peritoneal dialysis solutions have overfills declared on the bag label. The flexible bag has the capacity for drainage in excess of their stated fill volume for ultrafiltration from the patient.

DELFLEX peritoneal dialysis solutions with an attached stay•safe exchange set are available in the sizes and formulations shown in Table 1.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not heat in a microwave oven.

Get Ready

Aseptic technique must be used throughout the procedure and at its termination in order to reduce the possibility of infection.

The solution bag should remain in the carton and the overwrap intact until time of use.

Use only after checking for strength, clarity, amount, leaks, and expiration date.

Advise patients that DELFLEX peritoneal dialysis solution should not be heated in a microwave oven.

Disconnect from stay•safe DISC only when the blue dial is in position 4(●●●●) to ensure the fluid path of the stay•safe catheter extension set is sealed.

Care should be taken to ensure that there is not any leakage around the catheter, since if not controlled, the leakage can create edema from subcutaneous infiltration of the dialysis solution. The leakage will also create an inaccurate fluid balance measurement. If any leakage is identified, do not proceed with infusion and notify your physician.

Fresenius Medical Care North America

920 Winter Street

Waltham, MA 02451

1-800-323-5188

Made in Mexico

© 2020 Fresenius Medical Care. All Rights Reserved. Fresenius Medical Care, triangle logo, stay•safe, DELFLEX, are trademarks of Fresenius Medical Care Holding, Inc. or its affiliated companies.

DELFLEX peritoneal dialysis solutions with attached stay•safe exchange set are available in the sizes and formulations shown in Table 1[Dosage Forms and Strengths]. (3) DELFLEX peritoneal dialysis solutions are delivered in transparent, single-dose flexible bags. The solution is clear with color being slightly yellow to colorless.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (between 59°F and 86°F). See USP Controlled Room Temperature. Brief exposure to temperatures up to 40°C (104°F) may be tolerated provided the mean kinetic temperature does not exceed 25°C (77°F); however, such exposure should be minimized.

Keep DELFLEX and all medicines out of the reach of children.

Peritoneal dialysis may affect a patient's protein, water-soluble vitamin, potassium, sodium, chloride, bicarbonate, and magnesium levels and volume status. Monitor electrolytes and blood chemistry periodically and take appropriate clinical action.

Potassium is omitted from DELFLEX solutions because dialysis may be performed to correct hyperkalemia. In situations where there is a normal serum potassium level or hypokalemia, the addition of potassium chloride (up to a concentration of 4 mEq/L) may be indicated to prevent severe hypokalemia.

To avoid the risk of severe dehydration or hypovolemia and to minimize the loss of protein, it is advisable to select the peritoneal dialysis solution with lowest level of osmolarity consistent with the fluid removal requirements for that exchange.

Significant loss of protein, amino acids and water-soluble vitamins may occur during peritoneal dialysis. Replacement therapy should be provided as necessary.

Infectious and aseptic peritonitis has been associated with peritoneal dialysis therapy. Following DELFLEX use, inspect the drained fluid for the presence of fibrin or cloudiness, which may indicate the presence of peritonitis. Improper clamping or priming sequence may result in infusion of air into the peritoneal cavity, which may result in abdominal pain and/or peritonitis. If peritonitis occurs, treat with appropriate therapy.

Encapsulating peritoneal sclerosis (EPS), sometimes fatal, is a complication of peritoneal dialysis therapy.

Long term animal studies with DELFLEX peritoneal dialysis solutions have not been performed to evaluate the carcinogenic potential, mutagenic potential or effect on fertility.

Risk Summary

DELFLEX solutions consist of electrolytes, lactate, and bicarbonate at physiological levels, and glucose to facilitate ultrafiltration. While there are no adequate and well controlled studies in pregnant women, appropriate administration of DELFLEX 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 DELFLEX.

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 2 to 4% and 15 to 20%, respectively.

Principal Display Panel – 1.5% Dextrose 3000 mL Bag Label

DELFLEX ^®

PERITONEAL DIALYSIS SOLUTION

With

1.5% DEXTROSE

LOW MAGNESIUM / LOW CALCIUM

and attached

stay•safe ^®Exchange Set

CAT. NO. 054-30321

NDC 46163-206-95

3000 mL

(Approx. 60 mL excess)

The DELFLEX® peritoneal dialysis solutions (low magnesium/low calcium) are sterile, non-pyrogenic formulations of dextrose and electrolytes in water for injection, USP, for use in peritoneal dialysis. These solutions do not contain antimicrobial agents or additional buffers. The stay•safe exchange set utilizes an easy to use dial designed to eliminate the use of clamps and to prevent touch contamination of internal connection components. Composition, calculated osmolarity, pH, and ionic concentrations are shown in Table 2.

Dextrose, USP, is chemically designated D-glucose monohydrate (C ₆H ₁₂O ₆•H ₂O) a hexose sugar freely soluble in water. The structural formula is shown here:

Calcium chloride, USP, is chemically designated calcium chloride dihydrate (CaCl ₂•2H ₂O) white fragments or granules freely soluble in water.

Magnesium chloride, USP, is chemically designated magnesium chloride hexahydrate (MgCl ₂•6H ₂O) colorless flakes or crystals very soluble in water.

Sodium lactate solution, USP, is chemically designated (CH ₃CH(OH)COONa), a 60% aqueous solution miscible in water.

Sodium chloride, USP, is chemically designated (NaCl), a white, crystalline compound freely soluble in water.

Water for injection, USP, is chemically designated (H ₂O).

Hydrochloric Acid or Sodium Hydroxide may be added for pH adjustment. pH is 5.5 ± 0.5.

Exposure to temperatures above 25°C (77°F) during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period. Since the inner bag is compounded from a specific polyvinyl chloride, water may permeate from the inner bag into the overwrap in quantities insufficient to affect the solution significantly. Solutions in contact with the plastic inner bag can cause certain chemical components of the bag to leach out in very small amounts; however, the safety of the plastic formulation is supported by biological tests for plastic containers.

Over infusion of peritoneal dialysis solution volume into the peritoneal cavity may be characterized by abdominal distention, feeling of fullness and/or shortness of breath. Drain the peritoneal dialysis solution from the peritoneal cavity to treat over infusion.

Safety and effectiveness in pediatric patients have not been established.

Monitor patients with conditions known to increase the risk of lactic acidosis [e.g., severe hypotension or sepsis that can be associated with acute kidney failure, inborn errors of metabolism, treatment with drugs such as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)] for lactic acidosis before the start of treatment and during treatment with DELFLEX.

Solutions containing the lactate ion should be used with great care in patients with metabolic or respiratory alkalosis. Lactate should be administered with great care in those conditions in which there is an increased level or an impaired utilization of this ion, such as severe hepatic insufficiency.

None.

Solution related adverse reactions may include peritonitis, catheter site infection, electrolyte and fluid imbalances, hypovolemia, hypervolemia, hypertension, hypotension, disequilibrium syndrome, muscle cramping, abdominal pain, abdominal distension, and abdominal discomfort.

DELFLEX® is indicated in the treatment of chronic kidney failure patients being maintained on peritoneal dialysis

DELFLEX peritoneal dialysis solutions are hypertonic peritoneal dialysis solutions containing dextrose, a monosaccharide, as the primary osmotic agent. An osmotic gradient must be created between the peritoneal membrane and the dialysis solution in order for ultrafiltration to occur. The hypertonic concentration of glucose in DELFLEX solutions exert an osmotic pressure across the peritoneal membrane resulting in transcapillary ultrafiltration. Like other peritoneal dialysis solutions, DELFLEX solutions contain electrolytes to facilitate the correction of acid-base and electrolyte abnormalities. DELFLEX solutions contain a buffer, lactate, to help normalize acid-base abnormalities.

Compatible medications can be added via the medication port [ see Dosage and Administration ( 2.2) ]. The following medications have demonstrated stability with DELFLEX solutions: cefazolin, ceftazidime, gentamicin, and vancomycin [ see Clinical Pharmacology ( 12.3) ].

• Monitor patient for electrolyte, fluid, and nutrition imbalances. ( 5.1)
• Encapsulating Peritoneal Sclerosis (EPS) ( 5.2)
• Peritonitis: Initiate appropriate antimicrobial therapy ( 5.2)
• Monitor for Lactic Acidosis in patients at risk. ( 5.3)

For intraperitoneal dialysis only. ( 2)

DELFLEX® is intended for intraperitoneal administration only. Not for intravenous or intra-arterial administration.

The mode of therapy, frequency of treatment, formulation, exchange volume, duration of dwell, and length of dialysis should be selected by the physician responsible for the treatment of the individual patient.

Utilize the peritoneal dialysis solution with lowest level of osmolarity consistent with the fluid removal requirements for that exchange.

Do not store solutions containing additives.

DELFLEX peritoneal dialysis solutions are available in transparent single-dose flexible bags. The solution is clear with color being slightly yellow to colorless. All DELFLEX peritoneal dialysis solutions have overfills declared on the bag label. The flexible bag has the capacity for drainage in excess of their stated fill volume for ultrafiltration from the patient.

DELFLEX peritoneal dialysis solutions with an attached stay•safe exchange set are available in the sizes and formulations shown in Table 1.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not heat in a microwave oven.

Get Ready

Aseptic technique must be used throughout the procedure and at its termination in order to reduce the possibility of infection.

The solution bag should remain in the carton and the overwrap intact until time of use.

Use only after checking for strength, clarity, amount, leaks, and expiration date.

Advise patients that DELFLEX peritoneal dialysis solution should not be heated in a microwave oven.

Disconnect from stay•safe DISC only when the blue dial is in position 4(●●●●) to ensure the fluid path of the stay•safe catheter extension set is sealed.

Care should be taken to ensure that there is not any leakage around the catheter, since if not controlled, the leakage can create edema from subcutaneous infiltration of the dialysis solution. The leakage will also create an inaccurate fluid balance measurement. If any leakage is identified, do not proceed with infusion and notify your physician.

Fresenius Medical Care North America

920 Winter Street

Waltham, MA 02451

1-800-323-5188

Made in Mexico

© 2020 Fresenius Medical Care. All Rights Reserved. Fresenius Medical Care, triangle logo, stay•safe, DELFLEX, are trademarks of Fresenius Medical Care Holding, Inc. or its affiliated companies.

DELFLEX peritoneal dialysis solutions with attached stay•safe exchange set are available in the sizes and formulations shown in Table 1[Dosage Forms and Strengths]. (3) DELFLEX peritoneal dialysis solutions are delivered in transparent, single-dose flexible bags. The solution is clear with color being slightly yellow to colorless.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (between 59°F and 86°F). See USP Controlled Room Temperature. Brief exposure to temperatures up to 40°C (104°F) may be tolerated provided the mean kinetic temperature does not exceed 25°C (77°F); however, such exposure should be minimized.

Keep DELFLEX and all medicines out of the reach of children.

Peritoneal dialysis may affect a patient's protein, water-soluble vitamin, potassium, sodium, chloride, bicarbonate, and magnesium levels and volume status. Monitor electrolytes and blood chemistry periodically and take appropriate clinical action.

Potassium is omitted from DELFLEX solutions because dialysis may be performed to correct hyperkalemia. In situations where there is a normal serum potassium level or hypokalemia, the addition of potassium chloride (up to a concentration of 4 mEq/L) may be indicated to prevent severe hypokalemia.

To avoid the risk of severe dehydration or hypovolemia and to minimize the loss of protein, it is advisable to select the peritoneal dialysis solution with lowest level of osmolarity consistent with the fluid removal requirements for that exchange.

Significant loss of protein, amino acids and water-soluble vitamins may occur during peritoneal dialysis. Replacement therapy should be provided as necessary.

Infectious and aseptic peritonitis has been associated with peritoneal dialysis therapy. Following DELFLEX use, inspect the drained fluid for the presence of fibrin or cloudiness, which may indicate the presence of peritonitis. Improper clamping or priming sequence may result in infusion of air into the peritoneal cavity, which may result in abdominal pain and/or peritonitis. If peritonitis occurs, treat with appropriate therapy.

Encapsulating peritoneal sclerosis (EPS), sometimes fatal, is a complication of peritoneal dialysis therapy.

Long term animal studies with DELFLEX peritoneal dialysis solutions have not been performed to evaluate the carcinogenic potential, mutagenic potential or effect on fertility.