Prescription Drugs

CLINICAL PHARMACOLOGY Mechanism of Action NORMOCARB HF™ is a pharmacologically inactive solution. The concentrations of electrolytes are chosen to help to restore plasma levels to physiological concentrations. NORMOCARB HF™ is used as replacement solution to replace water and electrolytes removed during hemofiltration and hemodiafiltration. Bicarbonate in the solution is used as an alkalinizing buffer to normalize acid-base balance.

NORMOCARB HF™ (sodium chloride, magnesium chloride hexahydrate, and sodium bicarbonate) Electrolyte Concentrate DESCRIPTION NORMOCARB HF™ is a clear, sterile, nonpyrogenic, electrolyte concentrate used in Continuous Renal Replacement Therapy (CRRT) as a replacement solution in hemofiltration or hemodiafiltration. Composition Undiluted NORMOCARB HF™ 25 contains 90.73 g per Liter sodium chloride (NaCl), 2.06 g per Liter magnesium chloride hexahydrate (MgCl2•6H2O) and 28.35 g per Liter sodium bicarbonate (NaHCO3) in water for injection. Undiluted NORMOCARB HF™ 35 contains 82.84 g per Liter sodium chloride (NaCl), 2.06 g per Liter magnesium chloride hexahydrate (MgCl2•6H2O) and 39.70 g per Liter sodium bicarbonate (NaHCO3) in water for injection. NORMOCARB HF™ contains no bacteriostatic or antimicrobial agents.

INDICATIONS NORMOCARB HF™, after dilution, is indicated in adult and pediatric patients for use as a replacement solution in Continuous Renal Replacement Therapy (CRRT) to replace water and to correct electrolytes and acid-base imbalance. DOSAGE AND ADMINISTRATION Important Preparation Information NORMOCARB HF™ MUST BE DILUTED BEFORE USE. Dilute only with Sterile Water for Injection. For dilution, one 240 mL vial of NORMOCARB HF™ should be added to 3 Liters of Sterile Water for Injection to make 3.24 Liters of infusate solution. Shake to mix by rocking or rolling the bag and contents thoroughly. Additives can be introduced after initial dilution (see Additives below). Individualization of Treatment Pre- or Post-Filter: The volume of solution (diluted NORMOCARB HF™) administered will depend upon the fluid balance of the individual patient, the target fluid balance to be achieved, the body weight and the amount of fluid removed from the patient's circulation during the hemofiltration process. When administered post-filter, the replacement rate should not be greater than one third of the blood flow rate; e.g., for blood flow of 100 mL per min, equivalent to 6000 mL per hour, post-filter replacement rate should not exceed 2000 mL per hour. Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. NORMOCARB HF™ must not be used if a precipitate has been formed or if container seals have been damaged. Table 1 describes the components of diluted NORMOCARB HF™ 25 and NORMOCARB HF™ 35 solutions when prepared as directed. Table 1: Components of Diluted NORMOCARB HF™ 25 and NORMOCARB HF™ 35 Diluted NORMOCARB HF™ 25 Diluted NORMOCARB HF™ 35 Component mEq per Liter mEq per Liter Sodium (Na) 140 140 Magnesium (Mg) 1.5 (0.75 mMol per L) 1.5 (0.75 mMol per L) Chloride (Cl) 116.5 106.5 Bicarbonate (HCO3) 25 35 Total Anions 141.5 141.5 Total Cations 141.5 141.5 Theoretical Osmolarity 283 mOsm per Liter 283 mOsm per Liter pH 8.55 ± 0.25 8.55 ± 0.25 Diluted NORMOCARB HF™ should be used within 24 hours. It may be stored at normal room temperature or refrigerated (2° to 30°C). Do not freeze infusate solution or expose to excessive heat. Additives When introducing additives, use aseptic techniques. Potassium: Potassium chloride up to 4 mEq per Liter may be added to the diluted solution. Calcium: Calcium chloride up to 1.25 mMol per Liter (2.5 mEq per Liter) may be added to the diluted solution. Glucose: Up to 12 mL of D50W may be added to the diluted solution to provide a concentration of up to 10.2 mMol per Liter of dextrose. Phosphate: Potassium phosphate up to 1.2 mMol per Liter (2.4 mEq per Liter) may be added to the diluted solution. The total potassium concentration should not exceed 4 mEq per Liter. Drugs should not be added to NORMOCARB HF™. HOW SUPPLIED Dosage Forms And Strengths NORMOCARB HF™ is a Sterile Electrolyte Concentrate for Infusion. NORMOCARB HF™ comes in two strengths that differ in bicarbonate concentration. Undiluted NORMOCARB HF™ 25 contains 90.73 g per Liter sodium chloride (NaCl), 2.06 g per Liter magnesium chloride hexahydrate (MgCl2•6H2O) and 28.35 g per Liter sodium bicarbonate (NaHCO3) in water for injection. Undiluted NORMOCARB HF™ 35 contains 82.84 g per Liter sodium chloride (NaCl), 2.06 g per Liter magnesium chloride hexahydrate (MgCl2•6H2O) and 39.70 g per Liter sodium bicarbonate (NaHCO3) in water for injection. NORMOCARB HF™ is available as a clear, sterile, nonpyrogenic, bicarbonate infusate concentrate in single-use vials of 240 mL. NORMOCARB HF™ contains no bacteriostatic or antimicrobial agents. 240 mL vial NDC NORMOCARB HF™ 25 16951-0125-1 NORMOCARB HF™ 35 16951-0135-1 Storage and Handling Undiluted NORMOCARB HF™ should be stored at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Do not freeze. Do not use if a precipitate has formed or if container seals have been damaged. Manufactured by: Apotex Inc. Toronto, Ontario Canada M9L 1T9. Revised: 04/2012

PATIENT INFORMATION No information provided. Please refer to the WARNINGS AND PRECAUTIONS section.

OVERDOSE No information provided. CONTRAINDICATIONS None.

SIDE EFFECTS No information provided. DRUG INTERACTIONS No information provided.

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Serious Electrolyte, Acid-base, Glucose and Fluid Imbalances Fluid imbalance and electrolyte, acid-base, and glucose disturbances can occur during therapy. The patient's hemodynamic status, and fluid, electrolyte, glucose and acid-base balance should be monitored throughout the procedure. Use In Specific Populations Preganancy Pregnancy Category C NORMOCARB HF™ is a replacement solution of electrolytes and bicarbonate and is pharmacologically inactive. Animal reproduction studies have not been conducted with NORMOCARB HF™. While there are no adequate and well-controlled studies in pregnant women, appropriate administration of NORMOCARB HF™ with monitoring of fluid, electrolyte, acid-base and glucose balance, is not expected to cause fetal harm, or affect reproductive capacity. Maintenance of normal acid-base balance is important for fetal well being. Nursing Mothers NORMOCARB HF™ is a replacement solution of electrolytes and bicarbonate and is pharmacologically inactive. The components of NORMOCARB HF™ are excreted in human milk. Appropriate administration of NORMOCARB HF™ with monitoring of fluid, electrolyte, acid-base and glucose balance is not expected to harm a nursing infant. Pediatric Use No adequate and well-controlled studies have been conducted with NORMOCARB HF™ in adult or pediatric patients. Safety and effectiveness in pediatric patients newborn to 17 years of age were based on eight non-controlled published pediatric studies and one published pediatric scientific literature review. The exact composition of the buffer and electrolytes in the solution during CRRT were not described in adult or pediatric studies; however, plasma electrolyte levels were similar between adults and children. Geriatric Use No adequate and well-controlled studies have been conducted with NORMOCARB HF™ in elderly patients.