Potassium Phosphates

1 INDICATIONS AND USAGE Potassium Phosphates Injection is indicated as a source of phosphorus: • in intravenous fluids to correct hypophosphatemia in adults and pediatric patients when oral or enteral replacement is not possible, insufficient or contraindicated. • for parenteral nutrition in adults and pediatric patients when oral or enteral nutrition is not possible, insufficient or contraindicated. Potassium Phosphates Injection is a phosphorus replacement product indicated as a source of phosphorus: • in intravenous fluids to correct hypophosphatemia in adults and pediatric patients when oral or enteral replacement is not possible, insufficient or contraindicated. ( 1 ) • for parenteral nutrition in adults and pediatric patients when oral or enteral nutrition is not possible, insufficient or contraindicated. ( 1 )

2 DOSAGE AND ADMINISTRATION • Administer intravenously only after dilution or admixing in a larger volume of fluid. ( 2.1 ) • Potassium Phosphates Injection provides phosphorus 3 mmol/mL (potassium 4.4 mEq/mL). ( 2.2 , 2.4 ) • Monitor serum phosphorus, potassium, calcium, and magnesium concentrations. ( 2.2 , 2.4 ) • See full prescribing information for instructions on preparation and administration. ( 2.1 , 2.3 ) Recommended Dosage for Correction of Hypophosphatemia in Intravenous Fluids • Potassium Phosphates Injection is only for administration to a patient with a serum potassium concentration less than 4 mEq/dL; otherwise, use an alternative source of phosphorus. ( 2.1 ) • The dosage is dependent upon the individual needs of the patient, and the contribution of phosphorus and potassium from other sources. ( 2.2 ) • See full prescribing information for recommendations on initial or single dosing, repeated dosing, concentration and infusion rate. ( 2.1 , 2.2 ) Recommended Dosage for Administration in Parenteral Nutrition • Individualize the dosage based upon the patient's clinical condition, nutritional requirements, and the contribution of oral or enteral phosphorus and potassium intake. ( 2.4 ) • See full prescribing information for recommendations for daily and maximum dosage. ( 2.4 ) 2.1 Preparation and Administration in Intravenous Fluids to Correct Hypophosphatemia Preparation • Potassium Phosphates Injection is for intravenous infusion into a central or peripheral vein only after dilution. • Using aseptic technique, withdraw the required amount from the vial and add to 0.9% Sodium Chloride Injection, USP (normal saline) or 5% Dextrose Injection, USP (D5W). For adults and pediatric patients 12 years of age and older a total volume of 100 mL or 250 mL is recommended. For pediatric patients less than 12 years of age, use the smallest recommended volume, considering daily fluid requirements and the maximum concentration for peripheral and central administration shown in Table 1 . • The concentration of the diluted solution should take into consideration the age of the patient, the amounts of phosphorus and potassium in the dose, and is dependent upon whether administration will be through a peripheral or central venous catheter. The recommended maximum concentrations are shown in Table 1 : TABLE 1: Maximum Recommended Concentration of Potassium Phosphates Injection by Age and Route of Administration (Peripheral vs. Central) Patient Population Peripheral Venous Catheter Central Venous Catheter Adults and Pediatric Patients 12 Years of Age and Older phosphorus 6.8 mmol/100 mL (potassium 10 mEq/100 mL) phosphorus 18 mmol/100 mL (potassium 26.4 mEq/100 mL) Pediatric Patients Less than 12 Years of Age phosphorus 0.27 mmol/10 mL (potassium 0.4 mEq/10 mL) phosphorus 0.55 mmol/10 mL (potassium 0.8 mEq/10 mL) • Visually inspect the solution for particulate matter and discoloration before and after dilution and prior to administration. Do not administer unless solution is clear, and seal on the vial is intact. Administration • Check serum potassium and calcium concentrations prior to administration. Normalize the calcium before administering Potassium Phosphates Injection [see Contraindications (4) , Warnings and Precautions (5.3 , 5.4 )] . • Potassium Phosphates Injection is only for administration to a patient with a serum potassium concentration less than 4 mEq/dL [see Warnings and Precautions (5.3) ] . If the potassium concentration is 4 mEq/dL or more, use an alternative source of phosphorus. • Do not infuse with calcium-containing intravenous fluids [see Warnings and Precautions (5.4) ] . • The rate of administration may be dependent on the patient and the specific institution policy [see Dosage and Administration (2.2) ] . Storage and Stability • Single-Dose Vial (15 mL) o For single use only. Discard used vial, including any unused contents. • After dilution, the solution is stable for a maximum of 4 hours at room temperature 20°C to 25°C (68°F to 77°F) or 14 days under refrigeration at 2°C to 8°C (36°F to 46°F). 2.2 Dosage for Administration in Intravenous Fluids to Correct Hypophosphatemia Potassium Phosphates Injection provides phosphorus 3 mmol/mL (potassium 4.4 mEq/mL). The dosage is dependent upon the individual needs of the patient, and the contribution of phosphorus and potassium from other sources. Initial or Single Dose The phosphorus doses in Table 2 are general recommendations for an initial or single dose and are intended for most patients. Based upon clinical requirements, some patients may require a lower or higher dose. The maximum initial or single dose of phosphorus is 45 mmol (potassium 66 mEq) [see Warnings and Precautions (5.1) ] . In patients with moderate renal impairment (eGFR ≥30 mL/min/1.73 m 2 to <60 mL/min/1.73 m 2 ), start at the low end of the dose range [see Use in Specific Populations (8.6) ] . Monitor serum phosphorus, potassium, calcium and magnesium serum concentrations. TABLE 2: Recommended Initial or Single Dose of Potassium Phosphates Injection in Intravenous Fluids to Correct Hypophosphatemia in Adults and Pediatric Patients Serum Phosphorus Concentration Serum phosphorus reported using 2.5 mg/dL as the lower end of the reference range for healthy adults and pediatric patients 12 months of age and older. Serum phosphorus reported using 4 mg/dL as the lower end of the reference range for preterm and term infants less than 12 months of age. Serum phosphorus concentrations may vary depending on the assay used and the laboratory reference range. Phosphorus Dosage Weight is in terms of actual body weight. Limited information is available regarding dosing of patients significantly above ideal body weight; consider using an adjusted body weight for these patients. , up to a maximum of phosphorus 45 mmol (potassium 66 mEq) as a single dose. Corresponding Potassium Content 1.8 mg/dL to lower end of the reference range 0.16 mmol/kg to 0.31 mmol/kg potassium 0.23 mEq/kg to 0.46 mEq/kg 1 mg/dL to 1.7 mg/dL 0.32 mmol/kg to 0.43 mmol/kg potassium 0.47 mEq/kg to 0.63 mEq/kg Less than 1 mg/dL 0.44 mmol/kg to 0.64 mmol/kg potassium 0.64 mEq/kg to 0.94 mEq/kg Concentration and Intravenous Infusion Rate • The concentration of the diluted solution [see Table 1 , Dosage and Administration (2.1) ] and the infusion rate is dependent upon whether administration will be through a peripheral or central venous catheter. The maximum recommended infusion rates are shown in Table 3 for adults and pediatric patients 12 years of age and older. TABLE 3: Maximum Recommended Infusion Rate of Potassium Phosphates Injection for Adults and Pediatric Patients 12 Years of Age and Older Route of Administration Maximum Infusion Rate Peripheral Venous Catheter phosphorus 6.8 mmol/hour (potassium 10 mEq/hour) Central Venous Catheter phosphorus 15 mmol/hour (potassium 22 mEq/hour) Continuous electrocardiographic (ECG) monitoring and infusion through a central venous catheter is recommended for infusion rates higher than: • Potassium 10 mEq/hour for adults and pediatric patients weighing 20 kg or greater • Potassium 0.5 mEq/kg/hour for pediatric patients weighing less than 20 kg Repeated Dosing Additional dose(s) following the initial dose may be needed in some patients. Prior to administration of additional doses, assess the patient clinically, obtain serum phosphorus, calcium and potassium concentrations and adjust the dose accordingly. 2.3 Preparation and Administration in Parenteral Nutrition • Potassium Phosphates Injection is for intravenous infusion into a peripheral or central vein only after dilution and admixing . • Potassium Phosphates Injection is to be prepared only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). The key factor in the preparation is careful aseptic technique to avoid inadvertent touch contamination during mixing of solutions and addition of other nutrients. • Transfer the required amount of Potassium Phosphates Injection to the parenteral nutrition solution following the admixture of amino acids, dextrose, electrolytes solutions, and prior to lipids (if added). • Because additives may be incompatible, evaluate all additions to the parenteral nutrition container for compatibility and stability of the resulting preparation. • Calcium and phosphate ratios must be considered. Excess addition of calcium and phosphate, especially in the form of mineral salts, may result in the formation of calcium-phosphate precipitates [see Warnings and Precautions (5.2) ] . Calcium-phosphate stability in parenteral nutrition solutions is dependent upon the pH of the solution, temperature, and relative concentration of each ion. Discard if any precipitates are observed. • Inspect the final parenteral solution containing Potassium Phosphates Injection to ensure that: o precipitates have not formed during mixing or addition of additives and inspect again before administration. o the emulsion has not separated, if lipids have been added. Separation of the emulsion can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the admixed emulsion. • The final parenteral nutrition solution is for intravenous infusion into a peripheral or central vein. The choice of a peripheral or central venous route should depend on the osmolarity of the final infusate. Solutions with osmolarity of 900 mOsmol/L or greater must be infused through a central catheter [see Warnings and Precautions (5.7) ] . Storage • Protect the parenteral nutrition solution from light during storage. Stability • Single-Dose Vial (15 mL) o For single use only. Discard used vial, including any unused contents. • Use parenteral nutrition solution containing Potassium Phosphates Injection promptly after mixing. Any storage of the admixture should be under refrigeration from 2°C to 8°C (36°F to 46°F) and limited to a brief period of time, no longer than 24 hours. After removal from refrigeration, bring to room temperature and use promptly and complete the infusion within 24 hours. Discard any remaining admixture. 2.4 Dosage for Administration in Parenteral Nutrition Potassium Phosphates Injection provides phosphorus 3 mmol/mL (potassium 4.4 mEq/mL). The recommended daily dosage in parenteral nutrition is shown in Table 4 . Individualize the dosage based upon the patient's clinical condition, nutritional requirements, and the contribution of oral or enteral phosphorus and potassium intake. The amount of phosphorus that can be added to parenteral nutrition may be limited by the amount of calcium that is also added to the solution. TABLE 4: Recommended Daily Dosage of Potassium Phosphates Injection for Parenteral Nutrition for Adults and Pediatric Patients Patient Population Generally Recommended Phosphorus Daily Dosage (Potassium Content) Preterm and Term Infants Less than 12 Months 2 mmol/kg/day (potassium 2.9 mEq/kg/day) Pediatric Patients 1 year to Less Than 12 years 1 mmol/kg/day; up to 40 mmol/day (potassium 1.5 mEq/kg/day; up to 58.7 mEq/day) Adults and Pediatric Patients 12 Years of Age and Older 20 mmol/day to 40 mmol/day In patients with moderate renal impairment (eGFR ≥30 mL/min/1.73 m 2 to <60 mL/min/1.73 m 2 ), start at the low end of the dosage range. (potassium 29.3 mEq/day to 58.7 mEq/day) Monitoring Monitor serum phosphorus, potassium, calcium and magnesium concentrations and adjust the dosage accordingly.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Aluminum Toxicity [see Warnings and Precautions (5.5) ] • Hypomagnesemia [see Warnings and Precautions (5.6) ] • Vein Damage and Thrombosis [see Warnings and Precautions (5.7) ] The following adverse reactions in Table 5 have been reported in clinical studies or postmarketing reports in patients receiving intravenously administered potassium phosphates. Because some of these reactions were 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. TABLE 5: Adverse Reactions Reported in Clinical Studies or Postmarketing Reports with Intravenous Potassium Phosphates System Organ Class Adverse Reactions Metabolism and Nutrition Disorders pulmonary embolism due to pulmonary vascular precipitates [see Warnings and Precautions (5.2) ], hyperkalemia [see Warnings and Precautions (5.3) ] , hyperphosphatemia [see Warnings and Precautions (5.4) ], hypocalcemia [see Warnings and Precautions (5.5) ] , hypovolemia, and osmotic diuresis Cardiac Disorders hypotension, arrhythmia, heart block, cardiac arrest, bradycardia, chest pain, ECG changes [see Warnings and Precautions (5.1) ] , and edema Respiratory, Thoracic, and Mediastinal Disorders dyspnea [see Warnings and Precautions (5.2) ] Renal and Urinary Disorders acute phosphate nephropathy (i.e., nephrocalcinosis with acute kidney injury), decreased urine output, and transition to chronic kidney disease [see Warnings and Precautions (5.4) ] Gastrointestinal Disorders diarrhea, stomach pain Musculoskeletal and Connective Tissue Disorders weakness Nervous System Disorders confusion, lethargy, paralysis, paresthesia Adverse reactions include hyperkalemia, hyperphosphatemia, hypocalcemia, and hypomagnesemia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Hospira, Inc. at 1-800-441-4100 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

12.3 Pharmacokinetics Distribution Approximately 85% of serum phosphates is free and ultra-filterable and 15% is protein-bound. Elimination Intravenously infused phosphates not taken up by the tissues are excreted almost entirely in the urine. Serum phosphorus is believed to be filterable by the renal glomeruli and the major portion of filtered phosphorus (greater than 80%) is actively reabsorbed by the tubules.