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 tempe…

5 WARNINGS AND PRECAUTIONS • Serious Cardiac Adverse Reactions with Undiluted, Bolus, or Rapid Intravenous Administration : Administer only after dilution or admixing; do not exceed the recommended infusion rate. Continuous electrocardiographic (ECG) monitoring may be needed during infusion. ( 2.2 , 5.1 ) • Pulmonary Embolism due to Pulmonary Vascular Precipitates : If signs of pulmonary distress occur, stop the infusion and initiate a medical evaluation. ( 5.2 ) • Hyperkalemia : Increased risk in patients with renal impairment, severe adrenal insufficiency, or treated with drugs that increase potassium. Patients with cardiac disease may be more susceptible. Do not exceed the maximum daily amount of potassium or the recommended infusion rate. Continuous ECG monitoring may be needed during infusion. ( 5.3 , 7.1 ) • Hyperphosphatemia and Hypocalcemia : Monitor serum phosphorus and calcium concentrations during and following infusion. ( 5.4 ) • Aluminum Toxicity : Increased risk in patients with renal impairment, including preterm infants. ( 5.5 , 8.4 ). • Hypomagnesemia : Reported in patients with hypercalcemia and diabetic ketoacidosis. Monitor serum magnesium concentrations during treatment. ( 5.6 ) • Vein Damage and Thrombosis : Infuse concentrated or hypertonic solutions through a central catheter. ( 2.1 , 2.3 , 5.7 ) 5.1 Serious Cardiac Adverse Reactions with Undiluted, Bolus or Rapid Intravenous Administration Intravenous administration of potassium phosphates to correct hypophosphatemia in single doses of phosphorus 50 mmol and greater and/or at rapid infusion rates (over 1 to 3 hours) in intravenous fluids has resulted in death, cardiac arrest, cardiac arrhythmia (including QT prolongation), hyperkalemia, hyperphosphatemia, and seizures [see Overdosage ( 10 )]. In addition, inappropriate intravenous administration of undiluted or insufficiently diluted potassium phosphates as a rapid “IV push” has resulted in cardiac arrest, cardiac arrhythmias, hypotension, and death. Potassium Phosphates Injection is for intravenous infusion only after dilution or admixing . The maximum initial or single dose of Potassium Phosphates Injection in intravenous fluids to correct hypophosphatemia is phosphorus 45 mmol (potassium 66 mEq). The recommended infusion rate for administration through a peripheral venous catheter is approximately phosphorus 6.8 mmol/hour (potassium 10 mEq/hour). Continuous electrocardiographic (ECG) monitoring is recommended for higher infusion rates [see Dosage and Administration ( 2.1 , 2.2 )] . 5.2 Pulmonary Embolism due to Pulmonary Vascular Precipitates Pulmonary vascular emboli and pulmonary distress related to precipitates in the pulmonary vasculature have been described in patients receiving admixed products containing calcium and phosphate or parenteral nutrition. The cause of precipitate formation has not been determined in all cases; however, in some fatal cases, pulmonary emboli occurred as a result of calcium phosphate precipitates. Precipitation has occurred following passage through an in-line filter; in vivo precipitate formation may also have occurred. If signs of pulmonary distress occur, stop the parenteral nutrition infusion and initiate a medical evaluation. In addition to inspection of the solution [see Dosage and Administration ( 2.3 )] , the infusion set and catheter should also periodically be checked for precipitates. 5.3 Hyperkalemia Potassium Phosphates Injection may increase the risk of hyperkalemia, including life-threatening cardiac events, especially when administered in excessive doses, undiluted or by rapid intravenous infusion [see Warnings and Precautions ( 5.1 )] . Patients with severe renal impairment and end stage renal disease are at increased risk of developing life-threatening hyperkalemia, when administered intravenous potassium [see Contraindications ( 4 )] . Other patients at increased risk of hyperkalemia include those with severe adrenal insufficiency or treated concur…

4 CONTRAINDICATIONS Potassium Phosphates Injection is contraindicated in patients with: • hyperkalemia [see Warning and Precautions ( 5.3 )] • severe renal impairment (eGFR less than 30 mL/min/1.73m 2 ) or end stage renal disease [see Warning and Precautions ( 5.3 )] • hyperphosphatemia [see Warning and Precautions ( 5.4 )] • hypercalcemia or significant hypocalcemia [see Warning and Precautions ( 5.4 )] • hyperkalemia ( 4 ) • hyperphosphatemia ( 4 ) • hypercalcemia or significant hypocalcemia ( 4 ) • severe renal impairment (eGFR less than 30 mL/min/1.73m 2 ) or end stage renal disease ( 4 )

7 DRUG INTERACTIONS Use of Other Medications that Increase Potassium : Avoid use in patients receiving such products. If use cannot be avoided, closely monitor serum potassium concentrations. ( 5.3 , 7.1 ) 7.1 Other Products that Increase Serum Potassium Administration of Potassium Phosphates Injection to patients treated concurrently or recently with products that increase serum potassium (e.g., potassium- sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, digoxin, or the immunosuppressants tacrolimus and cyclosporine) increases the risk of severe and potentially fatal hyperkalemia, in particular in the presence of other risk factors for hyperkalemia [see Warnings and Precautions ( 5.3 )] . Avoid use of Potassium Phosphates Injection in patients receiving such products. If use cannot be avoided, closely monitor serum potassium concentrations [see Dosage and Administration ( 2.2 , 2.4 )] .

8.1 Pregnancy Risk Summary Administration of the recommended dose of Potassium Phosphates Injection is not expected to cause major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with Potassium Phosphates Injection. The estimated background risk of major birth defects and miscarriage for the indicated population is 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. Clinical Considerations Disease-associated Maternal and/or Embryo-Fetal Risk Phosphorus is an essential mineral element. Parenteral supplementation with potassium phosphates should be considered if a pregnant woman's requirements cannot be fulfilled by oral or enteral intake.

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 Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.