Potassium Phosphates

5 WARNINGS AND PRECAUTIONS • Serious Cardiac Adverse Reactions with Bolus, or Rapid Intravenous Administration : Do not exceed the recommended infusion rate. Continuous electrocardiographic (ECG) monitoring may be needed during infusion. ( 2.3 , 5.1 ) • 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. ( 5.2 , 7.1 ) • Pulmonary Embolism due to Pulmonary Vascular Precipitates : If signs of pulmonary distress occur, stop the infusion and initiate a medical evaluation. ( 5.3 ) • Hyperphosphatemia and Hypocalcemia : Monitor serum phosphorus and calcium concentrations during and following infusion. ( 5.4 ) • Hypomagnesemia : Reported in patients with hypercalcemia and diabetic ketoacidosis. Monitor serum magnesium concentrations during treatment. ( 5.5 ) • Vein Damage and Thrombosis : Infuse hypertonic solutions through a central catheter. ( 2.1 , 5.6 ) 5.1 Serious Cardiac Adverse Reactions with 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) has resulted in death, cardiac arrest, cardiac arrhythmia (including QT prolongation), hyperkalemia, hyperphosphatemia, and seizures [see Overdosage ( 10 )] . Continuous electrocardiographic (ECG) monitoring is recommended for infusion rates higher than potassium 10 mEq/hour [see Dosage and Administration ( 2.1 , 2.2 )] . 5.2 Hyperkalemia Potassium Phosphates in Sodium Chloride Injection may increase the risk of hyperkalemia, including life-threatening cardiac events, especially when administered in excessive doses or by rapid intravenous infusion [see Warnings and Precautions ( 5.1 )] . Patients with renal impairment and are at increased risk of developing life-threatening hyperkalemia, when administered intravenous potassium. Potassium Phosphates in Sodium Chloride Injection is contraindicated in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ) and dosage adjustment is required for patients with moderate renal impairment (eGFR ≥30 mL/min/1.73 m 2 to <60 mL/min/1.73 m 2 ) [see Dosage and Administration ( 2.2 ), Contraindications ( 4 ), Use in Specific Populations ( 8.6 )] . Other patients at increased risk of hyperkalemia include those with severe adrenal insufficiency or treated concurrently with other drugs that cause or increase the risk of hyperkalemia [see Drug Interactions ( 7.1 )] . Patients with cardiac disease may be more susceptible to the adverse effects of hyperkalemia. Consider the amount of potassium from all sources when determining the dose of Potassium Phosphates in Sodium Chloride Injection and do not exceed the maximum age-appropriate recommended daily amount of potassium. When administering Potassium Phosphates in Sodium Chloride Injection to correct hypophosphatemia, check the serum potassium concentration prior to administration [see Dosage and Administration ( 2.2 )] . Continuous electrocardiographic (ECG) monitoring is recommended for infusion rates higher than 10 mEq/hour [see Warnings and Precautions ( 5.1 ), Dosage and Administration ( 2.3 )] . 5.3 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 infusion and initiate a medical evaluation. In addition to inspection of the solution, the infusion set and catheter should also be checked periodically for precipitates. [see Dosage and Administration ( 2.1 )]. 5.4 Hyperphosphatemia and Hypocalcemia Hyperphosphatemia can occur with intravenous administration of potassium phosphates, especially in patients with renal impairment [see Contraindications ( 4 )] . Hyperphosphatemia can cause the formation of insoluble calcium phosphorus products with consequent hypocalcemia, neurological irritability with tetany, nephrocalcinosis with acute kidney injury, and more rarely, cardiac irritability with arrhythmias. Obtain serum calcium concentrations prior to administration and normalize the calcium before administering Potassium Phosphates in Sodium Chloride Injection. Potassium Phosphates in Sodium Chloride Injection is contraindicated in patients with hyperphosphatemia and/or hypercalcemia [see Contraindications ( 4 )] . Monitor serum phosphorus and calcium concentrations during treatment with Potassium Phosphates in Sodium Chloride Injection [see Dosage and Administration ( 2.3 )] . 5.5 Hypomagnesemia Intravenous infusion of phosphate has been reported to cause a decrease in serum magnesium (and calcium) concentrations when administered to patients with hypercalcemia and diabetic ketoacidosis. Monitor serum magnesium concentrations during treatment. 5.6 Vein Damage and Thrombosis The infusion of hypertonic solutions into a peripheral vein may result in vein irritation, vein damage, and/or thrombosis. The primary complication of peripheral administration is venous thrombophlebitis, which manifests as pain, erythema, tenderness or a palpable cord. Remove the catheter as soon as possible and initiate appropriate medical treatment if thrombophlebitis develops. When administered peripherally to correct hypophosphatemia, a generally recommended maximum concentration is phosphorus 6.8 mmol/100 mL (potassium 10 mEq/100 mL) [see Dosage and Administration ( 2.2 )]. 5.7 Laboratory Monitoring Monitor serum phosphorus, potassium, calcium, and magnesium concentrations during treatment [see Dosage and Administration ( 2.3 )] .

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Serious Cardiac Adverse Reactions with Bolus or Rapid Intravenous Administration [see Warnings and Precautions ( 5.1 )] • Hyperkalemia [see Warnings and Precautions ( 5.2 )] • Pulmonary Embolism due to Pulmonary Vascular Precipitates [see Warnings and Precautions ( 5.3 )] • Hyperphosphatemia and Hypocalcemia [see Warnings and Precautions ( 5.4 )] • Hypomagnesemia [see Warnings and Precautions ( 5.5 )] • Vein Damage and Thrombosis [see Warnings and Precautions ( 5.6 )] The following adverse reactions have been reported in clinical studies or post-marketing 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. Metabolism and Nutrition Disorders: hyperkalemia, hyperphosphatemia, hypocalcemia, hypovolemia, osmotic diuresis, pulmonary embolism Cardiac Disorders: arrhythmia, bradycardia, cardiac arrest, chest pain, ECG changes, edema, heart block, hypotension Respiratory, Thoracic, and Mediastinal Disorders: dyspnea Renal and Urinary Disorders: acute phosphate nephropathy (i.e., nephrocalcinosis with acute kidney injury), decreased urine output, transition to chronic kidney disease 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 .