POTASSIUM PHOSPHATES

Potassium Phosphates in 0.9% Sodium Chloride Injection, for intravenous use, is a phosphorus replacement product containing phosphorus 0.06 mmol/mL and potassium 0.088 mEq/mL. It is a sterile, non-pyrogenic, ready-to-use diluted solution containing a mixture of monobasic potassium phosphate, USP and dibasic potassium phosphate, USP in 0.9% sodium chloride. No dilution is required before administration. It is supplied in 250 mL single-dose intravenous infusion bag. Monobasic Potassium Phosphate is chemically designated KH 2 PO 4 , molecular weight 136.09, white, odorless crystals or granules freely soluble in water. Dibasic Potassium Phosphate is chemically designated K 2 HPO 4 , molecular weight 174.18, colorless or white granular salt freely soluble in water. Each mL contains 4.48 mg of monobasic potassium phosphate, USP and 4.72 mg of dibasic potassium phosphate, USP. Each mL contains phosphorus, 0.06 mmol (equivalent to 1.86 mg phosphorus); potassium, 0.088 mEq (equivalent to 3.40 mg of potassium); sodium chloride, USP, 9 mg and water for injection, USP (q.s.). Note: 1 mmol of phosphorus is equal to 1 mmol phosphate. This product contains no more than 25 mcg/L of aluminum. The pH is 5.8 to 7.2 and the osmolarity is 0.455 mOsmol/mL (calc).

Potassium Phosphates in Sodium Chloride Injection is indicated as a source of phosphorus to correct hypophosphatemia in adults and pediatric patients who weigh 40 kg or greater when oral or enteral replacement is not possible, insufficient, or contraindicated. Potassium Phosphates in Sodium Chloride Injection is a phosphorus replacement product indicated as a source of phosphorus to correct hypophosphatemia in adults and pediatric patients who weigh 40 kg or greater when oral or enteral replacement is not possible, insufficient or contraindicated. ( 1 )

Important Preparation Instructions Do NOT dilute prior to administration. ( 2.1 ) Use this potassium phosphates in sodium chloride injection product only in patients who require the entire 15 mmoL phosphorus dose (potassium 22 mEq) and not any fraction thereof. Otherwise, consider an alternative formulation of potassium phosphate. ( 2.1 ) Important Administration Instructions Potassium Phosphates in Sodium Chloride 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. ( 2.2 ) Use of this potassium phosphates in sodium chloride injection product increases the risk of hyperkalemia in patients weighing less than 40 kg, including life threatening cardiac events. ( 5.3 ) See full prescribing information for important administration instructions. ( 2.2 ) Recommended Dosage This product contains phosphorus 15 mmol and potassium 22 mEq (phosphorus 0.06 mmol/mL and potassium 0.088 mEq/mL). ( 2.3 ) Monitor serum phosphorus, potassium, calcium and magnesium concentrations. ( 2.3 ) See full prescribing information for recommendations on initial or single dosing, repeated dosing, concentration and infusion rate. ( 2.1 , 2.2 , 2.3 ) 2.1 Important Preparation Instructions Potassium Phosphates in Sodium Chloride Injection is for intravenous infusion into a central or peripheral vein. No dilution of this product is required. Use this potassium phosphates in sodium chloride injection product only in patients who require the entire 15 mmoL phosphorus dose (potassium 22 mEq) and not any fraction thereof. If a dose of potassium phosphate is required that does not equal 15 mmoL of Potassium phosphates in Sodium Chloride Injection, then an alternative formulation of potassium phosphates should be considered. Visually inspect the solution for particulate matter and discoloration prior to administration. Do not administer unless solution is clear. Always inspect the solution container before and after removal from the pouch. Place the solution container on a clean, flat surface. Remove the solution container from the pouch. Check the solution container for leaks by squeezing firmly. Discard if leaks are found. Immediately before inserting the infusion set, remove twist-off port from the infusion bag. Use a non-vented infusion set or close the air-inlet on a vented set. Close the roller clamp of the infusion set. Hold the base of the infusion port, twist, and push spike until fully inserted. The infusion port contains a membrane that helps prevent leakage after removing the spike. The infusion port is not intended to be spiked more than once. Suspend solution container from hanger hole. For single-dose only. Discard unused portion. 2.2 Important Administration Instructions Check serum potassium and calcium concentrations prior to administration. Normalize the serum calcium level before administering Potassium Phosphates in Sodium Chloride Injection [see Contraindications (4) , Warnings and Precautions (5.3 , 5.4 )] . Potassium Phosphates in Sodium Chloride 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. Use of this potassium phosphates in sodium chloride injection product increases the risk of hyperkalemia in adults and pediatric patients weighing less than 40 kg, including life threatening cardiac events [see Warnings and Precautions (5.3) ] . 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) ] . When administered peripherally, a generally recommended maximum concentration is phosphorus 6.8 mmol/100 mL (potassium 10 mEq/100 mL). 2.3 Recommended Dosage This potassium phosphates in sodium chloride injection product contains phosphorus 15 mmol and potassium 22 mEq (phosphorus 0.06 mmol/mL and potassium 0.088 mEq/mL). Patients with body weight greater than 96 kg will receive a dose of less than 0.16 mmol/kg phosphorus. The phosphorus doses in Table 1 are general recommendations for an initial or single dose of potassium phosphates and are intended for most patients [see Warnings and Precautions (5.1) ] . Consider overall volume status of the patient when determining whether Potassium Phosphates in Sodium chloride Injection is an appropriate product for phosphorus replacement. 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 concentrations. TABLE 1: Recommended Initial or Single Doses of Potassium Phosphates to Correct Hypophosphatemia in Adults and Pediatric Patients Weighing 40 kg or Greater Serum Phosphorus Concentration a Phosphorus Dosage b, c Corresponding Potassium Content 1.8 mg/dL to lower end of the reference range a 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 c Potassium 0.64 mEq/kg to 0.94 mEq/kg a 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 concentrations may vary depending on the assay used and the laboratory reference range. b 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. c This single-dose preparation of Potassium Phosphates in Sodium Chloride Injection contains phosphorus 15 mmol and potassium 22 mEq. Additional dose(s) following the initial dose may be needed in some patients. Intravenous Infusion Rate 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 2 for adults and pediatric patients 12 years of age and older. TABLE 2: Maximum Recommended Infusion Rate of Potassium Phosphates in Sodium Chloride Injection for Adults and Pediatric Patients Weighing 40 kg or Greater 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. 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.

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

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypomagnesemia [see Warnings and Precautions (5.5) ] Vein Damage and Thrombosis [see Warnings and Precautions (5.6) ] The following adverse reactions in Table 3 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. TABLE 3: Adverse Reactions Reported in Clinical Studies or Post-marketing 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 (5.4) ] , 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 Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 in Sodium Chloride 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 in Sodium Chloride Injection in patients receiving such products. If use cannot be avoided, closely monitor serum potassium concentrations [see Dosage and Administration (2.2) ] .