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) 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° to 25°C (68° to 77°F) or 14 days under …

3 DOSAGE FORMS AND STRENGTHS Potassium phosphates injection, USP is a sterile clear, colorless solution supplied as: phosphorus 15 mmol/5 mL (3 mmol/mL) and potassium 22 mEq/5 mL (4.4 mEq /mL) in a single-dose vial. phosphorus 45 mmol/15 mL (3 mmol/mL) and potassium 66 mEq/15 mL (4.4 mEq/mL) in a single-dose vial. phosphorus 150 mmol/50 mL (3 mmol/mL) and potassium 220 mEq/50 mL (4.4 mEq/mL) in Pharmacy Bulk Package vial. Injection: phosphorus 15 mmol/5 mL (3 mmol/mL) and potassium 22 mEq/5 mL (4.4 mEq/mL) in a single-dose vial. ( 3 ) phosphorus 45 mmol/15 mL (3 mmol/mL) and potassium 66 mEq/15 mL (4.4 mEq/mL) in a single-dose vial. ( 3 ) phosphorus 150 mmol/50 mL (3 mmol/mL) and potassium 220 mEq/50 mL (4.4 mEq/mL) as a Pharmacy Bulk Package vial.

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/1.73 m 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/1.73 m 2 ) or end stage renal disease. ( 4 )

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 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 5: 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 (5.5) ] , 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 Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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 USES IN SPECIFIC POPULATIONS 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. 8.2 Lactation Risk Summary Phosphorus and potassium are present in human milk. Administration of the recommended dose of potassium phosphates injection is not expected to cause harm to a breastfed infant. There is no information on the effects of potassium phosphates on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for potassium phosphates injection and any potential adverse effects on the breastfed child from potassium phosphates injection or from underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness of potassium phosphates injection have been established in pediatric patients as a source of phosphorus: in intravenous fluids to correct hypophosphatemia when oral or enteral replacement is not possible, insufficient, or contraindicated. for parenteral nutrition when oral or enteral nutrition is not possible, insufficient or contraindicated. Because of immature renal function, preterm infants receiving prolonged parenteral nutrition treatment with potassium phosphates injection may be at higher risk of aluminum toxicity [see Warnings and Precautions (5.5) ] . 8.5 Geriatric Use In general, dose selection of potassium phosphates injection for an elderly patient should be cautious, starting at the low end of the dosing range because of the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. It may be useful to monitor renal function during treatment [see Use in Specific Populations (8.6) ] . 8.6 Renal Impairment Potassium and phosphorus are known to be substantially excreted by the kidney and the risk of adverse reactions to potassium phosphates injection may be greater in patients with impaired renal function [see Warnings and Precautions (5.3 , 5.4 , 5.5) ] . Potassium phosphates injection is contraindicated due to the risk of hyperkalemia in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ) or end stage renal disease [see Contraindications (4) ] . 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 and monitor serum potassium, phosphorus, calcium and magnesium concentrations [see Dosage and Administration (2.2 , 2.4) ].

11 DESCRIPTION Potassium Phosphates Injection, USP, a phosphorus replacement product containing phosphorus 3 mmol/mL and potassium 4.4 mEq/mL. It is a sterile clear, colorless, non-pyrogenic, concentrated solution containing a mixture of monobasic potassium phosphate, USP and dibasic potassium phosphate, USP in water for injection. It is supplied as a 5 mL and 15 mL single-dose vials and a 50 mL Pharmacy Bulk Package vial. Monobasic potassium phosphate, USP is chemically designated potassium dihydrogen phosphate. The molecular formula is KH 2 PO 4 , molecular weight is 136.084 g/mol and the structural formula is as below: It appears as colorless crystals or white granular or crystalline powder. It is freely soluble in water and practically insoluble in alcohol. Dibasic potassium phosphate, USP is chemically designated dipotassium hydrogen phosphate. The molecular formula is K 2 HPO 4 , molecular weight is 174.18 g/mol and the structural formula is as below: It appears as colorless crystals or white granular or crystalline powder. It is freely soluble in water. Each mL of Potassium Phosphates Injection, USP contains monobasic potassium phosphate USP, 224 mg; dibasic potassium phosphate USP, 236 mg and water for injection. Each mL contains 3 mmol phosphorus (equivalent to 93 mg phosphorus) and 4.4 mEq potassium (equivalent to 170 mg of potassium). Note: 1 mmol of phosphorus is equal to 1 mmol phosphate. The pH is 6.0 to 7.0. This product contains no more than 900 mcg/L of aluminum [ see Warnings and Precautions (5.5) ] . The osmolarity is 7.4 mOsmol/mL (calc). The solution is administered after dilution or admixing by the intravenous route. 1 1

10 OVERDOSAGE Hyperphosphatemia Administration of excessive doses of intravenous potassium phosphates in intravenous fluids as a single-dose ranging from approximately 50 mmol to 270 mmol phosphorus and/or at rapid infusion rates (over 1 hour to 3 hours) has resulted in death, cardiac arrest, cardiac arrhythmia (including QT prolongation), hyperkalemia, hyperphosphatemia, seizures and tetany. Hyperphosphatemia is particularly a risk in patients with renal failure. Hyperphosphatemia leads in turn to hypocalcemia, which may be severe and to ectopic calcification, particularly in patients with initial hypercalcemia. Tissue calcification may cause hypotension and organ damage and result in acute renal failure. Hyperkalemia Excessive administration of phosphates given as potassium salts may also cause hyperkalemia. Manifestations of hyperkalemia include: Disturbances in cardiac conduction and arrhythmias, including bradycardia, heart block, asystole, ventricular tachycardia, ventricular fibrillation. Hypotension. Muscle weakness including paresthesia, muscular and respiratory paralysis. Management In the event of overdosage, discontinue infusions containing potassium phosphates immediately and institute general supportive measures, including ECG monitoring, laboratory monitoring and correction of serum electrolyte concentrations, especially potassium, phosphorus, calcium and magnesium.

16 HOW SUPPLIED/STORAGE AND HANDLING Potassium Phosphates Injection, USP is a sterile clear, colorless solution supplied as phosphorus 3 mmol/mL and potassium 4.4 mEq/mL as shown: Product Code Unit of Sale Strength Each 1693 NDC 80830-1693-5 Carton containing 25 units Phosphorus 15 mmol/5 mL and Potassium 22 mEq/5 mL NDC 80830-1693-1 5 mL single-dose, polypropylene vial NDC 80830-1693-3 Carton containing 5 units 1691 NDC 80830-1691-5 Carton containing 25 units Phosphorus 45 mmol/15 mL and Potassium 66 mEq/15 mL NDC 80830-1691-1 15 mL single-dose, polypropylene vial NDC 80830-1691-2 Carton containing 10 units 1692 NDC 80830-1692-5 Carton containing 25 units Phosphorus 150 mmol/50 mL and Potassium 220 mEq/50 mL NDC 80830-1692-1 50 mL fill Pharmacy Bulk Package, polypropylene vial NDC 80830-1692-2 Carton containing 10 units Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Pharmacy Bulk Package vial: Discard within 4 hours of initial entry [see Dosage and Administration (2.3) ] . For storage of admixed solution, see Dosage and Administration 2.1 , 2.3 .