Potassium Phosphates Prescribing Information

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 m2 to < 60 mL/min/1.73 m2), 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

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

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.

5.1 Serious Cardiac Adverse Reactions with 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)].

Potassium Phosphates in Sodium Chloride Injection is for intravenous infusion. No dilution of this product is required. The maximum initial or single-dose of potassium phosphates 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. 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 [see Dosage and Administration (2.3)], the infusion set and catheter should also periodically be checked for precipitates.

5.3 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 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 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 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. In patients with moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m2 to < 60 mL/min/1.73 m2), start at the low end of the dose range and monitor serum potassium, phosphorus, calcium, and magnesium concentrations [see Dosage and Administration (2.2), Use in Specific Populations (8.6)].

When administering Potassium Phosphates in Sodium Chloride Injection to correct hypophosphatemia, check the serum potassium concentration prior to administration. If the potassium concentration is 4 mEq/dL or more, do not administer Potassium Phosphates in Sodium Chloride Injection and use an alternative source of phosphorus [see Dosage and Administration (2.1)].

The maximum initial or single-dose of potassium phosphates to correct hypophosphatemia is phosphorus 45 mmol (potassium 66 mEq). The recommended infusion rate of potassium through a peripheral venous catheter is 10 mEq/hour. Continuous electrocardiographic (ECG) monitoring is recommended for higher infusion rates of potassium [see Dosage and Administration (2.2)].

5.4 Hyperphosphatemia and Hypocalcemia

Hyperphosphatemia can occur with intravenous administration of potassium phosphates, especially in patients with renal impairment. 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 (2.2)].

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 potassium phosphates 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.

5.7 Laboratory Monitoring

Monitor serum phosphorus, potassium, calcium, and magnesium concentrations during treatment [see Dosage and Administration (2.2)].

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)].

8.1 Pregnancy

Risk Summary

Administration of the recommended dose of Potassium Phosphates in Sodium Chloride Injection is not expected to cause major birth defects, miscarriage, or adverse maternal or fetal outcomes. Consider potassium phosphate replacement if correction of hypophosphatemia via the enteral route is not possible (see Clinical Considerations). Animal reproduction studies have not been conducted with Potassium Phosphates in Sodium Chloride Injection.

The 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. Intravenous replacement with potassium phosphate should be considered if a pregnant woman requires intravenous replacement to correct hypophosphatemia when the enteral route is not possible, insufficient or contraindicated.

8.2 Lactation

Risk Summary

Phosphorus and potassium are present in human milk. Administration of the recommended dose of Potassium Phosphates in Sodium Chloride Injection is not expected to cause harm to a breast-fed 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 in Sodium Chloride Injection and any potential adverse effects on the breastfed child from Potassium Phosphates in Sodium Chloride Injection or from underlying maternal condition.

8.4 Pediatric Use

Safety and effectiveness of Potassium Phosphates in Sodium Chloride Injection have been established in pediatric patients weighing 40 kg or more as a source of phosphorus to correct hypophosphatemia when oral or enteral replacement is not possible, insufficient, or contraindicated. However, this potassium phosphates in sodium chloride injection product is not approved for use in pediatric patients who weigh less than 40 kg because of the lack of an appropriate formulation.

8.5 Geriatric Use

In general, dose selection of Potassium Phosphates in Sodium Chloride 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 in Sodium Chloride Injection may be greater in patients with impaired renal function [see Warnings and Precautions (5.3, 5.4)].

Potassium Phosphates in Sodium Chloride Injection is contraindicated due to the risk of hyperkalemia in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m2) or end stage renal disease [see Contraindications (4)].

In patients with moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m2 to < 60 mL/min/1.73 m2), start at the low end of the dosage range and monitor serum potassium, phosphorus, calcium, and magnesium concentrations [see Dosage and Administration (2.2)].

12.1 Mechanism of Action

Phosphorus in the form of organic and inorganic phosphate has a variety of biochemical functions in all organs and tissues, including critical roles in nucleic acid structure, energy storage and transfer, cell signaling, cell membrane composition and structure, acid-base balance, mineral homeostasis, and bone mineralization.

12.2 Pharmacodynamics

The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of potassium phosphates have not been fully characterized.