warnings and cautions
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. (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 71 mEq). The recommended infusion rate is approximately phosphorus 6.4 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 phosphates 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 (2.1, 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 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 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 m 2 to <60 mL/min/1.73 m 2 ), start at the low end of the dose range and monitor serum potassium, phosphorus, calcium, and magnesium concentrations [ see Dosage and Administration (2.2, 2.4), Use in Specific Populations (8.6) ]. When administering POTASSIUM PHOSPHATES INJECTION in intravenous fluids 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 INJECTION and use an alternative source of phosphate [ see Dosage and Administration (2.1) ]. The maximum initial or single dose of POTASSIUM PHOSPHATES INJECTION in intravenous fluids to correct hypophosphatemia is phosphorus 45 mmol (potassium 71 mEq). The recommended infusion rate of potassium 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 INJECTION. POTASSIUM PHOSPHATES INJECTION is contraindicated in patients with hyperphosphatemia and/or hypercalcemia [ see Contraindications (4) ]. Monitor serum phosphorus and calcium concentrations during treatment with POTASSIUM PHOSPHATES INJECTION [ see Dosage and Administration (2.2) ]. 5.5 Aluminum Toxicity POTASSIUM PHOSHATES INJECTION contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration in patients with renal impairment. Preterm infants are particularly at risk for aluminum toxicity because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which also contain aluminum. Patients with renal impairment, including preterm infants, who receive greater than 4 to 5 mcg/kg/day of parenteral aluminum can accumulate aluminum to levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration. Exposure to aluminum from POTASSIUM PHOSPHATES INJECTION is not more than 4.9 mcg/kg/day when: adults weighing at least 45 kg are administered the recommended maximum dosage of phosphorus (45 mmol/day) for parenteral nutrition. pediatric patients 12 years of age and older weighing at least 40 kg are administered the recommended maximum dosage of phosphorus (40 mmol/day) for parenteral nutrition [ see Dosage and Administrations (2.4), Description (11) ]. When prescribing POTASSIUM PHOSPHATES INJECTION for use in parenteral nutrition solutions containing other small volume parenteral products, the total daily patient exposure to aluminium from the admixture should be considered and maintained at no more than 5 mcg/kg/day [ see Use in Specific Populations (8.4) ]. POTASSIUM PHOSPHATES INJECTION for parenteral nutrition is not recommended in adults weighing less than 45 kg or pediatric patients less than 12 years of age or weighing less than 40 kg due to the risks of aluminum toxicity [ see Indications and Usage (1.2) ]. 5.6 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. 5.7 Vein Damage and Thrombosis POTASSIUM PHOSPHATES INJECTION must be diluted and administered in intravenous fluids or used as an admixture in parenteral nutrition. It is not for direct intravenous infusion. 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 in intravenous fluids to correct hypophosphatemia, a generally recommended maximum concentration is phosphorus 6.4 mmol/100 mL (potassium 10 mEq/100 mL) [ see Dosage and Administration (2.1) ] Parenteral nutrition solutions with an osmolarity of 900 mOsm/L or greater must be infused through a central catheter [ see Dosage and Administration (2.3) ]. 5.8 Laboratory Monitoring Monitor serum phosphorus, potassium, calcium and magnesium concentrations during treatment [ see Dosage and Administration (2.2, 2.4) ].