Sodium Chloride and Potassium Chloride

INDICATIONS AND USAGE These solutions are indicated in patients requiring parenteral administration of potassium chloride and sodium chloride.

DOSAGE AND ADMINISTRATION These solutions should be administered only by intravenous infusion and as directed by the physician. The dose and rate of injection are dependent upon the age, weight and clinical condition of the patient. If the serum potassium level is greater than 2.5 mEq/liter, potassium should be given at a rate not to exceed 10 mEq/hour in a concentration less than 30 mEq/liter. Somewhat faster rates and greater concentrations (usually up to 40 mEq/liter) of potassium may be indicated in patients with more severe potassium deficiency. The total 24-hour dose should not generally exceed 200 mEq of potassium. Drug Interactions Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. (See PRECAUTIONS .)

WARNINGS Hypersensitivity Hypersensitivity and infusion reactions, including anaphylaxis and chills, have been reported with products containing potassium chloride and sodium chloride. Stop the infusion immediately if signs or symptoms of a hypersensitivity or infusion reaction develops. Appropriate therapeutic countermeasures must be instituted as clinically indicated. Electrolyte Imbalances Hyperkalemia Potassium-containing solutions, including Potassium Chloride in Sodium Chloride Injection, USP may increase the risk of hyperkalemia. Hyperkalemia can be asymptomatic and manifest only by increased serum potassium concentrations and/or characteristic electrocardiographic (ECG) changes. Cardiac conduction disorders (including complete heart block) and other cardiac arrhythmias, some fatal, can develop at any time during hyperkalemia. Continuous electrocardiogram (ECG) monitoring may be necessary to aid in the detection of cardiac arrhythmias due to hyperkalemia (see ADVERSE REACTIONS ). To avoid life threatening hyperkalemia, do not administer Potassium Chloride in Sodium Chloride Injection, USP as an intravenous push (i.e., intravenous injection manually with a syringe connected to the intravenous access) without a quantitative infusion device. Patients at increased risk of developing hyperkalemia and cardiac arrhythmias include those: with conditions predisposing to hyperkalemia and/or associated with increased sensitivity to potassium, such as patients with severe renal impairment, acute dehydration, extensive tissue injury or burns, certain cardiac disorders such as congestive heart failure or atrioventricular (AV) block (especially if they receive digoxin). who are at risk of experiencing hyperosmolality, acidosis, or undergoing correction of alkalosis (conditions associated with a shift of potassium from intracellular to extracellular space). treated concurrently or recently with agents or products that can cause or increase the risk of hyperkalemia (see DRUG INTERACTIONS ). with cardiac arrhythmias. Avoid use of Potassium Chloride in Sodium Chloride Injection, USP in patients with, or at risk for, hyperkalemia. If use cannot be avoided, use a product with a low amount of potassium chloride, infuse slowly and monitor serum potassium concentrations and ECGs. Hypernatremia and Hyperchloremia Electrolyte imbalances such as hypernatremia, hyperchloremia, and metabolic acidosis may occur with Potassium Chloride in Sodium Chloride Injection, USP. Conditions that may increase the risk of hypernatremia, fluid overload and edema (central and peripheral), include patients with: primary hyperaldosteronism; secondary hyperaldosteronism associated with, for example, hypertension, congestive heart failure, liver disease (including cirrhosis), renal disease (including renal artery stenosis, nephrosclerosis); and pre-eclampsia. Certain medications, such as corticosteroids or corticotropin, may also increase risk of sodium and fluid retention, see DRUG INTERACTIONS . Avoid Potassium Chloride in Sodium Chloride Injection, USP in patients with, or at risk for, hypernatremia or hyperchloremia. If use cannot be avoided, monitor serum sodium and chloride concentrations and acid-base balance. Rapid correction of hypernatremia is potentially dangerous with risk of serious neurologic complications. Excessively rapid correction of hypernatremia is also associated with a risk for serious neurologic complications such as osmotic demyelination syndrome (ODS) with risk of seizures and cerebral edema. Hyponatremia Potassium Chloride in Sodium Chloride Injection, USP may cause hyponatremia. Hyponatremia can lead to acute hyponatremic encephalopathy characterized by headache, nausea, seizures, lethargy, and vomiting. Patients with brain edema are at particular risk of severe, irreversible and life-threatening brain injury. The risk of hospital-acquired hyponatremia is increased in patients with cardiac or pulmonary failure, and in patients with non-osmotic vasopressin release (including SIADH) treated with high volume of hypotonic Potassium Chloride in Sodium Chloride Injection, USP. The risk for hyponatremia is increased in pediatric patients, elderly patients, postoperative patients, those with psychogenic polydipsia, and in patients treated with medications that increase the risk of hyponatremia (such as diuretics, certain antiepileptic and psychotropic medications). See DRUG INTERACTIONS . Patients at increased risk for developing complications of hyponatremia such as hyponatremic encephalopathy, include pediatric patients, women (in particular, premenopausal women), patients with hypoxemia, and patients with underlying central nervous system disease. Avoid Potassium Chloride in Sodium Chloride Injection, USP in patients with or at risk for hyponatremia. If use cannot be avoided, monitor serum sodium concentrations. Rapid correction of hyponatremia is potentially dangerous with risk of serious neurologic complications. Brain adaptations reducing risk of cerebral edema make the brain vulnerable to injury when chronic hyponatremia is too rapidly corrected, which is known as osmotic demyelination syndrome (ODS). To avoid complications, monitor serum sodium and chloride concentrations, fluid status, acid-base balance, and signs of neurologic complications. Fluid Overload Depending on the volume and rate of infusion, and the patient's underlying clinical condition, the intravenous administration of Potassium Chloride in Sodium Chloride Injection, USP can cause electrolyte disturbances such as overhydration/hypervolemia and congested states including central (e.g., pulmonary edema) and peripheral edema. Avoid Potassium Chloride in Sodium Chloride Injection, USP in patients with or at risk for fluid and/or solute overloading. If use cannot be avoided, monitor fluid balance, electrolyte concentrations and acid base balance as needed and especially during prolonged use.

CONTRAINDICATIONS Potassium Chloride in Sodium Chloride Injection, USP is contraindicated in patients with: Known hypersensitivity to potassium chloride and/or sodium chloride (see WARNINGS ). Clinically significant hyperkalemia (see WARNINGS ).

Drug Interactions Lithium Renal sodium and lithium clearance may be increased during administration of Potassium Chloride in Sodium Chloride Injection, USP and result in decreased lithium concentrations. Monitor serum lithium concentrations during concomitant use. Other Products that Cause Hyperkalemia Administration of Potassium Chloride in Sodium Chloride Injection, USP in patients treated concurrently or recently with products that are associated with hyperkalemia increases the risk of severe and potentially fatal hyperkalemia, in particular in the presence of other risk factors for hyperkalemia. Avoid use of Potassium Chloride in Sodium Chloride Injection, USP in patients receiving such products (e.g., potassium sparing diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or the immunosuppressants cyclosporine and tacrolimus). If use cannot be avoided, monitor serum potassium concentrations. Other Products that Affect Fluid and/or Electrolyte Balance Administration of Potassium Chloride in Sodium Chloride Injection, USP in patients treated concomitantly with medications associated with sodium and fluid retention may increase the risk of hypernatremia and volume overload. Avoid use of Potassium Chloride in Sodium Chloride Injection, USP in patients receiving such products, such as corticosteroids or corticotropin. If use cannot be avoided, monitor serum electrolytes, fluid balance, and acid-base balance. Other Drugs that Increase the Risk of Hyponatremia Administration of Potassium Chloride in Sodium Chloride Injection, USP in patients treated concomitantly with medications associated with hyponatremia may increase the risk of developing hyponatremia. Avoid use of Potassium Chloride in Sodium Chloride Injection, USP in patients receiving products, such as diuretics, and certain antiepileptic and psychotropic medications. Drugs that increase the vasopressin effect reduce renal electrolyte free water excretion and may also increase the risk of hyponatremia following treatment with intravenous fluids. If use cannot be avoided, monitor serum sodium concentrations.

ADVERSE REACTIONS Reactions which may occur because of the solutions or technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia. If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary. Nausea, vomiting, abdominal pain and diarrhea have been reported with potassium therapy. The signs and symptoms of potassium intoxication include paresthesias of the extremities, flaccid paralysis, listlessness, mental confusion, weakness and heaviness of the legs, hypotension, cardiac arrhythmias, heart block, electrocardiographic abnormalities such as disappearance of P waves, spreading and slurring of the QRS complex with development of a biphasic curve and cardiac arrest. Potassium-containing solutions are intrinsically irritating to tissues. Therefore, extreme care should be taken to avoid perivascular infiltration. Local tissue necrosis and subsequent sloughing may result if extravasation occurs. Chemical phlebitis and venospasm have also been reported. Should perivascular infiltration occur, I.V. administration at that site should be discontinued at once. Local infiltration of the affected area with procaine hydrochloride, 1%, to which hyaluronidase may be added, will often reduce venospasm and dilute the potassium remaining in the tissues locally. Local application of heat may also be helpful.

CLINICAL PHARMACOLOGY When administered intravenously, these solutions provide a source of water and potassium chloride with 0.9% sodium chloride. Intravenous solutions containing potassium chloride are particularly intended to provide needed potassium cation (K + ). Potassium is the chief cation of body cells (160 mEq/liter of intracellular water). It is found in low concentration in plasma and extracellular fluids (3.5 to 5.0 mEq/liter in a healthy adult). Potassium plays an important role in electrolyte balance. Normally about 80 to 90% of the potassium intake is excreted in the urine; the remainder in the stools and to a small extent, in the perspiration. The kidney does not conserve potassium well so that during fasting or in patients on a potassium-free diet, potassium loss from the body continues resulting in potassium depletion. A deficiency of either potassium or chloride will lead to a deficit of the other. Sodium chloride in water dissociates to provide sodium (Na + ) and chloride (Cl¯) ions. Sodium (Na + ) is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Chloride (Cl¯) has an integral role in buffering action when oxygen and carbon dioxide exchange occurs in the red blood cells. The distribution and excretion of sodium (Na + ) and chloride (Cl¯) are largely under the control of the kidney which maintains a balance between intake and output. Water is an essential constituent of all body tissues and accounts for approximately 70% of total body weight. Average normal adult daily requirement ranges from two to three liters (1.0 to 1.5 liters each for insensible water loss by perspiration and urine production). Water balance is maintained by various regulatory mechanisms. Water distribution depends primarily on the concentration of electrolytes in the body compartments and sodium (Na + ) plays a major role in maintaining physiologic equilibrium.