DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. Potassium sparing diuretics: Avoid concomitant use 7.1) Renin-angiotensin-aldosterone inhibitors: Monitor for hyperkalemia 7.2) Nonsteroidal Anti-Inflammatory drugs: Monitor for hyperkalemia 7.3) Potassium sparing diuretics: Avoid concomitant use 7.1) Renin-angiotensin-aldosterone inhibitors: Monitor for hyperkalemia 7.2) Nonsteroidal Anti-Inflammatory drugs: Monitor for hyperkalemia 7.3) 7.1 Potassium-Sparing Diuretics. Use with potassium-sparing diuretics can produce severe hyperkalemia. Avoid concomitant use.. 7.2 Renin-Angiotensin-Aldosterone System Inhibitors. Drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) including angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), spironolactone, eplerenone, or aliskiren produce potassium retention by inhibiting aldosterone production. Closely monitor potassium in patients receiving concomitant RAAS therapy.. 7.3 Nonsteroidal Anti-inflammatory Drugs (NSAIDs). NSAIDS may produce potassium retention by reducing renal synthesis of prostaglandin and impairing the renin-angiotensin system. Closely monitor potassium in patients on concomitant NSAIDs.

GERIATRIC USE SECTION.

8.5 Geriatric Use. Clinical studies of Potassium Chloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The most common adverse reactions to oral potassium salts are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea.. Most common adverse reactions are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea 6) To report SUSPECTED ADVERSE REACTIONS, contact Pharmaceutical Associates, Inc. at 1-800-845-8210 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. The potassium ion (K+) is the principal intracellular cation of most body tissues. Potassium ions participate in number of essential physiological processes including the maintenance of intracellular tonicity; the transmission of nerve impulses; the contraction of cardiac, skeletal, and smooth muscle; and the maintenance of normal renal function.The intracellular concentration of potassium is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to mEq per liter. An active ion transport system maintains this gradient across the plasma membrane.Potassium is normal dietary constituent, and under steady-state conditions the amount of potassium absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of potassium is 50 to 100 mEq per day.. 12.3 Pharmacokinetics. Based on published literature, the rate of absorption and urinary excretion of potassium from KCl oral solution were higher during the first few hours after dosing relative to modified release KCl products. The bioavailability of potassium, as measured by the cumulative urinary excretion of + over 24 hour post dose period, is similar for KCl solution and modified release products.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. Potassium chloride is contraindicated in patients on potassium sparing diuretics.. Concomitant use with potassium sparing diuretics. 4) Concomitant use with potassium sparing diuretics. 4).

DESCRIPTION SECTION.

11 DESCRIPTION. Potassium Chloride is white crystalline or colorless solid. It is soluble in water and slightly soluble in alcohol. Chemically, Potassium Chloride is K-Cl with molecular mass of 74.55.. Oral Solution 10%: Each 15 mL of solution contains 1.5 of potassium chloride, USP and the following inactive ingredients: citric acid anhydrous, FD&C Yellow 6, berry citrus flavor, potassium sorbate, purified water and sodium saccharin.. Oral Solution 20%: Each 15 mL of solution contains 3.0 of potassium chloride, USP and the following inactive ingredients: glycerin, potassium sorbate, purified water and sodium saccharin.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Dilute prior to administration 2.1, 5.1) Monitor serum potassium and adjust dosage accordingly 2.2, 2.3) Treatment of hypokalemia:Adults: Initial doses range from 40-100 mEq/day in 2-5 divided doses: limit doses to 40 mEq per dose. Total daily dose should not exceed 200 mEq 2.2) Pediatric patients aged birth to 16 years old: 2-4 mEq/kg/day in divided doses; not to exceed mEq/kg as single dose or 40 mEq whichever is lower; if deficits are severe or ongoing losses are great, consider intravenous therapy. Total daily dose should not exceed 100 mEq 2.3) Maintenance or Prophylaxis of hypokalemia: Adults: Typical dose is 20 mEq per day (2.2) Pediatric patients aged birth to 16 years old: typical dose is mEq/kg/day. Do not exceed mEq/kg/day 2.3) Adults: Initial doses range from 40-100 mEq/day in 2-5 divided doses: limit doses to 40 mEq per dose. Total daily dose should not exceed 200 mEq 2.2) Pediatric patients aged birth to 16 years old: 2-4 mEq/kg/day in divided doses; not to exceed mEq/kg as single dose or 40 mEq whichever is lower; if deficits are severe or ongoing losses are great, consider intravenous therapy. Total daily dose should not exceed 100 mEq 2.3) 2.1 Administration and Monitoring. MonitoringMonitor serum potassium and adjust dosages accordingly. For treatment of hypokalemia, monitor potassium levels daily or more often depending on the severity of hypokalemia until they return to normal. Monitor potassium levels monthly to biannually for maintenance or prophylaxis.The treatment of potassium depletion, particularly in the presence of cardiac disease, renal disease, or acidosis requires careful attention to acid-base balance, volume status, electrolytes, including magnesium, sodium, chloride, phosphate, and calcium, electrocardiograms and the clinical status of the patient. Correct volume status, acid-base balance and electrolyte deficits as appropriate.. AdministrationDilute the potassium chloride solution with at least ounces of cold water [see Warnings and Precautions (5.1)] Take with meals or immediately after eating.If serum potassium concentration is 2.5 mEq/L, use intravenous potassium instead of oral supplementation.. 2.2 Adult Dosing. Treatment of hypokalemiaDaily dose range from 40 to 100 mEq. Give in to divided doses; limit doses to 40 mEq per dose. The total daily dose should not exceed 200 mEq in 24 hour period.. Maintenance or ProphylaxisTypical dose is 20 mEq per day. Individualize dose based upon serum potassium levels.Studies support the use of potassium replacement in digitalis toxicity. When alkalosis is present, normokalemia and hyperkalemia may obscure total potassium deficit. The advisability of use of potassium replacement in the setting of hyperkalemia is uncertain.. 2.3 Pediatric Dosing. Treatment of hypokalemia. Pediatric patients aged birth to 16 years old: The initial dose is to mEq/kg/day in divided doses; do not exceed as single dose mEq/kg or 40 mEq, whichever is lower; maximum daily doses should not exceed 100 mEq. If deficits are severe or ongoing losses are great, consider intravenous therapy.. Maintenance or Prophylaxis. Pediatric patients aged birth to 16 years old: Typical dose is mEq/kg/day. Do not exceed mEq/kg/day.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Oral Solution 10%: 1.3 mEq potassium per mL.Oral Solution 20%: 2.6 mEq potassium per mL.. Oral Solution: 10%; 1.3 mEq potassium per mL 3) Oral Solution: 20%; 2.6 mEq potassium per mL 3) Oral Solution: 10%; 1.3 mEq potassium per mL 3) Oral Solution: 20%; 2.6 mEq potassium per mL 3).

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. Potassium Chloride Oral Solution, USP 10% (20 mEq/15 mL) is berry citrus flavored, orange-colored solution available as follows:NDC 0121-1680-16:16 fl oz (473 mL) Bottle.NDC 0121-1680-15:15 mL unit dose cup, in tray of ten cups.NDC 0121-2520-30:30 mL unit dose cup, in tray of ten cups.Potassium Chloride Oral Solution, USP 20% (40 mEq/15 mL) is an unflavored, clear, dye free/sugar free solution available as follows:NDC 0121-0841-15:15 mL unit dose cup, in tray of ten cups.. STORAGEStore at 25C (77F); excursions permitted to 15 30C (59 86F). [See USP Controlled Room Temperature].Dispense in tight, light-resistant container as defined in the USP.PROTECT from LIGHT and FREEZING.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Potassium Chloride is indicated for the treatment and prophylaxis of hypokalemia with or without metabolic alkalosis, in patients for whom dietary management with potassium-rich foods or diuretic dose reduction are insufficient.. Potassium Chloride is indicated for the treatment and prophylaxis of hypokalemia with or without metabolic alkalosis, in patients for whom dietary management with potassium-rich foods or diuretic dose reduction are insufficient.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. The potassium ion (K+) is the principal intracellular cation of most body tissues. Potassium ions participate in number of essential physiological processes including the maintenance of intracellular tonicity; the transmission of nerve impulses; the contraction of cardiac, skeletal, and smooth muscle; and the maintenance of normal renal function.The intracellular concentration of potassium is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to mEq per liter. An active ion transport system maintains this gradient across the plasma membrane.Potassium is normal dietary constituent, and under steady-state conditions the amount of potassium absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of potassium is 50 to 100 mEq per day.

NURSING MOTHERS SECTION.

8.2 Lactation. Risk SummaryThe normal potassium ion content of human milk is about 13 mEq per liter. Since potassium from oral supplements such as Potassium Chloride becomes part of the body potassium pool, as long as body potassium is not excessive, the contribution of potassium chloride supplementation should have little or no effect on the level in human milk.

OVERDOSAGE SECTION.

10 OVERDOSAGE. 10.1 Symptoms. The administration of oral potassium salts to persons with normal excretory mechanisms for potassium rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if potassium is administered too rapidly potentially fatal hyperkalemia can result.Hyperkalemia is usually asymptomatic and may be manifested only by an increased serum potassium concentration (6.5-8.0 mEq/L) and characteristic electrocardiographic changes (peaking of T-waves, loss of P-waves, depression of S-T segment, and prolongation of the QT-interval). Late manifestations include muscle paralysis and cardiovascular collapse from cardiac arrest (9-12 mEq/L).. 10.2 Treatment. Treatment measures for hyperkalemia include the following:Monitor closely for arrhythmias and electrolyte changes.Eliminate foods and medications containing potassium and of any agents with potassium-sparing properties such as potassium-sparing diuretics, ARBS, ACE inhibitors, NSAIDS, certain nutritional supplements and many others.Administer intravenous calcium gluconate if the patient is at no risk or low risk of developing digitalis toxicity.Administer intravenously 300 to 500 mL/hr of 10% dextrose solution containing 10 to 20 units of crystalline insulin per 1000 mL.Correct acidosis, if present, with intravenous sodium bicarbonate.Use exchange resins, hemodialysis, or peritoneal dialysis.In patients who have been stabilized on digitalis, too rapid lowering of the serum potassium concentration can produce digitalis toxicity.. Monitor closely for arrhythmias and electrolyte changes.. Eliminate foods and medications containing potassium and of any agents with potassium-sparing properties such as potassium-sparing diuretics, ARBS, ACE inhibitors, NSAIDS, certain nutritional supplements and many others.. Administer intravenous calcium gluconate if the patient is at no risk or low risk of developing digitalis toxicity.. Administer intravenously 300 to 500 mL/hr of 10% dextrose solution containing 10 to 20 units of crystalline insulin per 1000 mL.. Correct acidosis, if present, with intravenous sodium bicarbonate.. Use exchange resins, hemodialysis, or peritoneal dialysis.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 16 fl oz (473 mL). Delivers 16 fl oz (473 mL)NDC 0121-1680-16Potassium Chloride Oral Solution, USP 10%20 mEq per 15 mLDILUTE PRIOR TO ADMINISTRATIONRx ONLY16 fl oz (473 mL)PHARMACEUTICAL ASSOCIATES, INC.GREENVILLE, SC 29605X1680161120 R11/20. PRINCIPAL DISPLAY PANEL 16 fl oz (473 mL).

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of Potassium Chloride have been demonstrated in children with diarrhea and malnutrition from birth to 16 years.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Based on published literature, the rate of absorption and urinary excretion of potassium from KCl oral solution were higher during the first few hours after dosing relative to modified release KCl products. The bioavailability of potassium, as measured by the cumulative urinary excretion of + over 24 hour post dose period, is similar for KCl solution and modified release products.

PREGNANCY SECTION.

8.1 Pregnancy. There are no human data related to use of Potassium Chloride during pregnancy, and animal studies have not been conducted. Potassium supplementation that does not lead to hyperkalemia is not expected to cause fetal harm.The background risk for major birth defects and miscarriage in the indicated population is unknown. All pregnancies have 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 2-4% and 15-20%, respectively.

SPL UNCLASSIFIED SECTION.

2.1 Administration and Monitoring. MonitoringMonitor serum potassium and adjust dosages accordingly. For treatment of hypokalemia, monitor potassium levels daily or more often depending on the severity of hypokalemia until they return to normal. Monitor potassium levels monthly to biannually for maintenance or prophylaxis.The treatment of potassium depletion, particularly in the presence of cardiac disease, renal disease, or acidosis requires careful attention to acid-base balance, volume status, electrolytes, including magnesium, sodium, chloride, phosphate, and calcium, electrocardiograms and the clinical status of the patient. Correct volume status, acid-base balance and electrolyte deficits as appropriate.. AdministrationDilute the potassium chloride solution with at least ounces of cold water [see Warnings and Precautions (5.1)] Take with meals or immediately after eating.If serum potassium concentration is 2.5 mEq/L, use intravenous potassium instead of oral supplementation.

STORAGE AND HANDLING SECTION.

STORAGEStore at 25C (77F); excursions permitted to 15 30C (59 86F). [See USP Controlled Room Temperature].Dispense in tight, light-resistant container as defined in the USP.PROTECT from LIGHT and FREEZING.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Cirrhosis: Initiate therapy at the low end of the dosing range 8.5) Renal Impairment: Initiate therapy at the low end of the dosing range 8.6) 8.1 Pregnancy. There are no human data related to use of Potassium Chloride during pregnancy, and animal studies have not been conducted. Potassium supplementation that does not lead to hyperkalemia is not expected to cause fetal harm.The background risk for major birth defects and miscarriage in the indicated population is unknown. All pregnancies have 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 2-4% and 15-20%, respectively.. 8.2 Lactation. Risk SummaryThe normal potassium ion content of human milk is about 13 mEq per liter. Since potassium from oral supplements such as Potassium Chloride becomes part of the body potassium pool, as long as body potassium is not excessive, the contribution of potassium chloride supplementation should have little or no effect on the level in human milk.. 8.4 Pediatric Use. The safety and effectiveness of Potassium Chloride have been demonstrated in children with diarrhea and malnutrition from birth to 16 years.. 8.5 Geriatric Use. Clinical studies of Potassium Chloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.. 8.6 Cirrhotics. Patients with cirrhosis should usually be started at the low end of the dosing range, and the serum potassium level should be monitored frequently. [see 12.3 Pharmacokinetics 12.3) ]. 8.7 Renal Impairment. Patients with renal impairment have reduced urinary excretion of potassium and are at substantially increased risk of hyperkalemia. Patients with impaired renal function, particularly if the patient is on ACE inhibitors, ARBs, or nonsteroidal anti-inflammatory drugs should usually be started at the low end of the dosing range because of the potential for development of hyperkalemia. The serum potassium level should be monitored frequently. Renal function should be assessed periodically.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Gastrointestinal Irritation: Dilute before use, take with meals 5.1) Gastrointestinal Irritation: Dilute before use, take with meals 5.1) 5.1 Gastrointestinal Irritation. May cause gastrointestinal irritation if administered undiluted. Increased dilution of the solution and taking with meals may reduce gastrointestinal irritation [see Dosage and Administration (2.1)].