Potassium Chloride

1 INDICATIONS AND USAGE Potassium Chloride Oral Solution, USP 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 Oral Solution, USP 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. (1)

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 1 mEq/kg as a 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 1 mEq/kg/day. Do not to exceed 3 mEq/kg/day ( 2.3 ) 2.1. Administration and Monitoring Monitoring Monitor 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. Administration Dilute the potassium chloride solution with at least 4 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 hypokalemia: Daily dose range from 40 to 100 mEq. Give in 2 to 5 divided doses: limit doses to 40 mEq per dose. The total daily dose should not exceed 200 mEq in a 24 hour period. Maintenance or Prophylaxis Typical 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 a 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 2 to 4 mEq/kg/day in divided doses; do not exceed as a single dose 1 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 1 mEq/kg/day. Do not exceed 3 mEq/kg/day.

2.1. Administration and Monitoring Monitoring Monitor 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. Administration Dilute the potassium chloride solution with at least 4 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 hypokalemia: Daily dose range from 40 to 100 mEq. Give in 2 to 5 divided doses: …

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 )

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

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 Macleods Pharma USA, Inc. at 1-888-943-3210 or 1-855-926-3384 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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 ) 7.1 Potassium-Sparing Diuretics Use with potassium-sparing diuretic 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 E and impairing the renin angiotensin system. Closely monitor potassium in patients on concomitant NSAIDs.

7.1 Potassium-Sparing Diuretics Use with potassium-sparing diuretic 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 E and impairing the renin angiotensin system. Closely monitor potassium in patients on concomitant NSAIDs.

8 USE IN SPECIFIC POPULATIONS Cirrhosis: Initiate therapy at the low end of the dosing range ( 8.6 ) Renal Impairment: Initiate therapy at the low end of the dosing range ( 8.7 ) 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 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 2-4% and 15-20% respectively. 8.2 Lactation Risk Summary The 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. Cirrhosis 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 Clinical Pharmacology ( 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 the development of hyperkalemia. The serum potassium level should be monitored frequently. Renal function should be assessed periodically.

8.6. Cirrhosis 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 Clinical Pharmacology ( 12.3 )]

12.1 Mechanism of Action The potassium ion (K + ) is the principal intracellular cation of most body tissues. Potassium ions participate in a 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 mEq to 160 mEq per liter. The normal adult plasma concentration is 3.5 mEq to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane. Potassium is a 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 mEq to 100 mEq per day.

11 DESCRIPTION Potassium chloride, USP is a colorless crystals or white crystalline powder. It is soluble in water and practically insoluble in alcohol. It is soluble in water and slightly soluble in alcohol. Chemically, Potassium Chloride is KCl with a molecular mass of 74.55. Oral Solution 10%: Each 15 mL of solution contains 1.5 g of potassium chloride, USP and the following inactive ingredients: citric acid anhydrous, FD&C Yellow #6, glycerin, purified water, sodium benzoate, trisodium citrate dihydrate, sucralose, sodium chloride, sodium sulphate, propylene glycol, natural/artificial orange flavour. Oral Solution 20%: Each 15 mL of solution contains 3 g of potassium chloride, USP and the following inactive ingredients: citric acid anhydrous, FD&C Yellow#6, glycerin, purified water, sodium benzoate, trisodium citrate dihydrate, sucralose, sodium chloride, sodium sulphate, propylene glycol, natural/artificial orange flavour.

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 a lowering of the serum potassium concentration can produce digitalis toxicity.

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 a lowering of the serum potassium concentration can produce digitalis toxicity.

16 HOW SUPPLIED/STORAGE AND HANDLING Potassium Chloride Oral Solution, USP 10% (20 mEq/15 mL) is an orange flavored, clear orange-colored solution available as follows: NDC 0121-0948-16: 16 fl oz (473 mL) Bottle. NDC 0121-4948-15: 15 mL unit dose cup. Case contains 30 unit-dose cups of 15 mL (NDC 0121-4948-94), packaged in 3 trays of 10 unit-dose cups each, 40 unit-dose cups of 15 mL (NDC 0121-4948-40), packaged in 4 trays of 10 unit-dose cups each, 50 unit-dose cups of 15 mL (NDC 0121-4948-50), packaged in 5 trays of 10 unit-dose cups each, 80 unit-dose cups of 15 mL (NDC 0121-4948-80), packaged in 8 trays of 10 unit-dose cups each and 100 unit-dose cups of 15 mL (NDC 0121-4948-00), packaged in 10 trays of 10 unit-dose cups each. NDC 0121-1896-30: 30 mL unit dose cup. Case contains 40 unit-dose cups of 30 mL (NDC 0121-1896-40), packaged in 4 trays of 10 unit-dose cups each, 50 unit-dose cups of 30 mL (NDC 0121-1896-50), packaged in 5 trays of 10 unit-dose cups each and 100 unit-dose cups of 30 mL (NDC 0121-1896-00), packaged in 10 trays of 10 unit-dose cups each. Potassium Chloride Oral Solution, USP 20% (40 mEq/15 mL) is an orange flavored, clear orange-colored, solution available as follows: NDC 0121-2847-16: 16 fl oz (473 mL) Bottle. NDC 0121-2847-15: 15 mL unit dose cup. Case contains 30 unit-dose cups of 15 mL (NDC 0121-2847-94), packaged in 3 trays of 10 unit-dose cups each, 40 unit-dose cups of 15 mL (NDC 0121-2847-40), packaged in 4 trays of 10 unit-dose cups each, 50 unit-dose cups of 15 mL (NDC 0121-2847-50), packaged in 5 trays of 10 unit-dose cups each, 80 unit-dose cups of 15 mL (NDC 0121-2847-80), packaged in 8 trays of 10 unit-dose cups each and 100 unit-dose cups of 15 mL (NDC 0121-2847-00), packaged in 10 trays of 10 unit-dose cups each. STORAGE Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP. PROTECT from LIGHT and FREEZING.