Potassium Chloride

1 INDICATIONS AND USAGE Potassium Chloride Extended-Release Tablets are 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 is insufficient. Potassium Chloride Extended-Release Tablets are a potassium salt, 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 is insufficient. Error! Hyperlink reference not valid.

2 DOSAGE AND ADMINISTRATION Monitor serum potassium and adjust dosages accordingly (2.1) If serum potassium concentration is less than 2.5 mEq/L, use intravenous potassium instead of oral supplementation (2.1) Take with meals and with a glass of water or other liquid. Swallow tablets whole. (2.1) Treatment of hypokalemia: Typical dose range is 40-100 mEq per day in divided doses. Limit doses to 20 mEq per dose. (2.2) Prevention of hypokalemia: Typical dose is 20 mEq per day (2.2) 2.1 Monitoring and Administration If serum potassium concentration is less than 2.5 mEq/L, use intravenous potassium instead of oral supplementation. Monitoring Monitor serum potassium and adjust the dose based on serum potassium level. Monitor serum potassium periodically during maintenance therapy to ensure potassium remains in desired range. 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 Take potassium chloride extended-release tablets with meals and with a glass of water or other liquid. Do not take on an empty stomach because of its potential for gastric irritation [see Warnings and Precautions ( 5.1 )] . Swallow tablets whole without crushing, chewing or sucking. 2.2 Dosing Dosage must be adjusted to the individual needs of each patient. Dosages greater than 20 mEq per day should be divided such that no more than 20 mEq is given in a single dose. Treatment of hypokalemia: Typical dose range is 40-100 mEq per day. Prevention of hypokalemia: Typical dose is 20 mEq per day.

2.1 Monitoring and Administration If serum potassium concentration is less than 2.5 mEq/L, use intravenous potassium instead of oral supplementation. Monitoring Monitor serum potassium and adjust the dose based on serum potassium level. Monitor serum potassium periodically during maintenance therapy to ensure potassium remains in desired range. 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 Take potassium chloride extended-release tablets with meals and with a glass of water or other liquid. Do not take on an empty stomach because of its potential for gastric irritation [see Warnings and Precautions ( 5.1 )] . Swallow tablets whole without crushing, chewing or sucking.

2.2 Dosing Dosage must be adjusted to the individual needs of each patient. Dosages greater than 20 mEq per day should be divided such that no more than 20 mEq is given in a single dose. Treatment of hypokalemia: Typical dose range is 40-100 mEq per day. Prevention of hypokalemia: Typical dose is 20 mEq per day.

3 DOSAGE FORMS AND STRENGTHS Potassium Chloride Extended-Release Tablets, USP are available containing 600 mg or 750 mg of potassium chloride, USP (equivalent to 8 mEq or 10 mEq, respectively). • The 8 mEq (600 mg) tablets are light brown, film-coated, round, unscored tablets debossed with M on one side of the tablet and PC2 on the other side. • The 10 mEq (750 mg) tablets are peach, film-coated, round, unscored tablets debossed with M on one side of the tablet and PC1 on the other side. Tablets: 600 mg (8 mEq) and 750 mg (10 mEq) ( 3 )

4 CONTRAINDICATIONS Potassium chloride is contraindicated in patients on triamterene and amiloride. • Concomitant use with triamterene and amiloride Error! Hyperlink reference not valid.

6 ADVERSE REACTIONS The following adverse reactions have been identified with use of oral potassium salts. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most common adverse reactions to oral potassium salts are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea. There have been reports of hyperkalemia and of upper and lower gastrointestinal conditions including obstruction, bleeding, ulceration, perforation [see Warnings and Precautions ( 5.1 ) and Overdosage ( 10 )] . Skin rash has been reported rarely. Most common adverse reactions are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea (6) To report SUSPECTED ADVERSE REACTIONS, contact Advagen Pharma Ltd, at 866-488-0312 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

7.1 Triamterene and Amiloride Use with triamterene or amiloride can produce severe hyperkalemia. Avoid concomitant use [see Contraindications ( 4 )] .

7 DRUG INTERACTIONS Renin-angiotensin-aldosterone system inhibitors: Monitor for hyperkalemia (7.2) Nonsteroidal anti-inflammatory drugs: Monitor for hyperkalemia (7.3) 7.1 Triamterene and Amiloride Use with triamterene or amiloride can produce severe hyperkalemia. Avoid concomitant use [see Contraindications ( 4 )] . 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 Nonsteroidal anti-inflammatory drugs (NSAIDs) may produce potassium retention by reducing renal synthesis of prostaglandin E and impairing the renin-angiotensin system. Closely monitor potassium in patients receiving concomitant NSAID therapy.

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 Nonsteroidal anti-inflammatory drugs (NSAIDs) may produce potassium retention by reducing renal synthesis of prostaglandin E and impairing the renin-angiotensin system. Closely monitor potassium in patients receiving concomitant NSAID therapy.

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 Risk Summary There are no human data related to use of potassium chloride extended-release tablets during pregnancy, and animal reproduction 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 Safety and effectiveness of potassium chloride extended-release tablets in children have not been established. 8.5 Geriatric Use Clinical studies of potassium chloride extended-release tablets 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 Doses of potassium in patients with cirrhosis produce a larger increase in potassium levels compared to the response in normal patients. Based on published literature, the baseline corrected serum concentrations of potassium measured over 3 hours after administration in cirrhotic subjects who received an oral potassium load rose to approximately twice that of normal subjects who received the same load. Patients with cirrhosis should usually be started at the low end of the dosing range, and the serum potassium level should be monitored frequently. 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 RAAS inhibitors or NSAIDs, should usually be started at the low end of the dosing range because of the potential for development of hyperkalemia [see Drug Interactions ( 7.2 , 7.3 )] . The serum potassium level should be monitored frequently. Renal function should be assessed periodically.

8.1 Pregnancy Risk Summary There are no human data related to use of potassium chloride extended-release tablets during pregnancy, and animal reproduction 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 Th …

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 impulse; 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 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 to 100 mEq per day.

11 DESCRIPTION Potassium Chloride Extended-Release Tablets USP are a solid oral dosage form of potassium chloride containing 750 mg and 1,500 mg of potassium chloride, USP, equivalent to 10 mEq and 20 mEq of potassium, respectively, in a film-coated (not enteric-coated), wax matrix tablet. The chemical name is potassium chloride, and the structural formula is KCl. Potassium chloride, USP, occurs as a white, granular powder or as colorless crystals. It is odorless and has a saline taste. Its solutions are neutral to litmus. It is freely soluble in water and insoluble in alcohol. Each tablet contains the labeled amount of potassium chloride and the following inactive ingredients: colloidal silicon dioxide, hydrogenated vegetable oil, microcrystalline cellulose, polyvinyl acetate, povidone, sodium lauryl sulfate and triethyl citrate. The coating material of 10 mEq (750 mg) product contains ferrosoferric oxide, iron oxide yellow, mono- and di-glycerides, polyethylene glycol polyvinyl alcohol graft copolymer, polyvinyl alcohol, talc and titanium dioxide. The coating material of 20 mEq (1500 mg) product contains hypromellose and talc. FDA approved assay test differs from USP. FDA approved dissolution test specifications differ from USP.

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, potentially fatal hyperkalemia can result [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] . 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 P-waves, depression of S-T segments, and prolongation of the QT intervals). 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 1,000 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. The extended release feature means that absorption and toxic effects may be delayed for hours. Consider standard measures to remove any unabsorbed drug.

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, potentially fatal hyperkalemia can result [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] . 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 P-waves, depression of S-T segments, and prolongation of the QT intervals). 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 1,000 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. The extended release feature means that absorption and toxic effects may be delayed for hours. Consider standard measures to remove any unabsorbed drug.

16 HOW SUPPLIED/STORAGE AND HANDLING Potassium Chloride Extended-Release Tablets USP contains 600 mg or 750 mg of potassium chloride equivalent to 8 mEq and 10 mEq respectively. Potassium chloride is provided as extended-release tablets. Potassium Chloride Extended-Release Tablets USP 600 mg (8 mEq) are pink, circular, film-coated biconvex tablet debossed with “N 31” on one side and plain on other side. Bottles of 100 NDC 65862-986-01 Bottles of 500 NDC 65862-986-05 Cartons of 80 Tablets (20 X 4 Unit-Dose) NDC 65862-986-80 Cartons of 120 Tablets (20 X 6 Unit-Dose) NDC 65862-986-12 Potassium Chloride Extended-Release Tablets USP 750 mg (10 mEq) are white to off-white, circular, film-coated biconvex tablet debossed with “N 32” on one side and plain on other side. Bottles of 100 NDC 65862-987-01 Bottles of 1,000 NDC 65862-987-99 Cartons of 80 Tablets (20 X 4 Unit-Dose) NDC 65862-987-80 Cartons of 120 Tablets (20 X 6 Unit-Dose) NDC 65862-987-12 Store at 20 o to 25 o C (68 o to 77 o F) [see USP Controlled Room Temperature]. Protect from light and moisture. Dispense in a tight, light-resistant container with a child-resistant closure.