Potassium Chloride

INDICATIONS & USAGE SECTION BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE POTASSIUM CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT POTASSIUM PREPARATIONS, OR FOR PATIENTS WITH WHOM THERE IS A PROBLEM OF COMPLIANCE WITH THESE PREPARATIONS. For the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxication, and in patients with hypokalemic familial periodic paralysis. If hypokalemia is the result of diuretic therapy, consideration should be given to the use of a lower dose of diuretic, which may be sufficient without leading to hypokalemia. For the prevention of hypokalemia in patients who would be at particular risk if hypokalemia were to develop, e.g., digitalized patients or patients with significant cardiac arrhythmias. The use of potassium salts in patients receiving diuretics for uncomplicated essential hypertension is often unnecessary when such patients have a normal dietary pattern, and when low doses of the diuretic are used. Serum potassium should be checked periodically, however, and, if hypokalemia occurs, dietary supplementation with potassium-containing foods may be adequate to control milder cases. In more severe cases and if dose adjustment of the diuretic is ineffective or unwarranted supplementation with potassium salts may be indicated.

DOSAGE AND ADMINISTRATION The usual dietary intake of potassium by the average adult is 50 to 100 mEq per day. Potassium depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of potassium from the total body store. Dosage must be adjusted to the individual needs of each patient. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40 to 100 mEq per day or more are used for the treatment of potassium depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose. Each potassium chloride extended-release tablet, USP 20 mEq provides 1,500 mg potassium chloride, USP equivalent to 20 mEq of potassium. Each potassium chloride extended-release tablet, USP 15 mEq provides 1,125 mg potassium chloride, USP equivalent to 15 mEq of potassium. Each potassium chloride extended-release tablet, USP 10 mEq provides 750 mg potassium chloride, USP equivalent to 10 mEq of potassium. Potassium chloride extended-release tablets should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation (see WARNINGS ). Patients having difficulty swallowing whole tablets may try one of the following alternate methods of administration: a. Break the tablet in half, and take each half separately with a glass of water. b. Prepare an aqueous (water) suspension as follows: Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces). Allow approximately 2 minutes for the tablet(s) to disintegrate. Stir for about half a minute after the tablet(s) has disintegrated. Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw. Add another 1 fluid ounce of water, swirl, and consume immediately. Then, add an additional 1 fluid ounce of water, swirl, and consume immediately. Aqueous suspension of potassium chloride that is not taken immediately should be discarded. The use of other liquids for suspending potassium chloride extended-release tablets is not recommended.

3 DOSAGE FORMS AND STRENGTHS Potassium Chloride Extended Release Tablets, USP are supplied as: Potassium Chloride Extended Release Tablets, USP 8 mEq [600mg] are blue colored, circular biconvex film coated tablets plain on one side and debossed "P8" on another side. Potassium Chloride Extended Release Tablets, USP 10 mEq [750mg] are yellow colored, circular biconvex film coated tablets plain on one side and debossed "P10" on another side. Tablets: 600 mg (8 mEq) and 750 mg (10 mEq) (3)

CONTRAINDICATIONS Potassium supplements are contraindicated in patients with hyperkalemia since a further increase in serum potassium concentration in such patients can produce cardiac arrest. Hyperkalemia may complicate any of the following conditions: chronic renal failure, systemic acidosis, such as diabetic acidosis, acute dehydration, extensive tissue breakdown as in severe burns, adrenal insufficiency, or the administration of a potassium-sparing diuretic (e.g., spironolactone, triamterene, or amiloride) ( see OVERDOSAGE ). Extended-release formulations of potassium chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Potassium supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Potassium Chloride Extended-release Tablets ( see PRECAUTIONS : Information for Patients and DOSAGE AND ADMINISTRATION sections). All solid oral dosage forms of potassium chloride are contraindicated in any patient in whom there is structural, pathological (e.g., diabetic gastroparesis), or pharmacologic (use of anticholinergic agents or other agents with anticholinergic properties at sufficient doses to exert anticholinergic effects) cause for arrest or delay in tablet passage through the gastrointestinal tract.

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 hyperkalemia and of upper and lower gastrointestinal condition including obstruction, bleeding, ulceration, perforation. Skin rash has been reported rarely. To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993; email drugsafety@avkare.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The most common adverse reactions are nausea, vomiting, flatulence, abdominal pain/discomfort and diarrhea. (6) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993; email drugsafety@avkare.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS Triamterene and amiloride: Concomitant use is contraindicated (7.1) Renin-angiotensin-aldosterone inhibitors: Monitor for hyperkalemia (7.2) Nonsteroidal anti-inflammatory drugs: Monitor for hyperkalemia (7.3) 7.1 Triamterene or amiloride Use with triamterene or amiloride can produce severe hyperkalemia. Concomitant use is contraindicated [see Contraindications (4)] . 7.2 Renin-angiotensin-aldosterone 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 on concomitant RAAS inhibitors. 7.3 Nonsteroidal Anti-inflammatory Drugs (NSAIDs) NSAIDS may produce potassium retention by reducing renal synthesis of prostaglandin E and imparing 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 Risk Summary There are no human data related to use of Potassium Chloride Extended-release Tablets, USP 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 oral potassium becomes part of the body potassium pool, so 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 in the pediatric population have not been established. 8.5 Geriatric Use Clinical studies of Potassium Chloride extended-release 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 Based on publish 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 [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 [see Warnings and Precautions (5.2)] . 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. Potassium Chloride Extended-Release Tablets, USP 750 mg contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

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.

DESCRIPTION The Potassium Chloride Extended-Release Tablets, USP 20 mEq product is an immediately dispersing extended-release oral dosage form of potassium chloride containing 1,500 mg of microencapsulated potassium chloride, USP equivalent to 20 mEq of potassium in a tablet. The Potassium Chloride Extended-Release Tablets, USP 15 mEq product is an immediately dispersing extended-release oral dosage form of potassium chloride containing 1,125 mg of microencapsulated potassium chloride, USP equivalent to 15 mEq of potassium in a tablet. The Potassium Chloride Extended-Release Tablets, USP 10 mEq product is an immediately dispersing extended-release oral dosage form of potassium chloride containing 750 mg of microencapsulated potassium chloride, USP equivalent to 10 mEq of potassium in a tablet. These formulations are intended to slow the release of potassium so that the likelihood of a high localized concentration of potassium chloride within the gastrointestinal tract is reduced. Potassium chloride is an electrolyte replenisher. The chemical name of the active ingredient is potassium chloride, and the structural formula is KCl. Potassium chloride, USP occurs as a white crystalline powder or colourless crystals. It is odorless and has a saline taste. Its solutions are neutral to litmus. It is freely soluble in water, practically insoluble in ethanol. Potassium chloride is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated potassium chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of out-side agitation, potassium chloride extended-release tablets begin disintegrating into microencapsulated crystals within seconds and completely disintegrates within 1 minute. The microencapsulated crystals are formulated to provide an extended-release of potassium chloride. Inactive Ingredients: crospovidone, ethylcellulose, hydroxypropyl cellulose, microcrystalline cellulose, sorbitan monooleate, stearic acid and talc. FDA approved sample preparation in the assay differs from USP test. FDA approved dissolution specification differs from that of the USP.

OVERDOSAGE 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 intravenously, potentially fatal hyperkalemia can result (see CONTRAINDICATIONS and WARNINGS ). It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum potassium concentration (6.5 mEq to 8 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 mEq to 12 mEq/L). Treatment measures for hyperkalemia include the following: Patients should be closely monitored for arrythmias and electrolyte changes. 1. Elimination of 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. 2. Intravenous calcium gluconate if the patient is at no risk or low risk of developing digitalis toxicity. 3. Intravenous administration of 300 to 500 mL/hr of 10% dextrose solution containing 10 units to 20 units of crystalline insulin per 1,000 mL. 4. Correction of acidosis, if present, with intravenous sodium bicarbonate. 5. Use of exchange resins, hemodialysis, or peritoneal dialysis. In treating hyperkalemia, it should be recalled that 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.

HOW SUPPLIED Potassium Chloride Extended-Release Tablets, USP 10 mEq are white to off white, capsule shaped biconvex tablet with spotted appearance debossed with “PT 10” on one side and plain on other side. These are available in Bottles of 90 NDC 59651-429-90 Bottles of 100 NDC 59651-429-01 Bottles of 1,000 NDC 59651-429-99 Potassium Chloride Extended-Release Tablets, USP 15 mEq are white to off white, capsule shaped biconvex tablet with spotted appearance debossed with “PT 15” on one side and break line on other side. These are available in Bottles of 100 NDC 59651-430-01 Bottles of 1,000 NDC 59651-430-99 Potassium Chloride Extended-Release Tablets, USP 20 mEq are white to off white, capsule shaped biconvex tablet with spotted appearance debossed with “PT 20” on one side and break line on other side. These are available in Bottles of 90 NDC 59651-431-90 Bottles of 100 NDC 59651-431-01 Bottles of 500 NDC 59651-431-05 Storage Conditions: Keep tightly closed. Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep tightly closed. Dispense in a tight, light-resistant container as defined in the USP. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 038, India Issued: March 2021