POTASSIUM CHLORIDE

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, and perforation. 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 the manufacturer Adare at 1-877-731-5116, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

4 CONTRAINDICATIONS Potassium chloride extended-release capsules are contraindicated in patients on amiloride or triamterene. Concomitant use with triamterene and amiloride. ( 4 )

11 DESCRIPTION Potassium chloride extended-release capsules, USP, are an oral dosage form of microencapsulated potassium chloride containing 600 mg and 750 mg of potassium chloride, USP, equivalent to 8 mEq and 10 mEq of potassium, respectively. The chemical name of the active ingredient is potassium chloride and the structural formula is KCl. It has a molecular mass of 74.55. 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. Inactive ingredients: ethylcellulose, gelatin, magnesium stearate, sodium lauryl sulfate, titanium dioxide and edible black ink. The 10 mEq capsules also contain black iron oxide, FD&C blue No.1 and FD&C red No.3.

2 DOSAGE AND ADMINISTRATION Monitor serum potassium and adjust dosage accordingly ( 2.1 ) If serum potassium concentration is <2.5 mEq/L, use intravenous potassium instead of oral supplementation. ( 2.1 ) Treatment of hypokalemia: Adults: Typical doses range from 40-100 mEq/day in 2-5 divided doses; limit doses to 40 mEq per dose. ( 2.2 ) Pediatric patients: 2-4 mEq/kg/day in divided doses not to exceed 1 mEq/kg as a single dose or 20 mEq, whichever is lower; if deficits are severe or ongoing losses are great, consider intravenous therapy. ( 2.3 ) Maintenance or Prophylaxis of hypokalemia: Adults: Typical dose is 20 mEq per day ( 2.2 ) Pediatric patients: Typical dose is 1 mEq/kg/day. ( 2.3 ) 2.1 Administration and Monitoring If serum potassium concentration is <2.5 mEq/L, use intravenous potassium instead of oral supplementation. Monitoring Monitor serum potassium and adjust dosages accordingly. 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 with meals and with a full glass of water or other liquid. Do not take on an empty stomach because of the potential for gastric irritation [see Warnings and Precautions (5.1) ]. Patients who have difficulty swallowing capsules may sprinkle the contents of the capsule onto a spoonful of soft food. The soft food, such as applesauce or pudding, should be swallowed immediately without chewing and followed with a glass of water or juice to ensure complete swallowing of the microcapsules. Do not add to hot foods. Any microcapsule/food mixture should be used immediately and not stored for future use. 2.2 Adult Dosing Dosage must be adjusted to the individual needs of each patient. Dosages greater than 40 mEq per day should be divided such that no more than 40 mEq is given in a single dose. Treatment of hypokalemia: Typical dose range is 40-100 mEq per day. Maintenance or Prophylaxis: Typical dose is 20 mEq per day. 2.3 Pediatric Dosing Pediatric patients aged birth to 16 years old: Dosage must be adjusted to the individual needs of each patient. Do not exceed as a single dose 1 mEq/kg or 20 mEq, whichever is lower. Treatment of hypokalemia : The recommended initial dose is 2 to 4 mEq/kg/day in divided doses. If deficits are severe or ongoing losses are great, consider intravenous therapy. Maintenance or Prophylaxis : Typical dose is 1 mEq/kg/day.

1 INDICATIONS AND USAGE Potassium chloride extended-release capsules are indicated for the treatment and prophylaxis of hypokalemia in adults and children 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 capsules contain potassium chloride, 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. ( 1 )

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. 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 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 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.

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 (NSAIDS): Monitor for hyperkalemia ( 7.3 ) 7.1 Amiloride and Triamterene 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 produces potassium retention by inhibiting aldosterone production. Closely monitor potassium in patients taking drugs that inhibit RAAS. 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 taking NSAIDS.

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 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 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. 12.3 Pharmacokinetics Each crystal of KCl is microencapsulated and allows for the controlled release of potassium and chloride ions over an eight to ten-hour period. Specific Populations Cirrhotics 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.

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 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.

12.3 Pharmacokinetics Each crystal of KCl is microencapsulated and allows for the controlled release of potassium and chloride ions over an eight to ten-hour period. Specific Populations Cirrhotics 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.

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3 DOSAGE FORMS AND STRENGTHS 600 mg (8 mEq): White to ivory opaque capsules printed with “102” in black ink on the cap. 750 mg (10 mEq): Light blue opaque capsules printed with “103” in black ink on the cap. Extended-release capsules: 600 mg (8mEq) and 750 mg (10 mEq)

POTASSIUM CHLORIDE POTASSIUM CHLORIDE ETHYLCELLULOSE, UNSPECIFIED GELATIN, UNSPECIFIED MAGNESIUM STEARATE SODIUM LAURYL SULFATE TITANIUM DIOXIDE FERROSOFERRIC OXIDE FD&C BLUE NO. 1 FD&C RED NO. 3 POTASSIUM CHLORIDE POTASSIUM CATION light blue 103

ANDA208864

POTASSIUM CHLORIDE

POTASSIUM CHLORIDE

60687-653

HUMAN PRESCRIPTION DRUG

ORAL

Package/Label Display Panel – Carton – (750 mg) 10 mEq K NDC 60687- 653 -01 Potassium Chloride Extended-Release Capsules, USP (750 mg) 10 mEq K 100 Capsules (10 x 10) Rx Only Potassium Chloride Extended-Release Capsules, USP 10 mEq Contain: Microencapsulated KCl and are designed to release the active ingredient over an 8-to-10-hour period. Usual Dosage: See package insert for full prescribing information. Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep this and all drugs out of reach of children. FOR YOUR PROTECTION: Do not use if blister is torn or broken. The drug product contained in this package is from NDC # 63304-090, Sun Pharmaceutical Industries, Inc. Distributed by: American Health Packaging Columbus, Ohio 43217 765301 0465301/0122 (750 mg) 10 mEq K Potassium Chloride Extended-Release Capsules Carton

PACKAGING INFORMATION American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Sun Pharmaceutical Industries, Inc. as follows: (750 mg (10 mEq) / 100 UD) NDC 60687-653-01 packaged from NDC 63304-090 Distributed By: American Health Packaging Columbus, OH 43217 8465301/0922

17 PATIENT COUNSELING INFORMATION Inform patients to take each dose with meals and with a full glass of water or other liquid. Advise patients to seek medical attention if tarry stools or other evidence of gastrointestinal toxicity is noticed.

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.

8.4 Pediatric Use Clinical trial data from published literature have demonstrated the safety and effectiveness of potassium chloride in children with diarrhea and malnutrition from birth to 18 years.

8.1 Pregnancy Risk Summary There are no human data related to use of potassium chloride extended-release capsules during pregnancy and animal reproductive 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 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 capsules during pregnancy and animal reproductive 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, 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 Clinical trial data from published literature have demonstrated the safety and effectiveness of potassium chloride in children with diarrhea and malnutrition from birth to 18 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 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 [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 RAAS inhibitors 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 [see Drug Interactions (7.2 , 7.3) ] . The serum potassium level should be monitored frequently. Renal function should be assessed periodically.

16 HOW SUPPLIED/STORAGE AND HANDLING Potassium chloride extended-release capsules, USP, 8 mEq and 10 mEq contain 600 mg and 750 mg of potassium chloride (equivalent to 8 mEq and 10 mEq, respectively). Table 1: How Supplied Dose Color Printing NDC#: 60687-653-01 750 mg (10 mEq) light blue 103 Unit dose packages of 100 (10 x 10) Store at 20° to 25°C (68°-77°F); excursions are permitted to 15° to 30°C (59°-86°F) [see USP Controlled Room Temperature.] FOR YOUR PROTECTION: Do not use if blister is torn or broken. Rx only