klotrix (Potassium Chloride) tablet, film coated, extended release
[Bristol-Myers Squibb Company]
Klotrix® (potassium chloride) is a solid, oral dosage form of potassium chloride containing 750 mg of potassium chloride, USP (equivalent to 10 mEq of potassium) in a film-coated wax-matrix tablet. This formulation is intended to provide a controlled release of potassium from the matrix to minimize the likelihood of producing high, localized concentrations of potassium within the gastrointestinal tract.
Klotrix is an electrolyte replenisher. 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.
This product contains the following inactive ingredients: ethylcellulose, FD&C Yellow No. 6 (aluminum lake), glycerin, hydroxypropyl methylcellulose 2910, magnesium stearate, povidone, colloidal silicon dioxide, stearic acid, and titanium dioxide.
The potassium ion 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.
Potassium depletion will occur whenever the rate of potassium loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of potassium intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of potassium in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Potassium depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Potassium depletion may produce weakness, fatigue, disturbances of cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and, in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine.
If potassium depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, e.g., where the patient requires long-term, diuretic therapy, supplemental potassium in the form of high-potassium food or potassium chloride may be able to restore normal potassium levels.
In rare circumstances (e.g., patients with renal tubular acidosis) potassium depletion may be associated with metabolic acidosis and hyperchloremia. In such patients potassium replacement should be accomplished with potassium salts other than the chloride, such as potassium bicarbonate, potassium citrate, potassium acetate, or potassium gluconate.
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 LIQUIDS OR EFFERVESCENT POTASSIUM PREPARATIONS OR FOR PATIENTS IN WHOM THERE IS A PROBLEM OF COMPLIANCE WITH THESE PREPARATIONS.
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.
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, amiloride) (see OVERDOSAGE).
Controlled-release formulations of potassium chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to an enlarged left atrium. Potassium supplementation, when indicated in such patients, should be given as a liquid preparation.
All solid 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.
Hyperkalemia (see OVERDOSAGE)
In patients with impaired mechanisms for excreting potassium, the administration of potassium salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given potassium by the intravenous route but may also occur in patients given potassium orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic.
The use of potassium salts in patients with chronic renal disease, or any other condition which impairs potassium excretion, requires particularly careful monitoring of the serum potassium concentration and appropriate dosage adjustment.
Hypokalemia should not be treated by the concomitant administration of potassium salts and a potassium-sparing diuretic (e.g., spironolactone, triamterene, or amiloride), since the simultaneous administration of these agents can produce severe hyperkalemia.
Angiotensin converting enzyme (ACE) inhibitors (e.g., captopril, enalapril) will produce some potassium retention by inhibiting aldosterone production. Potassium supplements should be given to patients receiving ACE inhibitors only with close monitoring.
Solid oral dosage forms of potassium chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of potassium chloride are associated with an increased frequency of small bowel lesions (40–50 per 100,000 patient-years) compared to sustained-release, wax-matrix formulations (less than one per 100,000 patient-years). Because of the lack of extensive marketing experience with microencapsulated products, a comparison between such products and wax-matrix or enteric-coated products is not available. Klotrix is a wax-matrix tablet formulated to provide a controlled rate of release of potassium chloride and thus to minimize the possibility of a high local concentration of potassium near the gastrointestinal wall.
Prospective trials have been conducted in normal human volunteers in which the upper gastrointestinal tract was evaluated by endoscopic inspection before and after one week of solid oral potassium chloride therapy. The ability of this model to predict events occurring in usual clinical practice is unknown. Trials which approximated usual clinical practice did not reveal any clear differences between the wax-matrix and microencapsulated dosage forms.
In contrast, there was a higher incidence of gastric and duodenal lesions in subjects receiving a high dose of wax-matrix, controlled-release formulation under conditions which did not resemble usual or recommended clinical practice (i.e., 96 mEq per day in divided doses of potassium chloride administered to fasted patients, in the presence of an anticholinergic drug to delay gastric emptying). The upper gastrointestinal lesions observed by endoscope were asymptomatic and were not accompanied by evidence of bleeding (hem occult testing). The relevance of these findings to the usual conditions (i.e., nonfasting, no anticholinergic agent, smaller doses) under which controlled-release potassium chloride products are used is uncertain; epidemiologic studies have not identified an elevated risk, compared to microencapsulated products, for upper gastrointestinal lesions in patients receiving wax-matrix formulations. Klotrix (potassium chloride) should be discontinued immediately and the possibility of ulceration, obstruction or perforation considered if severe vomiting, abdominal pain, distension, or gastrointestinal bleeding occurs.
Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing potassium salt such as potassium bicarbonate, potassium citrate, potassium acetate, or potassium gluconate.
The diagnosis of potassium depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for potassium depletion. In interpreting the serum potassium level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body potassium, while acute acidosis per se can increase the serum potassium concentration into the normal range even in the presence of a reduced total body potassium. The treatment of potassium depletion, particularly in the presence of cardiac disease, renal disease, or acidosis, requires careful attention to acid-base balance and appropriate monitoring of serum electrolytes, the electrocardiogram, and the clinical status of the patient.
Physicians should consider reminding the patient of the following:
To take each dose with meals and with a full glass of water or other liquid.
To take this medicine following the frequency and amount prescribed by the physician. This is especially important if the patient is also taking diuretics and/or digitalis preparations.
To check with the physician if there is trouble swallowing tablets or if the tablets seem to stick in the throat.
To check with the physician at once if tarry stools or other evidence of gastrointestinal bleeding is noticed.
To take each dose without crushing, chewing, or sucking the tablets.
When blood is drawn for analysis of plasma potassium it is important to recognize that artifactual elevations can occur after improper venipuncture technique or as a result of in vitro hemolysis of the sample.
Potassium-sparing diuretic, angiotensin converting enzyme inhibitors: see WARNINGS.
Carcinogenicity, mutagenicity, and fertility studies in animals have not been performed. Potassium is a normal dietary constituent.
Animal reproduction studies have not been conducted with Klotrix (Potassium Chloride Slow-Release Tablet). It is unlikely that potassium supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.
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.
Safety and effectiveness in children have not been established.
One of the most severe adverse effects is hyperkalemia (see CONTRAINDICATIONS, WARNINGS, and OVERDOSAGE). There also have been reports of upper and lower gastrointestinal conditions including obstruction, bleeding, ulceration, and perforation (see CONTRAINDICATIONS and WARNINGS). The most common adverse reactions to oral potassium salts are nausea, vomiting, abdominal pain and discomfort, and diarrhea. These symptoms are due to irritation of the gastrointestinal tract and are best managed by diluting the preparation further, taking the dose with meals, or reducing the dose.
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 (6.5–8.0 mEq/L) and characteristic electrocardiographic changes (peaking of T-waves, loss of P-wave, 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).
Treatment measures for hyperkalemia include the following: (1) elimination of foods and medications containing potassium and of potassium-sparing diuretics; (2) intravenous administration of 300 to 500 mL/hr of 10% dextrose solution containing 10–20 units of insulin per 1,000 mL; (3) correction of acidosis, if present, with intravenous sodium bicarbonate; (4) 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 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 but is typically in the range of 20 mEq per day for the prevention of hypokalemia to 40–100 mEq per day or more for the treatment of potassium depletion. Dosage should be divided if more than 20 mEq per day is given so that no more than 20 mEq is given in a single dose.
Klotrix (potassium chloride) provides 10 mEq of potassium chloride.
Note: Klotrix Slow-Release Tablet must be taken without crushing, chewing, or sucking the tablets. Klotrix 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).
Following release of the potassium chloride, the expended wax-matrix, which is not absorbed, may be observed in the stool.
Each tablet containing 750 mg potassium chloride (equivalent to 10 mEq each potassium and chloride) is light orange, film-coated, debossed on one side with BL and on the other side with 770.
NDC 0087-0770-41 Bottles of 100
NDC 0087-0770-42 Bottles of 1000
NDC 0087-0770-43 Cartons of 100 individually wrapped tablets
Do not store at temperatures above 86° F (30° C).
Bristol-Myers Squibb Company
Princeton, NJ 08543 USA
|KLOTRIX (Potassium Chloride)|
Data are from FDA and U.S. National Library of Medicine.