Micro-K Extencaps capsules and Micro-K 10 Extencaps capsules are oral dosage forms of microencapsulated potassium chloride containing 600 and 750 mg, respectively, of potassium chloride USP equivalent to 8 and 10 mEq of potassium.
Dispersibility of potassium chloride (KCl) is accomplished by microencapsulation and a dispersing agent. The resultant flow characteristics of the KCl microcapsules and the controlled release of K + ions by the microcapsular membrane are intended to avoid the possibility that excessive amounts of KCl can be localized at any point on the mucosa of the gastrointestinal tract.
Each crystal of KCl is microencapsulated by a patented process with an insoluble polymeric coating which functions as a semi-permeable membrane; it allows for the controlled release of potassium and chloride ions over an eight- to ten-hour period. Fluids pass through the membrane and gradually dissolve the potassium chloride within the microcapsules. The resulting potassium chloride solution slowly diffuses outward through the membrane. Micro-K and Micro-K 10 are electrolyte replenishers. The chemical name of the active ingredient 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.
The inactive ingredients present are edible ink, ethylcellulose, FD&C Blue 2 Aluminum Lake, FD&C Yellow 6, gelatin, magnesium stearate, sodium lauryl sulfate, titanium dioxide. May contain FD&C Red 40 and Yellow 6 Aluminum Lakes.
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.
Potassium depletion may 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 slowly as a consequence of prolonged therapy with oral diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, severe diarrhea, or inadequate replacement of potassium in patients on prolonged parenteral nutrition. Potassium depletion due to these causes is usually accompanied by a concomitant deficiency 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.
Potassium depletion associated with metabolic alkalosis is managed by correcting the fundamental causes of the deficiency whenever possible and administering supplemental potassium chloride, in the form of high potassium food or potassium chloride solution, capsules or tablets. 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, or potassium acetate.
BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH SLOW-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 IN WHOM THERE IS A PROBLEM OF COMPLIANCE WITH THESE PREPARATIONS.
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 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 capsule 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 adjustments.
Hypokalemia should not be treated by the concomitant administration of potassium salts and a potassium-sparing diuretic (e.g., spironolactone or triamterene), 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.
Potassium chloride tablets have produced stenotic and/or ulcerative lesions of the small bowel and deaths, in addition to upper gastrointestinal bleeding. These lesions are caused by a high localized concentration of potassium ion in the region of a rapidly dissolving tablet which injures the bowel wall and thereby produces obstruction, hemorrhage, or perforation.
Micro-K® Extencaps® contain microcapsules which disperse upon dissolution of the hard gelatin capsule. The microcapsules are formulated to provide a controlled release of potassium chloride. The dispersibility of the microcapsules and the controlled release of ions from the microcapsules are intended to minimize the possibility of a high local concentration near the gastrointestinal mucosa and the ability of the KCl to cause stenosis or ulceration. Other means of accomplishing this (e.g., incorporation of KCl into a wax matrix) have reduced the frequency of such lesions to less than one per 100,000 patient years (compared with 40 to 50 per 100,000 patient years with enteric-coated KCl), but have not eliminated them. The frequency of GI lesions with Micro-K® Extencaps® is, at present, unknown. Micro-K® Extencaps® should be discontinued immediately and the possibility of bowel obstruction or perforation considered if severe vomiting, abdominal pain, distention, or gastrointestinal bleeding occurs.
Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing potassium salt, such as potassium bicarbonate, potassium citrate, or potassium acetate.
General 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 water or other suitable 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 capsules or if the capsules 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 capsule.
Laboratory Test Regular serum potassium determinations are recommended, especially in patients with renal insufficiency or diabetic nephropathy. 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.
Drug Interactions Potassium-sparing diuretic, angiotensin converting enzyme inhibitors (see ).
Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity and fertility studies in animals have not been performed. Potassium is a normal dietary constituent.
Pregnancy, Teratogenic Effects - Category C Animal reproduction stuides have not been conducted with Micro-K®. 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.
Nursing Mothers 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.
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Geriatric Use Clinical studies of Micro-K® Extencaps® 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.
One of the most severe adverse effects is hyperkalemia (see CONTRAINDICATIONS , and OVERDOSAGE ). Gastrointestinal bleeding and ulceration have been reported in patients treated with Micro-K® Extencaps® (see ). In addition to gastrointestinal bleeding and ulceration, perforation and obstruction have been reported in patients treated with other solid KCl dosage forms, and may occur with Micro-K® Extencaps®.
The most common adverse reactions to the oral potassium salts are nausea, vomiting, abdominal pain/discomfort, and diarrhea. These symptoms are due to irritation of the gastrointestinal tract and are best managed by taking the dose with meals, or reducing the amount taken at one time.
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 ). It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum potassium concentration and characteristic electrocardiogram 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.
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 to 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. 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.
Because of the potential for gastric irritation (see ), Micro-K Extencaps should be taken with meals and with a full glass of water or other liquid.
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 cool water or juice to ensure complete swallowing of the microcapsules. The food used should not be hot and should be soft enough to be swallowed without chewing. Any microcapsule/food mixture should be used immediately and not stored for future use.
Micro-K® Extencaps® are pale orange capsules, monogrammed Micro-K® and Ther-Rx/010, each containing 600 mg microencapsulated potassium chloride (equivalent to 8 mEq K) in bottles of 100 (NDC 64011-010-04), 500 (NDC 64011-010-08) and Dis-Co® unit dose packs of 100 (NDC 64011-010-11).
Micro-K® Extencaps® are pale orange and opaque white capsules, monogrammed Micro-K® 10 and Ther-Rx/009, each containing 750 mg microencapsulated potassium chloride (equivalent to 10 mEq K) in bottles of 100 (NDC 64011-009-04), 100 Unit-of-Use (NDC 64011-009-21), bottles of 500 (NDC 64011-009-08), and DisCo® unit dose packs of 100 (NDC 64011-009-11).
Store at controlled room temperature, between 20° C and 25° C (68° F-77° F).
Dispense in tight container.
A.H. Robins Company
Richmond, VA 23220
for Ther-Rx Corporation
St. Louis, MO 63045