Potassium Chloride 750 mg Tablet, Extended Release — NDC 0904-7292-61 (Billing 00904-7292-61)

WARNINGS 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. Interaction with Potassium-Sparing Diuretics 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.

Interaction with 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. Interaction with 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. Gastrointestinal Lesions 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 to 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. Potassium chloride is a tablet formulated to provide a controlled rate of release of microencapsulated 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 1 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 a 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 endoscopy were asymptomatic and were not accompanied by evidence of bleeding (Hemoccult testing). The relevance of these findings to the usual conditions (i.e. non-fasting, 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 micro-encapsulated products, for upper gastrointestinal lesions in patients receiving wax matrix formulations.

Potassium chloride extended-release tablets should be discontinued immediately and the possibility of ulceration, obstructio…

ADVERSE REACTIONS One of the most severe adverse effects is hyperkalemia (see CONTRAINDICATIONS , WARNINGS , and OVERDOSAGE ). There have also 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, flatulence, abdominal pain/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 amount taken at one time. To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions Potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (see WARNINGS ).