Potassium Citrate wax matrix extended-release tablet is indicated for:

• Renal tubular acidosis (RTA) with calcium stones
• Hypocitraturic calcium oxalate nephrolithiasis of any etiology
• Uric acid lithiasis with or without calcium stones

When Potassium Citrate is taken orally, the absorbed citrate is metabolized and produces an alkaline load in the body. This alkaline effect increases urinary pH and raises urinary citrate levels by enhancing citrate clearance without significantly changing serum citrate levels. Therefore, Potassium Citrate mainly increases urinary citrate by changing the kidney’s handling of citrate rather than by increasing the amount filtered through the kidneys.

Besides increasing urinary pH and citrate, Potassium Citrate also raises urinary potassium by approximately the amount present in the medicine. In some patients, it may temporarily reduce urinary calcium levels.

These effects help make the urine less favorable for the formation of stone-forming salts such as calcium oxalate, calcium phosphate, and uric acid. Increased urinary citrate binds with calcium, reducing calcium ion activity and lowering calcium oxalate saturation. Citrate also helps prevent the spontaneous formation of calcium oxalate and calcium phosphate crystals.

The rise in urinary pH also reduces calcium ion activity by increasing calcium binding to dissociated anions. It also increases the conversion of uric acid into the more soluble urate ion.

Potassium Citrate does not significantly change calcium phosphate saturation in urine because the increased citrate binding effect is balanced by the pH-related phosphate dissociation. Calcium phosphate stones are generally more stable in alkaline urine.

In patients with normal kidney function, urinary citrate begins to rise within the first hour after a single dose and continues for up to 12 hours. With repeated doses, maximum citrate excretion is usually reached by the third day, helping maintain a more constant urinary citrate level throughout the day. After stopping treatment, urinary citrate begins to decrease toward pre-treatment levels from the first day.

The increase in citrate excretion depends directly on the Potassium Citrate dose. Long-term treatment with 60 mEq/day may increase urinary citrate by about 400 mg/day and raise urinary pH by approximately 0.7 units.

In patients with severe renal tubular acidosis or chronic diarrhea syndrome, where urinary citrate may be very low (less than 100 mg/day), Potassium Citrate may be less effective in increasing urinary citrate. In such cases, a higher dose may be needed to achieve a satisfactory response. In patients with renal tubular acidosis who already have high urinary pH, Potassium Citrate may cause only a small increase in urinary pH.

Dosing Instructions: Treatment with extended release potassium citrate should be added to a regimen that limits salt intake (avoidance of foods with high salt content and of added salt at the table) and encourages high fluid intake (urine volume should be at least two liters per day). The objective of treatment with Potassium Citrate is to provide Potassium Citrate in sufficient dosage to restore normal urinary citrate (greater than 320 mg/day and as close to the normal mean of 640 mg/day as possible), and to increase urinary pH to a level of 6.0 or 7.0.

Monitor serum electrolytes (sodium, potassium, chloride and carbon dioxide), serum creatinine and complete blood counts every four months and more frequently in patients with cardiac disease, renal disease or acidosis. Perform electrocardiograms periodically. Treatment should be discontinued if there is hyperkalemia, a significant rise in serum creatinine or a significant fall in blood hemocrit or hemoglobin.

Severe Hypocitraturia: In patients with severe hypocitraturia (urinary citrate <150 mg/day), therapy should be initiated at a dosage of 60 mEq/day (30 mEq two times/day or 20 mEq three times/day with meals or within 30 minutes after meals or bedtime snack). Twenty-four hour urinary citrate and/or urinary pH measurements should be used to determine the adequacy of the initial dosage and to evaluate the effectiveness of any dosage change. In addition, urinary citrate and/or pH should be measured every four months. Doses of Potassium Citrate greater than 100 mEq/day have not been studied and should be avoided.

Mild To Moderate Hypocitraturia: In patients with mild to moderate hypocitraturia (urinary citrate > 150 mg/day) therapy should be initiated at 30 mEq/day (15 mEq two times/day or 10 mEq three times/day within 30 minutes after meals or bedtime snack). Twenty-four hour urinary citrate and/or urinary pH measurements should be used to determine the adequacy of the initial dosage and to evaluate the effectiveness of any dosage change. Doses of Potassium Citrate greater than 100 mEq/day have not been studied and should be avoided.

Potassium Citrate is contraindicated:

• In patients with hyperkalemia (or conditions that may lead to hyperkalemia), because a further increase in serum potassium may cause cardiac arrest. These conditions include chronic renal failure, uncontrolled diabetes mellitus, acute dehydration, strenuous physical exercise in unconditioned individuals, adrenal insufficiency, extensive tissue breakdown, or the use of potassium-sparing agents such as triamterene, spironolactone, or amiloride.
• In patients where tablet passage through the gastrointestinal tract may be delayed or obstructed, such as delayed gastric emptying, esophageal compression, intestinal obstruction or stricture, or in those taking anticholinergic medication.
• In patients with peptic ulcer disease because of its ulcer-forming potential.
• In patients with active urinary tract infection (with urea-splitting or other organisms, associated with calcium or struvite stones). Potassium Citrate may be less effective because bacteria can break down citrate, and the increase in urinary pH may encourage further bacterial growth.
• In patients with renal insufficiency (glomerular filtration rate less than 0.7 ml/kg/min), due to the risk of soft tissue calcification and increased chance of hyperkalemia.

Nausea, vomiting, diarrhea, and stomach pain may occur. Taking the medicine after meals helps reduce these side effects. An empty tablet shell may appear in the stool, which is harmless because the medicine has already been absorbed.

This medicine may rarely cause serious stomach or intestinal problems such as bleeding, blockage, or puncture. It may also increase potassium levels in the blood (hyperkalemia). Severe allergic reactions are rare.

Pregnancy Category C. Animal reproduction studies have not been conducted. It is not known whether Potassium Citrate can cause fetal harm or affect reproductive capacity. It should be used during pregnancy only when clearly needed.

Nursing Mothers: Human milk normally contains about 13 mEq/L of potassium ions. It is not known whether Potassium Citrate affects this level. It should be used during breastfeeding only if clearly necessary.

This medicine should not be used in patients with Addison's disease, current bladder infection, uncontrolled diabetes, severe heart disease (such as recent heart attack or heart damage), certain stomach or intestinal problems (such as diabetic gastroparesis, reduced gut movement, peptic ulcer, blockage), severe kidney disease, inability to make urine, potassium-restricted diet, high potassium levels, or severe dehydration.

Before using this medicine, inform your doctor if you have low calcium levels, severe diarrhea, heart problems (such as irregular heartbeat or heart failure), kidney disease, stomach or intestinal disorders, or severe tissue damage such as major burns. Before surgery, inform your doctor or dentist that you are taking this medicine.

Pediatric Use: Safety and effectiveness in children have not been established.

Treatment of overdose: Potassium salt overdose usually does not cause serious hyperkalemia in people without predisposing conditions, but monitoring is important. Hyperkalemia is often asymptomatic and may only be detected by increased serum potassium and ECG changes such as peaked T-wave, loss of P-wave, S-T depression, and prolonged QT interval. Severe cases may lead to muscle paralysis and cardiac arrest.

Treatment includes:

• Close monitoring for arrhythmias and electrolyte imbalance
• Stopping potassium-containing medicines and potassium-sparing agents such as potassium-sparing diuretics, ARBs, ACE inhibitors, NSAIDs, and supplements
• Avoiding high-potassium foods such as bananas, beans, milk, potatoes, spinach, salmon, and others
• Intravenous calcium gluconate if needed
• Intravenous dextrose solution with insulin
• Intravenous sodium bicarbonate if acidosis is present
• Hemodialysis or peritoneal dialysis
• Exchange resins may be used, but alone they are not sufficient for acute treatment

Rapid reduction of potassium in patients taking digitalis may cause digitalis toxicity.

Prevention of repeated kidney stone formation