Potassium Citrate

Potassium citrate is a citrate salt of potassium indicated for the management of:

• Renal tubular acidosis (RTA) with calcium stones (
  
  
  1.1 Renal tubular acidosis (RTA) with calcium stones

  Potassium citrate is indicated for the management of renal tubular acidosis

  [see Clinical Studies (14.1)].
  )
  
• Hypocitraturic calcium oxalate nephrolithiasis of any etiology (
  
  
  1.2 Hypocitraturic calcium oxalate nephrolithiasis of any etiology

  Potassium citrate is indicated for the management of Hypocitraturic calcium oxalate nephrolithiasis

  [see Clinical Studies (14.2)].
  )
  
• Uric acid lithiasis with or without calcium stones (
  
  
  1.3 Uric acid lithiasis with or without calcium stones

  Potassium citrate is indicated for the management of Uric acid lithiasis with or without calcium stones

  [see Clinical Studies (14.3)].
  )
  

Objective: 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 to 7.0.

• Severe hypocitraturia (urinary citrate < 150 mg/day): therapy should be initiated at 60 mEq per day; a dose of 30 mEq two times per day or 20 mEq three times per day with meals or within 30 minutes after meals or bedtime snack (
  
  
  2.2 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 extended-release tablets greater than 100 mEq/day have not been studied and should be avoided.
  )
  
• Mild to moderate hypocitraturia (urinary citrate >150 mg/day): therapy should be initiated at 30 mEq per day; a dose of 15 mEq two times per day or 10 mEq three times per day with meals or within 30 minutes after meals or bedtime snack (
  
  
  2.3 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 extended-release tablets greater than 100 mEq/day have not been studied and should be avoided.
  )
  

• 5 mEq tablets are uncoated, modified ball-shaped, and tan to yellowish in color. Each 5 mEq tablet is debossed with "USL" on one side and "070" on the other side.
• 10 mEq tablets are uncoated, elliptical-shaped, and tan to yellowish in color. Each 10 mEq tablet is debossed with "USL" on one side and "071" on the other side.

• Pregnant women: Animal reproduction studies have not been conducted. It is not known whether potassium citrate extended-release tablets can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Potassium citrate extended-release tablets should be given to a pregnant woman only if clearly needed (
  
  
  8.1 Pregnancy

  Animal reproduction studies have not been conducted. It is also not known whether potassium citrate extended-release tablets can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Potassium citrate extended-release tablets should be given to a pregnant woman only if clearly needed.
  )
  
• Nursing mothers: The normal potassium ion content of human milk is about 13 mEq/L. It is not known if potassium citrate extended-release tablets has an effect on this content. Potassium citrate extended-release tablets should be given to a woman who is breast feeding only if clearly needed (
  
  
  8.3 Nursing Mothers

  The normal potassium ion content of human milk is about 13 mEq/L. It is not known if potassium citrate extended-release tablets has an effect on this content. Potassium citrate extended-release tablets should be given to a woman who is breast feeding only if clearly needed.
  )
  
• Pediatric Use: Safety and effectiveness in children have not been established (
  
  
  8.4 Pediatric Use

  Safety and effectiveness in children have not been established.
  )
  

• Hyperkalemia: In patients with impaired mechanisms for excreting potassium, potassium citrate extended-release tablets administration can produce hyperkalemia and cardiac arrest. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of potassium citrate extended-release tablets in patients with chronic renal failure, or any other condition which impairs potassium excretion such as severe myocardial damage or heart failure, should be avoided (
  
  
  5.1 Hyperkalemia

  In patients with impaired mechanisms for excreting potassium, potassium citrate extended-release tablets administration can produce hyperkalemia and cardiac arrest. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of potassium citrate extended-release tablets in patients with chronic renal failure, or any other condition which impairs potassium excretion such as severe myocardial damage or heart failure, should be avoided. Closely monitor for signs of hyperkalemia with periodic blood tests and ECGs.
  )
  
• Gastrointestinal lesions: if there is severe vomiting, abdominal pain or gastrointestinal bleeding, potassium citrate extended-release tablets should be discontinued immediately and the possibility of bowel perforation or obstruction investigated (
  
  
  5.2 Gastrointestinal Lesions

  Because of reports of upper gastrointestinal mucosal lesions following administration of potassium chloride (wax-matrix), an endoscopic examination of the upper gastrointestinal mucosa was performed in 30 normal volunteers after they had taken glycopyrrolate 2 mg p.o. t.i.d., potassium citrate extended-release tablets 95 mEq/day, wax-matrix potassium chloride 96 mEq/day or wax-matrix placebo, in thrice daily schedule in the fasting state for one week. Potassium citrate extended-release tablets and the wax-matrix formulation of potassium chloride were indistinguishable but both were significantly more irritating than the wax-matrix placebo. In a subsequent, similar study, lesions were less severe when glycopyrrolate was omitted.

  Solid dosage forms of potassium chlorides have produced stenotic and/or ulcerative lesions of the small bowel and deaths. These lesions are caused by a high local concentration of potassium ions in the region of the dissolving tablets, which injured the bowel. In addition, perhaps because wax-matrix preparations are not enteric-coated and release some of their potassium content in the stomach, there have been reports of upper gastrointestinal bleeding associated with these products. The frequency of gastrointestinal lesions with wax-matrix potassium chloride products is estimated at one per 100,000 patient-years. Experience with potassium citrate extended-release tablets is limited, but a similar frequency of gastrointestinal lesions should be anticipated.

  If there is severe vomiting, abdominal pain or gastrointestinal bleeding, potassium citrate extended-release tablets should be discontinued immediately and the possibility of bowel perforation or obstruction investigated.
  )