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 Urocit-K is to provide Urocit-K 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.
In patients with severe hypocitraturia (urinary citrate
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 Urocit-K greater than 100 mEq/day have not been studied and should be avoided.
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., Urocit-K 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. Urocit-K 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 Urocit-K is limited, but a similar frequency of gastrointestinal lesions should be anticipated.
If there is severe vomiting, abdominal pain or gastrointestinal bleeding, Urocit-K should be discontinued immediately and the possibility of bowel perforation or obstruction investigated.
The pivotal Urocit-K trials were non-randomized and non-placebo controlled where dietary management may have changed coincidentally with pharmacological treatment. Therefore, the results as presented in the following sections may overstate the effectiveness of the product.
The effect of oral potassium citrate therapy in a non-randomized, non-placebo controlled clinical study of five men and four women with calcium oxalate/calcium phosphate nephrolithiasis and documented incomplete distal renal tubular acidosis was examined. The main inclusion criterion was a history of stone passage or surgical removal of stones during the 3 years prior to initiation of potassium citrate therapy. All patients began alkali treatment with 60-80 mEq potassium citrate daily in 3 or 4 divided doses. Throughout treatment, patients were instructed to stay on a sodium restricted diet (100 mEq/day) and to reduce oxalate intake (limited intake of nuts, dark roughage, chocolate and tea). A moderate calcium restriction (400-800 mg/day) was imposed on patients with hypercalciuria.
X-rays of the urinary tract, available in all patients, were reviewed to determine presence of pre-existing stones, appearance of new stones, or change in the number of stones.
Potassium citrate therapy was associated with inhibition of new stone formation in patients with distal tubular acidosis. Three of the nine patients continued to pass stones during the on-treatment phase. While it is likely that these patients passed pre-existing stones during therapy, the most conservative assumption is that the passed stones were newly formed. Using this assumption, the stone-passage remission rate was 67%. All patients had a reduced stone formation rate. Over the first 2 years of treatment, the on-treatment stone formation rate was reduced from 13±27 to 1±2 per year.
Eighty-nine patients with hypocitraturic calcium nephrolithiasis or uric acid lithiasis with or without calcium nephrolithiasis participated in this non-randomized, non-placebo controlled clinical study. Four groups of patients were treated with potassium citrate: Group 1 was comprised of 19 patients, 10 with renal tubular acidosis and 9 with chronic diarrheal syndrome, Group 2 was comprised of 37 patients, 5 with uric acid stones alone, 6 with uric acid lithiasis and calcium stones, 3 with type 1 absorptive hypercalciuria, 9 with type 2 absorptive hypercalciuria and 14 with hypocitraturia. Group 3 was comprised of 15 patients with history of relapse on other therapy and Group 4 was comprised of 18 patients, 9 with type 1 absorptive hypercalciuria and calcium stones, 1 with type 2 absorptive hypercalciuria and calcium stones, 2 with hyperuricosuric calcium oxalate nephrolithiasis, 4 with uric acid lithiasis accompanied by calcium stones and 2 with hypocitraturia and hyperuricemia accompanied by calcium stones. The dose of potassium citrate ranged from 30 to 100 mEq per day, and usually was 20 mEq administered orally 3 times daily. Patients were followed in an outpatient setting every 4 months during treatment and were studied over a period from 1 to 4.33 years. A three-year retrospective pre-study history for stone passage or removal was obtained and corroborated by medical records. Concomitant therapy (with thiazide or allopurinol) was allowed if patients had hypercalciuria, hyperuricosuria or hyperuricemia. Group 2 was treated with potassium citrate alone.
In all groups, treatment that included potassium citrate was associated with a sustained increase in urinary citrate excretion from subnormal values to normal values (400 to 700 mg/day), and a sustained increase in urinary pH from 5.6-6.0 to approximately 6.5. The stone formation rate was reduced in all groups as shown in.
A long-term non-randomized, non-placebo controlled clinical trial with eighteen adult patients with uric acid lithiasis participated in the study. Six patients formed only uric acid stones, and the remaining 12 patients formed mixed stones containing both uric acid and calcium salts or formed both uric acid stones (without calcium salts) and calcium stones (without uric acid) on separate occasions.
Eleven of the 18 patients received potassium citrate alone. Six of the 7 other patients also received allopurinol for hyperuricemia with gouty arthritis, symptomatic hyperuricemia, or hyperuricosuria. One patient also received hydrochlorothiazide because of unclassified hypercalciuria. The main inclusion criterion was a history of stone passage or surgical removal of stones during the 3 years prior to initiation of potassium citrate therapy. All patients received potassium citrate at a dosage of 30-80 mEq/day in three-to-four divided doses and were followed every four months for up to 5 years.
While on potassium citrate treatment, urinary pH rose significantly from a low value of 5.3 ± 0.3 to within normal limits (6.2 to 6.5). Urinary citrate which was low before treatment rose to the high normal range and only one stone was formed in the entire group of 18 patients.
NDC 0178-0600-01 Bottle of 100
Urocit-K 10 mEq tablets are uncoated, tan to yellowish in color, elliptical shaped, with MPC 610 debossed on one side and MISSION on the other, supplied in bottles as:
NDC 0178-0610-01 Bottle of 100
Urocit-K 15 mEq tablets are uncoated, tan to yellowish in color, modified rectangle shaped, with M15 debossed on one side and blank on the other, supplied in bottles as:
NDC 0178-0615-01 Bottle of 100
