stinal transit time: these agents (such as anticholinergics) can be expected to increase the gastrointestinal irritation produced by potassium salts. 7.3 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. 7.4 nonsteroidal anti-inflammatory drugs (nsaids) nsaids may produce potassium retention by reducing renal synthesis of prostaglandin e and impairing the renin-angiotensin system. closely monitor potassium in patients on concomitant nsaids.

dition 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. 5.2 gastrointestinal lesions 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 is limited, but a similar frequency of gastrointestinal lesions should be anticipated. if there is severe vomiting, abdominal pain or gastrointestinal bleeding, potassium citrate should be discontinued immediately and the possibility of bowel perforation or obstruction investigated.

atment with potassium citrate extended-release tablets is to provide potassium citrate extended-release tablets 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 hematocrit or hemoglobin. 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. 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 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. doses of potassium citrate extended-release tablets greater than 100 meq/day have not been studied and should be avoided.

stinal transit time: these agents (such as anticholinergics) can be expected to increase the gastrointestinal irritation produced by potassium salts. 7.3 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. 7.4 nonsteroidal anti-inflammatory drugs (nsaids) nsaids may produce potassium retention by reducing renal synthesis of prostaglandin e and impairing the renin-angiotensin system. closely monitor potassium in patients on concomitant nsaids.

human milk is about 13 meq/l. it is not known if potassium citrate has an effect on this content. potassium citrate should be given to a woman who is breastfeeding only if clearly needed. 8.4 pediatric use safety and effectiveness in children have not been established.

one-forming salts (calcium oxalate, calcium phosphate and uric acid). increased citrate in the urine, by complexing with calcium, decreases calcium ion activity and thus the saturation of calcium oxalate. citrate also inhibits the spontaneous nucleation of calcium oxalate and calcium phosphate (brushite). the increase in urinary ph also decreases calcium ion activity by increasing calcium complexation to dissociated anions. the rise in urinary ph also increases the ionization of uric acid to the more soluble urate ion. potassium citrate therapy does not alter the urinary saturation of calcium phosphate, since the effect of increased citrate complexation of calcium is opposed by the rise in ph-dependent dissociation of phosphate. calcium phosphate stones are more stable in alkaline urine. in the setting of normal renal function, the rise in urinary citrate following a single dose begins by the first hour and lasts for 12 hours. with multiple doses the rise in citrate excretion reaches its peak by the third day and averts the normally wide circadian fluctuation in urinary citrate, thus maintaining urinary citrate at a higher, more constant level throughout the day. when the treatment is withdrawn, urinary citrate begins to decline toward the pre?treatment level on the first day. the rise in citrate excretion is directly dependent on the potassium citrate dosage. following long-term treatment, potassium citrate at a dosage of 60 meq/day raises urinary citrate by approximately 400 mg/day and increases urinary ph by approximately 0.7 units. in patients with severe renal tubular acidosis or chronic diarrheal syndrome where urinary citrate may be very low (< 100 mg/day), potassium citrate may be relatively ineffective in raising urinary citrate. a higher dose of potassium citrate may therefore be required to produce a satisfactory citraturic response. in patients with renal tubular acidosis in whom urinary ph may be high, potassium citrate produces a relatively small rise in urinary ph.

(limited intake of nuts, dark roughage, chocolate and tea). a moderate calcium restriction (400 to 800 mg/day) was imposed on patients with hypercalciuria. x-rays of the urinary tract, available in all patients, were reviewed carefully 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. 14.2 hypocitraturic calcium oxalate nephrolithiasis of any etiology 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 to 6.0 to approximately 6.5. the stone formation rate was reduced in all groups as shown in table 1. table 1. effect of potassium citrate in patients with calcium oxalate nephrolithiasis. stones formed per year group baseline on treatment remission * any decrease i (n = 19) 12 ± 30 0.9 ± 1.3 58% 95% ii (n = 37) 1.2 ± 2 0.4 ± 1.5 89% 97% iii (n = 15) 4.2 ± 7 0.7 ± 2 67% 100% iv (n = 18) 3.4 ± 8 0.5 ± 2 94% 100% total (n = 89) 4.3 ±15 0.6 ± 2 80% 98% * remission defined as “the percentage of patients remaining free of newly formed stones during treatment”. 14.3 uric acid lithiasis with or without calcium stones 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 to 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.