PRINCIPAL DISPLAY PANEL - 15 mEq Bottle Label

NDC0178-0615-01

UROCIT**®-K15 mEq****(Potassium Citrate)**Extended-release tablet

15 mEq (1620 mg) per tablet

Rx only

100 Tablets

Mission Pharmacal Company

7 DRUG INTERACTIONS

7.1 Potential Effects of Potassium Citrate on Other Drugs

Potassium-sparing Diuretics:Concomitant administration of Urocit-K and a potassium-sparing diuretic (such as triamterene, spironolactone or amiloride) should be avoided since the simultaneous administration of these agents can produce severe hyperkalemia.

7.2 Potential Effects of Other Drugs on Potassium Citrate

Drugs that slow gastrointestinal 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 prostagladin E and impairing the renin-angiotensin system. Closely monitor potassium in patients on concomitant NSAIDs.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Animal reproduction studies have not been conducted. It is also not known whether Urocit-K can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Urocit-K should be given to a pregnant woman 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 Urocit-K has an effect on this content. Urocit-K 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.

11 DESCRIPTION

Urocit-K is a citrate salt of potassium. Its empirical formula is K3C6H507 • H20, and it has the following chemical structure:

Urocit-K yellowish to tan, oral wax-matrix tablets, contain 5 mEq (540 mg) potassium citrate, 10 mEq (1080 mg) potassium citrate and 15 mEq (1620 mg) potassium citrate each. Inactive ingredients include carnauba wax and magnesium stearate.

17 PATIENT COUNSELING INFORMATION

Tell patients to take each dose without crushing, chewing or sucking the tablet.

Tell patients to take this medicine only as directed. This is especially important if the patient is also taking both diuretics and digitalis preparations.

Tell patients to check with the doctor if there is trouble swallowing tablets or if the tablet seems to stick in the throat.

Tell patients to check with the doctor at once if tarry stools or other evidence of gastrointestinal bleeding is noticed. Tell patients that their doctor will perform regular blood tests and electrocardiograms to ensure safety.

L061001R0521

14 CLINICAL STUDIES

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.

14.1 Renal Tubular Acidosis (RTA) with Calcium Stones

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 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 5.6-6.0 to approximately 6.5. The stone formation rate was reduced in all groups as shown inTable 1.

Table 1. Effect of Urocit-K In Patients With Calcium Oxalate Nephrolithiasis.

*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 30-80 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.