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HIGHLIGHTS OF PRESCRIBING INFORMATION
4 CONTRAINDICATIONS
These highlights do not include al the information needed to use
FULL PRESCRIBING INFORMATION: CONTENTS*
Urocit®-K safely and effectively. See ful prescribing information
1 INDICATIONS AND USAGE
• In patients with hyperkalemia (or who have conditions pre-disposing them for Urocit®-K.
1.1 Renal tubular acidosis (RTA) with calcium stones to hyperkalemia), as a further rise in serum potassium concentration may 1.2 Hypocitraturic calcium oxalate nephrolithiasis of any etiology produce cardiac arrest. Such conditions include: chronic renal failure, Urocit®-K (Potassium Citrate) Extended-release tablets for oral use
1.3 Uric acid lithiasis with or without calcium stones uncontrol ed diabetes mel itus, acute dehydration, strenuous physical Initial U.S. Approval: 1985
2 DOSAGE AND ADMINISTRATION
exercise in unconditioned individuals, adrenal insufficiency, extensive tissue breakdown or the administration of a potassium-sparing agent ------------------------RECENT MAJOR CHANGES---------------------
(such as triamterene, spironolactone or amiloride). Dosage and Administration, Urocit®-K 15 mEq (2.2, 2.3) • In patients in whom there is cause for arrest or delay in tablet passage Dosage Forms and Strengths, Urocit®-K 15 mEq (3) 3 DOSAGE FORMS AND STRENGTHS
through the gastrointestinal tract, such as those suffering from delayed 4 CONTRAINDICATIONS
gastric emptying, esophageal compression, intestinal obstruction or 5 WARNINGS AND PRECAUTIONS
stricture, or those taking anticholin ergic medication. How Supplied/Storage and Handling, Urocit®-K 15 mEq (16) 12/2009 • In patients with peptic ulcer disease because of its ulcerogenic potential. ------------------------ INDICATIONS AND USAGE ---------------------
• In patients with active urinary tract infection (with either urea-splitting or Urocit®-K is a citrate salt of potassium indicated for the management of: 6 ADVERSE REACTIONS
other organisms, in association with either calcium or struvite stones). • Renal tubular acidosis (RTA) with calcium stones (1.1) The ability of Urocit®-K to increase urinary citrate may be attenuated by • Hypocitraturic calcium oxalate nephrolithiasis of any etiology (1.2) 7 DRUG INTERACTIONS
bacterial enzymatic degradation of citrate. Moreover, the rise in urinary • Uric acid lithiasis with or without calcium stones (1.3) 7.1 Potential Effects of Potassium citrate on Other Drugs pH resulting from Urocit®-K therapy might promote further bacterial ---------------------DOSAGE AND ADMINISTRATION ------------------
7.2 Potential Effects of Other Drugs on Potassium citrate Objective: To restore normal urinary citrate (greater than 320 mg/day and as 8 USE IN SPECIFIC POPULATIONS
• In patients with renal insufficiency (glomerular filtration rate of less close to the normal mean of 640 mg/day as possible), and to increase urinary than 0.7 ml/kg/min), because of the danger of soft tissue calcification and increased risk for the develop ment of hyperkalemia.
• 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 10 OVERDOSAGE
5 WARNINGS AND PRECAUTIONS
20 mEq three times per day with meals or within 30 minutes after meals 11 DESCRIPTION
5.1 Hyperkalemia
12 CLINICAL PHARMACOLOGY
In patients with impaired mechanisms for excreting potassium, Urocit®-K • Mild to moderate hypocitraturia (urinary citrate >150 mg/day): therapy administration can produce hyperkalemia and cardiac arrest. Potential y fatal should be initi ated at 30 mEq per day; a dose of 15 mEq two times per 14 CLINICAL STUDIES
hyperkalemia can develop rapidly and be asymptomatic. The use of Urocit®-K day or 10 mEq three times per day with meals or within 30 minutes 14.1 Renal tubular acidosis (RTA) with calcium stones in patients with chronic renal failure, or any other condition which impairs 14.2 Hypocitraturic calcium oxalate nephrolithiasis of any etiology potassium excretion such as severe myocardial damage or heart failure, 14.3 Uric acid lithiasis with or without calcium stones should be avoided. Closely monitor for signs of hyperkalemia with periodic --------------------DOSAGE FORMS AND STRENGTHS ----------------
15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
5.2 Gastrointestinal Lesions
-------------------------- CONTRAINDICATIONS -----------------------
17 PATIENT COUNSELING INFORMATION
Because of reports of upper gastrointestinal mucosal lesions fol owing • Patients with hyperkalemia (or who have conditions predisposing them administration of potassium chloride (wax-matrix), an endoscopic examination to hyperkalemia). Such condi tions include chronic renal failure, *Sections or subsections omitted from the ful prescribing information are of the upper gastrointestinal mucosa was performed in 30 normal volunteers uncontrol ed diabetes mel itus, acute dehydration, strenuous physical after they had taken glycopyrrolate 2 mg p.o. t.i.d., Urocit®-K 95 mEq/day, exercise in unconditioned individuals, adrenal insufficiency, extensive wax-matrix potassium chloride 96 mEq/day or wax-matrix placebo, in thrice FULL PRESCRIBING INFORMATION
daily schedule in the fasting state for one week. Urocit®-K and the wax-matrix • Patients for whom there is cause for arrest or delay in tablet passage 1 INDICATIONS AND USAGE
formulation of potassium chloride were indistinguishable but both were through the gastrointestinal tract such as those suffering from delayed 1.1 Renal tubular acidosis (RTA) with calcium stones
significantly more irritating than the wax-matrix placebo. In a subsequent, gastric emptying, esophageal compression, intestinal obstruction Potassium citrate is indicated for the management of renal similar study, lesions were less severe when glycopyrrolate was omitted.
tubular acidosis [see Clinical Studies (14.1)]. Solid dosage forms of potassium chlorides have produced stenotic and/ • Patients with peptic ulcer disease (4) 1.2 Hypocitraturic calcium oxalate nephrolithiasis of any etiology
or ulcerative lesions of the smal bowel and deaths. These lesions are caused • Patients with active urinary tract infection (4) Potassium citrate is indicated for the management of Hypocitraturic by a high local concentration of potassium ions in the region of the dissolving • Patients with renal insufficiency (glomerular filtration rate of less than calcium oxalate nephrolithiasis [see Clinical Studies (14.2)]. tablets, which injured the bowel. In addition, perhaps because wax-matrix 1.3 Uric acid lithiasis with or without calcium stones
preparations are not enteric-coated and release some of their potassium --------------------- WARNINGS AND PRECAUTIONS ------------------
Potassium citrate is indicated for the management of Uric acid lithiasis content in the stomach, there have been reports of upper gastrointestinal • Hyperkalemia: In patients with impaired mechanisms for excreting potas- with or without calcium stones [see Clinical Studies (14.3)]. bleeding associated with these products. The frequency of gastrointestinal sium, Urocit®-K administration can produce hyperkalemia and cardiac lesions with wax-matrix potassium chloride products is estimated at one per arrest. Potential y fatal hyperkalemia can develop rapidly and be 2 DOSAGE AND ADMINISTRATION
100,000 patient-years. Experience with Urocit®-K is limited, but a similar asymptomatic. The use of Urocit®-K in patients with chronic renal failure, 2.1 Dosing Instructions
frequency of gastrointestinal lesions should be anticipated.
or any other condition which impairs potassium excretion such as Treatment with extended release potassium citrate should be added to If there is severe vomiting, abdominal pain or gastrointestinal bleeding, severe myocardial damage or heart failure, should be avoided (5.1) a regimen that limits salt intake (avoidance of foods with high salt content Urocit®-K should be discontinued immediately and the possibility of bowel • Gastrointestinal lesions: if there is severe vomiting, abdominal pain or and of added salt at the table) and encourages high fluid intake (urine perforation or obstruction investigated. gastrointestinal bleeding, Urocit®-K should be discontinued immediately volume should be at least two liters per day). The objective of treatment with and the possibility of bowel perforation or obstruction investigated (5.2) Urocit®-K is to provide Urocit®-K in sufficient dosage to restore normal urinary 6 ADVERSE REACTIONS
citrate (greater than 320 mg/day and as close to the normal mean of 640 6.1 Postmarketing Experience
-------------------------- ADVERSE REACTIONS -----------------------
mg/day as possible), and to increase urinary pH to a level of 6.0 or 7.0. Some patients may develop minor gastrointestinal complaints during Some patients may develop minor gastrointestinal complaints such as Monitor serum electrolytes (sodium, potassium, chloride and carbon Urocit®-K therapy, such as abdominal discomfort, vomiting, diarrhea, loose abdominal discomfort, vomiting, diarrhea, loose bowel movements or nausea. dioxide), serum creatinine and complete blood counts every four months and bowel movements or nausea. These symptoms are due to the irritation of the These may be al eviated by taking the dose with meals or snacks or by more frequently in patients with cardiac disease, renal disease or acidosis. gastrointestinal tract, and may be al eviated by taking the dose with meals or Perform electrocardiograms periodical y. Treatment should be discontinued if snacks, or by reducing the dosage. Patients may find intact matrices in their there is hyperkalemia, a significant rise in serum creatinine or a significant fal To report SUSPECTED ADVERSE REACTIONS, contact Mission
Pharmacal Company at 1-800-298-1087 or FDA at 1-800-FDA-1088
2.2 Severe Hypocitraturia
7 DRUG INTERACTIONS
or www.fda.gov/medwatch
In patients with severe hypocitraturia (urinary citrate < 150 mg/day), 7.1 Potential Effects of Potassium citrate on Other Drugs
therapy should be initiated at a dosage of 60 mEq/day (30 mEq two times/ Potassium-sparing Diuretics: Concomitant administration of Urocit®-K -------------------------- DRUG INTERACTIONS -----------------------
day or 20 mEq three times/day with meals or within 30 minutes after meals and a potassium-sparing diuretic (such as triamterene, spironolactone or The fol owing drug interactions may occur with potassium citrate: or bedtime snack). Twenty-four hour urinary citrate and/or urinary pH mea- amiloride) should be avoided since the simultaneous administration of these • Potassium-sparing diuretics: concomitant administration should be surements should be used to determine the adequacy of the initial dosage agents can produce severe hyperkalemia.
avoided since the simultaneous administration of these agents can and to evaluate the effectiveness of any dosage change. In addition, urinary 7.2 Potential Effects of Other Drugs on Potassium citrate
citrate and/or pH should be measured every four months. Doses of Urocit®-K Drugs that slow gastrointestinal transit time: These agents (such as anti- • Drugs that slow gastrointestinal transit time: These agents (such as greater than 100 mEq/day have not been studied and should be avoided. cholinergics) can be expected to increase the gastrointestinal irritation produced anticholinergics) can be expected to increase the gastrointestinal irritation 2.3 Mild to Moderate Hypocitraturia
In patients with mild to moderate hypocitraturia (urinary citrate > 150 --------------------- USE IN SPECIFIC POPULATIONS ------------------
mg/day) therapy should be initiated at 30 mEq/day (15 mEq two times/day 8 USE IN SPECIFIC POPULATIONS
• Pregnant women: Pregnancy Category C; animal reproduction studies or 10 mEq three times/day within 30 minutes after meals or bedtime snack). 8.1 Pregnancy
have not been conducted. It is not known whether Urocit®-K can cause Twenty-four hour urinary citrate and/or urinary pH measurements should Pregnancy Category C
fetal harm when administered to a pregnant woman or can affect be used to determine the adequacy of the initial dosage and to evaluate the Animal reproduction studies have not been conducted. It is also not reproduction capacity. Urocit®-K should be given to a pregnant woman ef ectiveness of any dosage change. Doses of Urocit®-K greater than 100 mEq/ known whether Urocit®-K can cause fetal harm when administered to a day have not been studied and should be avoided. pregnant woman or can affect reproduction capacity. Urocit®-K should be • Nursing mothers: The normal potassium ion content of human milk is about 3 DOSAGE FORMS AND STRENGTHS
given to a pregnant woman only if clearly needed. 13 mEq/L. It is not known if Urocit®-K has an ef ect on this content. Urocit®-K • 5 mEq tablets are uncoated, tan to yel owish in color, modified bal 8.3 Nursing Mothers
should be given to a woman who is breast feeding only if clearly needed (8.3) shaped, with MPC 600 debossed on one side and blank on the other The normal potassium ion content of human milk is about 13 mEq/L. It is • Pediatric Use: Safety and effectiveness in children have not been • 10 mEq tablets are uncoated, tan to yel owish in color, el iptical shaped, not known if Urocit®-K has an effect on this content. Urocit®-K should be with 610 debossed on one side and MISSION on the other given to a woman who is breast feeding only if clearly needed. See 17 for PATIENT COUNSELING INFORMATION
• 15 mEq tablets are uncoated, tan to yel owish in color, modified rectangle 8.4 Pediatric Use
Revised: 12 /2009
shaped, with M15 debossed on one side and blank on the other Safety and effectiveness in children have not been established.
10 OVERDOSAGE
14.1 Renal tubular acidosis (RTA) with calcium stones
2. Pak, C. (1985). Long-Term Treatment of Calcium Nephrolithiasis with Treatment of Overdosage: The administration of potassium salts to The effect of oral potassium citrate therapy in a non-randomized, non- Potassium Citrate. The Journal of Urology 134, 11-19.
persons without predisposing conditions for hyperkalemia rarely causes placebo control ed clinical study of five men and four women with calcium 3. Preminger, G.M., K. Sakhaee, C. Skurla and C.Y.C. Pak. (1985). serious hyperkalemia at recommended dosages. It is important to recognize oxalate/calcium phosphate nephrolithiasis and documented incomplete distal Prevention of Recurrent Calcium Stone Formation with Potassium Citrate that hyperkalemia is usual y asymptomatic and may be manifested only by renal tubular acidosis was examined. The main inclusion criterion was a his- Therapy in Patients with Distal Renal Tubular Acidosis. The Journal of Urol- an increased serum potassium concentration and characteristic electrocar- tory of stone passage or surgical removal of stones during the 3 years prior diographic changes (peaking of T-wave, loss of P-wave, depression of S-T to initiation of potassium citrate therapy. Al patients began alkali treatment 4. Pak, C.Y.C., K. Sakhaee and C. Ful er. (1986). Successful Management segment and prolongation of the QT interval). Late manifestations include with 60-80 mEq potassium citrate daily in 3 or 4 divided doses. Throughout of Uric Acid Nephrolithiasis with Potassium Citrate. Kidney International 30, muscle paralysis and cardiovascular col apse from cardiac arrest.
treatment, patients were instructed to stay on a sodium restricted diet (100 Treatment measures for hyperkalemia include the fol owing: mEq/day) and to reduce oxalate intake (limited intake of nuts, dark roughage, 5. Hol ander-Rodriguez, J et al. (2006). Hyperkalemia, American Family 1. Patients should be closely monitored for arrhythmias and electrolyte chocolate and tea). A moderate calcium restriction (400-800 mg/day) was changes. 2. Elimination of medications containing potassium and of agents imposed on patients with hypercalciuria.
6. Greenberg, A et al. (1998). Hyperkalemia: treatment options. Semen with potassium-sparing properties such as potassium-sparing diuretics, X-rays of the urinary tract, available in al patients, were reviewed to ARBs, ACE inhibitors, NSAIDs, certain nutritional supplements and many determine presence of pre-existing stones, appearance of new stones, or others. 3. Elimination of foods containing high levels of potassium such as 16 HOW SUPPLIED/STORAGE AND HANDLING
almonds, apricots, bananas, beans (lima, pinto, white), cantaloupe, carrot Potassium citrate therapy was associated with inhibition of new stone Urocit®-K 5 mEq tablets are uncoated, tan to yel owish in color, modified juice (canned), figs, grapefruit juice, halibut, milk, oat bran, potato (with skin), formation in patients with distal tubular acidosis. Three of the nine patients bal shaped, with MPC 600 debossed on one side and blank on the other, salmon, spinach, tuna and many others. 4. Intravenous calcium gluconate if continued to pass stones during the on-treatment phase. While it is likely the patient is at no risk or low risk of developing digitalis toxicity. 5. Intrave- that these patients passed pre-existing stones during therapy, the most nous administration of 300-500 mL/hr of 10% dextrose solution containing conservative assumption is that the passed stones were newly formed. Using Urocit®-K 10 mEq tablets are uncoated, tan to yel owish in color, el iptical 10-20 units of crystal ine insulin per 1,000 mL. 6. Correction of acidosis, if this assumption, the stone-passage remission rate was 67%. Al patients shaped, with MPC 610 debossed on one side and MISSION on the other, present, with intravenous sodium bicarbonate. 7. Hemodialysis or peritoneal had a reduced stone formation rate. Over the first 2 years of treatment, the dialysis. 8. Exchange resins may be used. However, this measure alone is not on-treatment stone formation rate was reduced from 13±27 to 1±2 per sufficient for the acute treatment of hyperkalemia. Urocit®-K 15 mEq tablets are uncoated, tan to yel owish in color, modified Lowering potassium levels too rapidly in patients taking digitalis can 14.2 Hypocitraturic calcium oxalate nephrolithiasis of
rectangle shaped, with M15 debossed on one side and blank on the other, any etiology
Eighty-nine patients with hypocitraturic calcium nephrolithiasis or uric 11 DESCRIPTION
acid lithiasis with or without calcium nephrolithiasis participated in this non- Urocit®-K is a citrate salt of potassium. Its empirical formula is randomized, non-placebo control ed clinical study. Four groups of patients Storage: Store in a tight container.
0, and it has the fol owing chemical structure: were treated with potassium citrate: Group 1 was comprised of 19 patients, 10 with renal tubular acidosis and 9 with chronic diarrheal syndrome, Group 17 PATIENT COUNSELING INFORMATION
2 was comprised of 37 patients, 5 with uric acid stones alone, 6 with uric 17.1 Administration of Drug
acid lithiasis and calcium stones, 3 with type 1 absorptive hypercalciuria, 9 Tel patients to take each dose without crushing, chewing or sucking with type 2 absorptive hypercalciuria and 14 with hypocitraturia. Group 3 was comprised of 15 patients with history of relapse on other therapy and Tel patients to take this medicine only as directed. This is especial y Urocit®-K yel owish to tan, oral wax-matrix tablets, contain 5 mEq Group 4 was comprised of 18 patients, 9 with type 1 absorptive hypercalciu- important if the patient is also taking both diuretics and digitalis preparations.
(540 mg) potassium citrate, 10 mEq (1080 mg) potassium citrate and ria and calcium stones, 1 with type 2 absorptive hypercalciuria and calcium Tel patients to check with the doctor if there is trouble swal owing 15 mEq (1620 mg) potassium citrate each. Inactive ingredients include stones, 2 with hyperuricosuric calcium oxalate nephrolithiasis, 4 with uric tablets or if the tablet seems to stick in the throat.
acid lithiasis accompanied by calcium stones and 2 with hypocitraturia and Tel patients to check with the doctor at once if tarry stools or other hyperuricemia accompanied by calcium stones. The dose of potassium evidence of gastrointestinal bleeding is noticed.
12 CLINICAL PHARMACOLOGY
citrate ranged from 30 to 100 mEq per day, and usual y was 20 mEq Tel patients that their doctor wil perform regular blood tests and electro- 12.1 Mechanism of Action
administered oral y 3 times daily. Patients were fol owed in an outpatient When Urocit®-K is given oral y, the metabolism of absorbed citrate setting every 4 months during treatment and were studied over a period produces an alkaline load. The induced alkaline load in turn increases from 1 to 4.33 years. A three-year retrospective pre-study history for stone urinary pH and raises urinary citrate by augmenting citrate clearance without passage or removal was obtained and corroborated by medical records. measurably altering ultrafilterable serum citrate. Thus, Urocit®-K therapy Concomitant therapy (with thiazide or al opurinol) was al owed if patients had appears to increase urinary citrate principal y by modifying the renal handling hypercalciuria, hyperuricosuria or hyperuricemia. Group 2 was treated with of citrate, rather than by increasing the filtered load of citrate. The increased filtered load of citrate may play some role, however, as in smal comparisons In al groups, treatment that included potassium citrate was associated of oral citrate and oral bicarbonate, citrate had a greater effect on urinary 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 In addition to raising urinary pH and citrate, Urocit®-K increases urinary pH from 5.6-6.0 to approximately 6.5. The stone formation rate was reduced potassium by approximately the amount contained in the medication. In in al groups as shown in Table 1.
some patients, Urocit®-K causes a transient reduction in urinary calcium.
The changes induced by Urocit®-K produce urine that is less conducive Table 1. Effect of Urocit®-K In Patients With Calcium Oxalate
to the crystal ization of stone-forming salts (calcium oxalate, calcium Nephrolithiasis.
phosphate and uric acid). Increased citrate in the urine, by complexing with Stones Formed Per Year
MISSION PHARMACAL COMPANY, SAN ANTONIO, TX USA 78230 1355 calcium, decreases calcium ion activity and thus the saturation of calcium Baseline On Treatment Remission* Any Decrease
oxalate. Citrate also inhibits the spontaneous nucleation of calcium oxalate 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.
Urocit®-K therapy does not alter the urinary saturation of calcium * Remission defined as “the percentage of patients remaining free of newly 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. 14.3 Uric acid lithiasis with or without calcium stones
In the setting of normal renal function, the rise in urinary citrate fol- A long-term non-randomized, non-placebo control ed clinical trial with lowing a single dose begins by the first hour and lasts for 12 hours. With eighteen adult patients with uric acid lithiasis participated in the study. Six multiple doses the rise in citrate excretion reaches its peak by the third day patients formed only uric acid stones, and the remaining 12 patients formed and averts the normal y wide circadian fluctuation in urinary citrate, thus mixed stones containing both uric acid and calcium salts or formed both uric maintaining urinary citrate at a higher, more constant level throughout the acid stones (without calcium salts) and calcium stones (without uric acid) on day. When the treatment is withdrawn, urinary citrate begins to decline toward the pre-treatment level on the first day.
Eleven of the 18 patients received potassium citrate alone. Six of the 7 The rise in citrate excretion is directly dependent on the Urocit®-K dos- other patients also received al opurinol for hyperuricemia with gouty arthritis, age. Fol owing long-term treatment, Urocit®-K at a dosage of 60 mEq/day symptomatic hyperuricemia, or hyperuricosuria. One patient also received raises urinary citrate by approximately 400 mg/day and increases urinary pH hydrochlorothiazide because of unclassified hypercalciuria. The main inclu- sion criterion was a history of stone passage or surgical removal of stones In patients with severe renal tubular acidosis or chronic diarrheal syn- during the 3 years prior to initiation of potassium citrate therapy. Al patients drome where urinary citrate may be very low (<100 mg/day), Urocit®-K may received potassium citrate at a dosage of 30-80 mEq/day in three-to-four be relatively ineffective in raising urinary citrate. A higher dose of Urocit®-K divided doses and were fol owed every four months for up to 5 years.
may therefore be required to produce a satisfactory citraturic response. While on potassium citrate treatment, urinary pH rose significantly from In patients with renal tubular acidosis in whom urinary pH may be high, a low value of 5.3 ± 0.3 to within normal limits (6.2 to 6.5). Urinary citrate Urocit®-K produces a relatively smal rise in urinary pH.
which was low before treatment rose to the high normal range and only one stone was formed in the entire group of 18 patients.
14 CLINICAL STUDIES
The pivotal Urocit®-K trials were non-randomized and non-placebo
15 REFERENCES
control ed where dietary management may have changed coincidental y 1. Pak, C. (1987). Citrate and Renal Calculi. Mineral and Electrolyte with pharmacological treatment. Therefore, the results as presented in the fol owing sections may overstate the effectiveness of the product.

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