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.
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 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 preexisting 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.
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 in Table 1.
| 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". |
Table 1 | |||
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.
Urocit®-K is a prescription form of potassium citrate. It helps restore the chemicals in urine that stop crystals from forming, and reduces the formation of the two most common types of kidney stones: calcium oxalate and uric acid stones.
Important Safety Information
Urocit®-K is not for everyone. It has not been tested on children, pregnant women, or women who are breastfeeding, and it is unknown whether Urocit®-K can affect reproductive capacity, unborn children, or breast milk content. You should not take Urocit®-K if you are pregnant, may become pregnant, or are currently breastfeeding, unless your doctor has discussed the risks with you and determined that it is necessary.
Certain drugs can interact with Urocit®-K and lead to increased gastrointestinal (GI) irritation. Drug interactions can also lead to hyperkalemia, an excess of potassium in your blood that could lead to cardiac arrest or death. These serious and possibly fatal conditions can develop rapidly with no noticeable symptoms. Always talk to your doctor about any medications you are taking before starting a prescription of Urocit®-K.
If you have hyperkalemia, or any condition that puts you at risk for the condition or prevents your body from processing potassium normally, do not take Urocit®-K because it could lead to cardiac arrest. Conditions that may put you at risk include kidney failure, uncontrolled diabetes, severe dehydration, strenuous physical exercise if you're unconditioned, extensive tissue breakdown, or adrenal insufficiency (when your adrenal glands do not produce the correct amount of chemicals needed to regulate the function of your organs).
Do not take Urocit®-K if you have an active urinary tract infection, peptic ulcer disease, or conditions that slow or prevent the tablet from passing through your GI tract, such as compression of the esophagus, delayed gastric emptying, or narrowing or blockage of your intestines.
Take Urocit®-K only as directed. Do not crush, chew, or suck on the tablets, and check with your doctor if you experience any trouble swallowing tablets or if they seem to get stuck in your throat.
To ensure your safety during your prescription, your doctor may perform regular blood tests and EKGs (which analyze the electrical activity in your heart).
Some patients taking Urocit®-K may develop minor GI side effects such as abdominal discomfort, vomiting, diarrhea, loose bowel movements or nausea. To reduce these effects, take each dose of Urocit®-K with meals or snacks, or talk to your doctor about reducing the amount of your dosage.
If you experience severe vomiting, abdominal pain, tarry stools, or other signs of intestinal bleeding, stop taking Urocit®-K and see your doctor right away. These could be signs of a serious condition such as a perforated or blocked bowel.
To report negative side effects, contact Mission Pharmacal Company at 1-800-298-1087 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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