Potassium Citrate

Potassium Citrate is available in the following forms:

• Extended Release Tablet
• Oral Solution
• Oral Tablet

You should not use this medication if you have kidney failure, a urinary tract infection, uncontrolled diabetes, a peptic ulcer in your stomach, Addison's disease, severe burns or other tissue injury, if you are dehydrated, if you take certain diuretics (water pills), or if you have high levels of potassium in your blood (hyperkalemia).

You should not take potassium citrate tablets if you have problems with your esophagus, stomach, or intestines that make it difficult for you to swallow or digest pills.

Do not crush, chew, break, or suck on an extended-release tablet. Swallow the pill whole. Breaking or crushing the pill may cause too much of the drug to be released at one time. Sucking on a potassium tablet can irritate your mouth or throat.

Avoid lying down for at least 30 minutes after you take this medication.

Take this medication with a meal or bedtime snack, or within 30 minutes after a meal.

To be sure this medication is helping your condition, your blood may need to be tested often. Your heart rate may also be checked using an electrocardiograph or ECG (sometimes called an EKG) to measure electrical activity of the heart. This test will help your doctor determine how long to treat you with potassium. Do not miss any scheduled appointments.

Serious side effects of potassium citrate include uneven heartbeat, muscle weakness or limp feeling, severe stomach pain, and numbness or tingling in your hands, feet, or mouth.

Do not stop taking this medication without first talking to your doctor. If you stop taking potassium suddenly, your condition may become worse.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Belly pain.
• You may see the tablet shell in your stool. This is normal and not a cause for concern.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Postmarketing Experience

Some patients may develop minor gastrointestinal complaints during Potassium Citrate therapy, such as abdominal discomfort, vomiting, diarrhea, loose bowel movements or nausea. These symptoms are due to the irritation of the gastrointestinal tract, and may be alleviated by taking the dose with meals or snacks, or by reducing the dosage. Patients may find intact matrices in their feces.

Mechanism of Action

When Potassium Citrate is given orally, the metabolism of absorbed citrate produces an alkaline load. The induced alkaline load in turn increases urinary pH and raises urinary citrate by augmenting citrate clearance without measurably altering ultrafilterable serum citrate. Thus, Potassium Citrate therapy appears to increase urinary citrate principally by modifying the renal handling of citrate, rather than by increasing the filtered load of citrate. The increased filtered load of citrate may play some role, however, as in small comparisons of oral citrate and oral bicarbonate, citrate had a greater effect on urinary citrate.
In addition to raising urinary pH and citrate, Potassium Citrate increases urinary potassium by approximately the amount contained in the medication. In some patients, Potassium Citrate causes a transient reduction in urinary calcium. 
The changes induced by Potassium Citrate produce urine that is less conducive to the crystallization of stone-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 pretreatment 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.

The pivotal Potassium Citrate 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 to 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 to 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 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.

*Remission defined as “the percentage of patients remaining free of newly formed stones during treatment”.

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.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release, Oral:

Urocit-K 5: 5 mEq (540 mg)

Urocit-K 10: 10 mEq (1080 mg)

Urocit-K 15: 15 mEq (1620 mg)

Generic: 5 mEq (540 mg), 10 mEq (1080 mg), 15 mEq (1620 mg)

Kidney stones: For the management of renal tubular acidosis with calcium stones, hypocitraturic calcium oxalate nephrolithiasis of any etiology, and uric acid lithiasis with or without calcium stones.

ACE Inhibitors: Potassium Salts may enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy

Aliskiren: Potassium Salts may enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Aluminum Hydroxide: Citric Acid Derivatives may increase the absorption of Aluminum Hydroxide. Monitor therapy

Angiotensin II Receptor Blockers: Potassium Salts may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Anticholinergic Agents: May enhance the ulcerogenic effect of Potassium Citrate. Avoid combination

Eplerenone: May enhance the hyperkalemic effect of Potassium Salts. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Consider therapy modification

Heparin: May enhance the hyperkalemic effect of Potassium Salts. Monitor therapy

Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of Potassium Salts. Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Potassium Salts. Monitor therapy

Potassium-Sparing Diuretics: Potassium Salts may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Consider therapy modification

Avoid taking potassium supplements or using other products that contain potassium without first asking your doctor. Salt substitutes or low-salt dietary products often contain potassium. If you take certain products together you may accidentally get too much potassium. Read the label of any other medicine you are using to see if it contains potassium.

While taking this medication, avoid strenuous exercise if you are not in proper condition for it.

• confusion, anxiety, feeling like you might pass out;

• uneven heartbeat;

• extreme thirst, increased urination;

• leg discomfort;

• muscle weakness or limp feeling;

• numbness or tingly feeling in your hands or feet, or around your mouth;

• severe stomach pain, ongoing diarrhea or vomiting;

• black, bloody, or tarry stools; or

• coughing up blood or vomit that looks like coffee grounds.

Less serious side effects may include:

• mild nausea or upset stomach;

• mild or occasional diarrhea; or

• appearance of a potassium citrate tablet in your stool.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Data not available

Potassium citrate is a naturally-occurring molecule. If K+ products are necessary in a pregnant patient, close attention to the maternal serum K+ concentrations is recommended due to the risk of maternal and fetal cardiac arrhythmias associated with abnormal serum K+ concentrations. Data from the Michigan Medicaid Birth Defects Study, in which 104,339 deliveries between 1980 to 1983 and 229,101 deliveries between 1985 to 1992 were retrospectively studied, reveal conflicting data (written communication, Frank Rosa, MD, Food and Drug Administration, 1994). In these two studies, 116 and 166 women, respectively, were exposed to a related molecule, potassium chloride (KCl), during gestation. Of the 116 women from the 1980 to 1983 period, 14 defects were observed (7 were expected), of which 4 were cardiovascular abnormalities (1 was expected). These data are consistent with an association between KCl and birth defects. Of the 166 women from the 1985 to 1992 period, 8 defects were observed (7 were expected). There were no cases of cardiovascular abnormalities. There were no cases of cleft palate from either period studied. These data do not provide evidence of an association between KCl and birth defects.

Potassium citrate has been assigned to pregnancy category C by the FDA. Animal studies have failed to reveal evidence of teratogenicity. There are no controlled data in human pregnancy. Some experts consider potassium replacement to be indicated and relatively safe for pregnant women. Potassium citrate is only recommended for use during pregnancy when benefit outweighs risk.