CLASSES

Alkalinizing Agents
Potassium Supplements

DEA CLASS

Rx

DESCRIPTION

Potassium-containing alkalinizing agent used primarily to treat some nephrolithiasis conditions by raising urinary pH and citrate concentrations; provides a source of potassium supplementation.

COMMON BRAND NAMES

Urocit-K

HOW SUPPLIED

Potassium Citrate/Urocit-K Oral Tab ER: 5mEq, 10mEq, 15mEq

DOSAGE & INDICATIONS

†Indicates off-label use

MAXIMUM DOSAGE

100 mEq/day PO.

100 mEq/day PO.

100 mEq/day PO.

2 mEq/kg/day PO.

DOSING CONSIDERATIONS

No specific dosage guidelines are available; however, caution is advised for patients with severe hepatic impairment. Conversion of citrate salts to bicarbonate may be impaired in patients with hepatic failure. Dosage should be modified depending on clinical response. Monitor serum potassium levels.

CrCl >= 50 ml/min: Dosage should be modified depending on clinical response and degree of renal impairment, but no quantitative recommendations are available. Monitor serum potassium levels and renal function carefully to avoid development of hyperkalemia.
CrCl < 50 ml/min: Use is contraindicated according to the manufacturer for potassium citrate extended-release tablets (Urocit-K).
 
Intermittent hemodialysis
Use is contraindicated for patients with CrCl < 50 ml/min.

ADMINISTRATION

In general, do not administer with tomato juice due to the very high sodium content, which may be counterproductive to the patient's medication regimen and/or health condition.

STORAGE

Urocit-K:
- Store at controlled room temperature (between 68 and 77 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

Patients with hyperkalemic familial periodic paralysis should not receive potassium citrate because this form of the disease seems to be exacerbated by the exogenous administration of potassium.

Potassium citrate is generally contraindicated for patients with renal failure or severe renal impairment. The manufacturer for potassium citrate extended-release tablets (Urocit-K) provides a specific contraindication for patients with renal insufficiency (glomerular filtration rate of < 0.7 ml/kg/min, which corresponds to an estimated creatinine clearance (CrCl) < 50 ml/min in a 70 kg patient) due to the risk of soft tissue calcification and increased risk of hyperkalemia. As with other alkalinizing agents, use potassium citrate with caution in patients which lack normal renal mechanisms to avoid the development of metabolic alkalosis, especially in the presence of hypocalcemia. Potassium supplements are contraindicated in patients with hyperkalemia since a further increase in serum potassium concentration in such patients can produce cardiac arrest. Due to the risk of developing hyperkalemia, potassium supplementation is contraindicated &nbsp;in patients with adrenal insufficiency (untreated Addison's disease); acute dehydration; uncontrolled diabetes mellitus; strenuous physical exercise (especially unconditioned persons); in patients receiving salt substitutes, potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene), ACE inhibitors, or angiotensin II antagonists; or in patients with renal disease, renal failure, or renal impairment. Potassium supplements should also be used cautiously in patients with severe burns because these patients are prone to hyperkalemia secondary to extensive tissue breakdown and renal insufficiency. Potassium citrate should be used cautiously in patients with diarrhea. Because geriatric patients are more likely to have decreased renal function, potassium salts should be dosed cautiously based on an assessment of renal function and therapeutic goals. Serum potassium concentrations, serum electrolytes (sodium, potassium, chloride and carbon dioxide), and serum creatinine should be monitored every four months during therapy with potassium citrate extended-release tablets (Urocit-K). Treatment should be discontinued if there is hyperkalemia or a significant rise in serum creatinine.

Potassium supplements, such as potassium citrate, should be monitored closely in patients with cardiac arrhythmias (e.g., atrial fibrillation, atrial flutter, digitalis toxicity (except due to documented hypokalemia), and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia), including patients receiving digoxin or other antiarrhythmic therapy. Based on a multidisciplinary review of literature and clinical practice trends, the National Council on Potassium in Clinical Practice recommends that serum potassium concentrations >= 4 mEq/L be achieved and maintained in patients with hypertension, heart failure, and cardiac arrhythmias to minimize complications of potassium depletion. In addition, the Council recommends potassium supplementation for patients at risk for developing hypokalemia and associated complications. Potassium supplementation is specifically recommended for patients with potential for diuretic-induced potassium loss (e.g., receiving thiazide or loop diuretics), patients with high sodium intake (unwilling to reduce salt intake), and patients with reduced GI intake (e.g., GI disturbances, laxative abuse).

Potassium citrate extended-release tablets (Urocit-K) are contraindicated in patients in whom there is a risk of delayed passage through the GI tract. Patients with gastroparesis, peptic ulcer disease, or GI obstruction, esophageal stricture, or ileus should not receive oral solid dosage forms of potassium supplements such as Urocit-K due to the potential for gastrointestinal irritation. Esophageal obstruction or compression associated with enlarged left atrium is also a contraindication for potassium citrate extended-release tablets due to potential for delayed tablet passage, causing esophageal stricture and ulceration. In addition, drugs that decrease GI motility may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts (see Drug Interactions). To monitor the potential for GI bleeding, the manufacturer advises monitoring of complete blood count every four months during Urocit-K therapy. Treatment should be discontinued if there is a significant fall in blood hematocrit or hemoglobin.

Potassium citrate extended-release tablets (Urocit-K) are contraindicated for use in patients with active urinary tract infection (UTI) (either caused by urea-splitting organisms or other organisms) in association with either struvite or calcium renal stones. The ability of potassium citrate to increase urinary citrate may be attenuated by bacterial enzymatic degradation of citrate. Moreover, the rise in urinary pH resulting from potassium citrate therapy might promote further bacterial growth.

Potassium supplements, such as potassium citrate, should be used cautiously in patients with heat cramps (myalgia thermica) or muscle cramps until the cause can be determined. In some cases, heat cramps can be a result of high potassium.

Conversion of citrate salts (e.g., potassium citrate) to bicarbonate may be impaired in patients with severe hepatic disease or hepatic failure.

Serious metabolic alkalosis rarely occurs during treatment with potassium citrate. Metabolic alkalosis is more likely to occur in patients receiving excessive doses or in patients with impaired renal function. If untreated, metabolic alkalosis could result in compensatory hypoventilation, which can aggravate hypoxemia in patients with chronic obstructive pulmonary disease (COPD).

Use potassium citrate during pregnancy only if clearly needed. It is unknown whether potassium citrate can cause fetal harm when administered to a pregnant person or can affect reproduction capacity. Animal reproduction studies have not been conducted.

Use potassium citrate during breast-feeding only if clearly needed. The normal potassium content in breast milk is about 13 mEq/L; it is unknown if potassium citrate has an effect on this content.

ADVERSE REACTIONS

AV block / Early / Incidence not known
hyperkalemia / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
esophageal stricture / Delayed / Incidence not known
odynophagia / Delayed / Incidence not known
GI perforation / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
esophageal ulceration / Delayed / Incidence not known
GI obstruction / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known

confusion / Early / Incidence not known
hypotension / Rapid / Incidence not known
dysphagia / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
metabolic alkalosis / Delayed / Incidence not known

weakness / Early / Incidence not known
paresthesias / Delayed / Incidence not known
nausea / Early / Incidence not known
abdominal pain / Early / Incidence not known
diarrhea / Early / Incidence not known
vomiting / Early / Incidence not known

DRUG INTERACTIONS

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Acetaminophen; Aspirin: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acetaminophen; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Acrivastine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Aliskiren: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and aliskiren are used together. Concomitant use may increase the risk of hyperkalemia.
Aliskiren; Amlodipine: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and aliskiren are used together. Concomitant use may increase the risk of hyperkalemia.
Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and aliskiren are used together. Concomitant use may increase the risk of hyperkalemia.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and aliskiren are used together. Concomitant use may increase the risk of hyperkalemia.
Aliskiren; Valsartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and aliskiren are used together. Concomitant use may increase the risk of hyperkalemia. (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Aluminum Hydroxide: (Contraindicated) Avoid coadministration of antacids with citrate salts since increased absorption of aluminum can occur. In addition, some antacids like calcium carbonate, share the potential with the citrate salts for development of metabolic alkalosis, when given in higher dosage. (Major) Avoid coadministration of aluminum hydroxide with citrate salts due to the potential for increased absorption of aluminum. Patients at increased risk of aluminum accumulation include patients with renal impairment or renal failure.
Aluminum Hydroxide; Magnesium Carbonate: (Contraindicated) Avoid coadministration of antacids with citrate salts since increased absorption of aluminum can occur. In addition, some antacids like calcium carbonate, share the potential with the citrate salts for development of metabolic alkalosis, when given in higher dosage. (Major) Avoid coadministration of aluminum hydroxide with citrate salts due to the potential for increased absorption of aluminum. Patients at increased risk of aluminum accumulation include patients with renal impairment or renal failure.
Aluminum Hydroxide; Magnesium Hydroxide: (Contraindicated) Avoid coadministration of antacids with citrate salts since increased absorption of aluminum can occur. In addition, some antacids like calcium carbonate, share the potential with the citrate salts for development of metabolic alkalosis, when given in higher dosage. (Major) Avoid coadministration of aluminum hydroxide with citrate salts due to the potential for increased absorption of aluminum. Patients at increased risk of aluminum accumulation include patients with renal impairment or renal failure.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Contraindicated) Avoid coadministration of antacids with citrate salts since increased absorption of aluminum can occur. In addition, some antacids like calcium carbonate, share the potential with the citrate salts for development of metabolic alkalosis, when given in higher dosage. (Major) Avoid coadministration of aluminum hydroxide with citrate salts due to the potential for increased absorption of aluminum. Patients at increased risk of aluminum accumulation include patients with renal impairment or renal failure.
Aluminum Hydroxide; Magnesium Trisilicate: (Contraindicated) Avoid coadministration of antacids with citrate salts since increased absorption of aluminum can occur. In addition, some antacids like calcium carbonate, share the potential with the citrate salts for development of metabolic alkalosis, when given in higher dosage. (Major) Avoid coadministration of aluminum hydroxide with citrate salts due to the potential for increased absorption of aluminum. Patients at increased risk of aluminum accumulation include patients with renal impairment or renal failure.
Amiloride: (Major) The use of potassium supplements in patients treated with amiloride is generally contraindicated. Concomitant use may increase the risk of hyperkalemia. If potassium supplementation is used, monitor serum potassium concentrations closely.
Amiloride; Hydrochlorothiazide, HCTZ: (Major) The use of potassium supplements in patients treated with amiloride is generally contraindicated. Concomitant use may increase the risk of hyperkalemia. If potassium supplementation is used, monitor serum potassium concentrations closely.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Amlodipine; Benazepril: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Amlodipine; Celecoxib: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Amlodipine; Olmesartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Amlodipine; Valsartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Ammonium Chloride: (Major) It would be illogical to administer potassium salts, a systemic alkalinizer, concurrently with ammonium chloride, an acidifying agent.
Amphetamines: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Angiotensin II receptor antagonists: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Angiotensin-converting enzyme inhibitors: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Antacids: (Contraindicated) Avoid coadministration of antacids with citrate salts since increased absorption of aluminum can occur. In addition, some antacids like calcium carbonate, share the potential with the citrate salts for development of metabolic alkalosis, when given in higher dosage.
Aspirin, ASA: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Caffeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Carisoprodol: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Dipyridamole: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Omeprazole: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Oxycodone: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Pravastatin: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form. (Major) The therapeutic action of methenamine requires an acidic urine. Alkalinizing agents, such as citrate salts, can alkalinize the urine, thereby decreasing the effectiveness of methenamine by increasing the amount of non-ionized drug available for renal tubular reabsorption. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Atropine; Difenoxin: (Moderate) Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
Azilsartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Azilsartan; Chlorthalidone: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Benazepril: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form. (Major) The therapeutic action of methenamine requires an acidic urine. Alkalinizing agents, such as citrate salts, can alkalinize the urine, thereby decreasing the effectiveness of methenamine by increasing the amount of non-ionized drug available for renal tubular reabsorption. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Benzphetamine: (Major) Urinary alkalinizers, such as potassium citrate diminish the urinary excretion of benzphetamine. These medications increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of benzphetamine will be prolonged in the presence of potassium citrate. This combination should be avoided.
Bismuth Subsalicylate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Brompheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Bupivacaine; Meloxicam: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Candesartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Captopril: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Carbetapentane; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Carbinoxamine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Celecoxib: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Celecoxib; Tramadol: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Cetirizine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlorpheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Chlorpropamide: (Moderate) Urinary alkalinizing agents may increase the excretion of chlorpropamide by increasing renal clearance. Monitor for decreased efficacy of chlorpropamide (i.e., increased blood glucose) during coadministration. (Moderate) Urinary alkalinizing agents, like potassium citrate, may increase the excretion of chlorpropamide by increasing renal clearance. Monitor for decreased efficacy of chlorpropamide (i.e., increased blood glucose) during coadministration.
Choline Salicylate; Magnesium Salicylate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Codeine; Guaifenesin; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Colchicine: (Moderate) Colchicine is an alkaloid and its action is potentiated by alkalinizing agents like potassium citrate. The colchicine dose may need adjustment. (Moderate) The action of colchicine is potentiated by alkalinizing agents. The colchicine dose may need adjustment.
Cyclosporine: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and cyclosporine are used together. Concomitant use may increase the risk of hyperkalemia.
Desloratadine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dexbrompheniramine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Dextromethorphan; Quinidine: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible. (Major) Urinary alkalinization increases the renal tubular reabsorption of quinidine, resulting in higher quinidine serum concentrations which may lead to toxicity. Avoid citric acid; potassium citrate; sodium citrate administration to any patient receiving treatment with quinidine.
Diclofenac: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Diclofenac; Misoprostol: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Diflunisal: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Digoxin: (Minor) Potassium levels should be monitored closely in patients receiving digoxin and potassium supplementation. Both hypokalemia and hyperkalemia increase the risk of digoxin toxicity. Some patients at increased risk are patients with renal impairment, patients on diuretics, and patients who are on potassium-sparing medications concurrently. Monitor renal function, potassium concentrations, and digoxin concentrations and clinical response during concurrent treatment.
Diphenhydramine; Ibuprofen: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Diphenhydramine; Naproxen: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Diphenoxylate; Atropine: (Moderate) Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
Donepezil; Memantine: (Moderate) Increases in urinary pH may decrease elimination of memantine, resulting in drug accumulation and potential toxicity. (Moderate) Urinary alkalinizing agents may decrease the elimination of memantine, resulting in drug accumulation and potential toxicity. The clearance of memantine is reduced by about 80% under alkaline urine conditions at pH 8. Memantine should be used with caution with drugs known to increase urinary pH.
Drospirenone: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and drospirenone are used together. Concomitant use may increase the risk of hyperkalemia. Drospirenone has anti-mineralocorticoid activity, including the potential for hyperkalemia in high-risk patients, comparable to 25 mg of spironolactone.
Drospirenone; Estetrol: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and drospirenone are used together. Concomitant use may increase the risk of hyperkalemia. Drospirenone has anti-mineralocorticoid activity, including the potential for hyperkalemia in high-risk patients, comparable to 25 mg of spironolactone.
Drospirenone; Estradiol: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and drospirenone are used together. Concomitant use may increase the risk of hyperkalemia. Drospirenone has anti-mineralocorticoid activity, including the potential for hyperkalemia in high-risk patients, comparable to 25 mg of spironolactone.
Drospirenone; Ethinyl Estradiol: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and drospirenone are used together. Concomitant use may increase the risk of hyperkalemia. Drospirenone has anti-mineralocorticoid activity, including the potential for hyperkalemia in high-risk patients, comparable to 25 mg of spironolactone.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and drospirenone are used together. Concomitant use may increase the risk of hyperkalemia. Drospirenone has anti-mineralocorticoid activity, including the potential for hyperkalemia in high-risk patients, comparable to 25 mg of spironolactone.
Enalapril, Enalaprilat: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Enalapril; Felodipine: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Ephedrine: (Moderate) The renal elimination of ephedrine susceptible to changes in urinary pH. Potassium citrate is a urinary alkalinizing agent. Concomitant administration of ephedrine with urinary alkalinizers may increase the likelihood of adverse reactions. (Minor) The renal clearance of certain drugs can be affected by the administration of sodium citrate due to urinary alkalinization. Drug-induced urinary alkalization can increase the half-life of ephedrine by increasing tubular reabsorption.
Ephedrine; Guaifenesin: (Moderate) The renal elimination of ephedrine susceptible to changes in urinary pH. Potassium citrate is a urinary alkalinizing agent. Concomitant administration of ephedrine with urinary alkalinizers may increase the likelihood of adverse reactions. (Minor) The renal clearance of certain drugs can be affected by the administration of sodium citrate due to urinary alkalinization. Drug-induced urinary alkalization can increase the half-life of ephedrine by increasing tubular reabsorption.
Eplerenone: (Contraindicated) The use of potassium supplements in patients receiving eplerenone for the treatment of hypertension is contraindicated. Concomitant use may increase the risk of hyperkalemia. Minimize the risk of hyperkalemia with proper patient selection and monitoring.
Eprosartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Etodolac: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Fenoprofen: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Fexofenadine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Finerenone: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and finerenone are used together. Concomitant use may increase the risk of hyperkalemia.
Flecainide: (Moderate) Urinary alkalinization can decrease the renal clearance of flecainide, resulting in an increased elimination half-life and AUC for flecainide.
Flurbiprofen: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Fosinopril: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Guaifenesin; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Hydrocodone; Ibuprofen: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Hydrocodone; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form. (Major) The therapeutic action of methenamine requires an acidic urine. Alkalinizing agents, such as citrate salts, can alkalinize the urine, thereby decreasing the effectiveness of methenamine by increasing the amount of non-ionized drug available for renal tubular reabsorption. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Ibuprofen: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Ibuprofen; Famotidine: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Ibuprofen; Oxycodone: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Indomethacin: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Irbesartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Ketoprofen: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Ketorolac: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Lansoprazole; Naproxen: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Lisdexamfetamine: (Major) Urinary alkalinizers, such as potassium citrate, diminish the urinary excretion of amphetamines. These drug combinations should be avoided, especially in amphetamine overdose situations.
Lisinopril: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Lithium: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with lithium, especially patients who are stabilized on lithium, as urinary alkalinization increases the renal clearance of lithium. If coadministration can not be avoided, monitor lithium serum concentrations and patient clinical response very closely. Also of note, lithium clearance is increased if hypernatremia occurs.
Loratadine; Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Losartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Magnesium Hydroxide: (Contraindicated) Avoid coadministration of antacids with citrate salts since increased absorption of aluminum can occur. In addition, some antacids like calcium carbonate, share the potential with the citrate salts for development of metabolic alkalosis, when given in higher dosage.
Magnesium Salicylate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Meclofenamate Sodium: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Mefenamic Acid: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Meloxicam: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Memantine: (Moderate) Increases in urinary pH may decrease elimination of memantine, resulting in drug accumulation and potential toxicity. (Moderate) Urinary alkalinizing agents may decrease the elimination of memantine, resulting in drug accumulation and potential toxicity. The clearance of memantine is reduced by about 80% under alkaline urine conditions at pH 8. Memantine should be used with caution with drugs known to increase urinary pH.
Methamphetamine: (Major) As potassium citrate is a urinary alkalinizer, use will diminish the urinary excretion of and increase the half-life of amphetamines. The interaction of amphetamines with urinary alkalinizers is well documented. Avoid concurrent use, especially in amphetamine overdose situations.
Methenamine: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form. (Major) The therapeutic action of methenamine requires an acidic urine. Alkalinizing agents, such as citrate salts, can alkalinize the urine, thereby decreasing the effectiveness of methenamine by increasing the amount of non-ionized drug available for renal tubular reabsorption. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended.
Methenamine; Sodium Acid Phosphate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form. (Major) The therapeutic action of methenamine requires an acidic urine. Alkalinizing agents, such as citrate salts, can alkalinize the urine, thereby decreasing the effectiveness of methenamine by increasing the amount of non-ionized drug available for renal tubular reabsorption. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form. (Major) The therapeutic action of methenamine requires an acidic urine. Alkalinizing agents, such as citrate salts, can alkalinize the urine, thereby decreasing the effectiveness of methenamine by increasing the amount of non-ionized drug available for renal tubular reabsorption. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended.
Methenamine; Sodium Salicylate: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with methenamine, as an acidic urine is required for methenamine therapeutic efficacy. Alkalinized urine decreases methenamine efficacy by increasing the amount of non-ionized drug available for renal tubular reabsorption and inhibits the conversion of methenamine to formaldehyde, which is the active bacteriostatic form. (Major) The therapeutic action of methenamine requires an acidic urine. Alkalinizing agents, such as citrate salts, can alkalinize the urine, thereby decreasing the effectiveness of methenamine by increasing the amount of non-ionized drug available for renal tubular reabsorption. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Moexipril: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Nabumetone: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Naproxen: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Naproxen; Esomeprazole: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Naproxen; Pseudoephedrine: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Nebivolol; Valsartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Olmesartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Oxaprozin: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Penicillin G: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and high doses of penicillin G potassium are used together. Concomitant use may increase the risk for hyperkalemia. Penicillin G potassium contains 1.7 mEq of potassium per million units of penicillin G activity.
Perindopril: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Perindopril; Amlodipine: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Piroxicam: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Probenecid; Colchicine: (Moderate) Colchicine is an alkaloid and its action is potentiated by alkalinizing agents like potassium citrate. The colchicine dose may need adjustment. (Moderate) The action of colchicine is potentiated by alkalinizing agents. The colchicine dose may need adjustment.
Pseudoephedrine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Pseudoephedrine; Triprolidine: (Minor) Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Urinary alkalinizers allow for increased tubular reabsorption of pseudoephedrine. Concomitant administration of pseudoephedrine with urinary alkalinizers may increase the likelihood of pseudoephedrine adverse reactions.
Quinapril: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Quinidine: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible. (Major) Urinary alkalinization increases the renal tubular reabsorption of quinidine, resulting in higher quinidine serum concentrations which may lead to toxicity. Avoid citric acid; potassium citrate; sodium citrate administration to any patient receiving treatment with quinidine.
Quinine: (Moderate) Use caution if using potassium citrate and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Ramipril: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Sacubitril; Valsartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Salicylates: (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Salsalate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Sodium Polystyrene Sulfonate: (Contraindicated) Sodium polystyrene sulfonate is indicated for the treatment of hyperkalemia. Administration of all potassium salts should be discontinued whenever therapy with sodium polystyrene sulfonate is indicated.
Spironolactone: (Major) The use of potassium supplements in patients receiving spironolactone may increase the risk for hyperkalemia. Potassium supplements should generally be avoided in heart failure patients receiving spironolactone. Monitor serum potassium concentrations closely if concomitant use is necessary.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) The use of potassium supplements in patients receiving spironolactone may increase the risk for hyperkalemia. Potassium supplements should generally be avoided in heart failure patients receiving spironolactone. Monitor serum potassium concentrations closely if concomitant use is necessary.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Sulindac: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Sumatriptan; Naproxen: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Tacrolimus: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and tacrolimus are used together. Concomitant use may increase the risk of hyperkalemia.
Telmisartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Telmisartan; Amlodipine: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Tolmetin: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Trandolapril: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Trandolapril; Verapamil: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used together. Concomitant use may increase the risk of hyperkalemia.
Triamterene: (Major) The use of potassium supplements in patients treated with triamterene is generally contraindicated. Concomitant use may increase the risk of hyperkalemia. If potassium supplementation is used, monitor serum potassium concentrations closely.
Triamterene; Hydrochlorothiazide, HCTZ: (Major) The use of potassium supplements in patients treated with triamterene is generally contraindicated. Concomitant use may increase the risk of hyperkalemia. If potassium supplementation is used, monitor serum potassium concentrations closely.
Trimethoprim: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and trimethoprim are used together. Concomitant use may increase the risk of hyperkalemia.
Valdecoxib: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia.
Valsartan: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia.

PREGNANCY AND LACTATION

Use potassium citrate during pregnancy only if clearly needed. It is unknown whether potassium citrate can cause fetal harm when administered to a pregnant person or can affect reproduction capacity. Animal reproduction studies have not been conducted.

Use potassium citrate during breast-feeding only if clearly needed. The normal potassium content in breast milk is about 13 mEq/L; it is unknown if potassium citrate has an effect on this content.

MECHANISM OF ACTION

Mechanism of Action:•Urinary alkalinization for treatment of certain nephrolithiasis conditions: Potassium citrate treats certain nephrolithiasis conditions by raising urinary pH and citrate concentrations. 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 may 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 also play some role. Potassium citrate extended-release tablets (Urocit®-K) increase urinary potassium by approximately the amount contained in the dose. In some patients, potassium citrate causes a transient reduction in urinary calcium. The changes induced by potassium citrate produce a urine that is less conducive to the crystallization of certain 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 decreases calcium ion activity (by increasing calcium complexation to dissociated anions) and increases the ionization of uric acid to a 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 patients with severe renal tubular acidosis or chronic diarrheal syndromes 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 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.•Prevention or treatment of hypokalemia: Potassium salts such as potassium citrate may be used as a supplement to maintain potassium homeostasis. Potassium is actively transported into cells through a process facilitated by dextrose, insulin, and oxygen. Transport maintains a high potassium gradient across cell membranes, thus playing a vital role in electrical excitability of nerves and muscle. Relatively high intracellular potassium concentrations leads to passive diffusion out of the cell. The membrane gradient is responsible for the resting transmembrane electric potential, primarily determined by the diffusion of potassium out of the cell. Membrane depolarization will occur only when a current is applied to the nerve that exceeds the outward potassium current. This is usually accomplished by sodium rushing into the cell by fast inward channels, causing the action or 'spike' potential. Repolarization is partially but quickly attained by potassium flowing out of the cell through its own channel.Hydrogen ions are also in higher concentration inside cells. When the extracellular hydrogen ion concentration is increased, as occurs in acidosis, potassium shifts to the extracellular environment; when it is decreased, potassium ions move into the cells. Hypo- or hyperkalemia can initiate changes in concentration of other ions. In the former state, when potassium becomes depleted, as the ion leaves the cell it is exchanged with extracellular sodium and hydrogen ions to maintain electroneutrality. The redistribution of hydrogen ions causes intracellular acidosis and extracellular alkalosis. The opposite happens in hyperkalemia.Within or near the normal range of potassium balance, the ion plays a part in regulating renal synthesis of ammonia and in the pH of urine. A decrease in dietary intake of potassium stimulates renal synthesis of ammonia and increases urinary pH slightly by diminishing net acid secretion. If potassium loss is low, metabolic acidosis results. Greater potassium loss can cause systemic metabolic alkalosis and intracellular acidosis. Tubular secretion of potassium is inhibited by acidemia and stimulated by alkalemia.

PHARMACOKINETICS

Potassium citrate is administered orally.  Potassium first enters the extracellular fluid and is then actively transported into cells. Skeletal muscle accounts for the bulk of the intracellular store of potassium. Renal excretion of potassium normally is equal to the amount being absorbed in the diet. Potassium is freely filtered at the glomerulus and almost completely reabsorbed in the proximal tubule. Tubular secretion occurs in the late distal convoluted tubule and collecting duct, and accounts for the potassium excreted in the urine, which is about 10% of the amount filtered. Fecal elimination of potassium is minimal and plays no significant role in potassium homeostasis.
 
When potassium citrate is used to alkalinize the urine, urinary citrate and urinary pH values are important. In the setting of normal renal function, the rise in urinary citrate following a single dose of extended-release potassium citrate (Urocit-K) 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. The rise in citrate excretion is directly dependent on the potassium citrate dosage. Following long-term treatment, Urocit-K at a dosage of 60 mEq/day raises urinary citrate by approximately 400 mg/day and increases urinary pH by approximately 0.7 units. When potassium citrate therapy is withdrawn, urinary citrate begins to decline toward the pre-treatment level on the first day.