Potassium Citrate Er (potassium citrate)

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Citrate preparations (i.e., potassium citrate and citric acid, sodium citrate, sodium citrate and citric acid, tricitrates) are administered orally. Oral citrate solutions should be diluted with adequate amounts of water prior to administration to minimize the risk of GI complications, and followed by additional water after administration; palatability may be enhanced by chilling the solution before administration. For reconstitution of potassium citrate and citric acid for oral solution in single-dose packets, the contents of one packet should be mixed thoroughly with at least 180 mL of cool water or juice prior to administration and followed by additional water or juice after administration. Oral citrate solutions should preferably be taken after meals to avoid the saline laxative effect of the drug.

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Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Urinary Alkalinizers/Methenamine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Urinary alkalinizers may elevate urinary ph preventing the conversion of methenamine to formaldehyde and mandelic acid.(1)

CLINICAL EFFECTS: Concurrent administration may result in alkalinization of the urine causing methenamine to be less effective.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The Australian and UK manufacturers of methenamine state that concurrent use with agents that make urine alkaline or urine alkalinizing agents should be avoided.(2,3) Patients receiving concurrent therapy should be monitored for urinary ph and any worsening symptoms of their infection, including dysuria, flank pain, or fever.(1)

DISCUSSION: Administration of urinary alkalinizers may result in alkalinization of the urine resulting in therapeutic failure of methenamine. Formaldehyde is released by acid hydrolysis from methenamine resulting in bactericidal concentrations at urinary ph 5.0 to 5.5. Above urinary ph 6.0 there is insufficient quantities of formaldehyde and methenamine released to achieve a therapeutic response.(1) An in vitro study showed that methenamine efficacy is achieved when the urine pH is less than 5.7 to 5.85.(4)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Potassium Supplements/Eplerenone

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Eplerenone increases serum potassium levels.(1)

CLINICAL EFFECTS: Concurrent use of eplerenone with a potassium supplement may result in hyperkalemia.(1)

PREDISPOSING FACTORS: Renal impairment.

PATIENT MANAGEMENT: The manufacturer of eplerenone states that the use of eplerenone for the treatment of hypertension in patients receiving potassium supplements is contraindicated.(1)

DISCUSSION: The main risk of eplerenone therapy is hyperkalemia. The risk of hyperkalemia can be reduced by avoiding potassium supplements during eplerenone therapy.(1)

Potassium Supplements/Potassium Sparing Diuretics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Decreased renal excretion of potassium, resulting from administration of a potassium sparing diuretic.

CLINICAL EFFECTS: May observe hyperkalemia which may be severe or even fatal.

PREDISPOSING FACTORS: Renal function impairment.

PATIENT MANAGEMENT: If both drugs are administered, monitor potassium levels. Adjust the dose of the drugs accordingly. This combination should probably be avoided if possible.

DISCUSSION: The interaction is well documented. Patients with decreased renal function are especially at risk of developing hyperkalemia from this drug combination. A commonly held belief is that a potassium sparing diuretic formulated in combination with a thiazide diuretic, such as Dyazide, will not exhibit this interaction. Although the likelihood of hyperkalemia occurring may be reduced somewhat, a danger still exists.

Potassium Supplements/Trimethoprim

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Trimethoprim may increase serum potassium levels by reduction in potassium elimination.(1-3) The combination of trimethoprim and potassium supplements can have an additive effect on serum potassium resulting in potentially dangerous levels.

CLINICAL EFFECTS: Concurrent use of trimethoprim and potassium supplements may result in hyperkalemia, which may be severe.

PREDISPOSING FACTORS: Patients who are elderly, have any degree of renal insufficiency or heart failure have an increased risk for hyperkalemia.(1-9) Concomitant use with other drugs associated with hyperkalemia risk (e.g. ACE Inhibitors, angiotensin II receptor antagonists, aldosterone antagonists, NSAIDs) and high doses of trimethoprim further increase the risk for hyperkalemia.(1-8) Interaction risk and severity is greater in patients with multiple risk factors.

PATIENT MANAGEMENT: Assure adequate monitoring for hyperkalemia.(1-9) Patients receiving trimethoprim and a potassium supplement concurrently should have their serum potassium monitored at baseline and during treatment. Potassium supplementation may need to be held during antibiotic therapy, especially when other predisposing factors for hyperkalemia are present. Peak potassium increase due to trimethoprim is delayed and generally occurs after 4 or more days of therapy.(3,5,6) When possible, alternative antibiotic therapy should be considered in patients with one or more risk factors for hyperkalemia, e.g. renal impairment, heart failure, age > 65 years, and/or receiving additional meds associated with hyperkalemia risk (e.g. ACE inhibitors, angiotensin II receptor blockers, aldosterone antagonists, NSAIDs).(6)

DISCUSSION: A nested case-control study evaluated the risk for hyperkalemia in 19,194 patients with newly diagnosed heart failure. Over a mean follow-up of 3.9 years 2,176 cases of hyperkalemia (96.7% with a potassium value of => 5.5 mmol/L) were identified. Study authors found that trimethoprim independently increased the risk for hyperkalemia (OR 2.82; 95% CI 1.88-4.23).(4) A retrospective cohort study evaluated the risk for hospitalization due to hyperkalemia in 393,039 elderly women (age >65 years) treated for a urinary tract infection (UTI) with trimethoprim-sulfamethoxazole (TMP-SMX) or another antibiotic (amoxicillin, ciprofloxacin, norfloxacin, nitrofurantoin). Baseline renal function was similar in all five antibiotic groups. When compared with amoxicillin, TMP-SMX use was associated with a 3.3-fold increased risk for hospitalization due to hyperkalemia. Ciprofloxacin, norfloxacin, and nitrofurantoin were not associated with a risk for hyperkalemia.(9) A prospective study of hospitalized patients evaluated the risk for hyperkalemia in patients who received standard dose TMP-SMX (<= 320 mg trimethoprim, <= 1600 mg sulfamethoxazole daily) versus a control group who received a different antibiotic for at least 5 days. The two groups were similar in age, renal function and use of potassium altering medications. Serum potassium concentration increased in TMP-SMX patients by 1.21 mmol/L (CI 1.09 - 1.32 mmol/L), a change which was statistically significant in patients with a pretreatment serum creatinine = or > 1.2. In control patients, serum potassium decreased during antibiotic therapy (change not quantitated by authors).(5)

Solid Oral Potassium Tablets/Anticholinergics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16)

CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with anticholinergics may result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16)

PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21)

PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling.

DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. Some lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17)

Urinary Alkalinizers/Dextroamphetamine Transdermal

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Urinary alkalinizers decrease the renal elimination of dextroamphetamine.(1)

CLINICAL EFFECTS: Concurrent use of dextroamphetamine and urinary alkalinizers may result in increased dextroamphetamine levels and side effects.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Coadministration of dextroamphetamine with urinary alkalinizing agents should be avoided.(1)

DISCUSSION: Concurrent use of alkalinizing agents with dextroamphetamine decreases the renal elimination of dextroamphetamine. Co-administration of these should be avoided because of the potential of increased actions of dextroamphetamine.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Agents That Increase Potassium/Baxdrostat

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The combination of baxdrostat and agents that increase potassium such as aldosterone receptor antagonists, potassium-sparing diuretics, and potassium supplements can have an additive effect on serum potassium levels.

CLINICAL EFFECTS: Concurrent use of baxdrostat and agents that increase potassium may result in hyperkalemia, which may be severe.

PREDISPOSING FACTORS: More frequent monitoring is recommended for patients at increased risk of hyperkalemia (e.g., patients greater than or equal to 65 years or age, those with diabetes mellitus or chronic kidney disease).(1)

PATIENT MANAGEMENT: The manufacturer of baxdrostat states concurrent use with medications that may increase potassium warrants more frequent monitoring of serum potassium.(1) Assess serum potassium prior to initiation of baxdrostat and monitor periodically during treatment. Correct serum potassium abnormalities prior to initiation of baxdrostat.(1) If hyperkalemia occurs, treat hyperkalemia and consider interrupting or discontinuing baxdrostat. Consider more frequent monitoring of serum potassium in patients who restart baxdrostat after experiencing hyperkalemia. Permanently discontinue baxdrostat if clinically significant hyperkalemia recurs.(1)

DISCUSSION: Baxdrostat may increase potassium. Concurrent use with aldosterone receptor antagonists, potassium-sparing diuretics, and potassium supplements may have additive effects on serum potassium levels, resulting in hyperkalemia. The risk of hyperkalemia can be reduced by monitoring serum potassium more frequently when baxdrostat is administered concomitantly with these agents.

Potassium Supplements/Aliskiren

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aliskiren may decrease the renal excretion of potassium.

CLINICAL EFFECTS: Concurrent use of potassium supplements with aliskiren may result in hyperkalemia.

PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus.

PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with potassium supplements and aliskiren.

DISCUSSION: Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. Increased potassium levels have also been seen with aliskiren. Based on this data, serum potassium levels should be monitored in patients receiving potassium supplements with aliskiren.

Potassium Supplements/Angiotensin Ii Receptor Blocker (ARB)

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Angiotensin II receptor blockers (ARBs) may decrease the renal excretion of potassium.

CLINICAL EFFECTS: Concurrent use of potassium supplements with ARBs may result in hyperkalemia.

PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus.

PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with potassium supplements and ARBs.

DISCUSSION: Several studies have indicated that serum potassium levels increase when ARB therapy is initiated and decrease when the drug is lowered. Based on this data, serum potassium levels should be monitored in patients receiving potassium supplements with ARBs.

Potassium Supplements/Drospirenone

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Drospirenone has antimineralocorticoid activity and may cause hyperkalemia. Potassium supplements also increase potassium levels.(1)

CLINICAL EFFECTS: Concurrent use of drospirenone and potassium supplements may result in hyperkalemia.(1)

PREDISPOSING FACTORS: Renal insufficiency, hepatic dysfunction, adrenal insufficiency, and use of potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, heparin, and NSAIDs may increase potassium levels.(1)

PATIENT MANAGEMENT: Patients receiving drospirenone with a potassium supplement should have their serum potassium level checked during the first treatment cycle.(1)

DISCUSSION: Drospirenone has antimineralocorticoid activity comparable to 25 mg of spironolactone and may result in hyperkalemia. Concurrent use of potassium-supplements also increase potassium levels.(1)

Potassium Supplements/Selected Ace Inhibitors

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: ACE inhibitors may decrease the renal excretion of potassium. MECHANISM OF ACTION: ACE inhibitors may decrease the renal excretion of potassium.

CLINICAL EFFECTS: Concurrent use of potassium supplements with ACE inhibitors may result in hyperkalemia. CLINICAL EFFECTS: Concurrent use of potassium supplements with ACE inhibitors may result in hyperkalemia.

PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus. PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus.

PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with potassium supplements and ACE inhibitors. PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with potassium supplements and ACE inhibitors.

DISCUSSION: Several studies have indicated that serum potassium levels increase when ACE inhibitors is initiated and decrease when the drug is lowered. Based on this data, serum potassium levels should be monitored in patients receiving potassium supplements with ACE inhibitors. Selected ACE inhibitors linked to this monograph include: alacepril, cilazapril, delapril, imidapril, perindopril, spirapril, temocapril, and zofenopril. DISCUSSION: Several studies have indicated that serum potassium levels increase when ACE inhibitors is initiated and decrease when the drug is lowered. Based on this data, serum potassium levels should be monitored in patients receiving potassium supplements with ACE inhibitors. Selected ACE inhibitors linked to this monograph include: benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, quinapril, ramipril, and trandolapril.

Solid Oral Potassium Tablets/Inhaled Anticholinergics

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16)

CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with inhaled anticholinergics could potentially result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16)

PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21)

PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling.

DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. Some lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17) Constipation has been reported as a side effect of inhaled anticholinergic agents such as ipratropium(22) and tiotropium.(23)

Urinary Alkalinizers/Memantine; Amantadine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Memantine and amantadine elimination is impaired by urinary alkalinization.(1,2)

CLINICAL EFFECTS: Potentiation of memantine or amantadine effects may be observed.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor patient for adverse reactions such as dizziness, headache, or confusion if a urinary alkalinizer is required. The memantine or amantadine dose may need to be adjusted when a urinary alkalinizer is started or stopped.(1,2)

DISCUSSION: The clearance of memantine was reduced by about 80% under alkaline urine conditions at pH 8. Urine alkalinization may lead to an accumulation of memantine with a possible increase in adverse effects. Urine pH is also altered by diet and clinical state of the patient (e.g., renal tubular acidosis or severe infections of the urinary tract). Hence, memantine should be used with caution under these conditions.(1) A study in rats showed that concomitant administration of sodium bicarbonate with amantadine caused a decrease in amantadine renal clearance (1.16 vs. 0.76). Amantadine's area-under-the-curve (AUC) was increased approximately 78%.(3) A study in 12 healthy subjects showed that plasma concentrations of memantine are dependent on urine pH. Alkaline urine pH caused a 79% reduction in renal clearance.(4)

Urinary Alkalinizers/Quinidine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Quinidine elimination is impaired by urinary alkalinization.

CLINICAL EFFECTS: Potentiation of quinidine effects may be observed.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitoring quinidine levels and cardiac function may be indicated. The quinidine dose may need to be adjusted when a urinary alkalinizer is started or stopped.

DISCUSSION: Additional documentation is necessary to confirm this potential interaction.

Urinary Alkalinizers/Sympathomimetics

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Unionized sympathomimetic amines will be reabsorbed into systemic circulation from the distal tubules of the kidneys.

CLINICAL EFFECTS: Enhanced sympathomimetic activity and increased risk of sympathomimetic toxicity.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Watch patient for enhanced sympathomimetic side effects when urinary alkalinizers are concomitantly used. A lower dose of certain sympathomimetics may be required.

DISCUSSION: Signs and symptoms of sympathomimetic toxicity include euphoria, confusion, delirium, hallucinations and nervousness.

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• Esophageal dysmotility
• Esophageal obstruction
• Gastrointestinal obstruction
• Gastroparesis
• Hyperkalemia

• Chronic heart failure
• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Dehydration
• Diabetic ketoacidosis
• Metabolic acidosis
• Peptic ulcer
• Primary adrenocortical insufficiency
• Urinary tract infection

• Kidney disease with likely reduction in glomerular filtration rate (GFr)

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Rare or Very Rare

• Gastrointestinal hemorrhage
• Gastrointestinal irritation
• Gastrointestinal obstruction
• Gastrointestinal perforation
• Gastrointestinal ulcer
• Hyperkalemia

More Frequent

• Nausea
• Vomiting

Less Frequent

• Acute abdominal pain
• Diarrhea
• Loose stools

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No enhanced messaging available.

Controlled studies to date in pregnant women receiving potassium citrate have not shown a risk to the fetus in the first trimester of pregnancy and there is no evidence of risk in subsequent trimesters.

It is not known whether potassium citrate is distributed into milk. Because potassium freely distributes into and out of milk, use of potassium citrate by a nursing woman with normal plasma potassium concentrations should have no adverse effect on the nursing infant; milk potassium concentrations may be increased in hyperkalemic women.

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