Maxzide-25 Mg (triamterene/hydrochlorothiazide)

Dosage of triamterene should be individualized according to the patient's requirements and response. It has been theorized that abrupt withdrawal of triamterene may result in rebound kaliuresis; therefore, the drug should be withdrawn gradually. Experts state that diuretics should be administered at a dosage sufficient to achieve optimal volume status and relieve congestion without inducing an excessively rapid reduction in intravascular volume, which could result in hypotension, renal dysfunction, or both.

Dosage of hydrochlorothiazide should be individualized according to the patient's requirements and response. The lowest dosage necessary to produce the desired clinical effect should be used. If hydrochlorothiazide is added to the regimen of a patient stabilized on a potent hypotensive agent, dosage of the hypotensive agent should initially be reduced to avoid the possibility of severe hypotension.

Triamterene is administered orally. Triamterene has been administered IV+, but the poor solubility of the drug and acidity of the solutions make administration by this route extremely difficult and a parenteral dosage form currently is not available in the US.

Hydrochlorothiazide is administered orally.

There is no enhanced messaging for this drug.

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

Potassium Wasting Diuretics/Cisapride

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: Concurrent administration may result in additive effects on the QT interval.(1)

CLINICAL EFFECTS: Concurrent administration may result in prolongation of the QT interval, which may result in potentially life-threatening arrhythmias.(1)

PREDISPOSING FACTORS: The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2)

PATIENT MANAGEMENT: The manufacturer of cisapride states that cisapride should not be used in patients with uncorrected hypokalemia or who might experience a rapid reduction of plasma potassium, such as those patients taking potassium-wasting diuretics in the acute setting.(1) If concurrent therapy is deemed medically necessary, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting.

DISCUSSION: The manufacturer of cisapride states that QT prolongation, torsades de pointes (sometimes with syncope), cardiac arrest, and sudden death have been reported in patients who were not taking agents known to increase cisapride levels. Some of these patients had uncorrected electrolyte disorders such as hypokalemia. Therefore, the manufacturer of cisapride states that cisapride should not be used in patients with uncorrected hypokalemia or who might experience a rapid reduction of plasma potassium, such as those patients taking potassium-wasting diuretics in the acute setting.(1) There is no published documentation to support this interaction.

Selected Photosensitizers/Tretinoin-Mequinol

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: Tretinoin, anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are all known photosensitizers.(1)

CLINICAL EFFECTS: Concurrent use of tretinoin in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer states that tretinoin-mequinol should not be administered to patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides.(1)

DISCUSSION: Because of the risk of increased photosensitivity, the US manufacturer states that tretinoin-mequinol should not be administered to patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), methotrexate, phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides.(1)

Thiazide Diuretics/Dofetilide

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: Thiazide diuretics may decrease the excretion of dofetilide and may decrease potassium levels.(1)

CLINICAL EFFECTS: Concurrent use of dofetilide with a thiazide diuretic may result in elevated levels and clinical effects of dofetilide, as well as prolongation of the QT interval.(1)

PREDISPOSING FACTORS: Renal impairment may increase risk for excessive QTc prolongation as dofetilide is primarily renally eliminated. To prevent increased serum levels and risk for ventricular arrhythmias, dofetilide must be dose adjusted for creatinine clearance < or = to 60 mL/min.(1) The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, and advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2)

PATIENT MANAGEMENT: The manufacturer of dofetilide states that the concurrent use of dofetilide with hydrochlorothiazide, alone or in combination with triamterene, is contraindicated.(1) Other thiazides should also be considered contraindicated as well. If concurrent therapy is deemed medically necessary, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting.

DISCUSSION: In a study, hydrochlorothiazide (50 mg daily) alone or hydrochlorothiazide/triamterene (50 mg/100 mg daily) was administered with dofetilide (500 mcg twice daily) for 5 days following 2 days of diuretic use at half-dose. In patients receiving hydrochlorothiazide alone, the area-under-curve (AUC) and maximum concentration (Cmax) of dofetilide increased by 27% and by 21%, respectively. The pharmacodynamic effects of dofetilide increased by 197% (QTc increase over time) and by 95% (maximum QTc increase). In patients on combination hydrochlorothiazide/triamterene, dofetilide AUC and Cmax increased by 30% and by 16%, respectively. The pharmacodynamic effects of dofetilide increased by 190% (QTc increase over time) and by 84% (maximum QTc increase).(1) Dofetilide clearance was 16% lower in patients receiving thiazide diuretics.(1)

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.

Baxdrostat; Potassium-Spar Diuretics/Cyclosporine;Tacrolimus

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

MECHANISM OF ACTION: Concurrent use of cyclosporine(1) or tacrolimus(2) with baxdrostat(3) or a potassium-sparing diuretic may result in additive or synergistic effects on potassium levels.

CLINICAL EFFECTS: Concurrent use of cyclosporine(1) or tacrolimus(2) with baxdrostat(3) or a potassium-sparing diuretic may result in severe hyperkalemia.

PREDISPOSING FACTORS: Renal impairment increases the risk for hyperkalemia.

PATIENT MANAGEMENT: The US manufacturers of cyclosporine(1) and tacrolimus(2) state that potassium-sparing diuretics should not be used during therapy with these agents.

DISCUSSION: Hyperkalemia has been reported with cyclosporine, therefore, the US manufacturer states that potassium-sparing diuretics should not be used with cyclosporine.(1) In tacrolimus clinical trials, mild to severe hyperkalemia was reported in 31% of kidney transplant patients, 45% of US liver transplant patients, and 13% of European liver transplant patients. The manufacturer of tacrolimus states that potassium levels should be closely monitored in all patients maintained on tacrolimus and that potassium-sparing diuretics should be avoided during tacrolimus therapy.(2)

Diuretics/Sodium Phosphate Bowel Cleanser

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

MECHANISM OF ACTION: Bowel cleansing with sodium phosphate causes dehydration, decreased intravascular volume and hyperphosphatemia, which increases phosphate levels in the renal tubules. Abnormally high levels of calcium and phosphate in the renal tubules may precipitate out, resulting in renal injury.(1)

CLINICAL EFFECTS: Use of sodium phosphate for bowel cleansing in patients maintained on diuretics may increase the risk of acute phosphate nephropathy, which is an acute kidney injury associated with deposits of calcium phosphate crystal in the renal tubules that may result in permanent renal function impairment. Acute phosphate nephropathy presents as acute kidney injury with minimal proteinuria and a bland urine sediment.(2) Use of oral sodium phosphate products at laxative doses has not been associated with acute kidney injury.(3)

PREDISPOSING FACTORS: Patients who may be at an increased risk of acute phosphate nephropathy include those who are over age 55; are hypovolemic or have decreased intravascular volume; have baseline kidney disease, bowel obstruction, or active colitis; and who are using medications that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotension receptor blockers (ARBs) and possibly nonsteroidal anti-inflammatory drugs (NSAIDs).(2)

PATIENT MANAGEMENT: If possible, use an alternative agent for bowel cleansing.(1) Use sodium phosphate products with caution in patients taking medications that affect kidney function or perfusion, such as diuretics. Obtain baseline and post-procedure labs (electrolytes, calcium, phosphate, BUN, creatinine, and [in smaller, frail individuals] glomerular filtration rate). Instruct patients to drink sufficient quantities of clear fluids before, during, and after bowel cleansing and to avoid other laxatives that contain sodium phosphate. Consider hospitalization and intravenous hydration during bowel cleansing to support frail patients who may be unable to drink an appropriate volume of fluid or who may be without assistance at home.(2) Use of an electrolyte solution for rehydration may decrease the risk of acute phosphate nephropathy.(4,5)

DISCUSSION: Since May 2006, the FDA has received 20 reports of acute phosphate nephropathy associated with the use of Osmo Prep. Concomitant medications included ACE inhibitors or ARBs (11), diuretics (6), and NSAIDs (4).(2) In a retrospective review of colonoscopy patients, simultaneous use of ACE inhibitors or ARBs significantly increased the risk of acute kidney injury from oral sodium phosphate. Diuretic use was also a risk factor.(6) In a case series study of 21 cases of acute phosphate nephropathy in patients who had used oral sodium phosphate, 14 patients received an ACE inhibitor or ARB, 4 used a diuretic, and 3 used an NSAID.(7) Cases have also been reported with rectal products.(8)

Potassium Sparing Diuretics/Aldosterone Receptor Antagonists

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

MECHANISM OF ACTION: Aldosterone receptor antagonists increase serum potassium levels, as do potassium-sparing diuretics.(1-3)

CLINICAL EFFECTS: Concurrent use of aldosterone receptor antagonists with a potassium sparing diuretic may result in hyperkalemia.(1-3)

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-sparing diuretics is contraindicated.(1) The US manufacturer of spironolactone states that spironolactone should not be used with potassium-sparing diuretics.(2) The US manufacturer of finerenone states that more frequent monitoring of potassium may be necessary in patients on concomitant medications that impair potassium excretion or increase serum potassium levels.(3)

DISCUSSION: The one of the main risks of aldosterone receptor antagonist therapy is hyperkalemia. The risk of hyperkalemia can be reduced by avoiding potassium sparing diuretics during therapy.(1-3)

Potassium Sparing Diuretics/Potassium Supplements

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.

Selected Photosensitizers/Aminolevulinic Acid

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

MECHANISM OF ACTION: Aminolevulinic acid, anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are all known photosensitizers.(1)

CLINICAL EFFECTS: Concurrent use of aminolevulinic acid in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer states that aminolevulinic acid should be avoided in patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides for 24 hours before and after administration of aminolevulinic acid.(1)

DISCUSSION: Because of the risk of increased photosensitivity, the US manufacturer states that aminolevulinic acid should be avoided in patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides for 24 hours before and after administration of aminolevulinic acid.(1)

Selected Photosensitizers/Methoxsalen

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

MECHANISM OF ACTION: Methoxsalen causes photosensitivity due to residual drug which is present in all parts of the skin from photopheresis. Anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are other known photosensitizers.(1)

CLINICAL EFFECTS: Concurrent use of methoxsalen in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of methoxsalen states that concurrent use of methoxsalen with anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides should be avoided.(1)

DISCUSSION: All patients who have received methoxsalen become photosensitive. It is unknown what the risk of photosensitivity reactions is when methoxsalen is used concurrently with other photosensitizing agents.(1)

Selected Photosensitizers/Porfimer

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

MECHANISM OF ACTION: Porfimer causes photosensitivity due to residual drug which is present in all parts of the skin. Anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are other known photosensitizers.(1)

CLINICAL EFFECTS: Concurrent use of porfimer in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1)

PREDISPOSING FACTORS: Patients with any hepatic impairment and patients with severe renal impairment have reduced drug elimination and may remain photosensitive for 90 days or longer.(1)

PATIENT MANAGEMENT: The US manufacturer of porfimer states that concurrent use of porfimer with photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides should be avoided.(1) Since the photosensitive effect of porfimer may persist for at least 30 days (and for 90 days in some patients), it would be prudent to avoid other photosensitizing agents for at least 30 days after administration of porfimer.

DISCUSSION: All patients who have received porfimer become photosensitive. It is unknown what the risk of photosensitivity reactions is when porfimer is used concurrently with other photosensitizing agents. When porfimer was used in clinical trials, photosensitivity reactions occurred in about 20% of cancer patients and in 69% of high-grade dysplasia in Barretts esophagus patients. Most of the reactions were mild to moderate erythema, but they also included swelling, pruritus, burning sensation, feeling hot, or blisters. The majority of reactions occurred within 90 days of porfimer administration.(1)

Thiazide Diuretics/Lithium

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

MECHANISM OF ACTION: Lithium is eliminated unchanged by the kidney; thiazide induced sodium elimination may lead to decreased renal clearance of lithium.

CLINICAL EFFECTS: Lithium has a narrow therapeutic range; even modest, unintended increases in lithium concentration may result in lithium toxicity. Early symptoms of lithium toxicity may include: lethargy, muscle weakness or stiffness, new onset or coarsening of hand tremor, vomiting, diarrhea, confusion, ataxia, blurred vision, tinnitus and nystagmus. Severe toxicity may produce multiple organ dysfunction (e.g. seizures, coma, renal failure, cardiac arrhythmias, cardiovascular collapse) and may be fatal.

PREDISPOSING FACTORS: Risk factors for lithium toxicity include: renal impairment or worsening of existing renal disease, dehydration, low sodium diet, and concomitant use of multiple medications which may impair renal elimination of lithium (e.g. ARBs, ACE Inhibitors, NSAIDs, diuretics). Patients who require higher therapeutic lithium levels to maintain symptom control are particularly susceptible to these factors.

PATIENT MANAGEMENT: If concurrent therapy cannot be avoided, monitor closely to decrease the risk for lithium toxicity. Evaluate renal function and most recent lithium levels. If renal function is not stable, it would be prudent to withhold combination therapy until renal function is stable. If a thiazide diuretic is started, or if the dose is increased in a patient stabilized on lithium therapy, consider empirically lowering the lithium dose, and recheck lithium levels 5 to 7 days after diuretic initiation. Adjust lithium or thiazide dose as required and continue frequent (e.g. weekly) monitoring of lithium until levels have stabilized. If lithium is to be started in a patient stabilized on a thiazide diuretic, consider starting with a lower lithium dose and titrate slowly as half-life may be prolonged. Monitor lithium concentrations until stabilized on the combination. Counsel patient to assure they know signs and symptoms of lithium toxicity and understand the importance of follow-up laboratory testing.

DISCUSSION: This interaction is well documented.(1-15)

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.

Agents With Hyponatremia Risk/Desmopressin

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

MECHANISM OF ACTION: Carbamazepine, chlorpromazine, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants increase the risk of hyponatremia.(1-3)

CLINICAL EFFECTS: Concurrent use may increase the risk of hyponatremia with desmopressin.(1-3)

PREDISPOSING FACTORS: Predisposing factors for hyponatremia include: polydipsia, renal impairment (eGFR < 50 ml/min/1.73m2), illnesses that can cause fluid/electrolyte imbalances, age >=65, medications that cause water retention and/or increase the risk of hyponatremia (glucocorticoids, loop diuretics).

PATIENT MANAGEMENT: The concurrent use of agents with a risk of hyponatremia with desmopressin may increase the risk of hyponatremia. If concurrent use is deemed medically necessary, make sure serum sodium levels are normal before beginning therapy and consider using the desmopressin nasal 0.83 mcg dose. Consider measuring serum sodium levels more frequently than the recommended intervals of: within 7 days of concurrent therapy initiation, one month after concurrent therapy initiation and periodically during treatment. Counsel patients to report symptoms of hyponatremia, which may include: headache, nausea/vomiting, feeling restless, fatigue, drowsiness, dizziness, muscle cramps, changes in mental state (confusion, decreased awareness/alertness), seizures, coma, and trouble breathing. Counsel patients to limit the amount of fluids they drink in the evening and night-time and to stop taking desmopressin if they develop a stomach/intestinal virus with nausea/vomiting or any nose problems (blockage, stuffy/runny nose, drainage).(1)

DISCUSSION: In clinical trials of desmopressin for the treatment of nocturia, 4 of 5 patients who developed severe hyponatremia (serum sodium <= 125 mmol/L) were taking systemic or inhaled glucocorticoids. Three of these patients were also taking NSAIDs and one was receiving a thiazide diuretic.(2) Drugs associated with hyponatremia may increase the risk, including loop diuretics, carbamazepine, chlorpromazine, glucocorticoids, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants.(1,3-4)

Diuretics/Zoledronic Acid

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

MECHANISM OF ACTION: Concurrent use of zoledronic acid and a diuretic may have adverse effects on the renal system.(1,2)

CLINICAL EFFECTS: Concurrent use of zoledronic acid and a diuretic may result in renal dysfunction. Deterioration in renal function, acute renal failure requiring dialysis, and death have been reported.(1)

PREDISPOSING FACTORS: The interaction may be more likely in elderly patients, patients who are taking other drugs that impact renal function, patients with pre-existing renal compromise, and patients who are dehydrated.(1)

PATIENT MANAGEMENT: Patients should be adequately hydrated with 500 ml (2 glasses of water) before and after zoledronic acid administration.(1) Creatinine clearance should be monitored before and after therapy and zoledronic acid should not be administered in patients with a creatinine clearance less than 35 ml/min.(1,3)

DISCUSSION: Zoledronic acid has been associated with renal dysfunction, including deterioration in renal function, acute renal failure requiring dialysis, and death. Risk factors include advanced age, concomitant nephrotoxic agents, and dehydration.(1) The FDA has received 16 reports of fatal acute renal failure and 9 reports of renal injury requiring dialysis following the administration of Reclast (zoledronic acid).(3)

Hydrochlorothiazide/Topiramate

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

MECHANISM OF ACTION: Hydrochlorothiazide may increase levels of topiramate. Also, both agents may decrease potassium levels.(1,2)

CLINICAL EFFECTS: Concurrent use of hydrochlorothiazide may result in elevated levels of topiramate and hypokalemia.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor serum potassium and topiramate in patients receiving concurrent therapy. The dosage of topiramate may need to be adjusted, an alternative diuretic or potassium supplement may be needed.

DISCUSSION: In a study in 23 healthy subjects, concurrent hydrochlorothiazide (25 mg daily) increased the maximum concentration (Cmax) and area-under-curve (AUC) of topiramate (96 mg BID) by 27% and 29%, respectively. During concurrent therapy, 61% of patients had a serum potassium level less than 3.5 mEq/L, compared with 27% with topiramate alone and 25% with hydrochlorothiazide alone. During concurrent therapy, the mean decrease in serum potassium levels was -0.60 mEq/L, compared with -0.25 mEq/L with topiramate alone and -0.12 mEq/L with hydrochlorothiazide alone.(1)

K+ Sparing Diuretics/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 sparing diuretics with an ARB 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 a potassium sparing diuretic and an ARB. In all patients taking eplerenone who start taking an an ARB, check serum potassium and creatinine levels after 3-7 days of concurrent therapy.

DISCUSSION: In a nested case-control study of heart failure patients receiving continuous ACE inhibitor/ARB therapy (n = 1,491,894), the risk of hyperkalemia was significantly associated with spironolactone use (odds ratio (OR) = 13.59; confidence interval (CI) = 11.63-15.88).(20) In a systemic literature review and meta-analysis of 20 randomized controlled studies, it was found that treatment with spironolactone and ACEI/ARB combination therapy compared to ACEI/ARB therapy alone increased the mean serum potassium concentration by 0.19 mEq/L (95% CI, 0.12-0.26 mEq/L).(21) A retrospective cohort study in patients with hypertension, diabetes, and albuminuria between 2008 and 2018 examined the efficacy and safety of mineralocorticoid receptor antagonists eplerenone and spironolactone in combination with ACEI/ARB compared to ACEI/ARB alone. Hyperkalemia was more frequent in combination therapy patients (n=1,282) versus monotherapy (n=5,484) (22.3 vs 10.9 per 100 person-years for combination and monotherapy, respectively; HR = 1.78, 95% CI: 1.42, 2.24).(22) Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. There are case reports of hyperkalemia during concurrent therapy with ARBs and spironolactone and with aliskiren and spironolactone. Based on this data, serum potassium levels should be monitored in patients receiving concomitant ARBs with potassium sparing diuretics.

Kaluretics/Digitalis Glycosides

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

MECHANISM OF ACTION: Potassium-losing diuretics may result in potassium depletion which can predispose patients to digitalis toxicity.

CLINICAL EFFECTS: May observe increased arrhythmias, resulting from an increase in the cardiac response to digitalis. Symptoms of digoxin toxicity can include anorexia, nausea, vomiting, headache, fatigue, malaise, drowsiness, generalized muscle weakness, disorientation, hallucinations, visual disturbances, and arrhythmias.

PREDISPOSING FACTORS: Low body weight, advanced age, impaired renal function, hypokalemia, hypercalcemia, and/or hypomagnesemia may increase the risk of digoxin toxicity.

PATIENT MANAGEMENT: Monitor serum potassium status and give potassium replacements as needed.

DISCUSSION: This interaction is well documented. Most patients taking diuretics do not develop significant potassium depletion if they are on low doses of diuretics and have adequate potassium intake.

Potassium Sparing Diuretics/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 sparing diuretics 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 a potassium sparing diuretic and aliskiren. In all patients taking eplerenone who start taking aliskiren, check serum potassium and creatinine levels after 3-7 days of concurrent therapy.

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. There are case reports of hyperkalemia during concurrent therapy with ARBs and spironolactone and with aliskiren and spironolactone. Based on this data, serum potassium levels should be monitored in patients receiving concomitant aliskiren with potassium sparing diuretics.

Potassium Sparing Diuretics/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 sparing diuretics may also increase potassium levels.(1)

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

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

PATIENT MANAGEMENT: Patients receiving drospirenone with a potassium sparing diuretic 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 sparing diuretics may also increase potassium levels.(1)

Potassium Sparing Diuretics/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 decrease the renal excretion of potassium. MECHANISM OF ACTION: ACE inhibitors may decrease the renal excretion of potassium.

CLINICAL EFFECTS: Concurrent use of potassium sparing diuretics with an ACE inhibitor may result in hyperkalemia. CLINICAL EFFECTS: Concurrent use of potassium sparing diuretics with an ACE inhibitor 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 a potassium sparing diuretic and an ACE inhibitor. In all patients taking eplerenone who start taking an ACE inhibitor, check serum potassium and creatinine levels after 3-7 days of concurrent therapy. PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with a potassium sparing diuretic and an ACE inhibitors. In all patients taking eplerenone who start taking an ACE inhibitor, check serum potassium and creatinine levels after 3-7 days of concurrent therapy.

DISCUSSION: In a nested case-control study of heart failure patients receiving continuous ACE inhibitor/ARB therapy (n = 1,491,894), the risk of hyperkalemia was significantly associated with spironolactone use (odds ratio (OR) = 13.59; confidence interval (CI) = 11.63-15.88).(20) In a systemic literature review and meta-analysis of 20 randomized controlled studies, it was found that treatment with spironolactone and ACEI/ARB combination therapy compared to ACEI/ARB therapy alone increased the mean serum potassium concentration by 0.19 mEq/L (95% CI, 0.12-0.26 mEq/L).(21) A retrospective cohort study in patients with hypertension, diabetes, and albuminuria between 2008 and 2018 examined the efficacy and safety of mineralocorticoid receptor antagonists eplerenone and spironolactone in combination with ACEI/ARB compared to ACEI/ARB alone. Hyperkalemia was more frequent in combination therapy patients (n=1,282) versus monotherapy (n=5,484) (22.3 vs 10.9 per 100 person-years for combination and monotherapy, respectively; HR = 1.78, 95% CI: 1.42, 2.24).(22) Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. There are case reports of hyperkalemia during concurrent therapy with ARBs and spironolactone and with aliskiren and spironolactone. Based on this data, serum potassium levels should be monitored in patients receiving concomitant ACE inhibitors with potassium sparing diuretics. Selected ACE inhibitors linked to this monograph include: alacepril, cilazapril, delapril, imidapril, spirapril, temocapril, and zofenopril. DISCUSSION: In a nested case-control study of heart failure patients receiving continuous ACE inhibitor/ARB therapy (n = 1,491,894), the risk of hyperkalemia was significantly associated with concomitant spironolactone use (odds ratio (OR) = 13.59; confidence interval (CI) = 11.63-15.88).(20) In a systemic literature review and meta-analysis of 20 randomized controlled studies, it was found that treatment with spironolactone and ACEI/ARB combination therapy compared to ACEI/ARB therapy alone increased the mean serum potassium concentration by 0.19 mEq/L (95% CI, 0.12-0.26 mEq/L).(21) A retrospective cohort study in patients with hypertension, diabetes, and albuminuria between 2008 and 2018 examined the efficacy and safety of mineralocorticoid receptor antagonists eplerenone and spironolactone in combination with ACEI/ARB compared to ACEI/ARB alone. Hyperkalemia was more frequent in combination therapy patients (n=1,282) versus monotherapy (n=5,484) (22.3 vs 10.9 per 100 person-years for combination and monotherapy, respectively; HR = 1.78, 95% CI: 1.42, 2.24).(22) Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. There are case reports of hyperkalemia during concurrent therapy with ARBs and spironolactone and with aliskiren and spironolactone. Based on this data, serum potassium levels should be monitored in patients receiving concomitant ACE inhibitors with potassium sparing diuretics. Selected ACE inhibitors linked to this monograph include: benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, and trandolapril.

Selected Antihypertensives And Vasodilators/Apomorphine

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

MECHANISM OF ACTION: Apomorphine causes dose-dependent decreases in blood pressure. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1)

CLINICAL EFFECTS: Concurrent use of antihypertensives and apomorphine may result in orthostatic hypotension with or without dizziness, nausea, or syncope.(1)

PREDISPOSING FACTORS: The risk of orthostatic hypotension may be increased during dose escalation of apomorphine and in patients with renal or hepatic impairment.(1)

PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. Counsel patients about the risk of orthostatic hypotension.(1)

DISCUSSION: Healthy volunteers who took sublingual nitroglycerin (0.4 mg) concomitantly with apomorphine experienced a mean largest decrease in supine systolic blood pressure (SBP) of 9.7 mm Hg and in supine diastolic blood pressure (DBP) of 9.3 mm Hg, and a mean largest decrease in standing SBP and DBP of 14.3 mm Hg and 13.5 mm Hg, respectively. The maximum decrease in SBP and DBP was 65 mm Hg and 43 mm Hg, respectively. When apomorphine was taken alone, the mean largest decrease in supine SBP and DBP was 6.1 mm Hg and 7.3 mm Hg, respectively, and in standing SBP and DBP was 6.7 mm Hg and 8.4 mm Hg, respectively.(1)

Selected Antihypertensives/Tizanidine

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

MECHANISM OF ACTION: Tizanidine is an alpha-2 agonist. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1)

CLINICAL EFFECTS: Concurrent use of antihypertensives and tizanidine may result in hypotension.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. The risk of hypotension may be decreased by careful titration of tizanidine dosages and monitoring for hypotension prior to dose advancement. Counsel patients about the risk of orthostatic hypotension.(1)

DISCUSSION: Severe hypotension has been reported following the addition of tizanidine to existing lisinopril therapy.(2-4)

Selected Potassium Sparing Diuretics/Moexipril

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

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

CLINICAL EFFECTS: Concurrent use of potassium sparing diuretics with an ACE inhibitor such as moexipril 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 a potassium sparing diuretic and an ACE inhibitor such as moexipril. In all patients taking eplerenone who start taking moexipril, check serum potassium and creatinine levels after 3-7 days of concurrent therapy.

DISCUSSION: In a nested case-control study of heart failure patients receiving continuous ACE inhibitor/ARB therapy (n = 1,491,894), the risk of hyperkalemia was significantly associated with spironolactone use (odds ratio (OR) = 13.59; confidence interval (CI) = 11.63-15.88).(20) Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. There are case reports of hyperkalemia during concurrent therapy with ARBs and spironolactone and with aliskiren and spironolactone. Based on this data, serum potassium levels should be monitored in patients receiving concomitant moexipril with potassium sparing diuretics.

Thiazide & Related Diuretics/Cholestyramine; Colestipol

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

MECHANISM OF ACTION: Cholestyramine and colestipol, anionic exchange resins, bind thiazides and furosemide, preventing their absorption.

CLINICAL EFFECTS: Concurrent administration may result in decreased absorption of the diuretic, as well as decreased clinical effects. Decreased absorption of furosemide by 80-90% has been reported.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Available data suggest that colestipol may be preferable to cholestyramine. Separating administration times lessens the the extent of this interaction but still remains significant. Separate the administration of cholestyramine and the thiazide by at least four hours and that of colestipol by at least two hours. Separate the administration of furosemide and cholestyramine or colestipol by two to three hours.

DISCUSSION: Administration of cholestyramine or colestipol decreased total urinary excretion of hydrochlorothiazide by 85% and 43% respectively. These studies indicate that no dosing schedule will eliminate this interaction. Even four hours of separation reduces the absorption of hydrochlorothiazide by 35%. Similar reductions occurred to serum hydrochlorothiazide concentrations. In a study in six subjects, the concurrent administration of cholestyramine and furosemide resulted in a decrease in furosemide area-under-curve (AUC) by 90% and a decrease in furosemide's diuretic effects. Concurrent administration of furosemide and colestipol resulted in a decrease in furosemide AUC by 80% and a decrease in furosemide's diuretic effects.

Thiazide Diuretics/Allopurinol

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

MECHANISM OF ACTION: The exact mechanism is unknown. Allopurinol has been documented to cause Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), and Drug reaction with eosinophilia and systemic symptoms (DRESS).(1)

CLINICAL EFFECTS: Concurrent administration of allopurinol with thiazides may result in an increased incidence of rash which may be severe.

PREDISPOSING FACTORS: Patients who are HLA-B*58:01 positive or have impaired renal function may be at increased risk.

PATIENT MANAGEMENT: The manufacturer of allopurinol recommends monitoring renal function and reducing the dose of allopurinol in patients with concomitant thiazide diuretic use and impaired renal function. Discontinue allopurinol at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction when used with thiazide diuretics. Instruct patients to seek medical attention for any peeling skin rash or blisters.(1)

DISCUSSION: There are case reports of patients on concurrent thiazide diuretics and allopurinol developing SJS, TEN, or DRESS.(1,2)

Triamterene; Amiloride/Selected Nsaids

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

MECHANISM OF ACTION: The exact mechanism is unknown; however, nonsteroidal anti-inflammatory (NSAID) inhibition of prostaglandins may allow triamterene or amiloride- induced nephrotoxicity or hyperkalemia to occur in some patients.

CLINICAL EFFECTS: Possible renal failure or hyperkalemia.

PREDISPOSING FACTORS: Preexisting renal impairment.

PATIENT MANAGEMENT: When possible, avoid concurrent therapy with triamterene or amiloride with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents.

DISCUSSION: Acute renal failure and hyperkalemia have been reported in patients receiving concurrent therapy with therapeutic doses of triamterene or amiloride with NSAIDs. Although a majority of these reports have involved indomethacin, other NSAIDs have been implicated (diclofenac, flurbiprofen, and ibuprofen).

Triamterene; Amiloride/Selected Nsaids; Salicylates

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

MECHANISM OF ACTION: The exact mechanism is unknown; however, nonsteroidal anti-inflammatory (NSAID) inhibition of prostaglandins may allow triamterene or amiloride- induced nephrotoxicity or hyperkalemia to occur in some patients.

CLINICAL EFFECTS: Possible renal failure or hyperkalemia.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: When possible, avoid concurrent therapy with triamterene or amiloride with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents.

DISCUSSION: Although acute renal failure and hyperkalemia have only been reported in studies and case reports involving indomethacin, diclofenac, flurbiprofen, and ibuprofen with either triamterene or amiloride, the proposed mechanism suggests that all nonsteroidal anti-inflammatory agents may be capable of this interaction. Patients receiving diuretics are at an increased risk of NSAID-induced renal failure.

There is no enhanced messaging for this drug.

• Anuria
• Hyperkalemia
• Pregnancy
• Severe hepatic disease

• Acidosis
• Chronic kidney disease stage 2 (mild) GFR 60-89 ml/min
• 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
• Gout
• Hepatic failure
• Hyperuricemia
• Hypochloremic alkalosis
• Hypokalemia
• Hypomagnesemia
• Hyponatremia
• Hypotension
• Hypovolemia
• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Kidney stone
• Neonatal hyperbilirubinemia

• Basal cell carcinoma of skin
• Diabetes mellitus
• Disease of liver
• Folic acid deficient megaloblastic anemia
• Hypercalcemia
• Hypercholesterolemia
• Hyperparathyroidism
• Hyperuricemia
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Squamous cell carcinoma of skin
• Sympathectomy
• Systemic lupus erythematosus
• Type 1 diabetes mellitus
• Type 2 diabetes mellitus

There is no enhanced messaging for this drug.

More Frequent

• Hypochloremic alkalosis
• Hypokalemia
• Hyponatremia
• Hypotension

Less Frequent

• Hyperglycemia
• Hyperkalemia
• Hypomagnesemia
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Nephrotoxicity

Rare or Very Rare

• Abnormal hepatic function tests
• Acute pancreatitis
• Acute renal failure
• Acute respiratory distress syndrome
• Agranulocytosis
• Anaphylaxis
• Anaphylaxis
• Aplastic anemia
• Choroidal effusion
• Erythema multiforme
• Exfoliative dermatitis
• Gout
• Hemolytic anemia
• Hepatitis
• Hypercalcemia
• Hyperparathyroidism
• Hypersensitivity angiitis
• Hypersensitivity drug reaction
• Hyperuricemia
• Interstitial nephritis
• Interstitial nephritis
• Interstitial pneumonitis
• Jaundice
• Jaundice
• Kidney stone
• Leukopenia
• Megaloblastic anemia
• Metabolic acidosis
• Myopia
• Obstructive hyperbilirubinemia
• Purpura
• Secondary angle-closure glaucoma
• Skin rash
• Squamous cell carcinoma of skin
• Stevens-johnson syndrome
• Systemic lupus erythematosus
• Thrombocytopenic disorder
• Thrombocytopenic disorder
• Toxic epidermal necrolysis
• Vasculitis

Less Frequent

• Abdominal pain with cramps
• Abnormal sexual function
• Anorexia
• Diarrhea
• Dizziness
• Dizziness
• Fatigue
• Headache disorder
• Hyponatremia
• Nausea
• Orthostatic hypotension
• Skin photosensitivity
• Vomiting

Rare or Very Rare

• Anticholinergic toxicity
• Basal cell carcinoma of skin
• Blurred vision
• Constipation
• Diarrhea
• Erectile dysfunction
• Fatigue
• Fever
• Gastrointestinal irritation
• General weakness
• General weakness
• Headache disorder
• Hypercholesterolemia
• Hypertriglyceridemia
• Hyperuricemia
• Muscle spasm
• Nausea and vomiting
• Nervousness
• Paresthesia
• Sialoadenitis
• Skin rash
• Urticaria
• Vertigo
• Xanthopsia
• Xerostomia

No enhanced messaging available.

No enhanced messaging available.

There are no adequate and well-controlled studies using triamterene in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks (these include adverse effects reported in adults) to the fetus.

Since triamterene has been shown to distribute into milk in animals and may distribute into human milk, the drug should not be used in nursing women. If use of triamterene is deemed essential, nursing should be discontinued.

No enhanced messaging available.