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Aldactone
Classes
Aldosterone Antagonists
Administration
Hazardous Drugs Classification
NIOSH 2016 List: Group 2
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.
May be taken without regard to meals; however, should be taken consistently with respect to food.
The commercially available spironolactone oral suspension is not therapeutically equivalent to the tablets. In patients requiring a dose more than 100 mg, another formulation should be used.
Shake well before use.
Measure with a calibrated oral device to ensure accurate dosing.
Extemporaneous Formulas for Oral Suspension
NOTE: The extemporaneous preparation of spironolactone is not FDA-approved.
Several recipes resulting in DIFFERENT final concentrations have been described.
Adherence to stated techniques for preparation is recommended to obtain uniform suspensions and to avoid problems in formulation (e.g., excessively thick suspensions) during compounding.
- Method 1 (1 mg/mL suspension)
Pulverize ten (10) spironolactone 25 mg tablets.
Add a small amount of Purified Water, USP and allow to dissolve for 5 minutes.
Add 50 mL of 1.5% Carboxymethylcellulose and 100 mL of Simple Syrup NF and mix.
Use a sufficient quantity of purified water to produce a total volume of 250 mL.
Transfer to a glass bottle.
Shake well.
Storage: The resulting suspension is stable for 3 months at room temperature or refrigerated.
- Method 2 (2.5, 5, or 10 mg/mL suspension)
Add two hundred (200) spironolactone 25 mg (for 2.5 mg/mL concentration), 50 mg (for 5 mg/mL concentration), or 100 mg (for 10 mg/mL concentration) tablets to a large glass mortar.
Break with the pestle, and grind tablets until they and their film coats are a fine powder.
Slowly add 100 mL of Purified Water USP, and triturate to form a fine paste; any film coat particles should dissolve at this phase.
Gradually add 1900 mL of Cherry Syrup, NF in 3 steps as follows: 1) add about one-third of the cherry syrup to the paste, triturate well, and transfer the mortar contents to a large stainless steel container. 2) Rinse mortar with about one-third of cherry syrup and transfer contents to the stainless steel container. 3) Repeat step 2 with the remaining one-third cherry syrup.
Homogenize for 10 minutes at high speed using a laboratory model homogenizer.
Transfer the resulting suspension to amber glass bottles with constant stirring.
Shake well.
Storage: The resulting suspension is reported stable for 4 weeks at 5 and 30 degrees C.
- Method 3 (25 mg/mL suspension)
Add one hundred twenty (120) spironolactone 25 mg tablets to a large glass mortar.
Break with the pestle, and grind tablets into a fine powder.
Add approximately 40 mL of the chosen vehicle and mix to a uniform paste. Vehicle choices include: 1) a 1:1 mixture of Ora-Sweet and Ora-Plus 2) a 1:1 mixture of Ora-Sweet SF and Ora-Plus 3) cherry syrup.
Add geometric portions of the vehicle almost to volume and mix thoroughly after each addition.
Transfer the contents to a calibrated bottle and add enough vehicle to bring to a total volume of 120 mL.
Storage: The resulting suspension is reported stable for 60 days at 5 and 25 degrees C when protected from light.
Adverse Reactions
hyperkalemia / Delayed / 10.0
bradycardia / Rapid / Incidence not known
new primary malignancy / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
gout / Delayed / 0-1.0
hypomagnesemia / Delayed / Incidence not known
hyperuricemia / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
metabolic alkalosis / Delayed / Incidence not known
metabolic acidosis / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known
postmenopausal bleeding / Delayed / Incidence not known
tumorigenicity / Delayed / Incidence not known
gastritis / Delayed / Incidence not known
ataxia / Delayed / Incidence not known
confusion / Early / Incidence not known
hypovolemia / Early / Incidence not known
hypotension / Rapid / Incidence not known
dehydration / Delayed / Incidence not known
erythema / Early / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
fatigue / Early / Incidence not known
paresthesias / Delayed / Incidence not known
weakness / Early / Incidence not known
amenorrhea / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
mastalgia / Delayed / Incidence not known
menstrual irregularity / Delayed / Incidence not known
abdominal pain / Early / Incidence not known
vomiting / Early / Incidence not known
nausea / Early / Incidence not known
diarrhea / Early / Incidence not known
lethargy / Early / Incidence not known
headache / Early / Incidence not known
drowsiness / Early / Incidence not known
dizziness / Early / Incidence not known
polyuria / Early / Incidence not known
maculopapular rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
fever / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
Common Brand Names
Aldactone, CAROSPIR
Dea Class
Rx
Description
Potassium-sparing diuretic; used for edema, ascites, HTN, hypokalemia, acne vulgaris, polycystic ovary syndrome, female hirsutism, and to diagnose primary hyperaldosteronism; also improves survival and NYHA functional class, and reduces hospitalizations in NYHA Class IV heart failure.
Dosage And Indications
25 to 100 mg PO once daily or in divided doses. May increase dose at 2-week intervals. Dosage more than 100 mg/day usually does not increase effectiveness.
1 to 3.3 mg/kg/day PO given in 1 to 2 divided doses (Max: 100 mg/day). Doses up to 4 mg/kg/day PO given in 1 to 2 divided doses have been reported in an observational study of 100 patients (mean age 20.8 months, range 4 days to 21 years) with various indications, including co-administration with loop diuretics. Allow 72 hours between dosage adjustments due to the gradual onset of action.
1 to 3.3 mg/kg/day PO given in 1 to 2 divided doses. Doses up to 4 mg/kg/day PO given in 1 to 2 divided doses have been reported in an observational study of 100 patients (mean age 20.8 months, range 4 days to 21 years) with various indications, including co-administration with loop diuretics. Allow 72 hours between dosage adjustments due to the gradual onset of action.
20 to 75 mg/day PO in single or divided doses. Titrate dosage as needed every 2 weeks. Doses more than 75 mg/day generally do not provide additional reductions in blood pressure.
12.5 to 25 mg PO once daily, initially. May increase the dose to 50 mg PO once daily, if tolerated and clinically indicated. Guidelines recommend an aldosterone antagonist, in select patients, in combination with an angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI) and evidence-based beta blocker for patients with chronic reduced ejection fraction heart failure (HFrEF) to reduce morbidity and mortality. An aldosterone receptor antagonist is recommended in patients with HFrEF NYHA class II to IV with a GFR of more than 30 mL/minute and potassium less than 5 mEq/L. An aldosterone receptor antagonist may be considered to decrease hospitalizations in patients with preserved ejection fraction heart failure (HFpEF) with EF of 45% or more, elevated B-type natriuretic peptide (BNP) concentrations, or HF admission within 1 year, and estimated GFR of more than 30 mL/minute, creatinine less than 2.5 mg/dL, and potassium less than 5 mEq/L.
1 to 4 mg/kg/day PO in 1 to 4 divided doses (Max: 200 mg/day). Allow 72 hours between dosage adjustments due to the gradual onset of action.
1 to 2 mg/kg/day PO in 1 to 2 divided doses, initially, and then titrate to effect (Max: 3 to 4 mg/kg/day). In 11 infants (1 to 12 months of age) with congestive heart failure secondary to congenital heart disease, 1 to 2 mg/kg/day PO divided every 12 hours was used in combination with digoxin and chlorothiazide. Significant reductions in liver size, weight, and respiratory rate were seen compared to baseline and no significant differences in electrolyte abnormalities were noted compared to a group of infants receiving therapy with potassium supplements, digoxin, and chlorothiazide. In an observational study, 1 to 4 mg/kg/day PO in 1 to 2 divided doses was used in 100 patients (mean age 20.8 months, range 4 days to 21 years) with various indications. Allow 72 hours between dosage adjustments due to the gradual onset of action.
20 mg PO once daily, initially. May increase the dose to 37.5 mg PO once daily, if tolerated and clinically indicated. Guidelines recommend an aldosterone antagonist, in select patients, in combination with an angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI) and evidence-based beta blocker for patients with chronic reduced ejection fraction heart failure (HFrEF) to reduce morbidity and mortality. An aldosterone receptor antagonist is recommended in patients with HFrEF NYHA class II to IV with a GFR of more than 30 mL/minute and potassium less than 5 mEq/L. An aldosterone receptor antagonist may be considered to decrease hospitalizations in patients with preserved ejection fraction heart failure (HFpEF) with EF of 45% or more, elevated B-type natriuretic peptide (BNP) concentrations, or HF admission within 1 year, and estimated GFR of more than 30 mL/minute, creatinine less than 2.5 mg/dL, and potassium less than 5 mEq/L.
100 mg/day PO in single or divided doses, initially. May increase the dose after at least 72 hours if needed to obtain the desired effect when given as the sole agent for diuresis. Usual dose: 25 to 200 mg/day. Max: 400 mg/day.
1 to 4 mg/kg/day (Max: 200 mg/day) PO in 1 to 4 divided doses. Allow 72 hours between dosage adjustments due to the gradual onset of action.
1 to 2 mg/kg/day PO in 1 to 2 divided doses, initially. Increase the dose if needed to obtain the desired effect. Allow 72 hours between dosage adjustments due to the gradual onset of action. Max: 3 to 4 mg/kg/day. In 11 infants (1 to 12 months) with congestive heart failure secondary to congenital heart disease, 1 to 2 mg/kg/day PO divided every 12 hours was used in combination with digoxin and chlorothiazide. Significant reductions in liver size, weight, and respiratory rate were seen compared to baseline and no significant differences in electrolyte abnormalities were noted compared to a group of infants receiving therapy with potassium supplements, digoxin, and chlorothiazide. In an observational study, 1 to 4 mg/kg/day PO in 1 to 2 divided doses was used in 100 patients (mean age 20.8 months, range 4 days to 21 years) with various indications.
1 to 2 mg/kg/day PO in 1 to 2 divided doses, initially. Increase the dose if needed to obtain the desired effect. Allow 72 hours between dosage adjustments due to the gradual onset of action. Max: 3 to 4 mg/kg/day. In 11 infants (1 to 12 months) with congestive heart failure secondary to congenital heart disease, 1 to 2 mg/kg/day PO divided every 12 hours was used in combination with digoxin and chlorothiazide. Significant reductions in liver size, weight, and respiratory rate were seen compared to baseline and no significant differences in electrolyte abnormalities were noted compared to a group of infants receiving therapy with potassium supplements, digoxin, and chlorothiazide. In an observational study, 1 to 4 mg/kg/day PO in 1 to 2 divided doses was used in 100 patients (mean age 20.8 months, range 4 days to 21 years) with various indications.
75 mg/day PO in single or divided doses. May increase the dose after at least 5 days if needed to obtain the desired effect when given as the sole agent for diuresis. Max: 100 mg/day; use another formulation if more than 100 mg/day is required.
100 mg/day PO in single or divided doses, initially. May increase the dose after at least 5 days if needed to obtain the desired effect when given as the sole agent for diuresis. Usual dose: 25 to 200 mg/day.
1 to 4 mg/kg/day (Max: 200 mg/day) PO in 1 to 4 divided doses. Allow 72 hours between dosage adjustments due to the gradual onset of action.
1 to 2 mg/kg/day PO in 1 to 2 divided doses, initially. Increase the dose if needed to obtain the desired effect. Allow 72 hours between dosage adjustments due to the gradual onset of action. Max: 3 to 4 mg/kg/day. In 11 infants (1 to 12 months) with congestive heart failure secondary to congenital heart disease, 1 to 2 mg/kg/day PO divided every 12 hours was used in combination with digoxin and chlorothiazide. Significant reductions in liver size, weight, and respiratory rate were seen compared to baseline and no significant differences in electrolyte abnormalities were noted compared to a group of infants receiving therapy with potassium supplements, digoxin, and chlorothiazide. In an observational study, 1 to 4 mg/kg/day PO in 1 to 2 divided doses was used in 100 patients (mean age 20.8 months, range 4 days to 21 years) with various indications.
1 to 2 mg/kg/day PO in 1 to 2 divided doses, initially. Increase the dose if needed to obtain the desired effect. Allow 72 hours between dosage adjustments due to the gradual onset of action. Max: 3 to 4 mg/kg/day. In 11 infants (1 to 12 months) with congestive heart failure secondary to congenital heart disease, 1 to 2 mg/kg/day PO divided every 12 hours was used in combination with digoxin and chlorothiazide. Significant reductions in liver size, weight, and respiratory rate were seen compared to baseline and no significant differences in electrolyte abnormalities were noted compared to a group of infants receiving therapy with potassium supplements, digoxin, and chlorothiazide. In an observational study, 1 to 4 mg/kg/day PO in 1 to 2 divided doses was used in 100 patients (mean age 20.8 months, range 4 days to 21 years) with various indications.
100 to 400 mg/day PO in preparation for surgery. May use at lowest effective dosage for long-term maintenance therapy in patients unsuitable for surgery.
3 to 4 mg/kg/day PO divided twice daily has been used in combination with chlorothiazide or hydrochlorothiazide. Because of the potential effects on electrolytes, it may be prudent to begin with a lower dose and titrate as tolerated in patients at risk for electrolyte imbalance.
Initially, 25 mg PO 2 to 4 times daily. Alternatively, 100 mg PO once daily from day 12 of the cycle until menstruation was found to be statistically superior to placebo in relieving the feeling of bloatedness. Diuretic use should be limited to patients who demonstrate a premenstrual weight gain of more than 1.4 kg. Individualize dosage to achieve desired diuresis and minimize weight gain.
50 to 200 mg/day PO in 1 or 2 divided doses.
50 to 200 mg/day PO in 1 or 2 divided doses.
25 to 100 mg PO once or twice daily.
25 to 100 mg PO once or twice daily.
†Indicates off-label use
Dosing Considerations
In patients with cirrhosis, start with the lowest initial dose and titrate slowly. Use with caution in patients with hepatic disease; minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Renal ImpairmentTablets or Extemporaneous Suspension
CrCl 10 mL/minute/1.73 m2 or more: No dosage adjustment needed; however, monitor renal function closely as hyperkalemia is more likely to occur in patients with renal impairment. For heart failure patients with CrCl 30 to 49 mL/minute, clinical practice guidelines recommend 12.5 mg PO once daily or every other day for the first 4 weeks followed by 12.5 to 25 mg PO once daily.
CrCl less than 10 mL/minute/1.73 m2: Avoid use.
Suspension (CaroSpir)
CrCl more than 50 mL/minute/1.73 m2: No dosage adjustment needed.
CrCl 30 to 50 mL/minute/1.73 m2: Consider initial dosage of 10 mg PO once daily due to the risk of hyperkalemia.
Drug Interactions
Abiraterone: (Major) Avoid using spironolactone in persons with prostate cancer receiving abiraterone. Spironolactone has been observed to increase prostate-specific antigen (PSA) concentrations and has been associated with tumor progression in persons with prostate cancer treated with abiraterone. Spironolactone is considered an androgen receptor antagonist but may exhibit androgen agonism in the setting of abiraterone-related androgen depletion.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Acetaminophen; Aspirin: (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Consider a reduced dose of dihydrocodeine with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the dihydrocodeine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Concomitant use of dihydrocodeine with spironolactone may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If spironolactone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Spironolactone is a weak inhibitor of CYP3A, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with dihydrocodeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with spironolactone may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of spironolactone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If spironolactone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Spironolactone is a weak inhibitor of CYP3A4. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like spironolactone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If spironolactone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Acetaminophen; Ibuprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like spironolactone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If spironolactone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Acetaminophen; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetazolamide: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Acrivastine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Albuterol; Budesonide: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Aldesleukin, IL-2: (Moderate) Potassium sparing diuretics may potentiate the hypotension seen with aldesleukin, IL 2.
Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
Alfentanil: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like spironolactone can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If spironolactone is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with alfentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Aliskiren: (Moderate) Due to the risk of hyperkalemia, drugs that increase serum potassium concentration, such as potassium-sparing diuretics, should be used cautiously in patients taking aliskiren. Electrolytes should be routinely monitored in patients receiving aliskiren. Aliskiren can enhance the effects of diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Also, patients with hyponatremia or hypovolemia may become hypotensive and/or develop reversible renal insufficiency when given aliskiren and diuretics.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Due to the risk of hyperkalemia, drugs that increase serum potassium concentration, such as potassium-sparing diuretics, should be used cautiously in patients taking aliskiren. Electrolytes should be routinely monitored in patients receiving aliskiren. Aliskiren can enhance the effects of diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Also, patients with hyponatremia or hypovolemia may become hypotensive and/or develop reversible renal insufficiency when given aliskiren and diuretics.
Alprazolam: (Major) Avoid coadministration of alprazolam and spironolactone due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with spironolactone, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased alprazolam maximum concentration by 82%, decreased clearance by 42%, and increased half-life by 16%.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as spironolactone or other potassium-sparing diuretics, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Ambrisentan: (Moderate) Although no specific interactions have been documented, ambrisentan has vasodilatory effects and may contribute additive hypotensive effects when given with other antihypertensive agents. Patients receiving ambrisentan in combination with other antihypertensive agents should be monitored for decreases in blood pressure.
Amifostine: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
Amlodipine; Atorvastatin: (Minor) Because HMG-CoA reductase inhibitors may theoretically blunt adrenal and/or gonadal steroid production by interfering with cholesterol synthesis, the manufacturer recommends that caution should be exercised when atorvastatin is administered concomitantly with drugs that may decrease the concentrations or activity of endogenous hormones, such as spironolactone. The clinical relevance of these potential interactions has not been established.
Amlodipine; Benazepril: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Amlodipine; Celecoxib: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Amlodipine; Olmesartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Amlodipine; Valsartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
Amphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
Amphetamine; Dextroamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
Angiotensin II receptor antagonists: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Angiotensin-converting enzyme inhibitors: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Apomorphine: (Moderate) Use of potassium-sparing diuretics and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
Aripiprazole: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of spironolactone. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor. Adults receiving a combination of a CYP2D6 inhibitor and spironolactone for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A4; spironolactone is a weak CYP3A4 inhibitor. Additionally, monitor blood pressure and adjust spironolactone dose accordingly as aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Arsenic Trioxide: (Moderate) Use caution when using arsenic trioxide with potassium-sparing diuretics. Electrolyte abnormalities, such as increased potassium, may increase the risk for QT prolongation and torsade de pointes.
Articaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Aspirin, ASA: (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Barbiturates, such as butalbital, may potentiate orthostatic hypotension when given concomitantly with spironolactone. (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Aspirin, ASA; Caffeine: (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with spironolactone may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of spironolactone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If spironolactone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Spironolactone is a weak inhibitor of CYP3A4. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Aspirin, ASA; Dipyridamole: (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Aspirin, ASA; Omeprazole: (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like spironolactone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If spironolactone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Atorvastatin: (Minor) Because HMG-CoA reductase inhibitors may theoretically blunt adrenal and/or gonadal steroid production by interfering with cholesterol synthesis, the manufacturer recommends that caution should be exercised when atorvastatin is administered concomitantly with drugs that may decrease the concentrations or activity of endogenous hormones, such as spironolactone. The clinical relevance of these potential interactions has not been established.
Azelastine; Fluticasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Azilsartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Azilsartan; Chlorthalidone: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Beclomethasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Belladonna; Opium: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with opium. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Benazepril: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Benzhydrocodone; Acetaminophen: (Moderate) Consider a reduced dose of benzhydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like spironolactone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of benzhydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If spironolactone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to benzhydrocodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with benzhydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
Benzphetamine: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
Betamethasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Bismuth Subsalicylate: (Moderate) Monitor renal function periodically during concomitant use of spironolactone with bismuth subsalicylate. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and bismuth subsalicylate may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Monitor renal function periodically during concomitant use of spironolactone with bismuth subsalicylate. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and bismuth subsalicylate may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Brompheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Brompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Budesonide: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Budesonide; Formoterol: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Budesonide; Glycopyrrolate; Formoterol: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Bupivacaine; Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with spironolactone is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Bupivacaine; Meloxicam: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Buprenorphine: (Moderate) Concomitant use of buprenorphine and spironolactone can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when spironolactone is added after a stable buprenorphine dose is achieved. If concurrent use is necessary, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping spironolactone, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If spironolactone is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A4 and spironolactone is a CYP3A4 inhibitor. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with buprenorphine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Buprenorphine; Naloxone: (Moderate) Concomitant use of buprenorphine and spironolactone can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when spironolactone is added after a stable buprenorphine dose is achieved. If concurrent use is necessary, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping spironolactone, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If spironolactone is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A4 and spironolactone is a CYP3A4 inhibitor. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with buprenorphine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Butalbital; Acetaminophen: (Moderate) Barbiturates, such as butalbital, may potentiate orthostatic hypotension when given concomitantly with spironolactone.
Butalbital; Acetaminophen; Caffeine: (Moderate) Barbiturates, such as butalbital, may potentiate orthostatic hypotension when given concomitantly with spironolactone.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Barbiturates, such as butalbital, may potentiate orthostatic hypotension when given concomitantly with spironolactone. (Moderate) Concomitant use of codeine with spironolactone may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of spironolactone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If spironolactone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Spironolactone is a weak inhibitor of CYP3A4. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Barbiturates, such as butalbital, may potentiate orthostatic hypotension when given concomitantly with spironolactone. (Moderate) Concomitant use of codeine with spironolactone may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of spironolactone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If spironolactone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Spironolactone is a weak inhibitor of CYP3A4. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Monitor renal function and for decreased efficacy of spironolactone if coadministration with aspirin is necessary. The spironolactone dose may need to be titrated to higher maintenance dose. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and aspirin may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. Aspirin may reduce the efficacy of spironolactone. A single aspirin 600 mg dose inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including potassium-sparing diuretics. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics may increase the risk of acute phosphate nephropathy in patients receiving sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Candesartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Captopril: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Carbamazepine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of spironolactone; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and spironolactone is a CYP3A inhibitor.
Carbidopa; Levodopa: (Moderate) Monitor blood pressure during concomitant levodopa and potassium-sparing diuretic use due to risk for additive hypotension; a potassium-sparing diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor blood pressure during concomitant levodopa and potassium-sparing diuretic use due to risk for additive hypotension; a potassium-sparing diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Carbonic anhydrase inhibitors: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Cardiac glycosides: (Major) Monitor serum digoxin concentrations before initiating concomitant spironolactone. Reduce digoxin concentrations by decreasing the dose by approximately 15% to 30% or by modifying the dosing frequency and continue monitoring. Concomitant use increased digoxin concentrations by 25%. Spironolactone and its metabolites interfere with radioimmunoassays for digoxin and increase the apparent exposure to digoxin. It is unknown to what extent, if any, spironolactone may increase actual digoxin exposure. In persons taking concomitant digoxin, use an assay that does not interact with spironolactone.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Celecoxib: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Celecoxib; Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with spironolactone is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of spironolactone, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with tramadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Cetirizine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with spironolactone may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of spironolactone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like spironolactone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If spironolactone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Cholestyramine: (Moderate) Use caution if spironolactone is administered concurrently with cholestyramine. Hyperkalemic metabolic acidosis has been reported in patients given spironolactone concurrently with cholestyramine.
Choline Salicylate; Magnesium Salicylate: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and magnesium salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
Ciclesonide: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Cidofovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Citalopram: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and citalopram use; consider discontinuing citalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Citric Acid; Potassium Citrate; Sodium Citrate: (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.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with spironolactone and monitor for adverse reactions. If spironolactone is discontinued, monitor for lack of clozapine effect, and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is partially metabolized by CYP3A. Spironolactone is a weak CYP3A inhibitor. Additionally, monitor blood pressure and adjust spironolactone dose accordingly as clozapine may enhance the hypotensive effects of antihypertensive agents.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine: (Moderate) Concomitant use of codeine with spironolactone may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of spironolactone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If spironolactone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Spironolactone is a weak inhibitor of CYP3A4. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with spironolactone may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of spironolactone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If spironolactone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Spironolactone is a weak inhibitor of CYP3A4. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with spironolactone may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of spironolactone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If spironolactone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Spironolactone is a weak inhibitor of CYP3A4. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with spironolactone may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of spironolactone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If spironolactone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Spironolactone is a weak inhibitor of CYP3A4. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with spironolactone may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of spironolactone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If spironolactone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Spironolactone is a weak inhibitor of CYP3A4. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Co-Enzyme Q10, Ubiquinone: (Moderate) Monitor blood pressure during concomitant co-enzyme Q10 (ubiquinone) and potassium-sparing diuretic use. Concomitant use may result in additive hypotension.
Corticosteroids: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Corticotropin, ACTH: (Minor) Monitor serum electrolytes, particularly serum calcium concentrations, during concomitant corticotropin and potassium-sparing diuretic use. Corticotropin may accentuate the electrolyte loss associated with diuretic therapy.
Cortisone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Cosyntropin: (Major) Patients receiving spironolactone should omit their pre-test doses on the day selected for testing. Patients taking inadvertent doses of spironolactone may exhibit abnormally high basal plasma cortisol concentrations and a decreased response to the test.
Cyclosporine: (Major) Avoid concomitant use of cyclosporine and potassium-sparing diuretics, such as spironolactone, due to the risk of hyperkalemia. If concomitant use is necessary, closely monitor serum potassium concentrations. Additionally, closely monitor cyclosporine whole blood trough concentrations as appropriate and watch for cyclosporine-related adverse reactions as concurrent use may increase cyclosporine exposure. The dose of cyclosporine may need to be adjusted. Cyclosporine is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor.
Dalteparin: (Moderate) Monitor serum potassium during concomitant low molecular weight heparin (LMWH) and spironolactone use due to the risk for hyperkalemia. Cases of hyperkalemia have been reported with coadministration of LMWH and spironolactone.
Darifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Deflazacort: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Desloratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Desvenlafaxine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Dexamethasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Dexbrompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dexmethylphenidate: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Dextroamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Diazepam: (Moderate) Monitor for an increase in diazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with spironolactone is necessary. Concurrent use may increase diazepam exposure. Diazepam is a CYP3A substrate and spironolactone is a CYP3A inhibitor.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents.
Dichlorphenamide: (Moderate) Use dichlorphenamide and spironolactone together with caution. Metabolic acidosis is associated with the use of dichlorphenamide and has been reported with spironolactone in patients with decompensated hepatic cirrhosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Diclofenac; Misoprostol: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Diflunisal: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Digoxin: (Major) Monitor serum digoxin concentrations before initiating concomitant spironolactone. Reduce digoxin concentrations by decreasing the dose by approximately 15% to 30% or by modifying the dosing frequency and continue monitoring. Concomitant use increased digoxin concentrations by 25%. Spironolactone and its metabolites interfere with radioimmunoassays for digoxin and increase the apparent exposure to digoxin. It is unknown to what extent, if any, spironolactone may increase actual digoxin exposure. In persons taking concomitant digoxin, use an assay that does not interact with spironolactone.
Diphenhydramine; Ibuprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Diphenhydramine; Naproxen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Disopyramide: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with spironolactone is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
Dofetilide: (Moderate) Monitor for an increase in dofetilide-related adverse reactions, including QT prolongation, if coadministration with spironolactone is necessary as concurrent use may increase dofetilide exposure. Spironolactone is a weak CYP3A4 inhibitor. Dofetilide is a minor CYP3A4 substrate; however, because there is a linear relationship between dofetilide plasma concentration and QTc, concomitant administration of CYP3A4 inhibitors may increase the risk of arrhythmia (torsade de pointes).
Drospirenone: (Moderate) Monitor serum potassium concentration during concomitant drospirenone and potassium-sparing diuretic use due to increased risk for hyperkalemia. Drospirenone has anti-mineralocorticoid activity, including the potential for hyperkalemia.
Drospirenone; Estetrol: (Moderate) Monitor serum potassium concentration during concomitant drospirenone and potassium-sparing diuretic use due to increased risk for hyperkalemia. Drospirenone has anti-mineralocorticoid activity, including the potential for hyperkalemia.
Drospirenone; Estradiol: (Moderate) Monitor serum potassium concentration during concomitant drospirenone and potassium-sparing diuretic use due to increased risk for hyperkalemia. Drospirenone has anti-mineralocorticoid activity, including the potential for hyperkalemia.
Drospirenone; Ethinyl Estradiol: (Moderate) Monitor serum potassium concentration during concomitant drospirenone and potassium-sparing diuretic use due to increased risk for hyperkalemia. Drospirenone has anti-mineralocorticoid activity, including the potential for hyperkalemia.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Monitor serum potassium concentration during concomitant drospirenone and potassium-sparing diuretic use due to increased risk for hyperkalemia. Drospirenone has anti-mineralocorticoid activity, including the potential for hyperkalemia.
Duloxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Eliglustat: (Major) Coadministration of eliglustat and spironolactone is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Spironolactone is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Empagliflozin: (Moderate) Administer empagliflozin with caution in patients receiving diuretics. When empagliflozin is initiated in patients already receiving diuretics, volume depletion can occur. Patients with impaired renal function, low systolic blood pressure, or who are elderly may also be at a greater risk for volume depletion and perhaps symptomatic hypotension. Before initiating empagliflozin in patients with one or more of these characteristics, assess volume status and correct if necessary. Monitor for signs and symptoms after initiating therapy.
Empagliflozin; Linagliptin: (Moderate) Administer empagliflozin with caution in patients receiving diuretics. When empagliflozin is initiated in patients already receiving diuretics, volume depletion can occur. Patients with impaired renal function, low systolic blood pressure, or who are elderly may also be at a greater risk for volume depletion and perhaps symptomatic hypotension. Before initiating empagliflozin in patients with one or more of these characteristics, assess volume status and correct if necessary. Monitor for signs and symptoms after initiating therapy.
Empagliflozin; Linagliptin; Metformin: (Moderate) Administer empagliflozin with caution in patients receiving diuretics. When empagliflozin is initiated in patients already receiving diuretics, volume depletion can occur. Patients with impaired renal function, low systolic blood pressure, or who are elderly may also be at a greater risk for volume depletion and perhaps symptomatic hypotension. Before initiating empagliflozin in patients with one or more of these characteristics, assess volume status and correct if necessary. Monitor for signs and symptoms after initiating therapy.
Empagliflozin; Metformin: (Moderate) Administer empagliflozin with caution in patients receiving diuretics. When empagliflozin is initiated in patients already receiving diuretics, volume depletion can occur. Patients with impaired renal function, low systolic blood pressure, or who are elderly may also be at a greater risk for volume depletion and perhaps symptomatic hypotension. Before initiating empagliflozin in patients with one or more of these characteristics, assess volume status and correct if necessary. Monitor for signs and symptoms after initiating therapy.
Enalapril, Enalaprilat: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Enoxaparin: (Moderate) Monitor serum potassium during concomitant low molecular weight heparin (LMWH) and spironolactone use due to the risk for hyperkalemia. Cases of hyperkalemia have been reported with coadministration of LMWH and spironolactone.
Ephedrine: (Major) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by potassium-sparing diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Ephedrine; Guaifenesin: (Major) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by potassium-sparing diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Eplerenone: (Contraindicated) Eplerenone should not be used concomitantly with potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene) because of the increased risk of developing hyperkalemia. The combine use of these medications in patients with hypertension or renal impairment contraindicated.
Epoprostenol: (Moderate) Epoprostenol can have additive effects when administered with other antihypertensive agents. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
Eprosartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Escitalopram: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness.
Ethiodized Oil: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Etodolac: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Felodipine: (Moderate) Concurrent use of felodipine and spironolactone should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a sensitive CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor. Concurrent use of another weak CYP3A4 inhibitor increased felodipine AUC and Cmax by approximately 50%.
Fenoprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A substrate, and coadministration with CYP3A inhibitors like spironolactone can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If spironolactone is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with fentanyl. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Fexofenadine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or spironolactone; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased overall exposure to finerenone by 21%.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Monitor blood pressure during concomitant fish oil and potassium-sparing diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Flibanserin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including spironolactone, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Fludrocortisone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Flunisolide: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Fluoxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and fluoxetine use; consider discontinuing fluoxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Flurbiprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Fluticasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Fluticasone; Salmeterol: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Fluticasone; Umeclidinium; Vilanterol: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Fluticasone; Vilanterol: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Fluvoxamine: (Moderate) Patients receiving a diuretic during treatment with fluvoxamine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/L have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluvoxamine should be considered in patients who develop symptomatic hyponatremia.
Food: (Major) Licorice extract, which contains glycyrrhizic acid, possesses aldosterone-like properties. Thus, licorice candy and foods containing licorice extract should be avoided by patients taking spironolactone in order to not antagonize the drug's therapeutic actions.
Formoterol; Mometasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Fosinopril: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like spironolactone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If spironolactone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Haloperidol: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like spironolactone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If spironolactone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like spironolactone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If spironolactone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like spironolactone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If spironolactone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like spironolactone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If spironolactone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Hydrocortisone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Hydromorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with hydromorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
Ibritumomab Tiuxetan: (Major) Avoid coadministration of potassium phosphate and potassium-sparing diuretics as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations. (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.
Ibuprofen lysine: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Ibuprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Ibuprofen; Famotidine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like spironolactone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If spironolactone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Iloprost: (Moderate) Amiloride can have additive effects when administered with other antihypertensive agents. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
Indapamide: (Moderate) The effects of indapamide may be additive when administered with other antihypertensive agents or diuretics. This may be desira ble, but occasionally orthostatic hypotension may occur. Dosages should be adjusted based on clinical response.
Indomethacin: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and diuretics due to the risk of glomerulonephritis and nephrotoxicity.
Intravenous Lipid Emulsions: (Moderate) Monitor blood pressure during concomitant fish oil and potassium-sparing diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Iodine; Potassium Iodide, KI: (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.
Iodixanol: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Iohexol: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Iomeprol: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Iopamidol: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Iopromide: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Ioversol: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Irbesartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Isoproterenol: (Moderate) The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension.
Isosorbide Mononitrate: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension.
Isosulfan Blue: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Isradipine: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with spironolactone is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor.
Ixabepilone: (Moderate) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of spironolactone is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor.
Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Ketoprofen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Ketorolac: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Lemborexant: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with spironolactone as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; spironolactone is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Levodopa: (Moderate) Monitor blood pressure during concomitant levodopa and potassium-sparing diuretic use due to risk for additive hypotension; a potassium-sparing diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Levomilnacipran: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Levorphanol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with levorphanol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with spironolactone is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Lidocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor for lidocaine toxicity if coadministration with spironolactone is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with spironolactone is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Lisdexamfetamine: (Minor) Lisedexamfetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
Lisinopril: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Lithium: (Minor) The risk of lithium toxicity may be increased in patients receiving medications that affect kidney function and sodium excretion, such as diuretics. However, concurrent use of potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene) with lithium is generally regarded as safe. Lithium is primarily reabsorbed from the proximal tubules whereas potassium-sparing diuretics inhibit the endothelial sodium channel in the renal collecting duct thereby inhibiting reabsorption of sodium and lithium. In one small study evaluating concurrent use of lithium and spironolactone, lithium clearance was increased by 16%, which was not considered clinically significant. Amiloride has been safely used as a reversal agent for lithium-induced nephrogenic diabetes insipidus. There is a lack of evidence to evaluate the effect of lithium and triamterene co-administration, however, a significant interaction would not be expected due to the pharmacologic similarities with other potassium-sparing diuretics.
Lomitapide: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with spironolactone is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Spironolactone is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Lonafarnib: (Major) Avoid coadministration of lonafarnib and spironolactone; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. If coadministration is unavoidable, reduce to or continue lonafarnib at a dosage of 115 mg/m2 and closely monitor patients for lonafarnib-related adverse reactions. Resume previous lonafarnib dosage 14 days after discontinuing spironolactone. Lonafarnib is a sensitive CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Loratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Losartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Low Molecular Weight Heparins: (Moderate) Monitor serum potassium during concomitant low molecular weight heparin (LMWH) and spironolactone use due to the risk for hyperkalemia. Cases of hyperkalemia have been reported with coadministration of LMWH and spironolactone.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Magnesium Salicylate: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and magnesium salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Mannitol: (Major) Avoid use of other diuretics with mannitol, if possible. Concomitant administration may potentiate the renal toxicity of mannitol.
Meclofenamate Sodium: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Mefenamic Acid: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Mefloquine: (Moderate) Use mefloquine with caution if coadministration with spironolactone is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A4 and spironolactone is a weak CYP3A4 inhibitor.
Meloxicam: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Meperidine: (Moderate) Consider a reduced dose of meperidine with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, meperidine plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to meperidine. Meperidine is a substrate of CYP3A4 and spironolactone is a weak CYP3A4 inhibitor. Concomitant use with spironolactone can increase meperidine exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of meperidine. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with meperidine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Metformin; Repaglinide: (Moderate) A dose reduction of repaglinide and increased frequency of blood glucose monitoring may be required if coadministration with spironolactone is necessary. Repaglinide is a CYP2C8 substrate and spironolactone is a CYP2C8 inhibitor.
Methadone: (Moderate) Consider a reduced dose of methadone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, methadone plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to methadone. Methadone is a substrate of CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; spironolactone is a weak CYP3A inhibitor. Concomitant use with spironolactone can increase methadone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of methadone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with methadone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
Methazolamide: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension.
Methylphenidate Derivatives: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Methylphenidate: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Methylprednisolone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Midazolam: (Moderate) Use caution when midazolam is coadministered with spironolactone. Concurrent use may increase midazolam exposure leading to prolonged sedation. Midazolam is a sensitive CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Milnacipran: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Mirtazapine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and mirtazapine use; consider discontinuing mirtazapine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Mitotane: (Moderate) An isolated case report indicated that mitotane activity might be antagonized by the concurrent administration of spironolactone. Until more data are available to confirm an interaction, the use of spironolactone with mitotane should be approached with caution.
Moexipril: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Mometasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Morphine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a potassium-sparing diuretic and morphine; increase the dosage of the potassium-sparing diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Morphine; Naltrexone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a potassium-sparing diuretic and morphine; increase the dosage of the potassium-sparing diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Nabumetone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with spironolactone is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and spironolactone is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
Nanoparticle Albumin-Bound Sirolimus: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of spironolactone. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor.
Naproxen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Naproxen; Esomeprazole: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Naproxen; Pseudoephedrine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Nebivolol; Valsartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Nefazodone: (Minor) Although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring and dosage adjustments of either drug may be necessary.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Nimodipine: (Moderate) Monitor blood pressure and reduce the dose of nimodipine as clinically appropriate if coadministration with spironolactone is necessary. Concurrent use may increase nimodipine exposure. Nimodipine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Niraparib; Abiraterone: (Major) Avoid using spironolactone in persons with prostate cancer receiving abiraterone. Spironolactone has been observed to increase prostate-specific antigen (PSA) concentrations and has been associated with tumor progression in persons with prostate cancer treated with abiraterone. Spironolactone is considered an androgen receptor antagonist but may exhibit androgen agonism in the setting of abiraterone-related androgen depletion.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with spironolactone due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and spironolactone is a CYP3A4 inhibitor. Coadministration with another CYP3A4 inhibitor increased the AUC of nisoldipine by 30% to 45%.
Nitrates: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension.
Nitroglycerin: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
Non-Ionic Contrast Media: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Norepinephrine: (Moderate) Spironolactone may reduce the vascular responsiveness to norepinephrine. Caution should be exercised with coadministration of spironolactone and norepinephrine.
Octreotide: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and fluoxetine use; consider discontinuing fluoxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia. (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Oliceridine: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Olmesartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Olopatadine; Mometasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Oxaprozin: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Oxybutynin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with weak CYP3A4 inhibitors like spironolactone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If spironolactone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by diuretics. If these drugs are used together, closely monitor for changes in blood pressure.
Oxymorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when potassium-sparring diuretics are administered with oxymorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with spironolactone is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP2C8 substrate and spironolactone is a CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and potassium-sparing diuretics who are susceptible to hypotension.
Paroxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and paroxetine use; consider discontinuing paroxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Penicillin G: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
Pentazocine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when potassium-sparring diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Pentazocine; Naloxone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when potassium-sparring diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Pentobarbital: (Moderate) Barbiturates may potentiate orthostatic hypotension when given concomitantly with spironolactone.
Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
Perindopril: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Perindopril; Amlodipine: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Phenelzine: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and phenelzine use due to risk for additive hypotension.
Phenobarbital: (Moderate) Barbiturates, such as phenobarbital, may potentiate orthostatic hypotension when given concomitantly with spironolactone.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Barbiturates, such as phenobarbital, may potentiate orthostatic hypotension when given concomitantly with spironolactone.
Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Pimozide: (Major) Avoid concomitant use of pimozide and spironolactone. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate, and spironolactone is a weak CYP3A inhibitor.
Piroxicam: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Polyethylene Glycol; Electrolytes: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Potassium Acetate: (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.
Potassium Bicarbonate: (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.
Potassium Chloride: (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.
Potassium Citrate: (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.
Potassium Citrate; Citric Acid: (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.
Potassium Gluconate: (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.
Potassium Iodide, KI: (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.
Potassium Phosphate: (Major) Avoid coadministration of potassium phosphate and potassium-sparing diuretics as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations.
Potassium Phosphate; Sodium Phosphate: (Major) Avoid coadministration of potassium phosphate and potassium-sparing diuretics as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations.
Potassium: (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.
Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used.
Prednisolone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Prednisone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Prilocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Primidone: (Moderate) Barbiturates, such as primidone, may potentiate orthostatic hypotension when given concomitantly with spironolactone.
Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
Promethazine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Propafenone: (Moderate) Monitor for increased propafenone toxicity if coadministered with spironolactone; concurrent use may increase propafenone exposure and therefore increase the risk of proarrhythmias. Avoid simultaneous use of propafenone and spironolactone with a CYP2D6 inhibitor or in patients with CYP2D6 deficiency. Propafenone is a CYP3A4 and CYP2D6 substrate; spironolactone is a weak CYP3A4 inhibitor.
Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Pseudoephedrine; Triprolidine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Quinapril: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Ramipril: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Remifentanil: (Moderate) Opiate agonists like remifentanil may potentiate orthostatic hypotension when given concomitantly with spironolactone.
Repaglinide: (Moderate) A dose reduction of repaglinide and increased frequency of blood glucose monitoring may be required if coadministration with spironolactone is necessary. Repaglinide is a CYP2C8 substrate and spironolactone is a CYP2C8 inhibitor.
Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Rosiglitazone: (Moderate) Monitor for an increase in rosiglitazone-related adverse effects during concomitant use with spironolactone; adjust the dose of rosiglitazone based on clinical response. Coadministration may increase the exposure of rosiglitazone. Rosiglitazone is a CYP2C8 substrate and spironolactone is a CYP2C8 inhibitor.
Sacubitril; Valsartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Salsalate: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
Secobarbital: (Moderate) Barbiturates, such as secobarbital, may potentiate orthostatic hypotension when given concomitantly with spironolactone.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and methylphenidate use; a potassium-sparing diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Sertraline: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and sertraline use; consider discontinuing sertraline if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of spironolactone. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics may increase the risk of acute phosphate nephropathy in patients receiving sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as diuretics. In addition, use caution in patients receiving drugs where hypokalemia is a particular risk.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (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.
Solifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. Risk versus benefit should be addressed in patients receiving diuretics and solifenacin.
Sparsentan: (Moderate) Monitor potassium during concomitant use of sparsentan and potassium-sparing diuretics. Concomitant use increases the risk for hyperkalemia.
Streptozocin: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if spironolactone must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of spironolactone is necessary. If spironolactone is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like spironolactone can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If spironolactone is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Monitor serum potassium concentrations if trimethoprim and a potassium-sparing diuretic are used together. Concomitant use may increase the risk of hyperkalemia. The risk for trimethoprim-associated hyperkalemia is greatest in patients with additional risk factors for hyperkalemia such as age greater than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim.
Sulindac: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Sumatriptan; Naproxen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Tacrolimus: (Major) Avoid concomitant use of tacrolimus and potassium-sparing diuretics, such as spironolactone, due to the risk of hyperkalemia. If concomitant use is necessary, closely monitor serum potassium concentrations. Additionally, monitor tacrolimus serum concentrations as appropriate and watch for tacrolimus-related adverse reactions if coadministration with spironolactone is necessary. The dose of tacrolimus may need to be reduced. Tacrolimus is a sensitive CYP3A substrate with a narrow therapeutic range; spironolactone is a weak CYP3A inhibitor.
Tapentadol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when potassium-sparing diuretics are administered with tapentadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Telmisartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Telmisartan; Amlodipine: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Tizanidine: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and tizanidine use due to risk for additive hypotension.
Tolmetin: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
Tolterodine: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Tolvaptan: (Moderate) Monitor serum potassium concentrations closely if tolvaptan and potassium-sparing diuretics are used together. In clinical studies, hyperkalemia was reported at a rate 1% to 2% higher when tolvaptan was administered with potassium-sparing diuretics compared to administration of these medications with placebo.
Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with spironolactone is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of spironolactone, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with tramadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Tramadol; Acetaminophen: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with spironolactone is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of spironolactone, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist. Additionally, monitor for decreased diuretic efficacy and additive orthostatic hypotension when spironolactone is administered with tramadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Trandolapril: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Trandolapril; Verapamil: (Moderate) Monitor serum potassium concentrations closely if ACE inhibitors and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function.
Tranylcypromine: (Contraindicated) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated.
Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
Triamcinolone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with spironolactone and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and spironolactone is a weak CYP3A inhibitor.
Trimethoprim: (Moderate) Monitor serum potassium concentrations if trimethoprim and a potassium-sparing diuretic are used together. Concomitant use may increase the risk of hyperkalemia. The risk for trimethoprim-associated hyperkalemia is greatest in patients with additional risk factors for hyperkalemia such as age greater than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with spironolactone. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; spironolactone is a weak CYP3A4 inhibitor.
Valsartan: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
Venlafaxine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Vilazodone: (Moderate) Patients receiving vilazodone with medications known to cause hyponatremia, such as diuretics, may be at increased risk of developing hyponatremia. Hyponatremia has occurred in association with the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of vilazodone, as well as implementation of the appropriate medical interventions.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with spironolactone is necessary. Vinorelbine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Vortioxetine: (Moderate) Patients receiving a diuretic during treatment with vortioxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Clinically significant hyponatremia has been reported during therapy with vortioxetine. One case involving serum sodium levels lower than 110 mmol/l has occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of vortioxetine should be considered in patients who develop symptomatic hyponatremia.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with spironolactone is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Spironolactone is a weak CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Ziconotide: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Ziprasidone: (Moderate) Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents. Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope.
How Supplied
Aldactone/Spironolactone Oral Tab: 25mg, 50mg, 100mg
CAROSPIR/Spironolactone Oral Susp: 1mL, 5mg
Maximum Dosage
400 mg/day PO for tablets; 100 mg/day PO for oral suspension.
Geriatric400 mg/day PO for tablets; 100 mg/day PO for oral suspension.
AdolescentsSafety and efficacy have not been established; however, doses up to 4 mg/kg/day PO (Max: 200 mg/day PO) have been used off-label for edema due to nephrotic syndrome.
ChildrenSafety and efficacy have not been established; however, doses up to 4 mg/kg/day PO (Max: 200 mg/day PO) have been used off-label for edema due to nephrotic syndrome.
InfantsSafety and efficacy have not been established; however, doses up to 4 mg/kg/day PO have been used off-label.
NeonatesSafety and efficacy have not been established; however, doses up to 4 mg/kg/day PO have been used off-label.
Mechanism Of Action
Mechanism of Action: Spironolactone inhibits the effects of aldosterone on the distal renal tubules. Unlike amiloride and triamterene, spironolactone exhibits its diuretic effect only in the presence of aldosterone, and these effects are enhanced in patients with hyperaldosteronism. Aldosterone antagonism enhances sodium, chloride, and water excretion, and reduces the excretion of potassium, ammonium, and phosphate. Spironolactone does not inhibit renal transport mechanisms or carbonic anhydrase activity. In addition, spironolactone acts as an androgen receptor blocker by competitively inhibiting dihydrotestosterone at its receptor sites, and at high doses, spironolactone interferes with steroid synthesis in the adrenal glands and gonads. Sebum excretion rates also are reduced in a dose-dependent manner with spironolactone.
Spironolactone is a poor antihypertensive, but it does have modest hypotensive effects. The hypotensive mechanism of spironolactone is unknown. It is possibly due to the ability of the drug to inhibit aldosterone's effect on arteriole smooth muscle. Spironolactone also can alter the extracellular-intracellular sodium gradient across the membrane. In general, diuretics lower blood pressure by initially decreasing cardiac output and reducing plasma and extracellular fluid volume. Cardiac output and extracellular fluid volume eventually return to normal, but peripheral resistance is reduced, resulting in lower blood pressure. In general, diuretics worsen glucose tolerance and exert detrimental effects on the lipid profile.
Pharmacokinetics
Spironolactone is administered orally. Spironolactone is extensively metabolized, via hepatic pathways, to active metabolites. The clinical effects of spironolactone are partially due to canrenone, a metabolite. The parent drug and canrenone are greater than 90% plasma protein-bound. The duration of action after multiple doses of spironolactone is 2 to 3 days. Both unchanged drug (less than 10%) and its metabolites are excreted primarily in the urine. The remainder of a dose is excreted in the feces via biliary elimination. The half-life of spironolactone after a single dose is 1 to 2 hours. The half-life of canrenone ranges from 10 to 35 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4/5, CYP2C8
Spironolactone is rapidly and extensively metabolized primarily by CYP3A4/5, and to a lesser extent by CYP2C8. In vitro studies also show that spironolactone is an irreversible inhibitor of CYP3A4/5 and CYP2C8.
Approximately 60% to 90% of a dose of spironolactone is absorbed from the GI tract after oral administration. The peak plasma concentration of spironolactone occurs 0.5 to 1.5 hours after administration; the Cmax of the active metabolite canrenone occurs 2.5 to 5 hours after dosing. For an equivalent dose, the oral suspension results in 15% to 37% higher serum concentrations compared to the tablets; information about dose proportionality is limited, and based on comparative studies, doses of oral suspension higher than 100 mg may result in higher than expected plasma concentrations. Food will enhance absorption when given concurrently. A high fat and high calorie meal increases bioavailability of the oral suspension by about 90%. There is considerable first-pass elimination and significant enterohepatic recirculation. The onset of diuresis is gradual, with peak effects occurring on the third day after administration.
Pregnancy And Lactation
Avoid spironolactone in pregnancy or advise pregnant women of the potential risk to a male fetus. Because of its anti-androgenic activity and the requirement of testosterone for male morphogenesis, spironolactone may have the potential for adversely affecting sex differentiation of the male during embryogenesis. Animal studies report feminization of male fetuses and endocrine dysfunction in females exposed to spironolactone in utero. Animal offspring exposed to spironolactone during late pregnancy exhibited changes in the reproductive tract, including dose-dependent decreases in weights of the ventral prostate and seminal vesicle in males, ovaries and uteri that were enlarged in females, and other indications of endocrine dysfunction that persisted into adulthood. Limited data from published case reports and case series did not demonstrate an association between major malformations or other adverse pregnancy outcomes with spironolactone use.
Spironolactone is not present in breast-milk; however, canrenone, the major metabolite of spironolactone, does appear in breast-milk in low amounts that are not expected to be clinically relevant. Data from a breast-feeding woman at 17 days postpartum did not indicate any adverse effects on the breast-fed infant; long term effects on a breast-fed infant are unknown. There are no data on the effects of spironolactone on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for spironolactone and any potential adverse effects on the breast-fed child from spironolactone or from the underlying maternal condition. Previous American Academy of Pediatrics recommendations classified spironolactone as usually compatible with breast-feeding.