Spironolactone

Spironolactone comes as a tablet to take by mouth. It usually is taken once or twice a day. To help you remember to take spironolactone, take it around the same time(s) every day. Take spironolactone at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take spironolactone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor may start you on a low dose of spironolactone and gradually increase your dose.

Spironolactone controls high blood pressure, edema, heart failure, and hyperaldosteronism, but does not cure these conditions. It may take about 2 weeks or longer before the full effect of spironolactone occurs. Continue to take spironolactone even if you feel well. Do not stop taking spironolactone without talking to your doctor.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

• drowsiness
• confusion
• rash
• nausea
• vomiting
• dizziness
• diarrhea
• tingling in arms and legs
• loss of muscle tone
• weakness or heaviness in legs
• irregular or slow heartbeat

:

• There are no adequate studies in pregnant women. Aldactone may be harmful if used for treating gestational hypertension (high blood pressure during pregnancy).
• An active metabolite of Aldactone is secreted in breast milk. To avoid adverse effects in the newborn, mothers should avoid breastfeeding while taking Aldactone.

Mechanism of Action

Aldosterone antagonist with diuretic and antihypertensive effects; competitive binding of receptors at aldosterone-dependent Na-K exchange site in distal tubules results in increased excretion of Na+, Cl-, and water and retention of K+ and H+

Increases testosterone clearance and estradiol production; blocks conversion of potent androgens to weaker ones in peripheral tissues

Absorption

Increased with food

Bioavailability: 73% (tablet)

Onset: 2-4 hr (tablet)

Duration: 2-3 days (tablet)

Peak serum time: 3-4 hr (tablet); 0.5-1.5 hr (PO suspension); 2.5-5 hr (PO suspension, active metabolite)

Distribution

Protein bound: 90%

Metabolism

Metabolized by the liver and kidneys

Metabolites: Canrenone, 7-alpha-thiomethylspirolactone, 6-beta-hydroxy-7-alpha-thiomethylspirolactone (active)

Elimination

Half-life (tablet): Parent drug (1.3-1.4 hr); metabolite [canrenone] (9-23 hr)

Half-life (PO suspension): Parent drug (1-2 hr); metabolite [canrenone] (10-35 hr)

Excretion (tablet): Urine (47-57%); feces (35-41%)

Excretion (PO suspension): Urine

Spironolactone is part of the drug class:

• Aldosterone antagonists

If you take too much spironolactone call your doctor or Poison Contol Center, or seek emergency medical attention right away.

Aldosterone antagonist; a potassium-sparing diuretic.256 265

Storage

Oral

<25°C.256 265

Extemporaneously prepared oral suspensions in cherry syrup reported to be stable for 1 month at 2–8°C.a

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For spironolactone, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to spironolactone or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of spironolactone in the pediatric population. Safety and efficacy have not been established.

Geriatric

No information is available on the relationship of age to the effects of spironolactone in geriatric patients.

Pregnancy

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking spironolactone, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using spironolactone with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Eplerenone
• Triamterene

Using spironolactone with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Alacepril
• Amtolmetin Guacil
• Arginine
• Arsenic Trioxide
• Aspirin
• Benazepril
• Bromfenac
• Bufexamac
• Captopril
• Celecoxib
• Choline Salicylate
• Cilazapril
• Clonixin
• Delapril
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Digoxin
• Dipyrone
• Droperidol
• Droxicam
• Enalaprilat
• Enalapril Maleate
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Fosinopril
• Ibuprofen
• Imidapril
• Indomethacin
• Ketoprofen
• Ketorolac
• Levomethadyl
• Lisinopril
• Lithium
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Moexipril
• Morniflumate
• Nabumetone
• Naproxen
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Pentopril
• Perindopril
• Phenylbutazone
• Piketoprofen
• Piroxicam
• Potassium
• Pranoprofen
• Proglumetacin
• Propyphenazone
• Proquazone
• Quinapril
• Ramipril
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sodium Salicylate
• Sotalol
• Spirapril
• Sulindac
• Temocapril
• Tenoxicam
• Tiaprofenic Acid
• Tolfenamic Acid
• Tolmetin
• Trandolapril
• Trimethoprim
• Valdecoxib
• Zofenopril

Using spironolactone with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Digitoxin
• Gossypol
• Licorice

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of spironolactone. Make sure you tell your doctor if you have any other medical problems, especially:

• Addison's disease (adrenal problem) or
• Anuria (not able to pass urine) or
• Hyperkalemia (high potassium in the blood) or
• Kidney disease, severe—Should not be used in patients with these conditions.

• Electrolyte imbalance (eg, low chloride, magnesium, or sodium in the body) or
• Fluid imbalances (caused by dehydration, vomiting, or diarrhea) or
• Liver disease, severe (eg, cirrhosis)—Use with caution. May make these conditions worse.

In addition to the use of spironolactone, treatment for your high blood pressure may include weight control and changes in the types of foods you eat, especially foods high in sodium (salt) and potassium. Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet.

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well.

Remember that spironolactone will not cure your high blood pressure, but it does help control it. You must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease.

Dosing

The dose of spironolactone will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of spironolactone. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For edema:
    • Adults—At first, 100 milligrams (mg) per day, taken in either single or divided doses. Your doctor may adjust your dose if needed.
    • Children—Use and dose must be determined by your doctor.
  • For heart failure:
    • Adults—At first, 25 milligrams (mg) once a day. Your doctor may adjust your dose if needed and tolerated.
    • Children—Use and dose must be determined by your doctor.
  • For high blood pressure:
    • Adults—At first, 50 to 100 milligrams (mg) per day, taken in either single or divided doses. Your doctor may adjust your dose if needed.
    • Children—Use and dose must be determined by your doctor.
  • For low potassium in the blood:
    • Adults—25 to 100 milligrams (mg) per day.
    • Children—Use and dose must be determined by your doctor.
  • For too much aldosterone in the body:
    • Adults—400 milligrams (mg) for 4 days, or 400 mg per day for 3 to 4 weeks to diagnose the condition. Then, 100 to 400 mg per day after the diagnosis is confirmed.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of spironolactone, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• If you have an allergy to spironolactone or any other part of spironolactone.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Addison's disease, high potassium levels, or kidney disease.
• If you are not able to pass urine.
• If you are taking any of these drugs: Amiloride, eplerenone, or triamterene.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take spironolactone with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or very bad upset stomach or throwing up.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Signs of a very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
• Very bad dizziness or passing out.
• Feeling confused.
• Change in balance.
• Lowered interest in sex.
• Change in sex ability.
• Fever or chills.
• Sore throat.
• Any unexplained bruising or bleeding.
• Black, tarry, or bloody stools.
• Throwing up blood or throw up that looks like coffee grounds.
• A burning, numbness, or tingling feeling that is not normal.
• Slow heartbeat.
• Period (menstrual) changes.
• Breast pain.
• For males, enlarged breasts.
• Very bad and sometimes deadly liver problems have happened with this medicine. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

Severe heart failure

The Randomized Aldactone Evaluation Study (RALES) was a multinational, double-blind study in patients with an ejection fraction of ≤ 35%, a history of New York Heart Association (NYHA) class IV heart failure within 6 months, and class III–IV heart failure at the time of randomization. All patients were required to be taking a loop diuretic and, if tolerated, an ACE inhibitor. Patients with a baseline serum creatinine of >2.5 mg/dL or a recent increase of 25% or with a baseline serum potassium of >5.0 mEq/L were excluded.

Patients were randomized 1:1 to Spironolactone 25 mg orally once daily or matching placebo. Follow-up visits and laboratory measurements (including serum potassium and creatinine) were performed every four weeks for the first 12 weeks, then every 3 months for the first year, and then every 6 months thereafter. Dosing could be withheld for serious hyperkalemia or if the serum creatinine increased to >4.0 mg/dL. Patients who were intolerant of the initial dosage regimen had their dose decreased to one tablet every other day at one to four weeks. Patients who were tolerant of one tablet daily at 8 weeks may have had their dose increased to two tablets daily at the discretion of the investigator.

RALES enrolled 1663 patients (3% U.S.) at 195 centers in 15 countries between March 24, 1995 and December 31, 1996. The study population was primarily white (87%, with 7% black, 2% Asian, and 4% other), male (73%), and elderly (median age 67). The median ejection fraction was 0.26. Seventy percent were NYHA class III and 29% class IV. The presumed etiology of heart failure was ischemic in 55%, and non-ischemic in 45%. There was a history of myocardial infarction in 28%, of hypertension in 24%, and of diabetes in 22%. The median baseline serum creatinine was 1.2 mg/dL and the median baseline creatinine clearance was 57 mL/min. The mean daily dose at study end for the patients randomized to Spironolactone was 26 mg.

Concomitant medications included a loop diuretic in 100% of patients and an ACE inhibitor in 97%. Other medications used at any time during the study included digoxin (78%), anticoagulants (58%), aspirin (43%), and beta-blockers (15%).

The primary endpoint for RALES was time to all-cause mortality. RALES was terminated early, after a mean follow-up of 24 months, because of significant mortality benefit detected on a planned interim analysis. The survival curves by treatment group are shown in Figure 1.

Figure 1. Survival by Treatment Group in RALES

Spironolactone reduced the risk of death by 30% compared to placebo (p<0.001; 95% confidence interval 18% to 40%). Spironolactone reduced the risk of cardiac death, primarily sudden death and death from progressive heart failure by 31% compared to placebo (p <0.001; 95% confidence interval 18% to 42%).

Spironolactone also reduced the risk of hospitalization for cardiac causes (defined as worsening heart failure, angina, ventricular arrhythmias, or myocardial infarction) by 30% (p <0.001 95% confidence interval 18% to 41%). Changes in NYHA class were more favorable with Spironolactone: In the Spironolactone group, NYHA class at the end of the study improved in 41% of patients and worsened in 38% compared to improved in 33% and worsened in 48% in the placebo group (p <0.001).

Mortality hazard ratios for some subgroups are shown in Figure 2. The favorable effect of Spironolactone on mortality appeared similar for both genders and all age groups except patients younger than 55; there were too few non-whites in RALES to draw any conclusions about differential effects by race. Spironolactone's benefit appeared greater in patients with low baseline serum potassium levels and less in patients with ejection fractions <0.2. These subgroup analyses must be interpreted cautiously.

Figure 2. Hazard Ratios of All-Cause Mortality by Subgroup in RALES

Figure 2: The size of each box is proportional to the sample size as well as the event rate. LVEF denotes left ventricular ejection fraction, Ser Creatinine denotes serum creatinine, Cr Clearance denotes creatinine clearance, and ACEI denotes angiotensin-converting enzyme inhibitor.

• Antihypertensive
• Diuretic, Potassium-Sparing
• Mineralocorticoid (Aldosterone) Receptor Antagonists

Anuria; acute renal insufficiency; significant impairment of renal excretory function; hyperkalemia; Addison disease; concomitant use with eplerenone.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to spironolactone or any component of the formulation; concomitant use with heparin or low molecular weight heparin.

Administration with food increases the bioavailability of spironolactone. Excessive potassium intake (eg, salt substitutes, low-salt foods, bananas, nuts) should be avoided.

Abiraterone Acetate: Spironolactone may diminish the therapeutic effect of Abiraterone Acetate. Monitor therapy

ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alpha-/Beta-Agonists: Spironolactone may diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

AMILoride: May enhance the hyperkalemic effect of Spironolactone. Avoid combination

Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Analgesics (Opioid): May enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy

Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

AtorvaSTATin: May enhance the adverse/toxic effect of Spironolactone. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Canagliflozin: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Canagliflozin may enhance the hypotensive effect of Potassium-Sparing Diuretics. Monitor therapy

Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Monitor therapy

Cholestyramine Resin: May enhance the adverse/toxic effect of Spironolactone. Specifically, the risks of developing metabolic acidosis and hyperkalemia may be elevated with this combination. Monitor therapy

Ciprofloxacin (Systemic): Spironolactone may enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Monitor therapy

CycloSPORINE (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of CycloSPORINE (Systemic). Avoid combination

Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Digoxin: Spironolactone may increase the serum concentration of Digoxin. Spironolactone (and/or its metabolites) may also interfere with the assays used to determine Digoxin concentrations, falsely increasing or decreasing Digoxin concentrations. Monitor therapy

Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

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

Heparin: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Monitor therapy

Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Mitotane: Spironolactone may diminish the therapeutic effect of Mitotane. Management: Consideration should be given to discontinuing spironolactone prior to initiating mitotane in order to eliminate the risk of therapeutic failure of the mitotane. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Spironolactone may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitrofurantoin: May enhance the hyperkalemic effect of Spironolactone. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

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

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Monitor therapy

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification

Tacrolimus (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Tacrolimus (Systemic). Avoid combination

Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Triamterene: May enhance the hyperkalemic effect of Spironolactone. Avoid combination

Trimethoprim: May enhance the hyperkalemic effect of Spironolactone. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy