Spironolactone side effects and how to avoid them

Creator: SingleCare
Published: 2021-04-01T17:00:26-04:00

Side effects of spironolactone include elevated potassium, weight loss/gain, and emotional changes

By SingleCare Team | Updated on Jan. 5, 2023 Medically reviewed by Keith Gardner, R.Ph.

Spironolactone (brand names: Aldactone and CaroSpir) is a potassium-sparing diuretic (“water pill”) approved by the U.S. Food and Drug Administration (FDA) to treat congestive heart failure, high blood pressure (hypertension), edema (fluid retention) associated with liver cirrhosis or kidney problems, and hyperaldosteronism, an excess of the hormone aldosterone that can cause high blood pressure. Spironolactone is also prescribed off-label for the treatment of hirsutism, a condition that causes excessive hair growth primarily in women, female pattern hair loss, and adult acne.

Spironolactone primarily affects the kidneys, increasing the elimination of water and sodium but having the opposite effect on potassium. The reduction of water and sodium helps lower blood pressure in people with hypertension or hyperaldosteronism and helps to reduce fluid volume in people with edema. For heart failure, spironolactone helps prevent scarring and remodeling in the heart as well as improves heart function. Like all diuretics, however, spironolactone may not be right for everyone. Side effects, pre-existing medical conditions, and drug interactions may all require careful management.

Common side effects of spironolactone

The most common side effects of spironolactone are:

Breast enlargement or swelling (gynecomastia)
Elevated potassium levels in the blood (hyperkalemia)
Decreased sexual drive
Erectile dysfunction
Breast pain
Menstrual irregularities
Dehydration
Electrolyte disturbances
Nausea
Vomiting
Abdominal pain or cramps
Diarrhea
Gastric bleeding
Gastritis
Stomach ulcer
Headache
Dizziness
Drowsiness
Mental confusion
Muscle cramps

The most common side effects when taking spironolactone are mild stomach upset, nausea, or vomiting, particularly when taken on an empty stomach. These side effects should decrease once the body adjusts to the medicine.

Spironolactone may cause lightheadedness or dizziness, particularly when standing from a lying or sitting position. To minimize these effects, get up slowly when rising to a standing position.

Because spironolactone reduces the level of the male hormone testosterone, it may cause adverse sexual effects such as decreased sexual drive, erectile dysfunction, and enlarged breasts in men and decreased sexual drive, impaired lubrication, menstrual irregularities, and breast tenderness and pain in women.

Serious side effects of spironolactone

Spironolactone has several potentially severe side effects:

Severe hyperkalemia: Spironolactone reduces the body’s elimination of potassium, causing blood potassium levels to rise. Potassium levels that are too high (hyperkalemia) can affect the heart, leading to irregular heartbeats (arrhythmias) and, in severe cases, heart attack.
Electrolyte imbalances: Besides increasing potassium levels, spironolactone lowers levels of other electrolytes such as sodium, magnesium, and calcium. At severely low levels, these electrolyte imbalances can be hazardous.
Worsening kidney function: Decreasing water and sodium in the body can lead to dehydration, low blood volume, and ultimately compromise the ability of the kidneys to function. People taking certain types of medications, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), are more vulnerable to developing kidney problems while taking spironolactone.
Liver injury (hepatotoxicity): Though rare, some patients have experienced mixed hepatitis, a condition in which liver cell injury is combined with bile backing up in the liver.
Blood cell problems: Both low levels of white blood cells and low platelet levels have been reported in patients taking spironolactone, raising the risk of infections or bleeding episodes.
Hypersensitivity reactions: Allergic reactions such as itching, rash, or fever, or more severe allergic reactions, such as anaphylaxis (dizziness or difficulty breathing), are possible.

Potassium levels

Elevated potassium is a common side effect of spironolactone, but the incidence is undetermined. The likelihood of elevated blood potassium will depend on age, kidney function, other medical conditions, and other drugs being taken. In the groundbreaking study of spironolactone in heart failure treatment, the incidence of severe hyperkalemia was 2% for those taking spironolactone as opposed to 1% of the control, or placebo, group. Since that study, the incidence of severe hyperkalemia among heart failure patients has substantially increased. The bottom line is that potassium levels will need to be monitored, particularly in people who are older, have kidney problems, have diabetes, or are taking other drugs that raise the risk of developing high potassium.

If any of the signs or symptoms of high blood potassium are experienced while taking spironolactone, get immediate medical attention. These symptoms can include muscle weakness, fatigue, nausea, vomiting, tingling, trouble breathing, heart palpitations, irregular heartbeats, and chest pain.

Weight loss/gain

Weight changes are not a common side effect of spironolactone. As a diuretic, spironolactone increases the body’s elimination of water, temporarily decreasing body weight. This is not, however, real weight loss in terms of fat or other body tissues. Studies on women with polycystic ovary syndrome suggest that spironolactone may improve carbohydrate metabolism, but not by much.

Emotional side effects

Emotional changes are not listed as a side effect in the FDA-approved prescribing information for spironolactone, as found in the Prescriber’s Digital Reference. Still, some people taking spironolactone have self-reported anxiety and panic attacks in online medical forums. Without studies, though, the question remains open.

However, spironolactone can cause changes in the blood’s pH, causing either acidosis (too much acid) or alkalosis (too little acid). Research suggests that unprovoked panic attacks in people already prone to panic attacks may sometimes be triggered by acid-base imbalances.

Standard dosages

Indication	Standard Dosage
Heart failure	25 to 50 mg once daily
Hypertension	Total daily doses of 25 to 100 mg given in a single dose or divided doses
Edema	Total daily dose of 25 to 200 mg given in a single dose or divided doses
Hyperaldosteronism	100 to 400 mg once daily in preparation for surgery
Hirsutism (off-label)	50 to 200 mg once daily
Acne (off-label)	50 to 200 mg once daily

How long do spironolactone side effects last?

Most of the common side effects of spironolactone are temporary and will fade when the drug is discontinued. However, spironolactone’s active metabolites persist for a longer time in the body, so it may take a day or more for some temporary side effects to abate. Other side effects, such as minor electrolyte imbalances (including hyperkalemia), may take longer to resolve. Severe electrolyte imbalances will require IV electrolyte replacement in a medical setting. Low white blood cell counts, low platelet counts, and severe allergic reactions may take several days to resolve. Drug-induced liver and kidney injury could evolve into long-term or lifelong medical conditions.

Spironolactone contraindications & warnings

Long-term use of spironolactone is largely limited to relatively severe medical conditions, so the benefits of spironolactone often outweigh the risks. For some people with certain medical conditions, those risks may be too much for comfort.

Spironolactone is contraindicated for people with:

High potassium levels in their blood
Addison’s disease
Known hypersensitivity to the drug

Addison’s disease, or adrenal insufficiency, is a medical condition that can sometimes produce a deficiency of aldosterone, the hormone produced by the adrenal glands that regulates the elimination of water and sodium in the urine. Because spironolactone “blocks” aldosterone, giving spironolactone to someone with adrenal insufficiency risks potentially hazardous high blood potassium and low blood pressure.

Some people can be given spironolactone but may have medical conditions that require monitoring and possible treatment modifications. These include:

Kidney disease
Liver problems
Electrolyte abnormalities
Diabetes
Low blood volume

Overdose

A spironolactone overdose can be fatal, but the median lethal dose is extremely high, far greater than the maximum recommended dose of 400 mg per day. If too much spironolactone is taken, the symptoms are similar to spironolactone’s side effects: sleepiness, dizziness, mental confusion, drug rash, nausea, vomiting, or diarrhea. If a spironolactone overdose is suspected, seek emergency medical help.

Abuse and dependency

Spironolactone does not create physical dependency or cause withdrawal symptoms when discontinued. However, spironolactone is often abused, primarily by athletes seeking to rapidly lose weight or mask banned substances in the urine. For this reason, the World Anti-Doping Agency has banned the use of spironolactone by athletes both in and out of competition.

Children

Other than as a treatment for severe edema due to severe kidney disease, the safety and effectiveness of spironolactone use in children have not been established. Nevertheless, spironolactone is used in children as young as newborns to treat off-label medical conditions.

Pregnancy

Because spironolactone may disrupt the sex differentiation of a male fetus, spironolactone should be avoided during pregnancy. However, many of the conditions spironolactone treats also threaten the health of the fetus and the mother. Women who are pregnant or considering pregnancy should discuss the risks and benefits of taking spironolactone while pregnant.

Breastfeeding

Women who are breastfeeding or plan to breastfeed should consult with a healthcare provider before taking spironolactone.

In the body, spironolactone is metabolized, or broken down, into different substances that are responsible for the therapeutic and adverse effects of the medication. Canrenone is one of several important active metabolites. Spironolactone itself is not present in breast milk, but canrenone is, but in very tiny amounts. The long-term safety of exposing an infant to even these small amounts has not been determined.

Senior citizen

Spironolactone can be used to treat people older than 65, but kidney function may need to be tested and monitored.

Spironolactone interactions

Spironolactone can be taken with or without food, but should be taken in a consistent manner. Always take spironolactone with food or always take it without food. Taking spironolactone with food substantially increases the body’s absorption of spironolactone and the plasma concentration of its active form. As a result, taking spironolactone with food is like taking a bigger dose. That’s okay, as long as it remains consistent from day-to-day.

Spironolactone has several drug interactions.

Inspra (eplerenone)—CONTRAINDICATED: Spironolactone and eplerenone are very similar drugs. They are both potassium-sparing diuretics, work in the same way, and are used to treat the same medical conditions. Spironolactone is never to be used with eplerenone because of the risk of severe hyperkalemia.
OTHER CONTRAINDICATED DRUGS: Some drugs are never used with diuretics or potassium-sparing diuretics such as spironolactone. The central concern, again, is high blood potassium. These drugs include:
- Amiloride
- Marplan (isocarboxazid)
- Potassium bicarbonate
- Triamterene
Potassium: Because of the risk of high potassium levels, drugs or supplements containing potassium should be avoided.
Potassium-sparing diuretics: To prevent elevated blood potassium, potassium-sparing diuretics should be used with caution. Regular monitoring of potassium levels may be required.
Drugs that increase potassium levels: Elevated serum potassium is more likely when spironolactone is combined with drugs that have the potential to increase blood potassium levels. These include ACE inhibitors, angiotensin receptor blockers (or ARBs), nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and naproxen, the blood thinner heparin, and the antibiotic trimethoprim. NSAIDs may also reduce the therapeutic effectiveness of spironolactone.
Drugs that lower blood pressure: Spironolactone lowers blood pressure and is often prescribed along with other blood pressure medications. The combination, though, does carry a small risk of lowering blood pressure too much. Other drugs, such as nitrates, pulmonary hypertension medications, erectile dysfunction medications, opioids, antidepressants, and antipsychotic medications also lower blood pressure. Blood pressure monitoring may be required when drugs that lower blood pressure are combined. Alcohol, too, brings down blood pressure. People taking spironolactone are advised to limit the amount of alcohol they drink.
Drugs that increase blood pressure: Drugs that increase blood pressure will offset spironolactone’s therapeutic effects on blood pressure. These include caffeine, stimulants, amphetamines, ADHD medications, wakefulness agents, nasal decongestants, asthma medications (bronchodilators), corticosteroids, sympathomimetics, and weight loss medications. These drugs aren’t necessarily prohibited, but doses or therapies may need to be modified.
Nephrotoxic (kidney-damaging) drugs: Some drugs may damage the kidneys. The risk is increased when they are combined with a diuretic such as spironolactone. Significant nephrotoxic drugs include acetaminophen, NSAIDs, salicylates, aminoglycoside antibiotics, some antiviral drugs, some diabetes medications (GLP-1 agonists), and some chemotherapy drugs. Diuretics may also interfere with the elimination of these drugs, raising their concentration in the blood and the risk of their particular side effects. Some of these drugs may need to be avoided, but most will require caution and monitoring.
Spironolactone also increases the concentration of lithium (for bipolar disorder) and digoxin (for heart problems), raising the risk of side effects from those drugs. The combination may require regular monitoring.
Cholestyramine is used to treat high cholesterol. Cholestyramine combined with spironolactone raises the risk of too much acid in the blood due to high blood potassium.

How to avoid spironolactone side effects

1. Take spironolactone as directed

Take the dose as prescribed. Do not increase or decrease the dose. If effectiveness or side effects are a problem, talk to a healthcare provider about adjusting the dose.

2. Take spironolactone consistently with or without food

Like many prescription drugs, spironolactone tablets or oral solution can be taken with or without food. Either is okay, but just make sure to always take spironolactone with food or always take it without. Food greatly changes the amount of spironolactone that makes it into the body. Spironolactone works best as a steady-state medicine, so stay consistent in how it’s taken.

3. Tell the doctor about all medical conditions and medications

Because of the risk of side effects, the prescribing doctor or healthcare professional needs to know about all medical conditions and medications before prescribing spironolactone, including:

Any medical conditions, especially
- Addison’s disease
- High levels of potassium in the blood
- Diabetes
- Urination problems
- Electrolyte imbalances
- Renal impairment
- Liver disease
- Heart disease
All medications, over-the-counter medications, supplements, and remedies being taken

4. Keep all follow-up visits

To minimize adverse effects, follow-up visits and tests may be required to monitor blood pressure, electrolytes, blood volume, kidney function, and liver function. These follow-up visits can spot issues before they become serious problems, so keep them faithfully.

5. Be careful driving or operating machinery

Spironolactone can cause dizziness and sleepiness, so be cautious driving, operating machinery, or engaging in risky activities when taking spironolactone.

6. Cut down on salt

Cut back on salt or use salt substitutes. The beneficial effects of spironolactone on blood pressure or fluid retention are offset by a high salt intake.

7. Avoid potassium supplements

Spironolactone may cause high blood potassium, a potentially hazardous condition. Many spironolactone side effects are due to high potassium. It’s a good idea to avoid potassium supplements when taking spironolactone.

8. Do not substitute tablets and oral solution

Spironolactone oral solution is therapeutically different from spironolactone tablets. Doses will be different. Before switching formats, get a new prescription from a doctor or other healthcare professional.

Frequently asked questions about spironolactone

What are some health benefits of spironolactone?

Taking spironolactone in combination with other high blood pressure medicines for hypertension and heart failure can reduce the risk of strokes and heart attacks. It may also lessen the need for hospitalization due to heart failure.

Is spironolactone bad for HRT?

The goal of feminizing hormone therapy is the development of female sex characteristics and minimization of male secondary sex characteristics. Suppression and blocking of the male hormone testosterone leads to the suppression of male sexual characteristics and spironolactone is the most commonly used androgen blocker.

Is weight loss a side effect of spironolactone?/Does taking spironolactone cause weight gain?

Weight changes are not a common side effect of spironolactone. Amy weight loss is likely due to its diuretic activity, i.e., by causing the elimination of excess water from the body. There is no clinical evidence showing weight gain is caused by taking spironolactone.

Can spironolactone be used to treat COVID-19?

Spironolactone has been reported to provide protection during the various stages of COVID-19 infection, particularly in high risk patient groups such as those clinically obese and those with pre-existing hypertension.

Does spironolactone cause voice deepening?

There have been rare reports regarding spironolactone and alteration in voice pitch. Spironolactone may also cause hoarseness, particularly in women 60 years of age and older who have been taking the drug for less than one month.

How long does Spironolactone take to work for acne?

Although a decrease in acne breakouts and skin oiliness may be noticeable after a few weeks of treatment, it may take three to six months for spironolactone to have its full effect.