Spironolactone: Review of a ‘Water Pill’

Diuretics (water pills) are a decades-old group of medications that work by increasing the elimination of fluid and minerals through the urine. They are widely used to treat high blood pressure and swelling due to a number of causes.

Diuretics also have serious side effects, and their use must be carefully monitored to ensure that patients do not become dehydrated or depleted of certain vital minerals. For example, many diuretics cause depletion of the important mineral potassium from the body.

Spironolactone (ALDACTONE) is a type of diuretic known as an aldosterone blocker that removes less potassium from the body than other types of diuretics do. Doctors sometimes prescribe it for high blood pressure instead of another diuretic in the hope that it will prevent potassium depletion, but there is no guarantee that this will work.

Uses

Spironolactone is approved for treatment of high blood pressure, heart failure, swelling (water retention) associated with both liver failure and a certain type of kidney disease known as nephrotic syndrome, low blood potassium levels, and a rare hormonal disorder known as primary hyperaldosteronism.[1]

Treatment with spironolactone has been shown to greatly reduce the rate of complications and death in patients with severe heart failure.[2]

Side effects

Spironolactone can cause severe adverse effects. Its label carries a black-box warning, the Food and Drug Administration’s most prominent warning, on spironolactone’s cancer-causing effects in rats, along with a recommendation to use the drug cautiously and only if clearly necessary.[3]

Spironolactone is especially dangerous for people with kidney disease.[4],[5] It can cause kidney failure, hyperkalemia (high blood potassium levels),[6],[7],[8],[9] muscle paralysis[10] and mental confusion[11] in older adults. Some of these effects may be fatal.

Combining spironolactone with certain drugs increases the risk of hyperkalemia. These drugs include angiotensin-converting enzyme (ACE) inhibitors (for example, lisinopril [PRINIVIL, QBRELIS, ZESTRIL]), angiotensin II receptor blockers (ARBs, such as losartan [COZAAR]), the other aldosterone blocker eplerenone (INSPRA), the anticoagulant heparin,[12] the antibiotic trimethoprim-sulfamethoxazole (BACTRIM, SEPTRA)[13] and other drugs known to increase blood potassium levels. There is evidence that combining nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen [MOTRIN]) with a diuretic such as spironolactone plus either an ACE inhibitor or an ARB increases the risk of kidney injury.

Taking spironolactone with alcohol or the following other drugs might lead to a dangerous reaction: barbiturates (for example, pentobarbital), opioids (for example, oxycodone [OXAYDO, OXYCONTIN, XTAMPZA ER]), corticosteroids (for example, prednisone [RAYOS]), lithium (LITHOBID), digoxin (LANOXIN), and cholestyramine (PREVALITE).[14]

Spironolactone also appears to be associated with an increased risk of upper gastrointestinal adverse events (bleeding and ulcers). This risk may be more pronounced when spironolactone is combined with ulcer-inducing drugs such as NSAIDs, platelet inhibitors (for example, clopidogrel [PLAVIX]), corticosteroids, or anticoagulants (for example, warfarin [COUMADIN, JANTOVEN]).[15]

What You Can Do

If you have severe heart failure or primary hyperaldosteronism, you should be taking spironolactone, unless you have significant renal disease or an elevated blood potassium level. Because of its dangers, spironolactone should not be the first choice for treating high blood pressure or swelling due to water retention. If you have water retention due to liver or kidney disease, you should discuss with your doctor whether spironolactone is right for you.

If you have been diagnosed with mildly elevated blood pressure (up to 160/100), you initially should try to control it with diet and exercise.[16] A proper regimen includes a reduced-sodium, increased-potassium diet; frequent exercise; and, if you are overweight or obese, a healthy, gradual weight loss regimen. Should this fail to adequately control blood pressure, your doctor can start you on an anti-hypertensive medication regimen, ideally beginning with a thiazide diuretic and, if needed, an ACE inhibitor (if you are not black) or calcium channel blocker (if you are black; for example, amlodipine [NORVASC]).[17]

You should not use spironolactone just for its ability to keep potassium in the body. Patients needing extra potassium can adjust their diet or take potassium supplements. Both methods are equally effective[18] (see our article on “Potassium Supplementation” at WorstPills.org)[19] and are safer than using spironolactone.

Do not take spironolactone if you are diagnosed with any of the following conditions: acute kidney failure, significant chronic kidney disease, hyperkalemia or Addison’s disease (adrenal gland failure).[20] Never take spironolactone with eplerenone.[21]

Before you take spironolactone, tell your doctor if you are pregnant or breastfeeding, or if you have or have had allergies to drugs; diabetes; heart, kidney, or liver problems; menstrual problems; breast enlargement; high potassium levels, gout, or kidney stones.

If you are on spironolactone, do not use potassium supplements, salt substitutes (potassium chloride), or eat potassium-rich foods. While you are on spironolactone, your doctor should periodically monitor your blood pressure, kidney function and blood cell counts. Your doctor also should monitor your blood levels of potassium and sodium weekly when you are first starting the drug. If you plan to have any surgery, including dental, tell your doctor that you take this drug.

References

[1] Pfizer Inc. (G.D. Searle LLC). Label: spironolactone (ALDACTONE). October 2016. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0fed2822-3a03-4b64-9857-c682fcd462bc&audience=consumer. Accessed January 19, 2017.

[2] Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341(10):709-717.

[3] Pfizer Inc. (G.D. Searle LLC). Label: spironolactone (ALDACTONE). October 2016. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0fed2822-3a03-4b64-9857-c682fcd462bc&audience=consumer. Accessed January 19, 2017.

[4] Greenblatt DJ, Koch-Weser J. Adverse reactions to spironolactone. A report from the Boston Collaborative Drug Surveillance Program. JAMA. 1973;225(1):40-43.

[5] Neale TJ, Lynn KL, Bailey RR. Spironolactone-associated aggravation of renal functional impairment. N Z Med J. 1976;83(559):147-149.

[6] Greenblatt DJ, Koch-Weser J. Adverse reactions to spironolactone. A report from the Boston Collaborative Drug Surveillance Program. JAMA. 1973;225(1):40-43.

[7] Pongpaew C, Songkhla RN, Kozam RL. Hyperkalemic cardiac arrhythmia secondary to spironolactone. Chest. 1973;63(6):1023-1025.

[8] Yap V, Patel A, Thomsen J. Hyperkalemia with cardiac arrhythmia: Induction by salt substitutes, spironolactone, and azotemia. JAMA. 1976;236(24):2775-2776.

[9] Textbook of Adverse Drug Reactions, ed. D.M. Davies. New York: Oxford University Press; 1977. p. 237.

[10] Udezue EO, Harrold BP. Hyperkalaemic paralysis due to spironolactone. Postgrad Med J. 1980;56(654):254-255.

[11] Greenblatt DJ, Koch-Weser J. Adverse reactions to spironolactone. A report from the Boston Collaborative Drug Surveillance Program. JAMA. 1973;225(1):40-43.

[12] Pfizer Inc. (G.D. Searle LLC). Label: spironolactone (ALDACTONE). October 2016. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0fed2822-3a03-4b64-9857-c682fcd462bc&audience=consumer. Accessed January 19, 2017.

[13] Antoniou T, Gomes T, Mamdani MM, et al. Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: Nested case-control study. BMJ. 2011:343:d5228.

[14] Pfizer Inc. (G.D. Searle LLC). Label: spironolactone (ALDACTONE). October 2016. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0fed2822-3a03-4b64-9857-c682fcd462bc&audience=consumer. Accessed January 19, 2017.

[15] Verhamme K, Mosis G, Dieleman J, Stricker B, Sturkenboom M. Spironolactone and risk of upper gastrointestinal events: population based case-control study. BMJ. 2006;333(7563):330.

[16] New blood pressure treatment guidelines released. Worst Pills, Best Pills News. September 2014. /newsletters/view/918. Accessed January 19, 2017.

[17] New Blood Pressure Treatment Guidelines Released. Worst Pills, Best Pills News. September 2014. /newsletters/view/918. Accessed January 19, 2017.

[18] Papademetriou V, Burris J, Kukich S, Freis ED. Effectiveness of potassium chloride or triamterene in thiazide hypokalemia. Arch Int Med. 1985;145(11):1986-1990.

[19] Potassium supplementation. WorstPills.org. /chapters/view/43. Accessed January 19, 2017.

[20] Pfizer Inc. (G.D. Searle LLC). Label: spironolactone (ALDACTONE). October 2016. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0fed2822-3a03-4b64-9857-c682fcd462bc&audience=consumer. Accessed January 19, 2017.

[21] Ibid.