Drug Profile

Do Not Use: This is an irrational combination of ingredients and can lead to high blood potassium levels, kidney failure, confusion and paralysis.

This product, a combination of spironolactone (ALDACTONE) and hydrochlorothiazide (ESIDRIX, HYDRODIURIL, MICROZIDE), is used to treat high blood pressure (hypertension) and heart failure. Treatment with spironolactone, but not the combination of spironolactone and hydrochlorothiazide, has been shown to greatly reduce the rate of complications and death in patients with severe heart failure.[1]

Adverse effects

Spironolactone can cause severe adverse effects. It is especially dangerous for people with kidney disease.[2],[3] It can cause kidney failure, retention of too much potassium,[3],[4],[5],[6] muscle paralysis,[7] and mental confusion in older adults. These effects may be fatal.

Combining spironolactone and an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, which also are used to treat hypertension and heart failure, or with the antibiotic trimethoprim-sulfamethoxazole (BACTRIM, COTRIM, SEPTRA, SEPTRA DS) increases the risk of severe hyperkalemia.[8] (Read more in the December 2011 Worst Pills, Best Pills News.)

This risk may be more pronounced when spironolactone is combined with ulcer-inducing drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen [MOTRIN]), platelet-aggregation inhibitors (e.g., clopidogrel [PLAVIX]), corticosteroids (e.g., prednisone [DELTASONE]) and anticoagulants (e.g., warfarin [COUMADIN]).[9]

Spironolactone also appears to be associated with an increased risk of upper-gastrointestinal events (bleeding and ulcers). This risk may be more pronounced when spironolactone is combined with ulcer-inducing drugs such as nonsteroidal anti-inflammatory drugs, platelet inhibitors (for example, clopidogrel [PLAVIX]), corticosteroids (for example, prednisone [DELTASONE]) or anticoagulants (for example, warfarin[COUMADIN]).[10]

In addition to spironolactone’s dangers, there are good reasons not to use any fixed-combination drug for high blood pressure. A single drug is often enough to control high blood pressure. There is no reason to put yourself at extra risk by taking drugs you do not need.

First-line treatment for high blood pressure

If you have high blood pressure, the best way to reduce or eliminate your need for medication is by improving your diet, losing weight, exercising, and decreasing your salt and alcohol intake. Mild hypertension can be controlled by proper nutrition and exercise. If these measures do not lower your blood pressure enough and you need medication, hydrochlorothiazide, a water pill, is the drug of choice, starting with a low dose of 12.5 milligrams daily. It also costs less than other blood-pressure drugs.

There is growing evidence that thiazide diuretics, such as hydrochlorothiazide, significantly decrease the rate of bone mineral loss in both men and women because they reduce the amount of calcium lost in the urine.[11] Research now suggests that thiazide diuretics may protect against hip fracture.[12]

If your high blood pressure is more severe, and hydrochlorothiazide alone does not control it, another family of high blood pressure-lowering drugs may be added to your treatment. In this case, your doctor would prescribe the hydrochlorothiazide and the second drug separately, with the dose of each drug adjusted to meet your needs, rather than using a product that combines the drug in a fixed combination.

Whatever drugs you take for high blood pressure, once your blood pressure has been normal for a year or more, a cautious decrease in dose and renewed attention to nondrug treatment may be worth trying, according to The Medical Letter on Drugs and Therapeutics.[13]

An editorial in the British Medical Journal stated:

Treatment of hypertension is part of preventive medicine and like all preventive strategies, its progress should be regularly reviewed by whoever initiates it. Many problems could be avoided by not starting antihypertensive treatment until after prolonged observation. ... Patients should no longer be told that treatment is necessarily for life: the possibility of reducing or stopping treatment should be mentioned at the outset.[14]

Regulatory actions surrounding hydrochlorothiazide

2011: In March, the Food and Drug Administration (FDA) issued the following warning concerning the use of hydrochlorothiazide products:

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.[15]

In 2018, the FDA updated the drug product label of the combination drug spironolactone and hydrochlorothiazide to warn that aspirin may decrease the effectiveness of spironolactone.[16]