Drug Profile

Indapamide is a thiazide-like diuretic (water pill) that was approved by the Food and Drug Administration (FDA) in 1983 for the treatment of high blood pressure alone or in combination with other blood-pressure-lowering drugs. It also is approved for treatment of salt and water retention associated with congestive heart failure. The drug originally was listed as Limited Use in the 1999 edition of Worst Pills, Best Pills. We changed the drug’s designation to Do Not Use as a result of adverse drug reaction reports from Australia.

The August 2002 issue of the Australian Adverse Drug Reactions Bulletin reviewed reports of low blood levels of sodium (hyponatremia) induced by indapamide.[1]

Indapamide was first marketed in Australia in the mid-1980s and is the drug most commonly implicated in causing hyponatremia, with 164 cases being reported to the Australian authorities. Of these 164 reports, 68 also described low blood levels of potassium (hypokalemia). Over half (92) of the reports described symptoms including confusion, nausea, vomiting, dizziness, loss of appetite, malaise, fatigue, fainting, somnolence and convulsions. Most patients, 88%, were 65 years or over, and 82% were female.

The main symptoms of hyponatremia involve the central nervous system and include lethargy, confusion, stupor or coma.

Our search of the FDA adverse drug reaction database through the first quarter of 2002 found 222 reports of hyponatremia associated with the use of indapamide. The FDA conservatively estimates that for each adverse reaction reported, 10 go unreported.

The Australian authorities recommend that indapamide should be used cautiously and changes in conscious or mental state should prompt measurement of the blood sodium concentration. Our advice is that indapamide should not be used.

We can think of no reason why a patient should be placed at risk of developing hyponatremia when more effective, safer water pills that are less likely to cause hyponatremia — such as hydrochlorothiazide (MICROZIDE) — are available to treat 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 (see section on high blood pressure). If these measures do not lower your blood pressure enough and you need medication, hydrochlorothiazide (MICROZIDE) 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.[2] Research now suggests that thiazide diuretics may protect against hip fracture.[3]

If your high blood pressure is more severe, and hydrochlorothiazide alone does not control it, another family of 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.[4]

An editorial in the British Medical Journal (BMJ) 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.”[5]

The May 2012 issue of Worst Pills, Best Pills News highlighted a recent BMJ study indicating that patients taking several types of commonly used antihypertensive medications are at increased risk of developing gout, a type of arthritis.

The BMJ study also showed that a small number of other antihypertensive drugs appear to have the opposite effect, decreasing the risk of gout.

All patients should be informed of the risk of gout with diuretics, beta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors) and nonlosartan angiotensin II receptor blockers (ARBs) when starting these medications or whenever the dose of the medications is increased [6].

The April 2013 issue of Worst Pills, Best Pills News discusses another recent BMJ study. This study suggests that an increased risk of acute kidney injury (AKI) is associated with combining nonsteroidal anti-inflammatory drugs (NSAIDs) with two antihypertensive drugs: a diuretic plus either an ACE inhibitor or an ARB. The risk was found to be highest during the first 30 days of starting an NSAID in patients who also are already taking a diuretic plus an ACE inhibitor or an ARB.

The study found that patients currently using a triple-therapy combination — a diuretic, an ACE inhibitor or an ARB, and an NSAID — have a 31% greater risk of developing AKI than current users of a diuretic plus an ACE inhibitor or an ARB without an NSAID.[7]