Chlorthalidone vs. Hydrochlorothiazide: 4 Differences You Should Know About

Diuretics, also known as water pills, play a vital role in managing various health conditions, including high blood pressure (hypertension) and fluid retention. Of these, chlorthalidone (Thalitone) and hydrochlorothiazide (Microzide) — or “HCTZ” for short — are two first-choice options.

Chlorthalidone and HCTZ work in a similar way to remove extra salt and water from the body. But their chemical structures are slightly different. Because of this, HCTZ is considered a thiazide diuretic, and chlorthalidone is called a thiazide-like diuretic.

So, how do these two diuretics compare? Below we review four differences between chlorthalidone and HCTZ you and your healthcare provider might consider when choosing what’s right for you.

1. Chlorthalidone is considered the ‘preferred’ diuretic for high blood pressure, but HCTZ is also an effective option

Thiazide and thiazide-like diuretics are first-choice medications for treating high blood pressure. Of these, experts recommend chlorthalidone as the preferred option. This is because its effects last longer in the body, and it has been proven to lower the risk of cardiovascular disease.

However, some evidence suggests there’s not really a difference between chlorthalidone and HCTZ in terms of cardiovascular benefits. And chlorthalidone may be more likely than HCTZ to cause certain side effects, such as low potassium.

Despite chlorthalidone being the preferred option, HCTZ can be an effective alternative for many people. In fact, HCTZ is prescribed much more frequently than chlorthalidone.

2. Chlorthalidone lasts longer in the body and may be more potent than HCTZ

As mentioned above, chlorthalidone lasts longer in the body than other diuretics, including HCTZ. Chlorthalidone starts working within 2 to 3 hours, and its effects last for up to 72 hours. HCTZ, on the other hand, starts working within 2 hours and lasts for 6 to 12 hours.

Because of how long it lasts, you’ll usually take chlorthalidone once daily. Many people are also able to take HCTZ once daily, especially lower doses. But higher doses are sometimes split up into twice-daily dosing.

In addition to lasting longer, chlorthalidone may also be more potent (per milligram) than HCTZ. For example, lower chlorthalidone doses may have a greater effect on blood pressure compared to lower HCTZ doses. But there may be a trade-off between its potency and side effects.

3. Chlorthalidone may be more likely to cause kidney or electrolyte problems

Compared to HCTZ, some studies suggest that chlorthalidone may have a greater effect on electrolytes, including potassium and sodium. And it may also be more likely to cause kidney problems.

Certain people, such as older adults, may be more likely to develop these side effects. A retrospective study found that kidney problems and low potassium (hypokalemia) were more common in older adults taking chlorthalidone compared to those taking HCTZ.

However, more evidence is needed to confirm these differences. But depending on your age or other risk factors, your healthcare provider may decide that HCTZ is a better option.

4. Hydrochlorothiazide is available in more combination blood pressure pills for convenience

If you have high blood pressure, you may be prescribed more than one medication to help keep your blood pressure under control. In addition to diuretics, this often includes one of the following medication classes:

• Angiotensin-converting enzyme (ACE) inhibitors like lisinopril (Zestril)

• Angiotensin II receptor blockers (ARBs) like losartan (Cozaar)

• Calcium channel blockers like amlodipine (Norvasc)

Both chlorthalidone and HCTZ are available in combination blood pressure pills. But there are many more options that include HCTZ. Here are a few examples:

• Zestoretic (lisinopril / HCTZ)

• Lotensin HCT (benazepril / HCTZ)

• Hyzaar (losartan / HCTZ)

• Exforge HCT (amlodipine / valsartan / HCTZ)

Chlorthalidone is only available in the following combination pills:

• Tenoretic (atenolol / chlorthalidone)

• Edarbyclor (azilsartan / chlorthalidone)

Combination pills aren’t right for everyone. But for some, they can help cut down the number of pills you take every day and make it easier to stick with your treatment schedule. If you’re taking HCTZ with another blood pressure medication, there’s a good chance a combination pill is available.

Can you take chlorthalidone and hydrochlorothiazide together for hypertension?

No. You’ll typically be prescribed either chlorthalidone or HCTZ — not both. 

Once you reach a certain dose of either medication, you may have a higher risk of side effects without additional blood pressure benefits. Since chlorthalidone and HCTZ work in a similar way, this may also be the case if you take them together.

Ways to save on chlorthalidone and hydrochlorothiazide

Both chlorthalidone and HCTZ are available as lower-cost generics. Free GoodRx discounts can help make your prescription more affordable, with savings greater than 75% off the average retail price.

At certain pharmacies, the price of generic HCTZ is as low as $2.81, and the price of generic chlorthalidone is as low as $9.00.

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Written by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Patricia Pinto-Garcia, MD, MPH

Patricia Pinto-Garcia, MD, MPH, is a medical editor at GoodRx. She is a licensed, board-certified pediatrician with more than a decade of experience in academic medicine.

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