Switching From HCTZ To Chlorthalidone Due To Side Effects Of Hair Loss And Dry Mouth

In our latest question and answer, our pharmacist discusses thoughts on switching from HCTZ to chlorthalidone due to specific side effect concerns.

Question

I am treating a 54-year-old African American female patient who is taking hydrochlorothiazide (HCTZ) for hypertension. She has pre-diabetes and is morbidly obese, with minor swelling in her lower extremities. Her blood pressure is well-controlled with 25mg of HCTZ, but she reports experiencing adverse effects such as dry mouth and hair loss. I am considering switching her to another diuretic, such as chlorthalidone, to address these side effects. I would like to avoid using a CCB (Calcium Channel Blocker) due to the risk of edema. Can you provide any recommendations or thoughts on this as a pharmacist?

Asked by Logan On Jan 20, 2023

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Jan 23, 2023
Last updated Jan 23, 2023

Key points

  • A number of studies have shown chlorthalidone has equal or better effects on blood pressure control and cardiovascular outcomes when compared to hydrochlorothiazide.
  • Hydrochlorothiazide is a thiazide diuretic while chlorthalidone is a thiazide-like diuretic and have very similar side effect profiles.
  • One reported side effect of thiazide and thiazide-like diuretics is hair loss (i.e., alopecia). It appears to occur only rarely and at a similar rate between hydrochlorothiazide and chlorthalidone.
  • Due to the overall efficacy of chlorthalidone, and a similar side effect profile, it is a reasonable alternative to hydrochlorothiazide and is often the preferred diuretic choice according to many medical guidelines.

Answer

Thanks for reaching out! Asking a question about switching a patient from hydrochlorothiazide (HCTZ) to chlorthalidone is quite timely, as a major study was just published in the New England Journal of Medicine that compared the blood pressure effects and cardiovascular outcomes of individuals taking these drugs.

In your question, it seems like your patient is more concerned with certain side effects of hydrochlorothiazide, so I'll focus on that aspect.

Chlorthalidone Represents A Good & Oftentimes A Preferred Alternative To HCTZ

There has long been debate about what the most appropriate diuretic choice is for those who have hypertension (high blood pressure). Hydrochlorothiazide (HCTZ) has long been the primary diuretic used by many healthcare practitioners, but recently, chlorthalidone has become a more popular choice due to its longer duration of action, higher potency, and purported better blood pressure-lowering effects.

The study I referred to above from the New England Journal of Medicine, published in Dec 2022, provides good evidence that chlorthalidone is a fine alternative to HCTZ.

The study compared the effectiveness of chlorthalidone, a thiazide-like diuretic, to hydrochlorothiazide (HCTZ) in controlling hypertension, and most importantly, outcomes (e.g heart attacks, etc...).

The study included over 13,000 older male veterans with uncontrolled hypertension who were taking HCTZ and assigned to either continue taking HCTZ or switch to chlorthalidone.

The study found that chlorthalidone had similar blood-pressure-lowering effects and important outcomes like all-cause mortality, stroke, myocardial infarction, and hospitalization for heart failure were the same in each group.

It is worth mentioning that other studies, such as one published in the journal Hypertension in 2015, have not only found chlorthalidone to be comparable to HCTZ but in many cases, superior in terms of statistically significant health outcomes and blood pressure control.

I say all of this just to emphasize that in terms of how HCTZ and chlorthalidone compare in regard to their effects, they seem to be at least on par, with recent studies showing chlorthalidone is likely superior.

What About Side Effects?

Chlorthalidone and HCTZ are very similar diuretics (HCTZ is a 'thiazide' diuretic while chlorthalidone is a 'thiazide-like' diuretic. As such, their reported side effects are very similar and include:

  • Decreased electrolytes (e.g., potassium and sodium)
  • Increased uric acid, which can increase the risk of gout
  • Increased cholesterol
  • Increased blood sugar
  • Dizziness
  • Lightheadedness
  • Fluid loss

Now, I'll focus specifically on what you asked about, dry mouth and hair loss.

Dry Mouth And Hair Loss 

There really is not a lot to go on in terms of clinical studies documenting these types of side effects.

While dry mouth and hair loss have both been reported in those taking HCTZ and chlorthalidone, they appear to occur only rarely.

The side effect of dry mouth seems likely to be associated with how these drugs cause fluid loss and it seems to occur at an essentially equal rate between the drugs.

Diving into thiazide-associated hair loss has been more challenging.

In fact, I could find very few mentions of these drugs causing hair loss, and studies that refer to them generally do so simply by stating that thiazides, as a class, are associated with hair loss with no additional detail.

So, I decided to turn to FAERS (FDA Adverse Event Reporting System) for more insights. FAERS, by the way, is a database that contains information on adverse events and medication errors reported to the FDA.

It is important to note that while FAERS is a valuable resource for identifying potential safety concerns with medications, there are a few potential gaps that should be noted, such as:

  • Underreporting: FAERS relies on voluntary reporting of adverse events, which means that not all adverse events are reported. This can lead to an underestimation of the true incidence rate of a particular adverse event associated with a medication.
  • Lack of denominator data: FAERS does not provide information on the total number of people taking a particular medication, so it is not possible to calculate the rate of a particular adverse event.

Regardless, FAERS provides some valuable insights. Below are figures from FAERS on the side effect of alopecia (i.e. hair loss) for both HCTZ and chlorthalidone.

HCTZ Chlorthalidone FAERS reporting on alopecia

Please note the following:

  • Hydrochlorothiazide: Out of 24,272 reported side effects cases, alopecia was reported 133 times (0.54%)
  • Chlorthalidone: Out of 1,980 reported side effects cases, alopecia was reported 8 times (0.40%)

While hydrochlorothiazide has a much larger sampling size, the incidence rates of alopecia between it and chlorthalidone are quite similar (0.54% vs. 0.40%).

Again, we can't draw definitive conclusions on this data based on some of the downsides I mentioned about FAERS above, but it does give us insight here and my takeaway is that hair loss on both drugs is quite rare and occur essentially at the same rate.

Pharmacist Thoughts

As a general statement, not knowing your patient's specific medical history, it makes sense that chlorthalidone would be a potential alternative diuretic choice to HCTZ.

Studies show that it likely has stronger blood pressure-lowering effects and likely has better cardiovascular outcomes associated with it (or, at the very least, is right on par with HCTZ).

The side effects you are concerned about (dry mouth and hair loss) are both uncommon with data showing reports of hair loss occurring at essentially the same rate with both drugs.

As things equal, I think it is perfectly reasonable to give chlorthalidone a trial and see how your patient responds.

Final Words

Thanks so much for reaching out! Do so again anytime. I hope this was helpful.

References

  • An Overview of Alopecias, PubMed
  • Lichen planopilaris, PubMed
  • Drug-induced hair loss and hair growth. Incidence, management and avoidance, PubMed
  • Interventions for female pattern hair loss, PubMed
  • Beneficial Extracardiac Effects of Cardiovascular Medications, PubMed
  • Lichen planus, lichenoid drug reactions, and lichenoid mucositis, PubMed
  • FDA Adverse Event Reporting System (FAERS) Public Dashboard, FDA
  • THALITONE (chlorthalidone), AccessFDA
  • Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular Events, NEJM
  • Effects of thiazide-type and thiazide-like diuretics on cardiovascular events and mortality: systematic review and meta-analysis, PubMed

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 13 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical, program development, and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Dr. Brian Staiger also has herbalist training and educational certificates in the field of medical ethnobotany. Feel free to send him an email at Hello@HelloPharmacist.com! You can also connect with Dr. Brian Staiger on LinkedIn.

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