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Doxycycline Hyclate vs. Monohydrate

Dr. Leah Millheiser, MD Headshot

Medically reviewed by Leah Millheiser, MD

Written by Our Editorial Team

Last updated 5/26/2021

Imagine if you had to decide which medications were best for your afflictions. More than likely, you’re not a physician or pharmacist, and having to research pharmaceutical drugs, their effects, their risks and potential drug interactions would be a challenge, to put it mildly. 

Fortunately, when it comes to medications like doxycycline, you don’t have to do all of the work. You get to rely on the wisdom and education of physicians. That said, it doesn’t hurt to be informed. And if you’re considering doxycycline as a prescription drug treatment — whether for severe acne or another infection — it pays to know about your options.

TL;DR What You Should Know About the Two Types of Doxycycline

  • Doxycycline comes in two formulations: doxycycline hyclate and doxycycline monohydrate. 

  • These two forms of doxycycline are equally effective at treating a wide variety of conditions. 

  • The difference between doxycycline monohydrate and hyclate are at a molecular level, and would likely be unnoticeable to you. 

  • The dosing instructions vary from doxycycline hyclate to monohydrate, so the two cannot be used interchangeably. 

  • The two varieties of doxycycline may have pricing differences. At this time, doxycycline monohydrate is the cheaper option of the two. 

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What Is Doxycycline? 

Doxycycline is one of several prescription antibiotics known as a tetracycline. It is sold under brand names such as: Acticlate®, Doryx®, Monodox®, Oracea® and Vibramycin®. 

Though it is one of the most commonly prescribed acne medications, doxycycline is used to treat a wide variety of conditions. 

It may be prescribed for a variety of bacterial infections including those carried by animals and insects — such as lyme disease and rocky mountain spotted fever — or in food and water. It may be used to treat respiratory, intestinal, skin, eye, genital — such as chlamydia and gonorrhea — lymphatic and urinary tract infections. 

It is also effective at counteracting the effects of anthrax exposure and preventing malaria.

Doxycycline has been on the market since it’s FDA approval in the 1960s, so it has a long track record and is considered a safe and effective antibiotic.

What Is the Difference between Doxycycline Hyclate and Doxycycline Monohydrate? 

Doxycycline monohydrate and doxycycline hyclate are variations of the same drug, used to treat the same conditions. The differences are miniscule, particularly when it comes to actual size — the differences are molecular

If you want to get scientific, the differences boil down to some carbon, hydrogen, nitrogen and oxygen molecules. Also, the molecular weight of doxycycline monohydrate is about half that of doxycycline hyclate.

Another difference, according to the pharmaceutical manufacturer Pfizer, is the hyclate variation is water-soluble, while monohydrate is only “very slightly soluble in water.”  

Though these differences are “miniscule” in actual size, they do make a difference. Namely, the differences in doxycycline hyclate and doxycycline monohydrate come down to dosing or the amount you might have to take. 

Because of the different chemical compositions, it is not advisable to use these two forms interchangeably, and you should consult a healthcare professional before changing varieties.

Is Doxycycline Hyclate or Doxycycline Monohydrate Better? 

To get straight to the point: doxycycline hyclate and monohydrate are equally effective from a medical standpoint. So if you’re concerned one won’t work as well as the other, rest easy. 

That said, one practical area to scrutinize is price. It turns out that the price of these two doxycycline molecules have been particularly volatile in the past and prices can still be quite a bit different.

According to, a prescription comparison site, the average retail price of a commonly used monohydrate version is about 50 percent lower than the average retail price of the comparable hyclate version. 

That said, the prices you’d pay at some pharmacies may be similar and, what's more, we've even seen wholesale prices with hyclate being the cheaper of the two! 

All of this is to say: the whole “supply and demand” thing is alive and well. Keep an eye on the price tag of doxycycline. You can always check with your provider about other available options if the price looks off.

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A Note on Doxycycline Side Effects and Risks 

All prescription drugs come with potential side effects. With doxycycline, the most likely side effects include photosensitivity leading to sunburns and other skin irritations, and digestive distress including diarrhea. It’s important you report all disruptive side effects to your doctor, in case they’re a sign of a more serious reaction. 

Also, disclose all other medications you’re currently on before starting a doxycycline regimen — including supplements and over the counter drugs. Antacids, calcium supplements, and antidiarrheal medications are just a few that could cause problems when taken with doxycycline.  

Your doctor can help identify those that could increase your risks of adverse events or lessen the effectiveness of the doxycycline. 

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.