Doxycycline hyclate vs. monohydrate: what’s the difference?

The names of medications can be confusing. Drug names are often tricky to spell, tough to pronounce, and many sound alike. 

If you’re searching for an antibiotic called doxycycline, you’ll notice that comes as two different drugs. Keep reading to learn about doxycycline hyclate vs. monohydrate, and if one is better for treating things like acne and bacterial infections. 

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Doxycycline is an antibiotic that stops certain types of bacteria from growing. It treats a wide range of bacterial infections including (Patel, 2022):

• Lyme disease

• Malaria

• Periodontal (gum) disease

• Sexually transmitted infections (STIs), such as chlamydia, gonorrhea, and syphilis

• Rocky Mountain spotted fever

• Urinary tract infections (UTIs)

• Gastrointestinal infections

• Anthrax infection

Doxycycline also has anti-inflammatory effects, making it useful for treating inflammatory conditions. One example is rosacea, a skin condition that causes bumps and blemishes. Healthcare providers also prescribe doxycycline to treat acne, taking advantage of both its antibacterial and anti-inflammatory properties (Patel, 2022).

Here are some fast facts about doxycycline (FDA, 2008; Krout, 2015):

• Drug class: Tetracycline antibiotic

• Route: Oral

• Forms: Capsule, tablet, liquid suspension, delayed-release tablet

• Brand names: Monodox, Vibramycin, Acticlate, Doryx, Oracea, Adoxa, Periostat

• Generic names: doxycycline hyclate, doxycycline monohydrate

Doxycycline comes in a variety of strengths. The usual dosage is 100 mg taken once or twice daily. Be sure to follow the directions from your healthcare provider.

You may be wondering if there’s a big difference between these two medications. The short answer is, not really. They both contain the same powerful active ingredient: doxycycline. And both are effective against the same types of bacteria (DailyMed, 2017; DailyMed, 2021).

So if doxycycline hyclate and monohydrate are essentially the same thing, why the two names? Medications often have a second part to their name. For doxycycline, the second parts are monohydrate and hyclate. These names indicate what salt is attached to the active drug molecule. Salts are inactive ingredients but can be important for helping your system absorb drugs like doxycycline (Neubig, 2010).

Healthcare professionals often omit the salt name when talking about medications. That’s why it can be surprising when your prescription label has a drug name that’s slightly different than expected. If you have questions about your prescription, don’t hesitate to reach out to a pharmacist or healthcare provider for medical advice.

Both forms of doxycycline are effective at fighting the same types of bacteria. There are slight differences in their pharmacology like absorption and bioavailability, which are measures of how well a drug gets into your bloodstream.

A small study looking at how doxycycline gets absorbed after oral administration in 12 people found no differences between hyclate and monohydrate forms of doxycycline. However, they did point out that doxycycline monohydrate has a lower risk of irritating the esophagus (Malmborg, 1984).

To lower the risk of irritation in your esophagus, healthcare providers recommend drinking a full glass of water with each dose of doxycycline. You’ll also want to avoid laying down right after you take a dose. These points of advice apply to both the hyclate and the monohydrate versions (DailyMed, 2017; DailyMed, 2021; Krout, 2015).

Another pharmacological difference is that doxycycline hyclate fully dissolves in water, whereas doxycycline monohydrate only slightly dissolves in water. But, once either form absorbs into your system, they become active as doxycycline. Each are equally effective for treating acne and infections (Krout, 2015).  

Cost of doxycycline hyclate vs. monohydrate

Since the scientific differences aren’t significant, the cost of each drug may be a more practical comparison. The estimates below show the average retail price for doxycycline, according to GoodRx (GoodRx-a, n.d.; GoodRx-b, n.d.).

• Doxycycline monohydrate 100 mg, quantity of 30 capsules: $58.

• Doxycycline hyclate 100 mg, quantity of 30 capsules: $109.

• Doxycycline hyclate 100 mg, quantity of 30 tablets: $105.

Keep in mind that these prices are estimates and don’t take into account any insurance plans or discounts. 

Common side effects of doxycycline include (Patel, 2022):

• Diarrhea 

• Photosensitivity (increased skin sensitivity to sunlight, which may lead to sunburn)  

• Nausea  

• Vomiting 

• Skin rash or itching 

• Headaches 

• Tooth discoloration 

Doxycycline has the potential to interact with several different types of medications. The interaction risks are the same regardless if you take the hyclate or monohydrate version of doxycycline. The most important interactions with doxycycline to be aware of include (DailyMed, 2017; DailyMed, 2021):

• Calcium, aluminum, magnesium, and iron. Minerals can bind to doxycycline in your digestive tract and limit its absorption. This interaction can make doxycycline less effective. Calcium, aluminum, magnesium, and iron are found in supplements, multi-vitamins, laxatives, and antacids like Tums or Maalox. Many foods are also fortified with minerals. It is important to avoid products that contain these minerals two hours before or after taking doxycycline (Patel, 2022).

• Bismuth subsalicylate (Pepto Bismol). Bismuth may affect the absorption of doxycycline, potentially making the medication less effective.

• Oral contraceptives. It is possible that doxycycline and other antibiotics may make birth control pills less effective. If you’re taking birth control to prevent pregnancy, you may want to use a backup method like condoms while taking doxycycline.

• Blood thinners. Doxycycline has been reported to affect blood clotting. If you take a blood thinner drug, such as warfarin, your healthcare provider may monitor you more closely while you take doxycycline. They may tell you to adjust your warfarin dosage temporarily.

Doxycycline can be an effective treatment for a wide range of conditions. Do not hesitate to reach out to your healthcare provider if you have questions about this or other medications.

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How we reviewed this article

Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

Current version

May 25, 2022

Written by

Patricia Weiser, PharmD

Fact checked by

Chimene Richa, MD

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About the medical reviewer

Chimene Richa, MD

Dr. Richa is a board-certified Ophthalmologist and medical writer for Ro.