Doxycycline Hyclate vs. Monohydrate: A Clear, Simple Guide to Their Differences

Doxycycline hyclate (Acticlate, Doryx, Vibramycin) and doxycycline monohydrate (Monodox, Oracea) are antibiotics that treat several bacterial infections. These prescription-only medications work by stopping bacteria from growing and spreading, helping your body fight an infection.

Both versions of the medication share the same active ingredient: doxycycline. But they have different salt forms. 

Here, we’ll examine the differences between doxycycline hyclate and monohydrate, what these differences mean for treatment, and how to ensure you’re taking the right one.

What are the main differences between doxycycline hyclate and doxycycline monohydrate?

Doxycycline hyclate and monohydrate both treat bacterial infections. While the medications work the same way, your healthcare professional may choose to prescribe one form over another for various reasons. 

Here are the key differences between doxycycline hyclate and monohydrate:

• Chemical structure: Doxycycline hyclate dissolves in water with little effort, while doxycycline monohydrate doesn’t dissolve as well. This difference may affect how your body absorbs the medication. But both forms are stable in the blood once absorbed.

• Stomach-related side effects: Doxycycline monohydrate may be slightly gentler on the stomach, making it easier for some people to tolerate.

• Available dosage forms: Both forms are available in brand-name and generic versions and come as capsules and tablets. But doxycycline monohydrate is also available as a liquid (oral suspension). And doxycycline hyclate is also available as an injection.

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What is the salt form of a medication?

Medications are often combined with other substances, such as salts, during the medication manufacturing process. This is done to help them dissolve better in water or last longer after you take a dose. The specific salt a medication attaches to is called its salt form. This is where the terms doxycycline “monohydrate” and doxycycline “hyclate” come from.

While both forms of doxycycline contain the same active ingredient, the different salt forms can have a slight effect on how your body absorbs the medications. It can also affect how they feel in your stomach.

Doxycycline hyclate and monohydrate uses

When a healthcare professional prescribes one form of doxycycline over the other, they may take into account the infection being treated, the potential side effects, and whether insurance coverage is a factor. Here's a look at what each form is typically used for.

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Doxycycline hyclate

Doxycycline hyclate treats a wide range of bacterial infections in adults and children, but it doesn’t treat viral or fungal infections. These are some of the common conditions it treats:

• Lung infections, such as pneumonia

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

• Infections caused by ticks, mites, or fleas

• Lyme disease

• Urinary tract infections (UTIs)

• Severe acne

• Anthrax

• Plague

• Cholera

Doxycycline hyclate is also used for malaria prevention.

Doxycycline monohydrate

Doxycycline monohydrate generally manages the same infections as doxycycline hyclate. One notable difference is rosacea. A specific version of doxycycline monohydrate, called Oracea, is approved to treat this skin condition.

Good to know: Your healthcare professional may recommend taking a preventative dose of doxycycline after sex. This strategy is known as doxy PEP — or doxycycline post-exposure prophylaxis. Doxy PEP can reduce the risk of chlamydia, syphilis, and gonorrhea infections. Either form of doxycycline is fine to use for this purpose.

Doxycycline hyclate and monohydrate dosages

Doxycycline hyclate and monohydrate have similar recommended dosages overall.

Typical doxycycline hyclate dosages

Here are the typical dosages of doxycycline hyclate by age group: 

• Adults and children (weighing 99 lbs or more): The typical dosage is 100 mg by mouth once or twice daily, depending on how serious the infection is.

• Children 8 years and older (weighing less than 99 lbs): Your child's prescriber will calculate your child's dosage based on their body weight. The typical dosage is 2.2 mg/kg of body weight by mouth once or twice daily.

Typical doxycycline monohydrate dosages

Here are the typical dosages of doxycycline monohydrate by age group: 

• Adults and children weighing 99 lbs or more: The typical dosage is 200 mg by mouth on Day 1, followed by 100 mg once daily or 50 mg every 12 hours. For more severe infections, the dosage after Day 1 may be 100 mg by mouth every 12 hours.

• Children (weighing less than 99 lbs) with severe infections: The typical dosage is 2.2 mg/kg by mouth every 12 hours.

• Children 8 years and older (weighing less than 99 lbs) with less severe infections: The typical dosage is 4.4 mg/kg (divided into 2 doses) by mouth on Day 1, followed by 2.2 mg/kg per day.

Your healthcare professional may adjust your dosage based on why you’re taking the medication. For malaria prevention, for instance, people typically take 100 mg of doxycycline daily starting 1 to 2 days before traveling and continuing for 4 weeks after leaving an area with malaria. Lower dosages, such as 40 mg once daily or 20 mg twice daily, may be prescribed for conditions like rosacea or gum infections.

Doxycycline hyclate and monohydrate effectiveness

Both forms of doxycycline are highly effective at treating bacterial infections. There's no major difference in how well the two forms work, so you can trust that either one should work well for you. With either medication, the biggest factors that impact its effectiveness are: the infection being treated and the bacteria causing the infection.

Doxycycline hyclate and monohydrate side effects

Doxycycline hyclate may cause slightly more gut-related side effects, such as nausea, than doxycycline monohydrate. But both forms of doxycycline cause similar side effects. Most of these side effects are temporary and manageable.

Common doxycycline side effects include nausea and vomiting, diarrhea, and loss of appetite. You may also experience skin-related problems such as rashes, itching, or sun sensitivity, which can increase the risk of sunburn. Yeast infections, which can lead to oral thrush or vaginal itching and discharge, may also occur.

Although rare, doxycycline can also cause severe skin reactions, such as Stevens-Johnson syndrome, which requires immediate medical attention. Other rare but serious side effects include:

• Blurry vision or vision loss

• Irritation in the esophagus

• Liver damage, which may show up as yellowing of the skin or eyes, dark urine, or pain in the upper stomach 

• Anemia (low blood cell counts), which can lead to fatigue or weakness

• Tooth discoloration (for children younger than 8)

Managing doxycycline side effects

If you experience common side effects while taking doxycycline, try to be patient. Many doxycycline side effects typically go away after a few days, as the body adjusts to the medication.

Still, there are still ways to manage doxycycline side effects to make your treatment more comfortable. Here are a few tips, in no particular order:

• Try taking doxycycline with food.

• Since doxycycline can make your skin more sensitive to sunlight, avoiding prolonged sun exposure and using sunscreen when you’re outdoors is a good idea.

• After taking a dose of doxycycline, stay upright for at least 30 minutes to avoid throat irritation.

• It’s recommended to wear cotton underwear and avoid tight-fitting pants to reduce the risk of yeast infections. Also avoid douching and using vaginal sprays or deodorants.

If you have doxycycline side effects that don’t get better over time or get worse, contact a healthcare professional.

How to save on doxycycline hyclate and monohydrate

GoodRx can help you save on the average retail price of the generic versions of doxycycline hyclate and monohydrate. At certain pharmacies, the price for 14 capsules of 100 mg doxycycline hyclate may be as low as $6.72 with a free GoodRx discount. The same quantity and dose of generic doxycycline monohydrate may cost as little as $5.74 with a free GoodRx discount.

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Written by:

Goldina Erowele, PharmD, MBA

Dr. Goldina Ikezuagu Erowele is a transformative leader in healthcare with a distinguished record of advancing medication safety, operational efficiency, and cost management.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

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