Doxy-PEP is a preventive treatment that uses the antibiotic doxycycline to reduce the risk of getting certain bacterial sexually transmitted infections (STIs)—specifically chlamydia, gonorrhea, and syphilis. It can be taken as a single dose within 72 hours after condomless sex OR as part of a prevention plan if there is known risk.

MOA - of Doxy/PEP:

Inhibits Bacterial Protein Synthesis
Doxycycline binds to the 30S ribosomal subunit of susceptible bacteria, blocking the attachment of aminoacyl-tRNA to the mRNA-ribosome complex. This prevents the addition of new amino acids to the growing peptide chain, effectively halting bacterial protein synthesis and stopping bacterial growth 

Targets Key STI Pathogens Doxycycline is effective against:

Chlamydia trachomatis, Treponema pallidum (syphilis), and Neisseria gonorrhoeae.

Note with gonorrhea there are some studies showing a rise in resistance. Learn more about this from Soge et al. (2025)

Pharmacokinetics

Rapidly absorbed orally.

High tissue penetration, including genital and rectal mucosa.

Long half-life allows for effective post-exposure coverage.

Studies show Doxy PEP reduces the risk of gonorrhea by about 55-60%. It also decreases the risk of developing chlamydia and syphilis by about 80% (Luetkemeyer et al., 2023).

Consider - What do you know about their sexual health? The types of sex they are having and with whom? Then:

“Is this patient at risk for a bacterial STI?

“Do they have a history of STIs?”

“Are they part of a higher risk community including individuals who are gay, bisexual, a man who has sex with other men (MSM) or a transgender woman?”

Doxy PEP is not for everyone. It is currently recommended for adult gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW) with a history of an STI, such as gonorrhea, chlamydia, or syphilis, within the last 12 months.

Key points to consider and share:

Doxy PEP does NOT protect against HIV infection or other viral infections such as Herpes or HPV (a virus that can cause warts or pre-cancer changes in cells).  PrEP (Pre-Exposure Prophylaxis) is a medication taken to prevent HIV infection. Learn more about PrEP here.

How much should I prescribe?

Use a conversation with the patient about their risks and how often these may occur to drive amount. PRO-TIP: Access, stigma, and bias may influence how often they come to the office and how much they share about risk. Providing additional doses to meet their need is important as well as a trauma informed approach.

How should I code it?

Consider ICD-10 code  Z20.2 for Possible exposure to STI.

It has dangerous side-effects: FALSE - While it’s true that all medications can have side effects, Doxy PEP’s regimen, typically a short course of doxycycline, is well-tolerated by most individuals. These can address by taking the medication with a full glass of water.

It encourages risky behaviors: FALSE - Research and real-world experiences have shown that access to preventive measures like Doxy/PEP actually encourage more responsible sexual health practices and starts conversations about risk and protection. (Fredericksen et al., 2024)

Talking to patients about STIs will offend them FALSE -

Why Open Conversations About Sexual Health Matter

Empowering Informed Choices
Honest, respectful dialogue enables patients to make well-informed decisions about their sexual health, including adopting safer practices like consistent condom use.

Promoting Early Detection and Treatment
Routine STI screening and open discussions about symptoms support early diagnosis and timely treatment—key to preventing complications and reducing transmission.

Challenging Stigma Through Education
When providers speak openly and factually about STIs, they help dismantle the stigma and shame that often discourage individuals from seeking care.

Fostering Trust and Connection
Approaching sexual health with empathy and sensitivity builds trust, encouraging patients to share their concerns and engage more fully in their care.

STIs only impact other communities not here FALSE - STI’s such as chlamydia, syphilis, and gonorrhea are on the rise and impacting many including rural communities.

Doxy/PEP is billable to most insurances and generic versions are available. The average prescription will likely be less than $20 through insurance or GoodRX.

Try This: Connect it to something you know they care about -

If you are at a general/regular health visit:

“Your health is important to both of us. There are some risk factors that put you at higher risk for getting an STI. I would like to talk about starting some medications that can lower your risk. What do you know about Doxy/PEP?”

If you are at an appointment for STI testing, connect it to that:

“So you are here for STIs today because you may have been exposed. There are things we can do to lower your risk of in the future and prevent some bacterial STIs. I would like to talk about these options including Doxy/PEP.”

Offer Doxy/PEP as part of a broader toolkit for sexual wellness - Prescribe PROACTIVELY, don’t wait for patients to ask.

These conversations could also lend themselves to talking about PrEP to prevent HIV.

NORMALIZING SEXUAL HEALTH CONVERSATIONS:

Take a sexual history at every visit—just like blood pressure or smoking status.

Use affirming, nonjudgmental language. (Learn more here)

Ask about partners, practices, protection, past STIs, and pregnancy plans (the 5 Ps).

Offer Doxy/PEP as part of a broader toolkit for sexual wellness - Prescribe PROACTIVELY, don’t wait for patients to ask.

• This is Unlike HIV PrEP, Doxy PEP is not a daily medication. It is meant to be taken as needed within 72 hours of a condomless sexual encounter

• Take with a full glass of water or other non-alcoholic drink.

• Avoid dairy products (like milk or cheese), calcium, antacids, and multivitamins for two hours before and after taking doxycycline.

• Take with food if your stomach gets upset by the medication.

• Wear sunscreen or sun protective clothing and limit the amount of time you spend in direct sunlight it can make your skin more sensitive to the sunlight.

• Only take medication that was prescribed

Use this link and QR code to share information about Doxy/PEP. Pro tip: they may not be comfortable saying, “I dont know” or have myths needing busting.

-P.S. You can look there too.