Doxycycline Post-Exposure Prophylaxis (Doxy-PEP) for Bacterial STI Prevention
Doxycycline is NOT used for HIV post-exposure prophylaxis—it is used to prevent bacterial sexually transmitted infections (syphilis, chlamydia, gonorrhea) after condomless sex, and you should take 200 mg as a single dose within 72 hours after intercourse. 1
Critical Clarification
Doxycycline has no role in preventing HIV infection. 1 If you had high-risk exposure to HIV, you need actual HIV post-exposure prophylaxis (HIV PEP), which consists of antiretroviral medications, not doxycycline. 1 Doxycycline post-exposure prophylaxis (doxy-PEP) is specifically for preventing bacterial STIs like syphilis, chlamydia, and gonorrhea. 2
Who Should Use Doxy-PEP
The CDC recommends doxy-PEP for gay, bisexual, and other men who have sex with men (MSM) and transgender women who have had at least one bacterial STI (syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months. 2 This represents a strong recommendation based on high-quality evidence showing over 70% reduction in syphilis and chlamydia, and approximately 50% reduction in gonorrhea. 2
Evidence is currently insufficient to recommend for or against doxy-PEP in cisgender women, cisgender heterosexual men, transgender men, and other queer and nonbinary persons. 2
Exact Dosing Protocol
Take 200 mg of doxycycline (any formulation) as a single dose within 72 hours after oral, vaginal, or anal sex. 1, 2 The medication should be taken as soon as possible after sexual exposure for maximum effectiveness. 1, 2
Critical Dosing Limits
- Do not exceed 200 mg of doxycycline per 24-hour period. 1 If you have multiple sexual encounters within 24 hours, you still take only one 200 mg dose. 1
How to Take Doxycycline Properly
Essential Administration Steps
Take doxycycline on a full stomach (non-dairy food) with a full glass of water (at least 200 mL). 1, 3, 2 This minimizes gastrointestinal side effects and prevents esophageal irritation. 4, 3
Remain upright (sitting or standing) for at least 1 hour after taking the medication. 1, 3, 2 This is crucial to prevent esophagitis and esophageal ulceration. 3
Critical Drug and Food Interactions
Separate doxycycline by at least 2 hours (before AND after) from: 1, 4
- All dairy products (milk, yogurt, cheese, calcium-fortified orange juice) 4
- Antacids containing calcium, magnesium, or aluminum 1, 4
- Supplements containing calcium, iron, magnesium, or sodium bicarbonate 1, 4
The 2-hour separation applies in both directions—you cannot have dairy 2 hours before OR 2 hours after taking doxycycline. 4 Calcium chelates with doxycycline in the gastrointestinal tract, forming insoluble complexes that dramatically reduce drug absorption, which can lead to treatment failure and development of antimicrobial resistance. 4
Common Side Effects and Management
Expected Side Effects
- Photosensitivity (sun sensitivity) 1, 2
- Esophagitis and esophageal discomfort 1
- Gastrointestinal intolerance (nausea, vomiting, diarrhea) 1, 2
Prevention Strategies
- Use UVA-absorbing sunscreens and avoid prolonged direct sun exposure during treatment 4
- Consider taking doxycycline in the evening when possible to minimize photosensitivity reactions 4
- Taking with non-dairy food significantly reduces nausea (15.7% vs 5.9% when taken correctly) 4
Required Monitoring and Follow-Up
You must have STI screening at baseline and every 3-6 months while using doxy-PEP: 1, 2
- Gonorrhea and chlamydia testing at all anatomic sites of exposure (oral, rectal, urogenital) 2
- Serologic testing for syphilis 2
- HIV screening per CDC guidelines 1, 2
The ongoing need for doxy-PEP should be reassessed every 3-6 months. 2
Important Warnings
- No clinically significant interactions with gender-affirming hormonal therapy 1
- Review all medications (including over-the-counter drugs and supplements) with your provider, as doxycycline interacts with multiple medications 1
- Do not share this medication with others or use it for conditions other than what it was prescribed for 4
- Doxycycline does NOT prevent HIV infection—you still need HIV PrEP or HIV PEP for HIV prevention 1, 2
Efficacy Data
Doxy-PEP reduces the incidence of the first STI by approximately 46% overall (HR 0.538). 5 For individual infections, it reduces chlamydia by approximately 71% (RR 0.291). 5 The most efficient prescribing strategies are based on STI history rather than HIV status or PrEP use, with the number needed to treat for one year to avert one STI diagnosis being 2.4 when prescribed for 12 months after STI diagnosis. 6