What is DOXYpep (doxycycline)?

What is DOXYpep?

DOXYpep (doxycycline post-exposure prophylaxis) is a prevention strategy where 200 mg of doxycycline is taken as a single dose within 72 hours after condomless sex to prevent bacterial sexually transmitted infections, specifically reducing syphilis and chlamydia by over 70% and gonorrhea by approximately 50%. 1, 2

Who Should Use DOXYpep

The CDC specifically recommends DOXYpep for: 1, 2

• Gay, bisexual, and other men who have sex with men (MSM) with at least one bacterial STI (syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months
• Transgender women (TGW) with at least one bacterial STI in the past 12 months

Evidence is currently insufficient to recommend for or against DOXYpep in cisgender women, cisgender heterosexual men, transgender men, and other queer and nonbinary persons. 2 This represents a critical limitation—the intervention is only proven effective in MSM and TGW populations based on rigorous trial data. 3

Dosing Protocol

The specific dosing regimen is: 1, 2

• 200 mg doxycycline (any formulation) as a single dose
• Taken within 72 hours after oral, vaginal, or anal sex
• Maximum dose: 200 mg per 24-hour period (meaning if you have sex multiple times in one day, you still only take one dose)
• Take as soon as possible after exposure, but no later than 72 hours 2

Administration Instructions to Prevent Side Effects

To minimize esophagitis and gastrointestinal upset: 2

• Take on a full stomach with at least 200 mL (full glass) of water
• Remain upright for at least 1 hour after taking the medication
• Separate doxycycline by at least 2 hours from dairy products, antacids, and supplements containing calcium, iron, magnesium, or sodium bicarbonate 2

Required Monitoring and Comprehensive Care

DOXYpep is not a standalone intervention—it must be part of comprehensive sexual health care: 1, 2

At baseline (initial visit): 2

• Screen for gonorrhea and chlamydia at all anatomic sites of exposure (oral, rectal, urogenital)
• Serologic testing for syphilis
• HIV screening per CDC HIV PrEP guidelines

Every 3-6 months: 1, 2

• Repeat STI screening at anatomic sites of exposure
• Assess for doxycycline side effects
• Reassess ongoing need for DOXYpep
• Provide risk reduction counseling and condoms
• Counsel on HIV PrEP/PEP as indicated

Efficacy Data

The DoxyPEP trial demonstrated robust efficacy: 3

• STIs were present in 12% of quarters in the DOXYpep group versus 30.5% in standard care (relative risk 0.39,95% CI 0.31-0.49, p<0.0001)
• This translates to an absolute risk reduction of approximately 19 percentage points
• Efficacy was sustained during the open-label extension when participants knew they were receiving active treatment 3

Common Side Effects and Safety

The most common adverse effects include: 1, 4

• Photosensitivity (sun sensitivity)
• Gastrointestinal symptoms (nausea, vomiting, diarrhea)
• Esophageal erosion and ulceration (prevented by proper administration technique)

Most adverse effects resolve with discontinuation. 1 In the DoxyPEP trial, there was only one grade 2 laboratory abnormality and five grade 3 adverse events possibly or probably related to DOXYpep, with no serious adverse events attributed to doxycycline. 3

Antimicrobial Resistance Concerns

A critical consideration is the potential for antimicrobial resistance: 3

• Among participants with positive gonorrhea cultures, 27% taking DOXYpep versus 24% not taking DOXYpep had tetracycline resistance (minimum inhibitory concentration ≥2 μg/mL)
• This suggests no substantial increase in tetracycline resistance with DOXYpep use in the trial population
• Ongoing studies are evaluating long-term antimicrobial resistance patterns and population-level impact 2

What DOXYpep Does NOT Prevent

DOXYpep does not prevent: 4

• HIV infection (a common misconception among potential users) 5
• Mycoplasma genitalium
• Viral STIs (herpes, HPV, hepatitis)

Contraindications

DOXYpep should not be used in: 4

• Pregnancy
• Children under 8 years of age
• Severe liver dysfunction

Implementation Considerations

Recent research reveals important implementation insights: 5

• Knowledge of DOXYpep remains low (28% in one Los Angeles study), but interest is high (81%) once people learn about it
• Most prefer to obtain DOXYpep from a medical provider or over-the-counter at a pharmacy
• Preferred cost is $10-20 for a 1-month supply, though free or insurance-covered is ideal
• Greatest concerns include side effects, antibiotic resistance, and potential for decreased condom use