What are the risks and benefits of using Doxycycline?

Doxycycline Post-Exposure Prophylaxis (Doxy-PEP)

Doxy-PEP should be offered to gay, bisexual, and other men who have sex with men (MSM) and transgender women with at least one bacterial STI in the past 12 months, as it reduces syphilis and chlamydia by over 70% and gonorrhea by approximately 50%, with benefits substantially outweighing the low short-term risks. 1, 2

Who Should Receive Doxy-PEP

Strongly recommended for:

• MSM and transgender women with documented syphilis, chlamydia, or gonorrhea in the past 12 months 1
• This represents the highest-quality evidence from randomized trials showing clear morbidity reduction 3

May be considered through shared decision-making for:

• MSM and transgender women without recent STI diagnosis but engaging in high-risk sexual activities 1
• This approach targets those with behavioral risk even without documented infection 4

Insufficient evidence to recommend for:

• Cisgender women (trial in Kenyan women showed no efficacy, likely due to adherence issues) 1
• Cisgender heterosexual men 1
• Transgender men and other queer/nonbinary persons assigned female at birth 1

Dosing and Administration

The correct regimen is 200 mg doxycycline taken within 72 hours after condomless oral, vaginal, or anal sex, with a maximum of 200 mg per 24-hour period. 1, 2

• Take as soon as possible after sex (ideally within 24 hours, but effective up to 72 hours) 1
• Prescribe sufficient doses based on anticipated sexual activity until next visit 1
• Reassess ongoing need every 3-6 months 1, 2

Efficacy Data

The DoxyPEP trial demonstrated robust efficacy in both HIV-negative MSM on PrEP and people living with HIV 3:

In the PrEP cohort:

• Overall STI reduction: 66% (relative risk 0.34) 3
• Gonorrhea reduction: 55% (relative risk 0.45) 3
• Chlamydia reduction: 88% (relative risk 0.12) 3
• Syphilis reduction: 87% (relative risk 0.13) 3

In the PLWH cohort:

• Overall STI reduction: 62% (relative risk 0.38) 3
• Similar reductions across individual STIs 3

Benefits

Morbidity reduction:

• Prevents bacterial STIs that cause significant complications including neurosyphilis, infertility, and increased HIV transmission risk 1
• Number needed to treat for 1 year to prevent any STI: 2.2 in high-risk populations 1
• Prevents an average of 1.3 bacterial STIs annually per person 1

Quality of life:

• Reduces need for treatment courses and associated side effects 3
• Decreases anxiety and healthcare visits related to STI diagnoses 5
• High acceptability and feasibility in target populations 5

Risks and Adverse Effects

Short-term risks (well-documented and generally mild):

• Gastrointestinal symptoms (nausea, vomiting, diarrhea) - most common side effect 1, 2
• Photosensitivity reactions 1, 2
• Esophagitis and esophageal discomfort 1, 2
• In clinical trials: only 0.9-2.2% discontinued due to adverse events 1
• No serious adverse events attributed to doxycycline in major trials 1, 3

Long-term risks (theoretical and require monitoring):

• Antimicrobial resistance development in other pathogens (community-acquired pneumonia organisms, S. aureus) 1
• Tetracycline-resistant gonorrhea detected in 5 of 13 participants with gonorrhea in doxycycline groups vs 2 of 16 in standard care 3
• Microbiome changes (no long-term data available on intermittent use) 1
• Unknown effects from prolonged intermittent exposure 1

Critical caveat: The current data suggest overall benefit outweighs risks, but long-term resistance patterns and microbiome effects require ongoing surveillance as implementation expands 1

Risk Mitigation Strategies

To prevent esophagitis:

• Take with a full glass of water (at least 100 mL) 6
• Remain upright for at least 1 hour after taking doxycycline 1, 4
• Take on a full stomach 1

To prevent drug interactions:

• Separate doxycycline by at least 2 hours from dairy products, antacids, and supplements containing calcium, iron, magnesium, or sodium bicarbonate 1, 6, 4
• Review all medications including over-the-counter products for interactions 1
• No clinically relevant interactions with gender-affirming hormonal therapy 1

To prevent photosensitivity:

• Counsel patients about sun protection and avoiding excessive UV exposure 2

Comprehensive Sexual Health Approach

Doxy-PEP must be implemented within a broader prevention framework, not as a standalone intervention: 1, 4

At initial visit:

• Screen for gonorrhea and chlamydia at all anatomic sites of exposure (pharyngeal, rectal, urethral) 1
• Perform serologic testing for syphilis 1
• HIV testing per PrEP guidelines if on PrEP, or consider every 3-6 months if not 1
• Provide risk reduction counseling including condom use and partner reduction 1
• Discuss HIV PrEP if not already prescribed 1
• Ensure appropriate vaccinations 1

At follow-up visits every 3-6 months:

• Repeat STI screening at all exposure sites 1, 2, 4
• Repeat syphilis serology 4
• HIV screening per guidelines 2
• Assess for doxycycline side effects 1
• Reassess continued need for doxy-PEP 1, 2
• Provide ongoing risk reduction counseling 1

Patient Counseling Points

Essential discussion topics:

• Benefits: substantial reduction in bacterial STIs 1
• Known side effects: photosensitivity, GI symptoms, esophagitis 1, 4
• Potential for antimicrobial resistance development 1
• Unknown long-term effects on microbiome 1
• Proper administration timing and dosing limits 1
• Drug interactions and food/supplement separation 1, 4
• Doxy-PEP does not replace condoms or other prevention methods 1

Common Pitfalls to Avoid

Dosing errors:

• Do not exceed 200 mg per 24 hours even with multiple sexual encounters 1, 2
• Some users report taking incorrect dosages (21% in one survey used non-evidence-based dosing) 7

Population misapplication:

• Do not routinely prescribe for cisgender women based on current evidence 1
• Use clinical judgment for populations outside CDC recommendations 1

Incomplete implementation:

• Do not prescribe doxy-PEP without establishing regular STI screening schedule 1
• Do not use as replacement for comprehensive sexual health services 1, 4

Monitoring failures:

• Must reassess need every 3-6 months, not indefinite prescribing 1, 2
• Must screen for STIs every 3-6 months to detect breakthrough infections and resistance 1, 2

Special Considerations

Condom use:

• Most users (78.3%) report no change in condom use with doxy-PEP 7
• 17.2% report decreased condom use 7
• Emphasize that doxy-PEP does not prevent HIV or other viral STIs 1

Resistance monitoring:

• Population-level surveillance needed as implementation expands 1
• Individual resistance testing not routinely recommended but consider if treatment failures occur 1

Equity considerations:

• Focus implementation on subpopulations with highest STI burden for maximum population-level impact 1
• 25% of MSM account for 76% of bacterial STIs, making targeted implementation most efficient 1