What is the typical dosage and duration of doxycycline (Doxy) in the Doxy Pep (Doxycycline Post-Exposure Prophylaxis) regimen?

Doxycycline Post-Exposure Prophylaxis (Doxy PEP) Regimen

The standard Doxy PEP regimen is 200 mg of doxycycline (any formulation) taken as a single dose within 72 hours after condomless oral, vaginal, or anal sex, with a maximum of 200 mg per 24-hour period. 1, 2

Dosing Specifications

Key dosing parameters:

• Dose: 200 mg single dose 1, 3
• Timing: Within 72 hours after sexual exposure (ideally as soon as possible) 1, 2
• Frequency limitation: Not to exceed 200 mg per 24 hours 1, 2
• Formulation: Any doxycycline formulation is acceptable 1

This is fundamentally different from treatment dosing for established STIs, which uses 100 mg twice daily for 7 days. 4, 3 The Doxy PEP regimen is event-driven prophylaxis, not continuous daily therapy.

Target Population

CDC recommends Doxy PEP specifically for:

• Gay, bisexual, and other men who have sex with men (MSM) 1, 2
• Transgender women (TGW) 1, 2
• Who have had at least one bacterial STI (syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months 1, 2

The strength of this recommendation is AI (strong recommendation, high-quality evidence). 1

For MSM and TGW without a recent bacterial STI diagnosis but engaging in high-risk sexual activities, Doxy PEP may be discussed using shared decision-making, though this was not directly studied in trials. 1

No recommendation exists for cisgender women, cisgender heterosexual men, transgender men, or other queer/nonbinary persons assigned female at birth due to insufficient evidence. 1 A trial in cisgender Kenyan women showed no efficacy, likely due to adherence issues. 1

Efficacy Data

Doxy PEP reduces bacterial STI incidence by approximately two-thirds overall: 5, 6

• Chlamydia: 70-88% reduction 1, 2, 5, 6
• Syphilis: 73-87% reduction 1, 2, 6
• Gonorrhea: 50-57% reduction (less effective than for other STIs) 2, 5, 6

In the DoxyPEP trial, STIs were present in 12% of quarterly visits in the Doxy PEP group versus 30.5% in standard care (relative risk 0.39, p<0.0001). 5, 6

Prescription and Administration

Prescribing approach:

• Write prescription for self-administration 1
• Provide enough doses based on anticipated sexual activity until next visit 1
• Reassess ongoing need every 3-6 months 1, 2

Administration instructions to give patients:

• Take with a full glass of water (at least 100 mL) 7
• Remain upright for at least 1 hour after taking to prevent esophagitis 7, 3
• May take with food or milk if gastric irritation occurs 3
• Separate dosing by at least 2 hours from dairy products, antacids, and supplements containing calcium, iron, magnesium, or sodium bicarbonate 7

Required Ancillary Services

Doxy PEP must be implemented within comprehensive sexual health care: 1, 2

At initial visit:

• Screen for STIs at all anatomic sites of exposure (NAAT for gonorrhea/chlamydia, serology for syphilis) 1
• Screen for HIV per CDC PrEP guidelines if not on PrEP 1
• Counsel on benefits and harms including photosensitivity, esophagitis, GI intolerance, and antimicrobial resistance risk 1
• Discuss condom use and partner reduction strategies 1
• Link to HIV PrEP if HIV-negative and not already on PrEP 1

Ongoing monitoring:

• STI testing every 3-6 months at anatomic sites of exposure 1, 2
• HIV screening every 3-6 months for HIV-negative individuals 1, 2
• Reassess ongoing need for Doxy PEP every 3-6 months 1, 2

Adverse Effects and Safety

Common adverse effects (generally mild to moderate): 1

• Gastrointestinal symptoms (nausea, vomiting, diarrhea) 1
• Photosensitivity 1, 4
• Esophagitis and esophageal discomfort 1, 4

In the DoxyPEP trial, only one grade 2 laboratory abnormality and five grade 3 adverse events were possibly/probably related to doxycycline, with no serious adverse events attributed to the drug. 1, 5 Discontinuation rates due to adverse effects were low (0.9-1.5%). 1

Antimicrobial Resistance Concerns

Tetracycline resistance patterns observed: 1

• S. aureus carriage decreased overall (44% to 31%), but tetracycline-resistant S. aureus increased among carriers (5% to 13%) at 12 months 1
• Gonorrhea: 27-30% of isolates showed tetracycline resistance in Doxy PEP users versus 24% in controls 1, 5
• No significant resistance trends detected in C. trachomatis 1

The clinical significance of these resistance patterns remains uncertain and requires ongoing surveillance. 1 Current data suggest overall benefit outweighs resistance concerns in the short term, but long-term effects are unknown. 1

Critical Clinical Pearls

Common pitfalls to avoid:

• Do not prescribe Doxy PEP as daily continuous prophylaxis—it is event-driven only 1, 2
• Do not exceed 200 mg per 24-hour period even with multiple sexual encounters 1
• Do not prescribe without establishing comprehensive STI screening and follow-up plan 1
• Do not use in pregnancy or children under 8 years (though not the target population for this indication) 4

Doxy PEP is most appropriate for MSM and TGW with recurrent bacterial STIs who would benefit from intensive prevention efforts, not as a population-wide intervention. 8 It should be considered a targeted strategy for those at highest risk who account for the majority of bacterial STI burden. 1