Doxy-PEP

Doxycycline post-exposure prophylaxis — doxy-PEP — is a single 200 mg oral dose of doxycycline taken as soon as possible, and within 72 hours, after oral, vaginal, or anal sex. It is intended to be self-administered after exposure rather than taken daily, and patients should not exceed one 200 mg dose per 24-hour period (CDC). Patients are advised to take it with food and a full glass of water, avoid lying down for an hour, and stay separated from dairy, antacids, and iron, calcium, or magnesium supplements within two hours of dosing.

The CDC's 2024 clinical guideline, summarized in the MMWR, recommends that providers counsel doxy-PEP for gay and bisexual men and transgender women who have had a documented bacterial STI — syphilis, chlamydia, or gonorrhea — in the past twelve months. Across three large randomized trials, doxy-PEP reduced syphilis and chlamydia infections in this population by more than 70%, with smaller and more variable effects against gonorrhea (roughly 50% in the pooled data). The agency notes that long-term effects on antimicrobial resistance and the human microbiome remain under study, which is the main reason the formal recommendation has not yet been broadened.

Uptake outside the formally recommended group, including among lifestyle couples, is growing as the evidence accumulates and clinicians become more comfortable prescribing off-label. Doxy-PEP is not a substitute for routine STI testing, vaccination (HPV, hepatitis), or barrier methods; it covers three bacterial infections and offers no protection against HIV, herpes, hepatitis, or anything viral. Anyone using it should also screen for STIs and HIV every three to six months per CDC guidance.