Doxycycline Post-Exposure Prophylaxis Dosage
The recommended dosage for doxycycline post-exposure prophylaxis (doxy PEP) is 200 mg 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, 3
Target Population
Doxy PEP is specifically recommended by the CDC for gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW) who have had at least one bacterial STI diagnosed in the past 12 months. 1, 2, 3 Evidence for other populations remains insufficient for formal recommendations. 3
Dosing Specifics
- Dose: 200 mg of doxycycline (any formulation) as a single dose 1, 2, 3
- Timing: Take as soon as possible after sexual exposure, but no later than 72 hours post-exposure 1, 2, 3
- Frequency limitation: Do not exceed 200 mg in any 24-hour period 1, 2, 3
- Prescription quantity: Provide enough doses based on the patient's anticipated sexual activity until their next visit 1
Administration Instructions to Prevent Side Effects
- Take doxycycline on a full stomach with a full glass of liquid (at least 100 mL of water) 1, 4, 3
- Remain upright (do not lie down) for at least 1 hour after taking the medication to prevent esophagitis 1, 4, 3
- Separate doxycycline dosing by at least 2 hours from dairy products, antacids, and supplements containing calcium, iron, magnesium, or sodium bicarbonate 1, 4, 3
Clinical Efficacy
Doxy PEP reduces syphilis and chlamydia infections by more than 70% and gonococcal infections by approximately 50% in the target population. 2 This makes it particularly valuable for syphilis prevention, which was a primary driver for the CDC's 2024 guideline recommendation. 5
Monitoring and Follow-Up
- Initial visit: Screen for gonorrhea and chlamydia at all anatomic sites of exposure (oral, rectal, genital) and perform serologic testing for syphilis 1, 2
- Follow-up frequency: Reassess ongoing need for doxy PEP every 3-6 months 1, 2, 3
- STI screening: Perform bacterial STI testing at anatomic sites of exposure every 3-6 months 1, 2, 3
- HIV screening: For HIV-negative patients not on PrEP, consider HIV screening every 3-6 months 1, 2
Important Caveats and Pitfalls
Common dosing errors: In real-world use, only 51.6% of users take the recommended 200 mg dose correctly, with some using inappropriate antibiotics like amoxicillin or azithromycin instead of doxycycline. 6, 7 Additionally, 21% of users in one study took dosages other than the evidence-based 200 mg. 7
Side effects to counsel patients about: 1, 2, 3
- Photosensitivity (sun sensitivity)
- Esophagitis and esophageal discomfort
- Gastrointestinal symptoms (nausea, vomiting, diarrhea)
Antimicrobial resistance concerns: Doxy PEP use over 6 months increases the proportion of tetracycline resistance genes in the gut resistome from 46% to 51% in the metagenome and from 4% to 15% in the metatranscriptome. 8 However, no increases in other antimicrobial resistance gene classes were observed, and overall gut microbiome diversity remained unchanged. 8
Drug interactions: Review the patient's complete medication list, including over-the-counter medications, as doxycycline interacts with multiple drugs. 1 No clinically relevant interactions occur with gender-affirming hormonal therapy. 1
Comprehensive Sexual Health Context
Doxy PEP should not be prescribed in isolation but as part of a comprehensive sexual health approach that includes: 1, 2
- Risk reduction counseling
- Condom provision and counseling
- HIV PrEP linkage for HIV-negative patients
- HIV care linkage for people living with HIV
- Vaccination as appropriate