Doxycycline post-exposure prophylaxis (DoxyPEP) is when a person takes the antibiotic doxycycline (doxy) after sex to reduce their chance of getting chlamydia, gonorrhea, and syphilis. Chlamydia, gonorrhea, and syphilis can be transmitted during oral, frontal/vaginal, and anal sex. DoxyPEP does not prevent other STIs, such as HIV or Mpox.

Currently, the CDC recommends DoxyPEP for cisgender men and transgender women who have sex with men.  We don’t have much data right now on whether it is effective for people who were assigned a female sex at birth (AFAB) and have vaginal/frontal sex. One study has indicated that it may not be effective for preventing chlamydia, gonorrhea, and syphilis during vaginal/frontal sex, but there were very low rates of adherence (taking the medication) during that trial. That means that right now, it's hard to know if DoxyPEP truly doesn't work for AFAB people who have frontal/vaginal sex, or whether that study didn't show that it was effective because of the low adherence.  

Until we know whether low rates of medication adherence explained the lack of effectiveness in that trial, we cannot be sure that the medication is as protective for individuals engaging in frontal/vaginal sex as it is for individuals engaging in anal sex. There is no reason to think that DoxyPEP protection for individuals engaging in anal sex is different between people who were assigned a male sex at birth and AFAB people. Other studies are currently underway to see if DoxyPEP works for people who have frontal/vaginal sex.

At Fenway Health, we take an informed consent approach. If an AFAB patient is aware that we currently don’t have great effectiveness data around the use of DoxyPEP for AFAB people, we allow them to make the best decisions for themselves. We also make sure that they are not pregnant or chestfeeding because those are safety concerns.  

Different clinics and healthcare providers may take different approaches. While some clinics may also take an informed consent approach, others may only prescribe DoxyPEP to cisgender men and transgender women.

Take 200mg of doxycycline within 3 days (72 hours) of a sexual encounter. The sooner you take it, the more effective it is. It’s safe to take DoxyPEP daily, but never take it more than once a day. Taking it with food may reduce the likelihood of side effects such as nausea.

You need a prescription to take DoxyPEP. You may be able to get a prescription from your primary care provider, gender-affirming hormones provider, or a sexual health clinic. Clinics that specialize in LGBTQ+ health may be the most likely to be knowledgeable about DoxyPEP. You can also get DoxyPEP from some online telehealth services, like MISTR,Freddie, Wisp, and Q Care Plus.

Common side effects may include nausea and gastrointestinal upset. Taking doxycycline with food may help with this. Some people may also be more sensitive to sunlight while taking doxycycline, so using sunscreen and minimizing sun exposure is recommended. Frequent use of broad-spectrum antibiotics may be associated with frontal/vaginal yeast infections, although this was not seen in the trial of DoxyPEP in cisgender women. Talk to your doctor about any concerns you have before starting DoxyPEP, and reach out to them if you experience side effects.  

There are no specific risks of using DoxyPEP for STI prevention while having vaginal/frontal sex.

In general, we have not seen worsening antibiotic resistance with DoxyPEP to the point where it has been clinically significant. However, we are still monitoring for that, since we don’t have long term data. Read this article for more information about antibiotic resistance.

The likelihood of DoxyPEP reducing the effectiveness of hormonal contraceptives is generally considered low. Doxycycline does not typically interfere with most hormonal birth control methods, such as pills, patches, or injections. If a patient is on oral contraception, some clinicians might ask that they take the DoxyPEP at a different time, but mostly to avoid upsetting the stomach.

Yes, it is safe and effective to take DoxyPEP and PrEP at the same time.

You should still get tested for chlamydia, gonorrhea, syphilis, and HIV every 3 to 6 months.  DoxyPEP is not 100% effective. If you test positive for an STI while you are on DoxyPEP, you will still need treatment for it.

Doxycycline is generally inexpensive and covered by health insurance.