Researchers in Hong Kong took a group of hundreds of women who required emergency contraception between 2018 and 2022, and divided them into two groups: one that received levonorgestrel (the generic name for Plan B) and a placebo pill, and one that received levonorgestrel plus piroxicam, an anti-inflammatory medication often used for arthritis pain.

The combination of levonorgestrel and a placebo prevented 63% of pregnancies, while the levonorgestrel-piroxicam duo prevented 95% of pregnancies, researchers found.

“The levonorgestrel emergency contraceptive pill is one of the most popular choices of emergency contraception in many parts of the world, so finding out that there is a widely available medication which increases levonorgestrel’s efficacy when they are taken together is really exciting,” Dr. Sue Lo, of the Family Planning Association of Hong Kong and a coinvestigator on the study, said in a news release.

The research suggests that providers prescribing levonorgestrel for emergency contraception should consider also prescribing piroxicam, “as it improves efficacy with minor side effects,” Dr. Erica Cahill, an ob-gyn and clinical professor at Stanford Medicine, said in the news release.

Research from 1998 suggested that levonorgestrel prevented 95% of expected pregnancies if taken within 24 hours of unprotected sex, 85% if taken within 25 to 48 hours, and 58% if taken within 49 to 72 hours. But more recent research suggests that the drug’s efficacy might be lower. Levonorgestrel is effective only 81% to 90% of the time, according to a 2022 Kaiser Family Foundation report.

Why piroxicam apparently makes Plan B more effective

Levonorgestrel works by preventing or delaying a surge of hormones, disrupting the ovulation process, and preventing pregnancy from occurring, if taken in time. The study’s researchers aren’t completely certain why piroxicam appears to make the drug more effective. But they think it’s because it targets a different type of hormone, blocking ovulation, and, as a bonus, preventing the implantation of an embryo—something levonorgestrel alone can’t do.

The study had limitations. Women who were recently on hormonal contraception were excluded, as well as those who had unprotected sex more than once before needing emergency contraception. All participants were Asian and weighed less than 154 pounds. Women in different situations, or with different characteristics, may respond differently to the two-medication combination, the authors cautioned. Studies have shown that levonorgestrel is less effective in women with a higher BMI, particularly above 26.