Plan B May Be More Effective When Taken With an Arthritis Drug

Key Points

• Levonorgestrel—aka the morning-after pill—is a synthetic hormone and the world's most popular and widely available means of emergency contraception.
• A common arthritis medication, when taken with the morning-after pill, substantially reduced the risk of unintended pregnancies in a recent trial.
• Researchers suggest providers may want to offer both medications to people who've had unprotected sex.

Taking a common arthritis medication together with the morning-after pill could significantly reduce the risk of an unplanned pregnancy from unprotected sex, according to research.

When taken together within 24 hours of intercourse, piroxicam (an anti-inflammatory pain medication) and levonorgestrel (Plan B) prevented up to 95 percent of pregnancies, suggested the 2023 study published in The Lancet.

By comparison, taking levonorgestrel with a placebo prevented 63 percent of pregnancies in the same circumstances, according to the randomized, controlled trial.

Levonorgestrel is one of two widely used forms of emergency contraception, along with ulipristal acetate. The former is available in more countries.

Most scientists and medical professionals refer to a 1998 trial when discussing levonorgestrel's effectiveness. If someone takes levonorgestrel within a day after they've had unprotected sex, it can be up to 95 percent effective, the study suggested. When taken 24 to 48 or 72 hours after sexual intercourse, it could be up to 85 or 58 percent effective, respectively.

The morning-after pill doesn't work when taken more than 72 hours after sex, according to Mayo Clinic.

More recent research suggests the morning-after pill may be less effective than previously thought, according to a press release. Factors such as obesity and certain medications can also diminish Plan B's effectiveness.

"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 that increases levonorgestrel's efficacy when they are taken together is really exciting," said Sue Lo, M.D., a senior doctor with the Family Planning Association of Hong Kong and a co-investigator of the study, in a statement.

Approximately half of pregnancies in the United States are unintended, according to the Office of Disease Prevention and Health Promotion.

What you should know about safer sex

• How to Make Talking About Safe Sex Sexier: Having this conversation with a partner doesn't have to be awkward—it can be fun, too.
• Selecting the Birth Control That's Right for You: When it comes to birth control, choose the type that's best suited to your lifestyle.
• How Do I Know When TikTok Promotes Birth Control Misinformation?: Here's an assortment of contraceptive myths TikTokers are pushing.

How did researchers test piroxicam's contraceptive potential?

The trial included 860 women who accessed levonorgestrel at a community sexual and reproductive health service in Hong Kong between 2018 and 2022 within 72 hours of unprotected sex.

Half of the women took a 1.5 milligram (mg) dose of Plan B and 40 mg of piroxicam, while the other half took levonorgestrel and a placebo. Participants and healthcare providers didn't know who had received which treatment.

The women were asked to follow up two weeks later. There was no significant difference in side effects between the two groups. Of the 836 who returned, one of the 418 who took piroxicam and levonorgestrel had become pregnant, compared to seven who'd taken Plan B and a placebo.

Plan B is an essential and unique form of contraception because it's taken orally, only used when sexually active and can be taken after intercourse, said Erica Cahill, M.D., an OB-GYN and clinical assistant professor at Stanford University School of Medicine, who wasn't involved in the study.

These findings could lead to the development of more effective oral emergency contraception methods, said Raymond H.W. LI, M.D., the lead study author and clinical associate professor at the University of Hong Kong.

How does piroxicam help prevent pregnancy after unprotected sex?

Levonorgestrel primarily works by suppressing, preventing or delaying ovulation, said Alyssa Dweck, M.D., an OB-GYN in Mount Kisco, New York, and a sexual and reproductive health expert at INTIMA, who wasn't involved in the study.

Progesterone also thins the uterine lining and thickens cervical mucus, making it more difficult for sperm to reach an egg if ovulation occurs.

Piroxicam may enhance Plan B's effectiveness by inhibiting prostaglandin synthesis, according to Li.

"Prostaglandins help to ready the uterine lining for fertilization and may facilitate sperm motility," Dweck said. "Prostaglandins are thought to be involved with ovulation as well."

Cox2 (cyclo-oxygenase) is a key enzyme—or converter—in prostaglandin creation, Cahill said. If that enzyme is blocked, it can't rearrange proteins to create prostaglandins.

As a Cox2 inhibitor, piroxicam suppresses prostaglandin synthesis, which may influence ovulation, uterine lining and sperm motility, reducing the chances of pregnancy, Dweck said. Plan B is typically ineffective once ovulation has occurred. When taken with piroxicam, however, the combined effects on the uterine lining and sperm motility may reduce the risk of fertilization.

Can I take Plan B while on birth control?

If you take birth control pills correctly, there's no need to take the morning-after pill after you've had unprotected sex. However, you can take the Plan B pill while on a different method of birth control without complications.

If you missed a dose of birth control, take the dosage as soon as possible and continue with the pack as usual.

When switching birth control pills, if you're using a combination formula, start taking your new pack within five days of the start of your period to ensure protection, according to Planned Parenthood.

Otherwise, you'll need to use a barrier contraceptive method for seven days while taking the new medication and to help prevent sexually transmitted infections (STIs), if you are or have been having sex with multiple partners.

Progestin-only pills become effective after two days, provided you take them at the same time each day. If you're uncertain, taking Plan B is a safe, effective way to reduce risk.

How many birth control pills equal a Plan B One-Step?

If you don't have access to emergency contraception but have birth control pills, taking multiple pills can reduce your chances of pregnancy after unprotected sex, according to Planned Parenthood.

The number of pills varies depending on the brand of birth control you're taking. Generally, you'll need to take four or five, though some brands require six.

Call your doctor or a sexual health clinic if you have any questions or concerns.

The bottom line

More research is needed to better understand piroxicam's potential contraceptive properties, the study authors wrote. It's unknown whether the effects apply to a broader, more diverse population, including people with higher-than-average body mass indexes (BMI), for whom Plan B is less effective.

However, the evidence thus far suggests providers may want to consider offering piroxicam along with levonorgestrel to reduce unintended pregnancies, Cahill said.