Taking Anti-Inflammatory Medication with Plan B Improves Effectiveness

A new study published in the Lancet provides a new route for improving the effectiveness of oral emergency contraceptives. According to the study, taking an anti-inflammatory pill alongside Plan B significantly increases the drug’s efficacy.

Levonorgestrel, also called Plan B or the morning-after pill, is an emergency oral contraceptive that can be taken within 72 hours of unprotected sex to prevent pregnancy. In a StatPearls chapter, authors note that, despite FDA approval only applying for use within 72 hours, some people have used the drug off-label for 96 hours with minor efficacy.

The drug works by binding to progesterone and androgen receptors, causing a cascade that delays or prevents ovulation. With that in mind, the drug is ineffective if taken after ovulation.

Despite being the first-line emergency contraceptive method, levonorgestrel Planned Parenthood estimates that the medication is only 75–89% effective within three days. For many patients, this reduced efficacy is a vital concern.

However, the recent Lancet study demonstrated a tool that could improve the drug’s effectiveness at preventing unintended pregnancies: an anti-inflammatory medication.

In a randomized, double-blind, placebo-controlled clinical trial, researchers evaluated the efficacy of levonorgestrel alone compared to levonorgestrel with a cyclo-oxygenase inhibitor (piroxicam). The participants were women who had unprotected sex and sought care at major reproductive health centers in Hong Kong.  

Approximately 418 patients were assigned to each group, including the experimental group, which received 1.5 mg of levonorgestrel and 40 mg of piroxicam, and the control group, which received 1.5 mg of levonorgestrel and a placebo, within 72 hours of unprotected sex.

Within two weeks after the patient’s next expected period, they had a pregnancy test to assess the efficacy of the medication. Only one woman in the experimental group, 0.2% of the group, had an unintended pregnancy. Comparatively, seven patients in the placebo group became pregnant, accounting for 1.7%.

In-depth data analysis concluded that 1.5 mg of levonorgestrel and 40 mg of piroxicam could prevent 94.7% of pregnancies. Meanwhile, 1.5 mg of levonorgestrel alone only effectively prevented 63.4% of pregnancies.

“Oral piroxicam 40 mg co-administered with levonorgestrel improved efficacy of [emergency contraception] in our study. Piroxicam co-administration could be considered clinically where levonorgestrel [emergency contraception] is the option of choice,” concluded the researchers in the study.