Combination therapy increases efficacy of emergency contraception

Emergency contraception treatment with levonorgestrel plus piroxicam is significantly more effective than levonorgestrel monotherapy, researchers reported on August 16, 2023 in the Lancet.

“Overall, this study suggests that anyone administering levonorgestrel 1.5 mg as emergency contraceptive pills should consider the addition of 40 mg piroxicam orally, as it improves efficacy with minor side-effects,” said outside commentator Erica Cahill, MD, Clinical Assistant Professor of Obstetrics and Gynecology and Complex Family Planning at Stanford University Medical School in Palo Alto, California.

In this randomized, placebo-controlled trial, the investigators enrolled women seeking levonorgestrel treatment within 72 hours of having unprotected sex. They were randomized in a 1:1 ratio to receive a single dose of levonorgestrel 1.5 mg plus either piroxicam 40 mg or placebo.

An appointment was scheduled for one to two weeks after the next expected period. If a normal period had not occurred already, a pregnancy test was carried out at that time.

The researchers recruited 860 women (430 in each group) between Aug 20, 2018, and Aug 30, 2022.

One (0.2%) of 418 efficacy-eligible women in the levonorgestrel-plus-piroxicam group became pregnant, compared with seven (1.7%) of 418 in the placebo group.

Using a standard predictive model to evaluate the data, the researchers reported that levonorgestrel plus piroxicam prevented 94.7% of expected pregnancies compared with 63.4% for levonorgestrel plus placebo.

“We noted no significant difference between the two groups in the proportion of women with advancement or delay of their next period, or in the adverse event profile,” the authors noted.

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