Adding oral piroxicam to levonorgestrel improves emergency contraception efficacy

Key takeaways:

• Women receiving levonorgestrel plus piroxicam had a lower likelihood of pregnancy vs. those receiving levonorgestrel plus placebo.
• Overall, levonorgestrel plus piroxicam prevented 94.7% of expected pregnancies.

Oral piroxicam administered along with levonorgestrel improved emergency contraception efficacy without increasing the risk for adverse outcomes, according to trial data published in The Lancet.

Piroxicam is an NSAID and an inhibitor of the cyclooxygenase enzyme, whereas levonorgestrel is a first-line oral emergency contraceptive pill.

“Prostaglandins facilitate several reproductive processes including ovulation, fertilization, tubal function and embryo implantation,” Raymond Hang Wun Li, MD, from the department of obstetrics and gynecology at the School of Clinical Medicine at the University of Hong Kong and Family Planning Association of Hong Kong, and colleagues wrote. “It is therefore possible that an inhibitor of the cyclooxygenase enzyme, the key enzyme involved in prostaglandin production, might act synergistically with oral emergency contraception methods to improve their efficacy in regulating both ovulary and post-ovulary processes.”

Li and colleagues conducted a randomized, double-blind, placebo-controlled trial with 860 women who received levonorgestrel within 72 hours of unprotected sexual intercourse from August 2018 to August 2022 from a major community sexual and reproductive health service in Hong Kong. All participants were randomly assigned to a single supervised dose of levonorgestrel 1.5 mg plus oral piroxicam 40 mg (n = 430; mean age, 31 years) or levonorgestrel 1.5 mg plus placebo (n = 430; mean age, 30 years).

Researchers followed up with all participants 1 to 2 weeks after their next expected period and obtained pregnancy status by history or pregnancy test. The primary efficacy outcome was the proportion of prevented pregnancies.

Compared with 1.7% of women who received levonorgestrel plus placebo, 0.2% of women who received levonorgestrel plus piroxicam were pregnant during follow up (OR = 0.2; 95% CI, 0.02-0.91; P= .036). Levonorgestrel 1.5 mg plus piroxicam 40 mg prevented 94.7% of expected pregnancies compared with 63.4% of prevented pregnancies with levonorgestrel 1.5 mg plus placebo.

In addition, researchers observed no significant difference between those who received piroxicam and those who received placebo in the proportion of women with advancement or delay of their next period by more than 7 days (25% for piroxicam group vs. 23% for placebo) or adverse events including fatigue or weakness (10% for piroxicam group vs. 12% for placebo), nausea (8% for both groups), lower abdominal pain (7% for both groups), dizziness (6% for both groups) and headache (5% for piroxicam group vs. 6% for placebo).

“[Piroxicam plus levonorgestrel] can be considered where levonorgestrel emergency contraception is the option of choice,” the researchers wrote. “The strength of this recommendation and changes in clinical guidelines may be determined upon demonstration of reproducible results in further studies.”