Levonorgestrel-piroxicam combo prevents pregnancy after unprotected sex

The use of levonorgestrel (LNG) plus piroxicam, as oral emergency contraception (EC) after unprotected sexual intercourse (UPSI), resulted in a significantly greater number of pregnancies prevented compared with LNG plus placebo, according to a study presented at RCOG 2023.

“Effective EC is important for reducing unwanted pregnancies after UPSI or after a recognized contraceptive failure,” said lead author Dr Raymond Li from the Department of Obstetrics and Gynaecology at the University of Hong Kong, Hong Kong.

The most commonly used oral EC regimens are LNG and ulipristal acetate (UPA), which should be taken within 72 and 120 hours, respectively, before UPSI. However, “both LNG and UPA are effective as an EC only when given before, not after, ovulation,” Li said.

Therefore, “we need improvement in the efficacy of oral EC methods, particularly one with effective postovulatory action,” he noted.

The researchers conducted a double-blind, placebo-controlled trial involving 860 healthy women (mean age 32 years) who were requesting EC within 72 hours of a single act of UPSI in the current menstrual cycle. Participants were randomly assigned to receive LNG 1.5 mg in addition to piroxicam 40 mg or placebo (n=430 in each group). [RCOG 2023, abstract OP.0038]

Within 6 weeks of follow-up, patients who received LNG plus piroxicam had a significantly higher proportion of pregnancies prevented compared with those who received LNG plus placebo (94.7 percent vs 63.3 percent; p<0.0001).

This result translated to a significantly lower rate of EC failure, defined as the number of pregnancies observed, in the LNG plus piroxicam group than in the LNG plus placebo group (0.24 percent vs 1.67 percent; odds ratio, 0.197; p=0.036). Only one pregnancy was reported in the piroxicam group, whereas seven pregnancies occurred in the placebo group.

In terms of changes in the menstrual cycle, both piroxicam and placebo groups showed no significant differences in the advancement or delay (>7 days) of the next menstrual period (17 percent vs 16 percent and 8 percent and 7 percent, respectively).

There was also no significant difference in the incidence of adverse events (AEs), such as fatigue/weakness (10.3 percent vs 11.4 percent), nausea (7.7 percent vs 8.1 percent), and lower abdominal pain (7.4  percent vs 6.9 percent), between the piroxicam and placebo groups.

“This is the first randomized trial to demonstrate that oral piroxicam 40 mg co-administered with LNG significantly improves the EC efficacy, [in terms of pregnancy prevention after UPSI,] without aggravating the AEs,” said Li.

“This may be considered clinically where LNG-EC is the option of choice,” he suggested.