Adding oral piroxicam to oral levonorgestrel significantly improved the efficacy of emergency contraception, based on data from 860 women.
Oral hormonal emergency contraception (EC) is the most widely used EC method worldwide, but the two currently available drugs, levonorgestrel and ulipristal acetate (UPA), are not effective when given after ovulation, wrote Raymond Hang Wun Li, MD, of the University of Hong Kong, and colleagues. Previous studies suggest that cyclo-oxygenase (COX) inhibitors may disrupt follicular rupture and prevent ovulation, but data on their use in combination with current oral ECs are lacking, the researchers said.
In a study published in The Lancet, the researchers randomized 430 women to receive a single oral dose of 1.5 mg levonorgestrel plus 40 mg of the COX-2 inhibitor piroxicam or 1.5 mg levonorgestrel plus a placebo. The study participants were women aged 18 years and older who requested EC within 72 hours of unprotected sex and who had regular menstrual cycles between 24 and 42 days long. The median age of the participants was 30 years; 97% were Chinese. The median time from intercourse to treatment was 18 hours for both groups.
The primary outcome was the percentage of pregnancies prevented, based on pregnancy status 1-2 weeks after treatment.
One pregnancy occurred in the piroxicam group, compared with seven pregnancies in the placebo group, which translated to a significant difference in the percentage of pregnancies prevented (94.7% vs. 63.4%, P < .0001).
No trend toward increased failure rates appeared based on the time elapsed between intercourse and EC use in either group, and no differences appeared in the return or delay of subsequent menstrual periods between the groups.
The most common adverse events (reported by more than 5% of participants in both groups) included fatigue or weakness, nausea, lower abdominal pain, dizziness, and headache.
The choice of piroxicam as the COX inhibitor in conjunction with levonorgestrel for the current study had several potential advantages, the researchers wrote in their discussion. These advantages include the widespread availability and long-acting characteristics of piroxicam, which is also true of levonorgestrel, they said.
The findings were limited by several factors including the generalizability to other settings and populations, the researchers noted. The efficacy of the levonorgestrel/piroxicam combination in women with a body mass index greater than 26 kg/m2 may be lower, but the current study population did not have enough women in this category to measure the potential effect, they said. The study also did not examine the effect of piroxicam in combination with ulipristal acetate.
However, the results are the first known to demonstrate the improved effectiveness of oral piroxicam coadministered with oral levonorgestrel for EC, they said.
“The strength of this recommendation and changes in clinical guidelines may be determined upon demonstration of reproducible results in further studies,” they added.
Pill combination shows potential and practicality
Oral emergency contraception on demand is an unmet need on a global level, Erica P. Cahill, MD, of the department of obstetrics and gynecology and division of family planning services at Stanford (Calif.) University, wrote in an accompanying editorial.
Dr. Cahill noted the longer half-life of piroxicam compared with other COX-2 inhibitors, which made it a practical choice. Although the study was not powered to evaluate secondary outcomes, bleeding patterns consistent with use of EC pills were observed. Documentation of these patterns is worthwhile, Dr. Cahill said, “because people using emergency contraceptive pills might also be using fertility awareness methods and need to know when they can be certain they are not pregnant.”
Overall, the study supports the addition of 40 mg piroxicam to 1.5 mg levonorgestrel as emergency contraception, said Dr. Cahill. Future studies can build on the current findings by evaluating repeat dosing of the piroxicam/levonorgestrel combination and by evaluating the combination of COX-2 inhibitors and ulipristal acetate to prevent pregnancy, she said.
The study received no outside funding. The researchers and Dr. Cahill had no financial conflicts to disclose.