August 16, 2023

expert reaction to RCT of levonorgestrel taken with an anti-inflammatory drug (piroxicam) as an emergency contraceptive

A study published in The Lancet looks at the use of levonorgestrel plus piroxicam as oral emergency contraception.

Dr Janet Nooney, Expert Scientific Assessor in the MHRA Benefit Risk Management Unit, said:

“This study raises an interesting possible improvement in emergency contraceptive effect when levonorgestrel is used in combination with piroxicam tablets (a non-steroidal anti-inflammatory drug [NSAID]).  The trial studied Chinese women within a relatively narrow age and body weight range and most women took the treatment sooner after unprotected intercourse than can occur in real world usage.  Many other factors can contribute to failure of emergency contraception, including when in the menstrual cycle it is taken.  The study size did not allow analysis of the impact of these factors, and it is not yet clear if the study’s findings could apply for routine use. 

“Importantly, in the UK oral piroxicam tablets are no longer recommended for acute pain relief or inflammatory conditions as it is associated with serious gastro-intestinal side effects and rare but possibly fatal skin reactions*.  These side effects may limit its suitability for wider use in combination with emergency contraception.

“Further work would be needed to see if similar effects on emergency contraception are seen in a wider population (including younger women with higher body weights) than was studied in the trial and with an alternative NSAID that is authorised for use in a broader population.”

*(note to editors: piroxicam is only recommended in the UK as second line therapy for symptomatic relief of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis at a maximum daily dose of 20mg)

Dr Janet Barter, President of the Faculty of Sexual and Reproductive Healthcare said:

“We welcome the findings of this new study which has the potential to improve the efficacy of emergency contraception, which is very exciting. However, it is important to note that this was a relatively small study and further robust studies will be required to establish safety and effectiveness of this combination of drugs for all patients. We will undertake a full review of the study when it is available and issue guidance to our members.

“There are currently three forms of emergency contraception available in the UK – oral levonorgestrel (LNG), oral ulipristal acetate (UPA) and the emergency copper intrauterine device (IUD).

“Women should be made aware by the provider of oral emergency contraception that a copper IUD is the most effective option. A copper IUD can be inserted up to 5 days after the first unprotected intercourse in a natural menstrual cycle, or up to 5 days after the earliest likely date of ovulation (whichever is later).”

Prof Richard Anderson, Elsie Inglis Professor of Clinical Reproductive Science, Deputy Director of MRC Centre for Reproductive Health, University of Edinburgh, said:

“This is a great and well conducted study. It’s been known for a long time that anti-inflammatory drugs can interfere with ovulation by preventing the egg being released from the follicle. Here a long-acting drug of that type, piroxicam, is added to ‘standard’ emergency contraception as levonorgestrel works less well close to the time the egg is going to be released, which is when the anti-inflammatory drug should work. So by taking two drugs they hoped that it would make the levonorgestrel method more effective, and indeed that is what they showed, with the combination preventing 95% of expected pregnancies, compared to 63% with levonorgestrel on its own. There was no difference in side-effects between the groups, including the proportion of women having a late period- a source of major anxiety.  This is a big difference in effectiveness, and easily and cheaply translatable into normal clinical practice, although only with this specific drug.”

‘Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial’ by Raymond Hang Wun Li et al. was published in The Lancet at 23:30 UK time on Wednesday 16^th August, which is also when the embargo will lift.

DOI: https://doi.org/10.1016/S0140-6736(23)01240-0

Declared interests

Prof Richard Anderson: “No conflicts of interest.”

For all other experts, no reply to our request for DOIs was received.