The warning made by HRA Pharma, the French manufacturer behind Norvelo emergency contraceptive pills, that the product is ineffective in women who weigh more than 80kg (12st 7lb) and has reduced effectiveness in women over 75kg is a major one, especially given the relatively small amount of data on which it appears to be based.
The decision was based on a 2011 meta-analysis that combined data from two studies comparing levonorgestrel, the active ingredient in the Norvelo contraceptive, to another emergency contraceptive called ulipristal acetate (UPA). A total of 1731 women took levonorgestrel pills, 38 of whom became pregnant, while 1714 women took UPA, 22 of whom became pregnant. Obese women accounted for 13.6% of the total study population, and overweight women accounted for 21.6%.
The move has also raised alarm in the US over Plan B emergency pills, which have an identical formula to Norvelo. The FDA in the US said it was reviewing the research.
While the study that sparked these concerns raises important concerns about the efficacy of levonorgestrel emergency contraception in overweight and obese women, the relatively small number of these women in the study and low number of pregnancies means we should be cautious in applying the results too broadly. Two important questions remain to be answered: how might obesity affect levonorgestrel emergency contraception, and what are the risks of changing the labelling on these pills based on the current evidence?
You are generally considered to be overweight if you have a BMI (your weight in kilogrammes divided by your height in metres) of around 25 to 29 and obese between 30 to 40. It is estimated that around 15-20% of pregnant women in the UK are overweight or obese, rising to more than a half in the US.
And there are numerous ways that obesity can affect how a drug interacts with the body. Obese individuals may absorb a drug faster through the gut, have a different metabolism and serum concentrations of a drug, and can eliminate a drug either faster or slower from the body. This all depends on the various characteristics of a drug.
One study that investigated the pharmacokinetics of an oral contraceptive pill containing levonorgestrel found that the maximum serum concentration in the body and time taken to achieve it were not different in normal weight and obese women. It was noted that obese women had a larger area under the concentration-time curve and that levonorgestrel had a longer half-life – this means that it took a greater overall exposure and a longer time to reach a steady state of concentration. The findings were in women who had taken a daily pill for 21 days, and it is unclear how these findings relate to a one-time dose of levonorgestrel as in an emergency contraception pill.
Without a clearer understanding of the pharmacokinetics of levonorgestrel as an emergency contraception in normal weight and obese women, it remains difficult to interpret the available data. For instance, it is unclear whether giving a larger dose of levonorgestrel to obese women would counteract the apparent decreased efficacy of a current recommended dose.
Ultimately, the decision of whether to allow overweight and obese women to continue using levonorgestrel as an emergency contraception must balance benefit and risk. While the meta-analysis that underpinned the decision does indicate reduced efficacy in women with a BMI greater than 25 kg/m2, what are the risks to obese women taking this regimen?
There are no medical dangers associated with levonorgestrel as an emergency pill and the risks of obesity during pregnancy are well known – these can include developing gestational diabetes or more complications during childbirth.
Until there are additional data to support the conclusion that these pills are ineffective in overweight and obese women, it seems most prudent to encourage the use of more effective emergency contraceptives, such as the copper IUD or UPA, but this doesn’t mean taking away levonorgestrel as an option.