I don’t usually turn to Twitter for my medical news. Celebrity gossip? Sure. Political updates? You bet. Clinical information relevant to the care of my patients? Not so much.
So I was a wee bit unprepared this morning for this:
Teva makes an estimated $60 million a year on Plan B. How much of that is threatened by this news? http://t.co/bTE1RqVt8E
— NickBaumann (@NickBaumann) November 25, 2013
“What’s this?” thought I. Which immediately changed to “WTF?!??!” and “Yikes!” when I clicked on through.
From Mother Jones:
The European manufacturer of an emergency contraceptive pill identical to Plan B, also known as the morning-after pill, will warn women that the drug is completely ineffective for women who weigh more than 176 pounds, and begins to lose effectiveness in women who weigh more than 165 pounds. HRA Pharma, the French manufacturer of the European drug, Norlevo, is changing its packaging information to reflect the weight limits. European pharmaceutical regulators approved the change on November 10, but it has not been previously reported.
[snip]
Anna Glasier, a professor of obstetrics and gynecology at the University of Edinborough, published research in 2011 showing emergency contraceptive pills that use levonorgestrel are prone to fail in women with a higher body mass index. [emphasis added]
Um… holy crap.
From the abstract to the study linked above:
The risk of pregnancy was more than threefold greater for obese women compared with women with normal body mass index (odds ratio (OR), 3.60; 95% confidence interval (CI), 1.96-6.53; p< .0001), whichever EC was taken. However, for obese women, the risk was greater for those taking levonorgestrel (OR, 4.41; 95% CI, 2.05-9.44, p=.0002) than for UPA users (OR, 2.62; 95% CI, 0.89-7.00; ns)
I don’t subscribe to the journal and I don’t see it as part of Children’s Hospital’s institutional subscriptions, either. I will assume that it was a well-designed and executed study comparing levonorgestrel (the hormone in Plan B, a commonly-used form of emergency contraception [EC], now available without a prescription) with a different, prescription-only form of EC. Regardless of its quality, however, it’s only one study and as such not necessarily something that would make me do a spit-take with my morning coffee.
What’s striking is that the manufacturer’s own review is prompting a change in its labeling and how surprising those weight limits are. As the Mother Jones article notes, the average weight for American women is 166 lbs, and 176 lbs isn’t in the range that would qualify most people as obese.
Even though I’m the adolescent medicine specialist in my practice, I don’t do a lot of contraceptive counseling these days. (Most of our patients seeking that kind of advice opt for one of the female providers in my office.) The last time I attended the annual conference in pediatric and adolescent gynecology sponsored by the medical school where I’m on faculty was a few years ago, before the study out of Scotland was published. I wasn’t aware of its findings, though if I look for them specifically I can find some information out there.
However, I checked with a colleague who did attend the conference when it was held a couple of months ago, and she says there was no mention at all of a link between obesity and lowered EC efficacy rates. And if the weight limit for maximum efficacy is 165 lbs and for any efficacy is 176 lbs, that’s a really big deal! I didn’t expect that preventing pregnancy with EC in a significant number of American women to be just another story medical providers have been telling ourselves.
It is dismaying to consider that such a significant factor in the effectiveness of a medication I’ve dispensed to God knows how many patients was not detected in premarket clinical trials. I’m also a bit confounded that I had to search for information regarding the Contraception study, and that its results weren’t more widely publicized within the medical community. (As a pediatrician, albeit one with specialized interest in that area, it is admittedly quite plausible that I missed information that received more attention in other specialty areas like OB/GYN or family medicine. I do plan to attend that same conference again next year, and will be listening extra hard for mention of this issue.)
If this news is only coming to me through happenstance as of now, I can only imagine that the overwhelming majority of American women who might consider using this medication have no idea how much their weight might be affecting its potential benefit to them. I certainly hope Teva plans to alter its package materials in accordance with its European counterpart, and would politely suggest they go to some additional length to inform women that their medication may not be quite so effective a back-up plan as they once thought.
So does the medical profession know, basically, what’s up with those results?
Is it just a question of not taking enough for body mass? If a woman who weighed 200+ pounds took an extra half a pill, would it be effective? Or is it more complicated than that?Report
Honestly, I don’t know how to answer that question. The mechanism by which EC prevents pregnancy has been a subject of some debate in itself, and how to better accomplish it for women with higher BMI is a question for scientists with greater expertise in the area of reproductive endocrinology than I.Report
It must have taken a lot of research to pinpoint that ineffectiveness starts at precisely165 pounds and becomes total at exactly 176.Report
Five kilo steps seems like a reasonable size for experimental design, but yah, weight isn’t BMI and in individual cases the correlation between gross BMI and the biochemical markers of obesity-induced morbidity isn’t that strong (as opposed to large population aggregates, where the p value on BMI to markers _is_ pretty good). I suspect 🙂 it’s probably unrealistic for labelling to say something like “may not be effective if the following function of your HDL/LDL level, triglycerides, resting HR, … is greater than X”).Report
Measuring central adiposity isn’t that hard.
Some might argue it’s easier than BMI,
as not everyone has a scale at their disposal.Report
In fact, the study itself does measure BMI rather than weight. Which the study authors admit is a weakness, or at least an area needing further study, since they can’t say exactly what the cause of failure is, so they don’t know how it effects (inter alia) women who are heavy because they’re tall.Report
Since those recommendations are based on internal data analyses, I have no idea how they arrived at those numbers.Report
It was a small joke: 75-80 kg is much more obviously an approximate range than 165-176 lbs.Report
Semi-OT:
How do you feel about the American Board of Obstricians threatening loss of certification for OB-GYNs who treat men for Anal Cancer?
http://www.slate.com/blogs/xx_factor/2013/11/25/the_american_board_of_obstetrics_gynecology_cracks_down_on_ob_gyns_treating.htmlReport
Short answer: ARGH! ARGH! ARGH! ARGH! ARGH!!!!!
Medium answer: This would be a prime example of a non-governmental entity enforcing the powers of its cartel such that licensure should be a relatively small-potatoes concern for libertarians.
Long answer: That post I’ve been mulling about board certification for lo these many months.Report
*groan*
So I wonder who I’ll go see for a mammogram? Like, if these bright-bulbs decide I’m “male.”Report
Ungated version of the study is available here. Note that it’s not placebo controlled, merely a comparison between different drugs and different conditions. It clearly demonstrates that Plan B (levonorgestrel) is significantly less effective in overweight and (especially) obese women than it is in women with lower weight, and that it’s less effective than the newer ulipristal acetate in those women. Which is good to know, along with the data point that ulipristal acetate may not be more effective than levonorgestrel in other women.
Because it’s not placebo-controlled, it doesn’t demonstrate by itself that levonorgestrel is completely ineffective even in obese women. There’s a citation to another study that apparently reveals the pregnancy rate among women who don’t use emergency contraception at all, but I haven’t been able to find an ungated full version of that study, and I don’t know if it’s actually valid to compare pregnancy rates in different study populations like that, particularly since it’s comparing just a subset of one study population (obese women) to another study population where weight is not measured (according to the JSTOR preview).Report
I suspect designing a study with a placebo group who agreed to have unprotected sex and risk an unintended pregnancy would be tough to get past an IRB.
Again, if this were only one study, I would be less exercised. But the decision to make such a start change in the labeling is quite striking to me.Report
If only most research used an IRB…Report
Most research does use an IRB, including all human subjects research receiving federal funding.Report
And how often have you warned your pateints about the extreme dangers of Tylenol? How many hundreds (or even thousands by some estimates) of people out there SUFFER TOTAL LIVER FAILURE BECAUSE THIS OVER THE COUNTER DEADLY MED ISN’T CONTROLED? The standard dose is very close to a deadly dose (just taking two or three other meds that also contain tylenol can do it. That is far too easy for a over-the-counter med.) Worse, just a drink or two with a standard dose can also kill someone’s liver. This drug is far too dangerous to be over-the-counter and doctors need to warn people of the dangers due to it being in so many other meds.Report
Um, you don’t read my writing much, do you?Report
Yea, Russ, why are you so eager to kill people?Report
Russell, if you treat pregnancy, do you treat pneumonoultramicroscopicsilicovolcanoconiosis?! Huh? Do you? Do you know how many people pneumonoultramicroscopicsilicovolcanoconiosis kills every year via hypergrammatization? HOW MANY HUNDREDS OF PEOPLE SUFFER SPELLING DEATH because someone even came up with this word?Report
This song is really about Russell, but “Death Pediatrician” didn’t scan as well.Report
This explains the veritable epidemic of people dying of acetaminophen overdoses out there. You’d think that the FDA might have regulated such a dangerous poison, but clearly they’ve been bought of by Big OTCPharma.
Thanks for being willing to speak truth to power, @dbrown .Report
Given how dangerous Tylenol is in moderately excess doses, it really is astonishing that there aren’t more deaths than there are.Report
On a less sarcastic note, intelligent people I know (well, lawyers and accountants, anyway) do not know that Tylenol and aspirin are different drugs. These are also people who have little caution about over-the-counter medicine because if the FDA released it for that kind of sale, it must be pretty safe, right?
Still it remains the case that people are not dropping like gassed flies from this drug. Something is happening that mitigates the risk that the doc noted in his earlier linked post — what that something is I’ve no idea.Report
In light of this new information, is it a bad idea to argue that Obamacare shouldn’t cover Plan B for women who weigh more than 176 pounds?Report
Only if done in this way:
http://www.youtube.com/watch?v=ZlN_0hQS7-IReport
In light of this new information, is it a bad idea to argue that Obamacare shouldn’t cover Plan B for women who weigh more than 176 pounds?
Who’s doing the arguing, a medical advisory panel or a political action committee?Report