The FDA’s Nonprescription Drugs Advisory Committee and Pediatric Advisory Committee have together recommended that “pain relief” be removed from the label of Tylenol for babies and toddlers and other brands of acetaminophen* because there is no reliable evidence that it relieves pain better than placebo in children under age two.
This will surprise many parents who reach for these common pain relief drops when their little ones are teething or have an earache or a sore throat. Not surprisingly, the over-the-counter drug industry trade group (CHPA) objects to the findings of the expert panel.
The advisory panel recommended that the acetaminophen label should say it’s for “fever reduction” and nothing else. But here’s the thing – in most cases the fever is helping the child by activating the immune system and fighting the infection. I don’t routinely recommend treating a typical fever unless it is interfering with a child’s ability to sleep or to drink liquids (both are even more important for healing than the fever). If the fever is high or prolonged, it is wise to consult with a physician.
If we don’t give acetaminophen to babies and toddlers for pain, and we rarely give it for fever – this will change the landscape of over-the-counter medications for young children.
Acetaminophen is the most common cause of acute liver failure in the US. It has been estimated to cause three times as many cases of liver failure as all other drugs combined. While the serious problems usually come from overdoses, in babies and small children the dose that can cause harm may be not many times more than the recommended dose.
Most dosage charts that parents see list a dose based on age, or suggest that parents ask a doctor for the dose. And dosage concentrations have varied in various formulations. Together, this confusion has led to overdosing and to fatalities in several dozen healthy young children over the last decade.
The FDA panel has recommended that all liquid acetaminophen come in the same concentration, that all packages contain dosing information for children down to 6 months of age, and that the dose be based on the child’s weight.
I applaud these recommendations and hope they will be formally adopted by the FDA. If so, I expect they will result in safer children. As parents we don’t have to wait, though, to change our own practices.
As many of our readers have pointed out, this isn’t new news. The joint meeting of the FDA Advisory Committee for Nonprescription Drugs and the FDA Pediatric Advisory Committee took place on May 17th and 18th 2011. I wrote this article on May 18th. In March of 2015, someone on Facebook found this post and began to share it, even though the post had not been updated for four years. This took us by surprise, but pointed out the Tylenol for babies and toddlers is still an important topic to parents of young children.
The dozen or so manufacturers of acetaminophen were unable to point to evidence that convinced the doctors, nurses, pharmacists, and patient advocates present at the joint FDA Advisory Committee and Pediatric Advisory Committee meeting that oral, OTC-strength acetaminophen relieves pain in children 6 months to 2 years old. The experts reviewed all 10 studies that addressed this question and concluded there was no compelling evidence for pain relief (unlike fever reduction, which is clear cut). You can read the entire FDA panel transcript here [as of June 15, 2018, the transcript is no longer on the FDA web site, but the archive copy is available]. They often used the word analgesia, which is a medical word for pain relief.
It appears to have been a spirited discussion. At the hearing, the Director of Pain Medicine at Seattle Children’s Hospital said, for example,
“it would be a horrendous disservice to young children to label this product as having any kind of analgesic effects because I think that if we assume that it does, and people are walking around giving acetaminophen to children thinking it’s analgesic and it’s not, you’re going to have a lot of children stuffing pain that should not be.”
“So I would argue extremely strongly that unless there are data to convince us that this product is analgesic in young children, that that should not only not be on the label but should be made extremely clear to the public and professionals alike that the analgesic effects of acetaminophen in younger children have not been shown.” (page 106)
But despite their strong decision, it was never made extremely clear to the public or to professionals that pain relief for younger children had not been shown. (Though this little post has certainly been passed around recently!)
At the FDA meeting, the experts on the panel pointed out that we get it wrong about 20% of the time when we extrapolate that because something works in older kids or adults it will also work in babies or toddlers. Babies’ livers (for instance) function differently than older kids’.
Susan Baker, Professor of Pediatrics at Women and Children’s Hospital gave a great example of this. Doctors used to commonly give reflux medications to colicky babies because many of these babies have reflux, the medications (PPIs) work in older children, and the babies are clearly in pain. Doctors thought they worked for babies; parents thought they worked – but the FDA used a ‘cattle prod’ to make the manufacturers do studies to show they really worked, better than just waiting, because these drugs also had side effects. Turned out – babies’ reflux is different and the meds didn’t work at all.
Here’s what Dr. Baker said:
“I would like to point out that this was the situation with PPIs before the FDA took that on. Every baby was put on PPIs in high doses because they were all perceived to be in pain. When you demanded that appropriate studies be done, they were done by almost every manufacturer of PPIs, and my group participated in every one of them. And in fact, they did zip, zero, nothing. They did absolutely nothing. We could say why didn’t we just simply extrapolate that data down to babies and then continue to use it as we have been?”
“But because of the very good data that we were able to obtain, because you used a cattle prod, we know that that was worthless, and perhaps we saved babies from being on PPIs for an indeterminate period of time. We know that PPIs are a risk factor for a C. diff, and so on.”
“We don’t know a lot of that stuff about acetaminophen right now. And I think that we need to step up to the plate…”
Unsurprisingly, the manufacturers were not pleased with the decision of the advisory groups and wasted no time in speaking up. They also voluntarily agreed to change the concentrations on their new labels to make them consistent, instead of different concentrations for different ages, to reduce overdose (a major problem). When the FDA made its decision on the new labels, they chose to disregard the recommendations of their advisory groups about pain relief. This is not unusual. They weigh many issues in their larger deliberations, not just the findings of the physicians, nurses, pain specialists, pharmacists, and patient advocates.
Pain relief on the label is unchanged for children under age 2.
The latest major scientific reviews of pain medications in infants I can find today were published in 2014. We are perhaps better now at measuring pain in babies, using validated combinations of heart rate, oxygen levels, blood pressure, as well as facial expressions, cries, and sometimes hormone levels.
We do know and have known that oral acetaminophen relieves pain in older children and adults. But the studies looking for pain relief from oral acetaminophen in babies have been disappointing. (For instance, in babies getting a heel prick, there was no discernible difference between babies who got or didn’t get oral acetaminophen). But heel prick pain is different than teething pain, which is different than an earache.
The thing about kids less than two years old is that it’s a pivotal time of development – so much so that there is an important emerging area of science called the Developmental Origins of Health and Disease (DOHaD). A combination of maternal and environmental factors early in life can have a long-term effect on health. Because acetaminophen is one of the most widely used medications at that age, because we know acetaminophen is a powerful drug, and because we know so little about the effects at that age (having not even shown pain relief), to me it seems an important area for research – or at least not to cover over the questions.
I’m not saying oral acetaminophen doesn’t work – I’m saying we don’t know enough. And we should. Babies’ pain is important. Which questions to study and how to study them is a great discussion to have.
In the comments below, you’ll see that many parents and nurses report that they use Tylenol (acetaminophen) for their babies and toddlers and it works for them. That experience is compelling. I still think it’s sad that when it comes to commonly used medicines in infants and toddlers that the effects have often not been well-studied.
Wouldn’t it be great if parents’ experience of clinical observation and of changes in vital signs – and the experience of thousands of others – were collected and explored, since the medicine is being given anyway. We could learn so much about the timing of effect, for instance, which might be very different in babies than in older kids.
With medical-grade sensors becoming far less expensive and far more available, I’m looking forward to parents being able to get better answers to lots of questions. One person doing this is powerful (and can answer the question for a particular child). With lots of us doing it we could learn so much so quickly!
When ResearchKit was released by Apple two weeks ago, it was able to do in only 24 hours what would typically take 50 medical centers a year to do – recruit 10,000 people into a medical study.
These 2011 FDA Advisory Committees had all the available medical literature available to them in trying to answer their question – but there was very little data, gathered over many years, involving very few children, with mediocre results at best – so they had little choice but to say there’s not enough evidence to conclude that acetaminophen relieves pain in kids 6 month to 2 years.
If 10,000 parents measured objective criteria, we could know in a day.
The next question would be, if it works, is it the acetaminophen in Tylenol (the ‘active ingredient’) or is it another ingredient (such as the high fructose corn syrup and other sweeteners) or a combination of the ingredients. We know more about the power of sugar than acetaminophen to relieve pain in babies
FYI: The ‘inactive’ ingredients in Cherry-Flavored Infant’s Tylenol include: anhydrous citric acid, butylparaben, FD&C red no. 40, flavors, glycerin, high fructose corn syrup, microcrystalline cellulose and carboxymethylcellulose sodium, propylene glycol, purified water, sodium benzoate, sorbitol solution, sucralose, and xanthan gum.
Various types of ‘sugar water’ have been shown to significantly relieve pain in babies. Also, there are large studies showing that coal-based FD&C dyes can affect behavior. The sorbitol and sucralose might play a role. There’d still a lot to sort out – but we could do it.
Tylenol (acetaminophen) can be very safe at the right dose, but it deserves respect. Acetaminophen is responsible for more overdoses, and overdose deaths [the original report is no longer on the —– site, but as of June 15, 2018 you can read the archive report here] than any other drug product.
Acetaminophen poisoning was responsible for [the original report is no longer available, but as of June 15, 2018 you can read the archived report here]:
Those aren’t big numbers for 28 billion doses given in the US, but every one is important when it’s your child.
In addition, too much acetaminophen is the single biggest cause of acute liver failure in US. Some studies suggest acetaminophen can cause asthma, I’m not convinced about that yet.
The drug manufacturers suggest dosing errors are parents’ faults.
Thankfully in 2011, the FDA Committees voted for standardized liquid dosing. But many parents aren’t aware that acetaminophen is an ingredient in over 600 different easy to buy over-the-counter medicines that are used to relieve symptoms including in medicines labeled as pain relievers, fever reducers, sleep aids, cough, cold and allergy management. Using these medicines in combination can lead to accidental overdose — even when parent think they are within the correct limits.
At the 2011 joint FDA meeting, they discussed acetaminophen to reduce fever in babies and toddlers. On page 6 of the minutes of the FDA Advisory Committees[the original report is no longer on the —– site, but as of June 15, 2018 you can read archive copy here], it says that the committees agree that acetaminophen is effective at reducing fever in kids under 2.
Keep in mind, often fevers help kids to heal and are better untreated.
Personally, I use Tylenol (acetaminophen) often, confidently, but thoughtfully. This is the approach I recommend for my patients as well.
*FDA Advisory Committee Meeting Minutes [Last accessed on the FDA site April 1, 2015. Available here as of June 15, 2018.]
FDA Meeting Transcript: Day One [Last Accessed on the FDA site on March 30, 2015. Available here as of June 15, 2018.]
FDA Meeting Transcript: Day Two [Last Accessed on the FDA site on March 30, 2015. Available here as of June 15, 2018.]
OTC Industry Supports FDA Advisory Committee Recommendations on New Dosing Instructions. May 18, 2011.
Lee WM. “Drug-Induced Hepatotoxicity.” New England Journal of Medicine, July 31, 2003, 349:474-485
“Pain management in newborns.” Clinics in perinatology. yr:2014 vol:41 iss:4 pg:895
“Neonatal pain.” Paediatric anaesthesia. yr:2014 vol:24 iss:1 pg:39
This American Life: “Use Only As Directed” Act 2: Babies [Last accessed June 15, 2018.]
We’ve known much of this for over a decade:
PERSONAL HEALTH; With Tylenol and Children, Overdosing Is Perilously Easy