Posted tagged ‘FDA’

What happened to those pain-killing ear drops?

August 14, 2017

The Pediatric Insider

© 2017 Roy Benaroch, MD

MJ wrote in about her daughter. In the past, she used to use a prescription drop called Auralgan (benzocaine plus antipyrine) for ear pain, but it’s been taken off the market. What happened to it? Was it unsafe? Can she start buying it from Canada? What other options are there?

The FDA got tough on Auralgan and several other similar ear drops – AB Otic, Aurodex, Auroto, and other brands – in 2015. To my knowledge, there wasn’t any specific incident or allegation that these products caused any problems. But they’ve never been shown to be safe, and they’ve never been shown to be effective.

For many years these and other older “grandfathered” drugs were cheerfully sold alongside other prescriptions. But all new drug applications submitted to the FDA must include proof of both safety and effectiveness – that’s been the law since 1938, though what’s passed for “proof” has varied. Many older drugs, like these ear drops, slipped though when things were less stringent. But the FDA has always had the right to ask for more proof from the manufacturers.

I don’t really know why these drops got the FDA’s attention. It is true that there’s never been any proof of effectiveness. A German study cited in the non-discontinued products’ insert showed that children given Auralgan for earache did improve – but they didn’t compare the responses with a placebo, and we know that ear aches get better on their own, anyway. There was also a study from Pittsburgh in 1997 – the authors say they showed that topical Auralgan was “likely to provide additional relief” when given along with acetaminophen. But their study showed no statistical difference in pain scores at 3 of the 4 time periods, meaning that Auralgan was equivalent to their placebo (olive oil drops.)

There’s also no science reason to even think these drops would work. The two ingredients, benzocaine and antipyrine, are not effective when applied to the skin – they only work when injected or swallowed. Benzocaine has some activity when rubbed onto a mucus membrane, like on your tongue or gums, but that’s not what’s inside your ears. And: it makes absolutely no sense to use these to treat middle ear pain (like an ear infection, or the pain you get in an airplane), because drops in your ear canal don’t get into your middle ear. That’s like treating stomach pain by pulling on a finger. OK, bad example (ref: grandpa). Anyway, you get the idea.

Real Drugs are only supposed to be marketed in the USA with FDA approval, which requires proof of safety, effectiveness, and quality control manufacturing standards. For ear pain, if you want to stick with a Real Drug, acetaminophen is a pretty good choice. MJ asked about buying Auralgan from Canada – it looks like it’s still on the market up there. I found one place selling it for $142. That’s one expensive placebo.

Or, MJ could wander outside of the realm of Real Drugs. The 1997 study used olive oil as a placebo, and that’s safe – and you could use the leftovers in a salad. Or you could look in the alt-med, “alternative medicine” section of the drug store – there are ear drops there, but they’re not FDA regulated, so purveyors can sell whatever they’d like. You don’t know what you’re getting in those bottles, and there’s no reason to think they’d work any better than olive oil, pickle brine, or ranch dressing.


Lead, mercury, arsenic—the mystery ingredients lurking in your supplements

December 22, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

Vitamins, minerals, and supplements are a huge industry—about $32 billion sold in the USA in 2012. You might think someone in the government would keep an eye on all of those pills to make sure they’re safe, or maybe make sure that what’s in the bottle is what it says on the label.

Fat chance. Current regulations allow essentially no scrutiny of supplements. Anything that had been sold before 1994 can continue to be sold, no questions asked. Though newer substances are supposed to be registered, they don’t have to await approval before hitting the shelves. It is up the FDA, afterwards, to figure out which of these are harmful. That’s in stark contrast to genuine medications, which have to be proven safe and effective before they’re sold.

In 2013, an extensive study using DNA testing looked at several supplements, finding that many pills made of fillers, rice, and weeds. Almost all of the samples contained cheap fillers not listed on the label, and many contained weeds and contaminants that could cause genuine illness. These were bottles of supplements purchased from several retail outlets from the US and Canada, from a variety of companies. Only 2 of the 12 companies had products that were accurately labeled without contamination.

Now, a new study has shown similar problems with both US- and Indian-manufactured Ayurvedic compounds. 193 samples obtained though internet sale sites were analyzed, and 20% contained toxic amounts of lead, mercury, or arsenic.

Previous studies, reviewed here, have shown that many supplements are adulterated with pharmaceutical products—real drugs—not shown on the label, and not legally sold without a prescription. When the FDA investigates, these companies can change the name of the product and keep selling it. Under current law, it is impossible for anyone to enforce safety standards, or even insist that product labels accurately reflect what’s in the bottle. People are not getting what they’re paying for, and people are getting sick from taking potent or toxic chemicals they didn’t expect.

It’s time for vitamins, supplements, and minerals to come out of the shadows. If they’re safe and effective, they ought to be sold—but if they’re just a load of toxic crap and fillers, they ought to be thrown out, and the companies who’re selling them driven out of business. Why are we giving these huge, profitable companies a free pass to lie about what they’re selling and what their products can do to us?

Is the FDA’s antidepressant warning killing people?

October 27, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

In 2004, the FDA launched a program to “strengthen safeguards for children treated with antidepressant medication.” Among other steps, they started requiring manufacturers of several kinds of antidepressants to include a warning in their product labeling, a so-called “black box,” that explicitly and loudly proclaimed a risk for children taking these medications. The warning said that children taking these medications were at an increased risk of suicidal thoughts and behaviors. Later, the black box warning was expanded to include young adults. The warning was required to be added to the labeling of medications including Prozac, Zoloft, Celexa, Wellbutrin, and several other medications.

What prompted this action was an observation from studies of children taking these medications that in the weeks after starting them, there seemed to be increased thoughts of suicide. Not suicide attempts, and not deaths from suicide (there were actually no suicide deaths at all among the study groups), but self-reported thoughts about suicide.

Now, depression is a serious illness—and suicide is a very serious consequence of depression. People with major depression have about a 15% cumulative lifetime risk of death by suicide, so this is a very significant and serious problem not to be taken lightly. We know that people with depression often think of suicide, and are at grave risk for attempting suicide—is it possible that anti-depressant medications actually make this risk worse?

A June, 2014 study from The British Medical Journal has looked at the consequences of the FDA’s decision (and the ensuing broad media coverage.) Researchers examined data from a total of 2.5 million teens and young adults from 11 health care plans in the United States. After the warning, the use of these medications dropped by about 24-31% (depending on age grouping.) This was accompanied by an increase in the rate of suicide attempts, by 22-34%. The rate of deaths from suicide did not change at all—just the rate of attempted suicides.

So, no, the FDA’s warning, based on this study, didn’t increase actual deaths. But it did increase suicide attempts, which likely means it increased the rate and severity and consequences of depression. It certainly hasn’t done any good. The warning has scared many families and doctors away from one mode of therapy for depression. Antidepressant medications aren’t perfect—they do have important side effects, and they don’t always work, and they’re certainly not for everyone with symptoms of depression—but they can be one important part of the treatment of some depressed adolescents. It’s a shame that this misguided “black box warning” is doing more harm than good.

Pediatricians can’t always follow FDA medication labels

March 27, 2014

The Pediatric Insider

© 2014 Roy Benaroch, MD

You know those little packets of paper, folded over eight times, written in type that can’t possibly be seen? You’ve seen them glommed onto the side of stock bottles of medications, or shoved into the paper box alongside a tube of prescription ointment. That unreadable thing is the official “product information”, often called the “label”, required for every FDA-approved medication. It contains all sorts of information, including lists of side effects (Nausea! Anal leakage! Growing a tail!) and what a medicine is “supposed” to be used for.

But often, that information isn’t the best information. It’s just what the FDA approved. Science marches on, and new published information is not routinely included in the product insert. Doctors who pay attention know that there’s usually a whole lot of more-reliable, more-specific, and more-accurate information about here than what’s on the label.

The discrepancy is especially stark with babies and children. According to a new AAP report, “Off Label Use of Drugs in Children,” less than 50% of medications have information about pediatric usage in the FDA-approved product labeling. If you have a child who has been prescribed medication, it’s almost certain that at least some of them have been used “off-label,” in a way that is not specifically approved by the FDA.

As the AAP report outlines, using drugs in this way is not incorrect, unethical, or inappropriate:

The absence of labeling for a specific age group or for a specific disorder does not necessarily mean that the drug’s use is improper for that age or disorder. Rather, it only means that the evidence required by law to allow inclusion in the label has not been approved by the FDA.

Those sound like weasel legal words, I know—but it worth understanding what the FDA’s role here is. The FDA is empowered to regulate the manufacturing, labeling, advertisement, and safety of medications. For a drug to be “FDA approved” for sale in the US, a sponsor has to provide information usually including two large, randomized trials to prove that medicine is safe and effective. Safe in the population studied, and effective for the disease studied. The FDA “approves” the drug for sale using specific parameters from these studies, and does not allow the sponsoring company to promote the use of the medication for any other purpose.

But once a drug is approved, a licensed physician can legally prescribe it for any use. The FDA does not regulate the practice of medicine or how doctors use medication (that can be regulated by state medical boards, if a doctor does stupid or unethical things with a prescription pad.) It is up to licensed prescribers to use their own judgment, based on the totality of the evidence, to make prescribing recommendations. Limiting our knowledge to what’s in the product information sheet—which is seldom modified or updated after a drug is approved—would be unethical and foolish.

In most circumstances, using a drug off-label (for an indication or age not explicitly approved in the FDA label) is not “experimental” or “research.” As long as it’s in a patient’s best interests, using a medication this way does not require any specific information be shared with the patient, beyond what we should be talking about with any medication (risks, benefits, side effects, etc.) However, it’s usually best for doctors to talk about the off-label use in cases where off-label prescribing is unusual or cutting-edge. In pediatrics, that’s seldom the case. We write off-label meds every day, in ways that have sometimes been used for decades, and I would bet that most pediatricians don’t even know when they’re doing it.

That’s because the best therapeutic decision making is not based on the label. It’s based on all of the evidence out there: published studies, experience, judgment, and the best interests of the patient.

Acetaminophen safety alert

August 14, 2009

The Pediatric Insider

© 2009 Roy Benaroch, MD

Kelly posted, “After the FDA’s recent announcement about the dangers of acetaminophen overdose, I now think twice before using it for me or my family.  What’s your take on whether the drug is safe in the prescribed dosages – particularly for kids?”

In June, 2009 the FDA released information from an advisory committee studying the safety of medications containing acetaminophen (most commonly known by the brand name Tylenol.) They pointed out that acetaminophen can cause acute and chronic liver injury, which can be fatal. Since then, the manufacturer has started an advertising campaign defending the safety of their product. So who to believe?

Acetaminophen is very, very safe—when taken correctly by people who are not already at risk for liver problems. But it turns out in practice that many, many people have been injured because they didn’t take the medicine right, or didn’t realize that acetaminophen isn’t always safe for everyone.

Who shouldn’t take acetaminophen? Anyone with chronic liver damage or liver disease. The main group are adults who consume too much alcohol. It turns out that not everyone tells their doctor about their alcohol habits, so doctors haven’t necessarily warned people about this. Other causes of chronic liver problems are obesity (so-called “fatty liver” has become the most common cause of liver disease in adolescents), the use of other medicines that affect the liver, and hepatitis. For most children (excluding overweight adolescents), the chance of having liver disease is very, very small.

How do you take acetaminophen correctly? Read the label. Use the included dosing device, and if you’re not sure how to use it, ask your doctor or pharmacist. Don’t combine multiple medications that contain acetaminophen, and make sure that if your child does take other medicines every day, you know if there are interactions between that and acetaminophen (or any other over-the-counter meds you might try.)

One specific recommendation from the FDA committee was to insist that all children’s and infant’s acetaminophen products be sold at the same concentration, simplifying dosing instructions. Right now there are several different strengths of liquids, chewables, and “Junior” tablets that are unnecessary and confusing.

Also, don’t use acetaminophen (or any other medicine) unless you really need to. Fever itself doesn’t necessarily need to be treated with medication (see here and here), but if your child feels lousy, you ought to try to help her feel better.

Alternatives to Tylenol include Motrin or Advil (both are brands of ibuprofen, see here for comparisons), or a non-medical approach like cool towels to reduce a fever, or a gentle heating pad to reduce ear pain.

If your child is in pain or has a fever, acetaminophen is a good safe medication to use. Just use it carefully and correctly, and check with your doctor or pharmacist if there’s any reason to think that your child has liver disease or is on any other chronic daily medication.

Want some lead with your herbs?

August 28, 2008

A Boston University researcher has found that about 20% of a sampling of traditional Indian remedies sold in the United States had toxic levels of lead, mercury, or arsenic. In a study published this month in the prestigious Journal of the American Medical Association, about 200 products made by 37 different manufacturers representative of Ayurvedic Medicine were analyzed. It’s especially alarming because these are products meant to be taken daily to improve overall health. Almost all of the contaminated specimens were made here in the USA.

A daily dose of mercury can’t be good.

The FDA is specifically forbidden from regulating “herbs and supplements.” These products might contain what it says on the label, or might not; they might be contaminated with heavy metals or powerful, non-regulated drugs, or they might just contain essentially nothing at all. Their labels can make just about any sort of health-related claim without fear of regulatory reprisals, and without fear that anyone could actually expect some kind of proof that the product does what it says. No safety data is collected or expected.

Shopping in the “supplement” aisle of a big chain drug store or health food store is entirely a guessing game. Most of the products are merely a waste of money, but at least some of them are far, far worse. Beware.