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Should Prescribers Discuss FDA’s Drug Warnings?

What happens when prescribers ignore FDA drug warnings? Patients are harmed or die. We share stories about montelukast and amiodarone.

Physicians, nurse practitioners and physician associates can all prescribe medications. But they are admonished to “do no harm.” That puts them in a double bind. Every single drug that they recommend has the potential to cause side effects. One way to get around this dilemma is to reveal the FDA’s drug warnings before sending the patient out the door with a new prescription. How well do health practitioners abide by this principle?

Are the FDA’s Drug Warnings Ignored?

Informing people about the pros and cons of their medicines is challenging. The Food and Drug Administration has not figured out a good way to do this. So far as we can tell, the FDA doesn’t seem terribly concerned about communicating the cautions it requires.

It seems that the agency has pretty much thrown in the towel when it comes to shaping what prescribers do or do not do. The FDA figures that if it requires a black box warning on a medicine, its job is done. End of discussion!

That black box represents the most serious warning for a given medicine. In theory it is supposed to get a prescriber’s attention that there is a very dangerous or even life-threatening adverse reaction associated with the medicine under consideration.

When Prescribers Ignore FDA’s Drug Warnings:

Many prescribers don’t spend a lot of time discussing potential benefits and risks with their patients. In fact, they might not be fully aware of the risks, relying on past impressions they have formed of the drug they have chosen.

Humans get into habits, and prescribers are no exception. When a drug first comes out, they may make an effort to learn how well it works and what side effects it may cause. But after prescribing it for months or years, doctors rarely go back to the official information to check on whether anything has changed.

Singulair (Montelukast) for Asthma and the FDA’s Drug Warnings:

One example of delayed discovery is linked to the asthma medicine montelukast (Singulair). The FDA approved this oral drug in 1998.

Seven million people in the US take montelukast daily to control asthma symptoms. Doctors also prescribe it to prevent wheezing associated with exercise.

By 2008, the FDA had received reports of mood changes and suicidal behavior in patients taking Singulair. It undertook a review of “neuropsychiatric events (mood and behavioral changes)” and published the results in the summer of 2009.

The agency noted that:

“In the clinical trial data submitted by manufacturers, neuropsychiatric events were not commonly observed.”

Despite that seeming dismissal, the FDA covered its derriere by advising healthcare professionals and patients to be aware of symptoms such as:

“agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), and tremor.”

The FDA went so far as to offer advice:

Advice to patients and healthcare professionals
• Patients and healthcare professionals should be aware of the potential for neuropsychiatric events with these medications.
• Patients should talk with their healthcare providers if these events occur.
• Healthcare professionals should consider discontinuing these medications if patients develop neuropsychiatric symptoms.

It’s not clear how many families were informed about such adverse reactions. We suspect that the warning did not work as well as the Food and Drug Administration anticipated.

FDA’s Drug “Advice” Becomes a Black Box Warning:

More than a decade later, in 2020, the agency took more aggressive action. The FDA’s drug warning for Singulair reached the equivalent of the military’s DEFCON 1.

The FDA issued a black box warning! It was supposed to alert prescribers to scary symptoms like aggression, depression or suicidal thoughts.

The Singulair (Montelukast) Black Box:

WARNING: SERIOUS NEUROPSYCHIATRIC EVENTS

“Serious neuropsychiatric (NP) events have been reported with the use of SINGULAIR. The types of events reported were highly variable, and included, but were not limited to, agitation, aggression, depression, sleep disturbances, suicidal thoughts and behavior (including suicide). The mechanisms underlying NP events associated with SINGULAIR use are currently not well understood.

“Because of the risk of NP events, the benefits of SINGULAIR may not outweigh the risks in some patients, particularly when the symptoms of disease may be mild and adequately treated with alternative therapies. Reserve use of SINGULAIR for patients with allergic rhinitis who have an inadequate response or intolerance to alternative therapies. In patients with asthma or exercise-induced bronchoconstriction, consider the benefits and risks before prescribing SINGULAIR.

“Discuss the benefits and risks of SINGULAIR with patients and caregivers when prescribing SINGULAIR. Advise patients and/or caregivers to be alert for changes in behavior or new NP symptoms when taking SINGULAIR. If changes in behavior are observed, or if new NP symptoms or suicidal thoughts and/or behavior occur, advise patients to discontinue SINGULAIR and contact a healthcare provider immediately.”

Did the FDA’s Drug Warnings Work?

How well are such dangers communicated to patients or their families? We have heard from readers of this column who were not warned by their health care providers.

Patients Share Singulair Experiences:

LL reported:

“My 14-year-old son had been on Singulair for several years and was recently diagnosed with depression. His doctor wanted to prescribe antidepressants. Some online research revealed that this might be a side effect of the Singulair. My son has now been off the medicine for about three weeks and is a happy boy again, not even a moody teenager.”

D said:

“I started having problems with my marriage several months ago, not long after I started taking montelukast. I had taken Singulair as a child and it worked well for my asthma. Recently, though, I have had suicidal thoughts, weird dreams, fatigue, depression and mood swings. I take responsibility for my relationship issues, but the side effects made it harder to address them. If I didn’t have a loving wife who helped me see the connection with the medicine, I could have lost my marriage.”

What If the FDA’s Drug Warnings Don’t Work?

Despite the black box warning, it’s not clear that patients are being adequately informed. In fact, it’s hard to see exactly how to get people’s attention about this type of safety issue.

The Singulair (montelukast) story is not unusual. We have lost count of how many people have not been warned adequately about FDA drug warnings, including black box notifications. There is no more pointed example than the heart rhythm drug amiodarone (Cordarone, Pacerone).

The Pacerone (Amiodarone) Black Box:

“WARNING: PULMONARY, HEPATIC AND CARDIAC TOXICITY

“Pacerone is intended for use only in patients with the indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity.

“Pacerone can cause pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis) that has resulted in clinically manifest disease at rates as high as 17% in some series of patients. Pulmonary toxicity has been fatal about 10% of the time. Obtain a baseline chest X-ray and pulmonary-function tests, including diffusion capacity, when Pacerone therapy is initiated. Repeat history, physical exam, and chest X-ray every 3 to 6 months.

“Pacerone can cause hepatoxicity, which can be fatal. Obtain baseline and periodic liver transaminases and discontinue or reduce dose if the increase exceeds three times normal, or doubles in a patient with an elevated baseline. Discontinue Pacerone if the patient experiences signs or symptoms of clinical liver injury.

“Pacerone can exacerbate arrhythmias. Initiate amiodarone hydrochloride in a clinical setting where continuous electrocardiograms and cardiac resuscitation are available.”

Let me explain all that. The FDA makes it very clear that amiodarone should not be prescribed for any irregular heart rhythm unless it is “life threatening.” Specifically, the drug has only been approved for “life-threatening recurrent ventricular fibrillation.” That is literally cardiac arrest! VFib is not compatible with life.

Notice that the FDA has not approved amiodarone for atrial fibrillation. It is rarely a life-threatening arrhythmia.

Cynthia describes a tragic situation because her doctors did not pay attention to the black box warning:

“Five years ago I had a valve replacement, and about a year ago I was having Afib. My cardiologist gave me AMIODARONE 200mg. Then, after a few months, I started having shortness of breath and just didn’t feel my normal self. So he did a cardiac catheter procedure. The results were pulmonary fibrosis, which is scarred lung tissue, and pulmonary arterial hypertension, which is high blood pressure in the arteries in the lungs 🫁. Life expectations are as little as 2.5 years or more. I have a 3 year-old grandson whom I will never get to see grow up.”

Joan describes what happened to her husband after receiving amiodarone for atrial fibrillation:

“My healthy husband went for a physical because he was going to retire, and they found Afib. They put him on amiodarone, and within five weeks he could not function and went in for a cardioversion.

“They said he was not getting enough oxygen, and he went into the ICU for three weeks and was diagnosed with lung poisoning due to that drug and was intubated. He never woke up and got worse each day and went into perpetual care and was put on morphine. My beloved husband died, and I am so sorry I watched him take that drug each day.”

Final Words:

Sadly, the FDA has not figured out an effective strategy for warning prescribers how to prevent such tragedies. When something terrible happens, the agency’s attitude seems to be, it’s not our fault that health care providers don’t know how to warn patients adequately. The result of both FDA and provider inactions is that too many people have suffered or died.

A New People’s Pharmacy Initiative!

Because we believe this issue of such importance, we are beginning a campaign that would:

  1. Require the FDA to create a red box warning for patients written in language normal people could understand. Instead of the medicalese seen above in the black box warnings for montelukast and amiodarone, this warning would contain wording that everyone could understand
  2. Require physicians, nurse practitioners, physician associates and pharmacists to inform patients about any red box warning before writing or filling a prescription.
  3. Obtain a signed consent form that the patient has been warned about the red box warning and agrees to take the medicine after being fully informed of the risks.

Please share your thoughts or experiences in the comment section below. Do you think this red box warning is a good idea? If not, please let us know why not. This is a radical idea. We will need your support if you think it is worthwhile. Please share this article with friends, family and legislators. You can do that by scrolling to the top of the page and using the icons. Thank you!

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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