slideshow widget

Thursday, December 20, 2012

1983: Alupent available over the counter

In March of 1983 a thin, high shouldered 13-year-old boy named Rick Frea (me) walked into the Revco Pharmacy in Shoreline, Michigan, found his way to the cold and allergy section, and plucked a little gold, green and white box off the shelf.  He checked the label, which said:  Alupent Inhalation Aerosol with mouthpiece (metaproterenol sulphate).  His blue lips spread into a huge smile, "Could it be this easy?" he thought.

He walked stiffly and anxiously to check out, afraid the clerk would say something, especially considering he just bought one from the pharmacist six days ago.  But that one was empty, of no use to him, and now he needed a new one.  He felt guilty about squirting it empty so quick, and now that it was over the counter he wouldn't have to guilt his way past the pesky pharmacist.

As he stepped out into the cool March air a sense of relief brushed through him.  His lungs felt stiff and heavy, although he learned to fake that he could breathe normal.  But I can't take a puff here, he thought.  Don't want that pesky pharmacist to have any chance to see me.  

He briskly walked across the parking lot, across U.S. 31, and into the wooded pines onto a trail that went up a hill and out of distance of the cars and the K-mart, Revco and Eberhardt shoppers across  the street, and there was no way that pesky pharmacist would see him (as though the pharmacist had nothing better to do).  He stopped, ripped open the box, cast it aside, and held the full inhaler in his grasp.  He took off the little white round cap, and inserted the mouthpiece into his mouth.

A week later he repeated these actions, and walked through the Revco with an equal amount of guilt and anxiety.  Only the next time he used his own money, considering he was afraid to ask his mother for fear that she would question his over use.

Three months later the product wasn't on the shelves.  He asked the clerk, and she said, while chomping on her gum, "Yeah, well, ah, that's the medicine they decided couldn't be on the shelves anymore.  You'll have to talk to the pharmacist."  No way am I going to do that, he thought, and he left the store disappointed.

Instead, he huffed and puffed his way back home and stressed about telling his mom she needed to spend money on a new inhaler.  Now he was back to where he was in February.  He didn't tell his mom how bad he was breathing, and so she took her time coming home that evening.  Rick anxiously watched for her from the living room window.

Soon it was dark, and lights approached the driveway.  It was her.  "Mom, you have my inhaler?"  She said, "I forgot it. I just got you one last week, though.  What happened to that one?"  So then Rick confessed how miserable he felt, and so his mother went back to the pharmacy she just left. Now Rick felt guilty to go along with anxious and short of breath. He was to the point of panic, yet he managed to stay calm, somehow, someway.  It's what he always did.

So such was the dilemma of being a thirteen year old hardluck asthmatic in 1983.  Someone felt his pain by allowing for the inhaler to be purchased over the counter, yet someone else didn't care about Rick, and took the inhaler back off the shelves.  Yet the sun  rose again the next day, and his breathing continued, at least enough to keep him at home and alive.

The ironic thing was, his doctor knew about his overuse, and even gave him permission.  Rick  specifically brought it up once:  "Um," he said while sitting on the edge of the doctor bed, fingers pressed into the paper covering, "Is it... do you think, um, that it's okay that I'm using my inhaler a lot?  I mean, um, er, sometimes I feel guilty about this."

The doctor new him for a year now, and even came to the office special on his nights off to see the boy.  A couple times he even gave an injection of Susphrine to the boy in his office, which always brought about instant relief.  So he new how bad his asthma was; that it was worse than your typical case.  The doctor was silent a moment, as though searching for the right words. "Don't feel guilty about it.  It's something you need," Dr. Oliver said, speaking slowly. "The alternative is you'll damage your heart if you can't breathe.  I think you need it.  You need to breathe."

Thinking about this conversation all these years later has Rick still wondering why his doctor never gave Rick a warning about using his inhaler too much.  Yet these were different times.  There were no great asthma medicines, and asthma wisdom was different back when Dr. Oliver went to medical school.  He did what was best for the times.  Yet, as we know, when we learn better we do better.

The boy didn't feel comfortable with his doctor's answer, though.  He could tell the doctor didn't feel comfortable with what he said either.  Yet, again in retrospect, Rick knows words can sometimes be hard to find.  The doctor must have known if it weren't for that little inhaler there would be no life in Rick's life.  Rick wasn't able to do much as it was, but if he didn't have that inhaler, he wouldn't be able to even sit in his favorite chair watching his favorite show without suffering.  He'd simply stay in his bedroom, with the window open, gasping for air.

Surely, you're thinking, he could go to the emergency room, but that only gave relief for a while.  Supposedly he could live in a bubble.  He could be on systemic steroids, but there were risks to those medicines too, far greater risks than Alupent.  So the doctor gave Rick what he wanted, what he needed, and continued to renew his Alupent prescription.  Yet his doctor worried a great deal about young Rick Frea, and it's for that reason he met him and his mom so many times after hours at his office.

For the record, this boy was on all the best asthma medicine.  He had an inhaler called Vanceril (Beclomethasone) that he took two puffs of every eight hours.  He had a dry powdered capsule that he inhaled by using the spinhaler twice a day.  But even with all that medicine, he continued to suffer from asthma.  He had what he would define twenty-five years later as hardluck asthma.

So by July of 1983 Alupent was no longer available over the counter.  Rick's mom said she read that seven kids died from overusing it, so the FDA took it off the market, although this was merely heresy.  Regardless, he would no longer be able to bypass the doctor and pharmacist.  Yet it really didn't matter for this asthmatic, because he never stopped seeing his doctor, and he was on all the best asthma medicines.  He may not have been a gallant asthmatic (another term Rick later defined), but considering his age and all the medicines he was ordered to take, he did fairly well.

Twenty-five years later, with his asthma controlled thanks to better asthma medicines, he was asked to write a weekly column for the Health Central Network about living with asthma.  After defining the eleven types of asthmatics, he wrote a column about how Alupent used to be available over the counter.  His editor read it and said, "Can you prove it was available over the counter?"  Rick surfed the Internet and found nothing on the subject.  The column was scrapped.

On January 4, 2012, while his two older children were at school, and his wife relaxing at home, he took his one year old son and three year old daughter to the library.  After story and craft, while the kids were playing with Mrs. Sue's toys, Rick searched for a book that might interest him.  By mere luck he found a book called "Breathing Space: How allergies Shape Our Lives and Landscapes," by Gregg Mittman.

He quickly perused the book and, by mere chance, came upon "Chapter 6: An Inhaler in Every Pocket."  This was a well written chapter on the history of inhalers, and considering Rick was writing his own version of this history for his blog, Hardluck Asthma, he was especially interested.  What really sparked his interest was what Mittman wrote on page 243:
From 1973 to 1985, an estimated 6 billion doses of metraproterenol sulfate (that's Alupent) had been consumed by asthmatic Americans...
Let's stop there a moment.  Considering back in 1983 Rick went through an inhaler on average of one week, and there are about 200 puffs in each inhaler, that means that Rick alone was responsible for over 10,000 of those 6 billion doses.  Wow!

Although, it should be noted, that sometimes Rick was able to make it two weeks, and occasionally a month, with one inhaler.  So even if he was able to have a few good months in the mix, at a minimum he inhaled over 5,000 puffs that year.  That is a stunning amount of puffs.

Now, back to Mittman:
...while revenues from the sale of 20 million inhalers helped sustain the U.S. economy as well as Boehringer Ingelheim.  In the 1970s, growing public skepticism about the health care industry and rising inflation in health care costs spurred the FDA to take action.  It began a systematic review of prescription drugs that might merit OTC (over the counter) status for metaproterenol sulfate inhalers -- specifically Alupent and Metaprel, made by Dorsey Laboratories.  Basing its decision on available evidence, the FDA argued that Alupent and Metaprel were as safe as and 'more effective than currently available OTC epinephrine (inhalers)' such as Primitine Mist.
The first time Alupent was squirted into my mouth was by my doctor in 1980.  At first Rick used it exactly as prescribed, which was no more often than every 4-6 hours.  But after a while he realized his breathing was heavy between puffs, and the idea of taking an extra puffs rolled over in his mind.  Finally he just did it.  Nothing bad happened.  So then he did it again.

Before long he was a bronchodilatoraholic (yet another term Rick later coined), using his inhaler much more often than the manufacturer and physician recommendation.  There were nights his heart was beating so loud in his chest he got on his hands and knees and prayed that he'd wake up in the morning, and every morning his prayer came true.  It's based on this side effect that the Rick Frea of 2012 thought the idea to pull Alupent back off the shelves was probably a good idea.  Mittman continues:
In March 1983, boehringer Ingelheim launched an intensive television advertising campaign notifying asthma patients that "prescription strength" Alupent was not available without the need to see a doctor."
Yay!!   Here is where the young Rick Frea jumped for joy.  Yet the joy was short lived.
The AAAI (American Academy of Allergy and Immunology), the American College of Allergy, and other medical organizations and clinicians were up in arms.  England's bronchodilator scare of the 1960s came to the forefront of doctor's minds, but an awareness of lost market share in allergic bodies no doubt did as well.  James Mann, an FDA physician, told the New York Times that such critics were simply opposed to 'the whole concept of over-the-counter marketing' with its emphasis on self-medication by patients."  But when the threat of a congressional inquiry by the House Subcommitte for Oversights and Investigations appeared, the FDA rescinded its ruling.  In less than three months, Alupent and Metaprel were removed from the cough and cold sections of drugstore shelves and were back on the pharmacist's shelf as prescription-only drugs."
So what happened in 1960 that scared the medical profession so much?   Well, you have to realize that the first rescue inhaler to be introduced to the market occurred in 1956 with the release of Medihaler Epi (epinephrine) and Medihaler Iso (Isopreterenol).  They were both available over the counter, and you'd guess correctly if you said asthmatics flocked to their local pharmacies in search of one of these inhalers, and quickly fell in love with them.  For the first time ever they had access to convenient quick relief, and they could keep it in their pockets.  It became known as the rescue inhaler, quick relief inhaler, pressurized inhaler, puffer, and metered dose inhaler (because it had a controlled dose).

As noted by Mittman:
During the 1960s, their rate of growth far exceeded that of antihistamines in the allergy drug trade.  With over $37 million in sales in 1970, prescribed bronchodilators had surpassed the earnings of antihistamines by over $1 million.  Asthma, once a small, specialized niche market for the drug industry, was starting to look like a field for lucrative growth and market expansion."
So this was good, right?  It was especially good for asthmatics, right?  Well, what happened next made people leery of the OTC rescue inhaler market.  Mittman writes:
By the late 1960s, medical opinion considered the use of bronchodilator inhalers as the most likely explanation for the marked increase in asthma deaths... pressurized inhalers first became available in England in 1960.  Over the next five years, their sales increased four-fold.  Inhalers such as medihaler-Iso were those most commonly found in the medicine cabinets of patients who died.  Of the patients who died, 86 percent had inhaled bronchodilators within the last month of their life.  
So, was the increase in asthma related deaths the result of the inhalers, or just a sign of the increase in the number of people being diagnosed with asthma?  Were overuse of inhalers killing people?  Or, was it because asthmatics were staying home and depending on their inhalers when they should have gone to get help?  Was it just due to lack of education?  Mittman notes this, and says:
Correlation, however, does not prove causation.  Researchers cited many reasons why inhaler use might be a factor in the rise in asthma deaths.  One explanation suggested that the deaths simply reflected cases of patients with severe asthma who had relied on self-medication with OTC bronchodilators rather than seeking medical attention.  Other hypotheses focused on the side effects of chemicals in the freon-propelled, metered dose inhalers.  Once in the circulatory system, isoproterenol might readily induce abnormal heart rhythyms in an organ already sensitized by low levels of arterial oxygen or by the flourinated hydrocarbons used as propellants.  Alternately, excessive use of bronchodilators might cause a rebound effect by exacerbating rather than reducing the constriction of the airways.  Whatever reason, Britain's Committee on Safety of Drugs believed the evidence warranted a ban on direct sales to the public of bronchodilator inhalers.  And asthma deaths promptly declined.  
Yet in the United States the medicine remained on the shelves, and sales spiked from "3.3 million in 1964 to 5.1 million in 1968."  And with what happened in Britain on their minds, physicians observed "disturbing reports of abuse." by patients "addicted" to their rescue inhalers, many of whom died with the inhaler clutched in their grasp.

Mittman continues:
The abuse of bronchodilators prompted American physicians to urge caution in treating asthma through drugs alone.  In 1969, the Allergy committee of the American College of Chest Physicians voted to urge the FDA to limit availability of OTC bronchodilator drugs.  Possible harmful effects also led to greater caution among physicians in prescribing metered-dose inhalers.  (By 1970) refill prescriptions of Riker's medihaler-Iso plummeted by more than 40 percent."
So now, instead of using a medicine that would help them, many asthmatics resorted to the old technique of suffering through an asthma attack instead of using their readily available rescue inhaler.  Scientists still do not know why the spike in deaths in the 1960s, yet the rescue inhaler is still believed by many to be the cause.  

While an epinephrine inhaler marketed as Primatene Mist was displayed next to the Alupent inhaler in March of 1983, Rick bought only one of them once.  He didn't think the inhaler did any good.  He puffed through that inhaler in only a few days.  Unlike what his doctor said about Primatene Mist, he didn't notice any side effects from using it this much.  As a matter of fact, Alupent had more side effects, he thought, than the OTC epinephrine inhaler.  By 1983 Isoproterenol was no longer available as an inhaler, so Rick never had the option to try it, which may have been a good thing, as Iso was believed to be much more potent than Epi.

The Alupent inhaler was much better, he decided, and, according to his doctor, much safer.  And this kind of frustrated Rick, because if it was safer, then why was it taken off the shelves in July 1983? It made no sense.  Yet he was unaware of the 1960 scare and, in a pre-Internet world, had no real means of learning about it.  Yet it was through a book written by Gregg Mittman in 2007 that he learned the answers so many years later.

After the July 1983 decision by the FDA asthmatics could still use rescue medicine, yet at least their pharmacist and doctor would know about it.  To get the medicine, the pharmacist would question the asthmatic, and this happened to me quite a bit.  It's always annoying when a pharmacist does this, yet the professional is just doing his or her job.

To continue getting it the doctor would have to write the prescription, as doctor Oliver so duly did for Rick Frea. In 1985 Rick was introduced to another rescue inhaler called Albuterol (Ventolin), and this one is even safer than Alupent.  So this opens the door for another debate: should Ventolin be available over the counter?

For more respiratory therapy history, click on over to my Hardluck Asthma blog.


  1. Mittman, Gregg, "Breathing Space: How Allergies Shape OUr Lives and landscapes," 2007, New Haven and London, Yale University Press, pages 206-250.  Mittman's book is a must buy, as he provides an easy to read history of allergies and asthma.  I endorse this book.

Facebook Page (new)

No comments: