About a year ago, I wrote a blog on the introduction of Imitrex (sumatriptan) Injection, a drug indicated for the treatment of migraine headaches. At the end of that blog I wrote:

I loved selling Imitrex Injection, my District was exceptional at it, and I said as much on my license plate. By the end of 1993, the launch year for Imitrex Injection, thousands of patients are taking Imitrex and sales exceed $150 million dollars.

But then the problems began…

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Indeed, they did. The FDA has very specific guidelines concerning the number and type of clinical studies required to prove safety and effectiveness of a pharmaceutical product before they authorize or “approve” it

And that’s why many doctors are reluctant to prescribe a drug until it’s been on the market for years, and also why there is a robust system in place, called the FDA Adverse Event Reporting System (FAERS) designed to capture events that fall outside of the expected. And Imitrex Injection had its fair share of events reported early in its marketed life, but none were more serious than an event reported in 1994, months after launch the previous year, of a 41 year old woman who died within hours of an Imitrex Injection.

Every drug sold in the US carries a complete description of the drug along with safety information. The Package Insert (PI) or ‘Label’ for Imitrex carried a warning about possible constriction of coronary (heart) arteries. At its core, Imitrex is a vasoconstrictor that exerts its effect by exciting Serotonin subtype 5HT1B/D receptors, which are found primarily on cranial (head) arteries involved in the migraine process. But the human body is rarely neatly compartmentalized, and some 5HT1B/D receptors are also distributed on coronary arteries.

It was thought that perhaps the ‘triptan sensations’ of pressure, warmth, heaviness and tightness were possibly due to impact on coronary vessels. But ECG, PET, Angiography and many other fancy studies had difficulty tracing these sensations to coronary vessel constriction. Still, the caution against using in patients with coronary disease was prudently included in the PI.

Still, this death prompted a closer look at the safety of Imitrex by Glaxo, the FDA, as well as media news outlets. Soon, the popular news magazine show 20/20 slapped together a piece on the dangers of Imitrex. It wasn’t pretty. They misrepresented the many adverse events reported to FAERS as all serious and included virtually nothing from the extensive interviews they held with Glaxo scientists and executives. This also spurred lawyers across the country to send out post cards, like this, searching for others who may have used Imitrex Injection and had serious events.

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Working with the FDA, Glaxo sent out correspondence (called “Dear Doctor” letters) to all physicians across the country letting them know about these serious events and reminding them not to use Imitrex in patients with risk factors for coronary artery disease, and to be sure of the migraine diagnosis. The PI (Package Insert) was amended to strengthen this contraindication and Glaxo Sales Representatives across the country made multiple calls on each physician to specifically review the changes to the PI, and reinforce the importance of proper patient selection. By the end of 1994, after over 24 million doses of Imitrex were used, there were a total of 4 deaths possibly attributed to the Injection (based on timing). Glaxo worked with the FDA once again to strengthen the contraindications, precautions and warnings, while ensuring that prescribing physicians were informed through the mail as well as personal visits.

So, you may be asking, “Why was Imitrex allowed to remain available if there was the potential for even one additional death”? This is an important question that every drug must answer, and everybody has an opinion. From my perspective, I don’t think removing Imitrex from the market was ever truly considered. In fact, one of the three FDA reviewers charged with regulating Imitrex wrote that

“If there are to be potent drugs like sumatriptan [Imitrex]– society must be willing to tolerate the injury they will cause to some proportion of those who use them.”

A surprising statement? Perhaps not when one considers the impact of migraine on the 30 million sufferers in America, and on society in general. According to a recent study published in the Lancet, migraine attacks are the second-largest global contributor to years lived with disability. They come with a huge economic cost too, causing an estimated 35 million sick days to be taken each year in the US alone. Migraine affects more Americans than Diabetes and Asthma…combined.

Over the course of my 3 years in Marketing, dozens of letters to Glaxo from migraine sufferers crossed my desk. I don’t want to get in trouble with GSK, so I’ll refrain from including excerpts here, but let me assure you that the stories of sufferers would rip your heart out. They included years lost to migraine, careers lost, family lost. Divorce. Insufferable pain. Addiction. Depression. Attempted suicide. And always eternal thanks for the drug that became their “personal miracle”.

The good news? Doctors learned to identify the most appropriate patients for Imitrex, and in 1995 there were no serious cardiovascular reports in the US with Imitrex Injection.

More good news? Plans were progressing nicely on the launch of the Tablet version, which would make sumatriptan available to millions more sufferers. And the launch of the Tablet and Nasal versions of Imitrex makes for another interesting story….

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