We have an opioid crisis in America. This is not news – and it didn’t begin with the influx of Fentanyl across the Mexican border. That’s only the latest edition of this ongoing problem and the most fatal.
At a recent April subcommittee hearing, Food and Drug Administration Commissioner Robert Califf blamed the pharmaceutical industry for a lack of nonaddictive nonopioid pain medications. In his telling, the FDA is waiting with open arms for any new analgesics that industry may develop: “We need to do everything we can do to push industry and make this happen.”
That’s a noble perspective coming from someone within the industry himself. But there’s much more to this story. Fortunately, we have an insider’s perspective from the pharmaceutical industry. Charles L. Hooper, writing for The Wall Street Journal, formerly worked for Syntex, a large pharmaceutical company. Hooper says this about FDA Commissioner Califf’s statement: “He’s partially right: The government should commit itself to supporting private innovation. But it is disingenuous to blame industry for a dearth of treatments. Consider the evolution of the drug Toradol – generic name ketorolac – a case study in the agency’s propensity to scuttle effective medicine.”
Several decades ago, Syntex discovered and developed ketorolac: a nonsteroidal anti-inflammatory drug, or NSAID, used to provide morphine levels of pain relief without the same abuse potential as opioids. The FDA approved the drug in 1989, and it soon hit the market under the brand name Toradol IV/IM, joining other popular though less potent NSAIDs such as Advil, Motrin, and aspirin.
Before approval, an FDA employee suggested that Toradol IV/IM be given with a loading dose – that is, twice the standard amount. Against their better judgment, Syntex employees complied. The loading dose turned out to be a disaster: Gastrointestinal bleeding killed 97 patients worldwide between 1990 and 1993. The FDA subsequently changed Toradol IV/IM’s label and instructions, eliminating the guidance for double dosages, but by that point the reputational damage had been done.
While injectable Toradol IV/IM continues to be used in emergency rooms and post-op recovery rooms, many physicians remain skeptical of regular doses. When Syntex developed an oral version and submitted it to the FDA, the agency approved it, but gave it a label that essentially precluded its common use – they limited its dosage to about a third of its effective amount and imposed a strict limit of five days usage – also mandating the oral tablets follow an injection or intravenous dose of Toradol IV/IM. In other words, you can’t get Toradol oral treatment from your pharmacist unless you’ve received an injection of it in the emergency room or operating room.
A personal word is warranted here: I have suffered six times in my life with the pain of kidney stones. As anyone who has shared that experience can testify, kidney stones can produce some of the most excruciating pains imaginable. I have received opioid treatments including fentanyl and morphine. While both can be effective, they are usually accompanied by severe constipation – a regular side effect of opioids. Toradol has provided me with the same pain relief as morphine but without the constipation. I carry Toradol tablets in my travel kit and had to use them recently when I experienced another kidney stone during a trans-Atlantic flight.
Hooper says, “A bottle of ketorolac oral tablets should be in almost every American’s medicine cabinet today. It probably never will be. Now that ketorolac is generic, there’s no way to make money on getting the proper dose approved. The FDA could admit that it was wrong and adjust its approval accordingly – but that would require a healthy dose of humility. If Mr. Califf is serious about doing everything to bring beneficial drugs to market, here is a perfect place to start.”
