If Opiates Are Killing Americans, Why Won't the FDA Let Us Try an Alternative?

As the DEA relentlessly tightens regulations on pain meds, the FDA refuses to approve a safer alternative already being used in similar countries.

For more than a decade, patients who've needed certain controlled medications have suffered from ill-advised, untenable policies the U.S. government has instituted, allegedly to mitigate the ever-surging numbers of drug overdose deaths. These policies have been a dismal failure on multiple fronts: Not only have deaths continued to surge, but the terrifying intrusion of the Drug Enforcement Administration (DEA) into the practice of medicine has had a chilling effect on patients and their physicians. 

As the DEA relentlessly tightens production quotas on medications for pain and ADHD, it has begun tracking every pill, making doctors increasingly reluctant to prescribe any controlled drugs and leaving many patients in a lurch. Perhaps worse, DEA production quotas have caused the back-order of multiple drugs—an increasingly common burden for patients, even those fortunate to have doctors willing to risk a DEA drug bust for simply doing their job.

The ill and disabled suffer the most. Virtually all patients who have diseases or chronic pain conditions will say that the emergency department is the single worst place to go for relief from severe pain. Doctors and hospitals are often more concerned about law enforcement looking over their shoulders than patient care. Patients desperate for pain relief often turn to street drugs, where they fall victim to counterfeit pills that contain fentanyl (or worse) instead of a legal opioid. 

By contrast, doctors in Australia, Canada, the United Kingdom, and throughout Europe have been using a fixed-dose, inhaled general anesthesia medicine that effectively reduces acute pain—a medication denied to Americans by a seemingly indifferent Food and Drug Administration (FDA). 

Doctors commonly used methoxyflurane (Penthrane) as a general anesthetic in the 1960s and 1970s. But, because it had toxic effects on the liver and kidneys, anesthesiologists gradually stopped using it and turned to safer anesthetics. In 2005, the FDA removed methoxyflurane from the market.

However, an Australian company, Medical Developments International, has been marketing a lower-dose, self-administered, single-use nasal inhaler version of methoxyflurane for 30 years. Its brand name is Penthrox, though many people refer to it as the "green whistle," because of the package it comes in. People living in Europe have had access to the green whistle since 2015, and Canadian patients have had it since 2018. 

In 2020, a randomized controlled clinical trial in the U.K. demonstrated that the drug saved an average of 71 minutes in providing pain relief to accident and emergency department patients. Likewise, a 2020 Australian trial found that a methoxyflurane inhaler "was associated with clinically significant lower pain scores compared to standard therapy." While it may cause drowsiness in some people, methoxyflurane at this low dose has few adverse effects, such as liver and kidney toxicity, and there are no reported cases of addiction or abuse. 

In 2022, the FDA finally lifted its "clinical hold" on methoxyflurane nasal inhalers and has allowed its manufacturer to resume FDA-supervised clinical trials. Unfortunately, this is an unnecessary waste of time.

This is hardly the first time the FDA has been behind the times, blocking Americans from accessing medications that are readily available in other advanced countries. People in Europe were able to purchase nonsedating antihistamines like Claritin over the counter (OTC) in the 1990s, but the FDA didn't permit Americans to do this until 2002, instead forcing them to use more dangerous sedating OTC antihistamines, such as Benadryl. 

It took 12 years and 4 months (beginning in 2001) for the FDA to finally give women the freedom to buy the emergency contraceptive Plan B over the counter, while during this same time, women in the U.K., Canada, and countries in Europe already had OTC access to the drug. And while women in over 100 other countries can get birth control without a prescription, American women still have to get a prescription for all but one.

Australians have been free to purchase the opioid overdose antidote naloxone OTC since 2016, and Italians have had it available to them since 1996. It wasn't until 2023 that the FDA allowed Americans to buy the drug without a prescription and only in its nasal spray form. 

Now, while Americans are having more and more difficulty getting access to pain-relieving opioids, the FDA forces them to wait for an alternative to opioids that people in much of the developed world have been using for years.

One way lawmakers can bypass the FDA's long and arduous approval process is through a reform called international reciprocity—allowing American doctors and patients access to drugs and medical devices approved by regulatory agencies in similar countries. Labels on such products should plainly state "Not FDA-approved" but should state which country's agency has approved them. 

Reciprocal approval already exists among the European Union states plus Iceland, Liechtenstein, and Norway. There is no logical reason that Americans shouldn't be able to access products approved in countries such as Canada, France, England, Switzerland, Australia, New Zealand, and Israel.

If Congress enacted reciprocity, Americans in pain would be able to get relief from methoxyflurane while the FDA deliberates. This common-sense action has enormous potential upside and little to no downside. Congress should act without delay.