What Makary’s Plan For Expanding OTC Drug Access Could Mean For Safety

Marty Makary, commissioner of the Food and Drug Administration, said he believes “everything should be over the counter” unless a drug is unsafe, addictive or requires monitoring, or “if it could be used for some nefarious purpose.” He also said that regulators need to get away from their “paternalistic mindset.” While he initially referred to anti-nausea medicines and vaginal estrogen, where else might a move to OTC status for drugs take us?

Drug Safety And OTC Status

Some drugs are readily available OTC in other countries, but not in the U.S. Methocarbamol (Robaxin), a muscle relaxant, is one example. It is considered safe and unlikely to be abused.

More notably, for more than 25 years, the American College of Obstetricians and Gynecologists has urged that oral contraceptives be available OTC to reduce barriers to access. They stated they support “over-the-counter access to hormonal contraception without age restrictions” because of its “potential to decrease unintended pregnancy.” They noted that it is generally safe and that the risk of blood clots, a major concern, is small compared to the risk of clots during pregnancy or post-partum. Despite the long-standing recommendation, only progestin-only oral contraceptives are available OTC in the U.S. In contrast, OTC oral contraceptives containing estrogen and progestin are available in more than 100 countries.

Mifepristone is the target of many antiabortion groups. It’s a drug used in combination with misoprostol for a medical abortion. The first drug blocks progesterone and stops the pregnancy; the second causes uterine contractions, causing the tissue to be expelled as it would be during a miscarriage. Mifepristone can now be prescribed only under the FDA’s risk evaluation and mitigation strategy. Numerous studies and global experience support its safety. A CNN report showed that mifepristone had a death rate of 5 per million users. In comparison, the death rate for penicillin was 20, and for Viagra was 49 per million. Makary and Robert F. Kennedy Jr have vowed to again review the safety of mifepristone.

If Makary were only concerned about safety, then he might want to consider acetaminophen (Tylenol, paracetamol, and panadol) and non-steroidal anti-inflammatories like ibuprofen (Advil, Motrin), naproxen (Naprosyn, Aleve), and celecoxib (Celebrex).

Since acetaminophen is often used in combination with other medications for pain or antihistamines (e.g., DayQuil, Theraflu, Midol), it’s easy to lose track of how much you are taking. The maximum daily dose for adults is 4,000 mg. Overdose or prolonged use can cause serious liver toxicity, which may be fatal.

Similarly, NSAIDs can cause serious GI bleeding and kidney and cardiovascular damage, but are widely available OTC.

There was a brouhaha last fall after President Trump linked Tylenol during pregnancy to autism, and said, “Don’t take Tylenol if you’re pregnant, and don’t give Tylenol to your child.” The problem with that is that there is no clear data that Tylenol causes autism^⁠. The Society for Maternal-Fetal Medicine issued a strong rebuttal, stating, “Untreated fever, particularly in the first trimester, increases the risk of miscarriage, birth defects, and premature birth.” Acetaminophen remains the safest drug available to treat pain and fever in pregnancy.

Will Antibiotics Be Next To Go OTC?

While not specifically mentioning antibiotics, one might expect that “everything should be over the counter” would include antibiotics.

A major concern is that making antibiotics OTC would fuel antimicrobial resistance. As Sir Alexander Fleming noted long ago [1945], ”The greatest possibility of evil in self-medication [with penicillin] is the use of too-small doses, so that, instead of clearing up the infection, the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out which can be passed on to other individuals and perhaps from there to others…” In a 2019 report from the CDC, AMR pathogens caused more than 2.8 million infections in the U.S. each year and more than 35,000 deaths.

Since then, there’s been a dramatic increase in a particular type of “superbug,” a very drug-resistant bacteria called NDM-producing carbapenem-resistant Enterobacterales. These NDM-CRE bacteria are often initially found in hospitals or nursing homes, and then spread to the community. They are extraordinarily difficult to treat, with only limited and toxic antibiotics available.

In the U.S., antibiotics for human use are not currently OTC. In Europe, an estimated 7% of antibiotics are taken without a prescription, with higher rates in some countries than others.

OTC antibiotic use is high in India and Southeast Asia, and growing in South America and Africa.

In a recent study of patients undergoing Endoscopic retrograde cholangiopancreatography, 83 % of patients in India carried drug-resistant bacteria. It was lower in the other countries: 31.5% in Italy, 20.1% in the U.S., and 10.8% in the Netherlands.

One suggestion to curb OTC sales is that pharmacists be allowed to prescribe antibiotics for infections that can be diagnosed based on symptoms alone—like uncomplicated cystitis, impetigo, and conjunctivitis. Point-of-care testing, such as for Strep throat or UTI, would further benefit in reducing overuse. With additional training, this model could be extended to community health workers.

The World Health Organization had a global consultation to discuss possible interventions to reduce OTC use. They note, “Access to free, high-quality primary health care, the availability of universal health coverage, and a trusted public health system are critical aspects across all countries influencing patients’ health-care-seeking behaviour.” Inability to access health care and inconveniences are obstacles that promote self-medication. With more people becoming uninsured in the U.S., one is likely to see this happening more, with people using leftover medications or those from friends, for example. Note, too, that the U.S. has withdrawn from participating in the WHO, thus ending any collaboration on this growing problem, and public health systems are struggling due to budget cuts.

Makary should be cautious about extending OTC status to antibiotics, which would likely fuel resistance. As Dame Sally Davies, Chief Medical Officer UK, said, “We really are facing, if we don’t take action now, a dreadful post-antibiotic apocalypse.”