The Drug Warnings You May Never See—Until It’s Too Late

With more than 400 black box warnings, it’s hard for many physicians to keep track.

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The most serious drug warnings in U.S. medicine often go unnoticed by the very people they’re meant to protect.

Just ask Michele Mason.

In 2023, her 27-year-old daughter, Alisa, was prescribed a seven-day course of Levaquin for pneumonia at an urgent care clinic in Arizona. Neither she nor her mother had ever heard of the drug—or the risks it carried.

“I picked up her prescription, and not a word was said,” Michele Mason told The Epoch Times. “I had never even heard of black box warnings.”

A boxed warning—often called a black box warning because of its bold black border—is the most serious safety alert of the U.S. Food and Drug Administration (FDA). It signals to doctors and pharmacists that a drug carries serious risks.

Halfway through the treatment, Alisa Mason’s arm began to tremble, causing her to drop coffee cups. Within days, she was overwhelmed by unexplained symptoms—nerve pain, muscle weakness, and relentless joint pain. Even washing dishes became painful. Unable to work, she moved back to Michigan to live with her mother.

“I don’t know if she’ll ever be able to work again,” Michele Mason said. “And doctors just look at you like you’re crazy.”

Alisa Mason suffered an adverse reaction to fluoroquinolone antibiotics—a drug class flagged with the FDA’s highest safety warning. In 2008, the agency cautioned that these antibiotics could cause permanent nerve damage, tendon ruptures, and severe effects on the muscles and nervous system. But Alisa Mason was never warned. The urgent care doctor called it a “strong antibiotic,” and the pharmacy technician dispensed it without comment.

Alisa Mason’s experience is more common than many think. Black box warnings often arrive years after a drug has been widely prescribed. Even then, many patients remain unaware until they suffer the consequences firsthand.

What Is a Black Box Warning?

Black box warnings appear at the top of a drug’s prescribing information in both printed and online materials. However, they are often absent from prescription labels. According to critics, this leaves patients uninformed about serious risks.

Black box warnings vary in severity. Some flag life-threatening risks, such as organ failure or suicidal thoughts. Others highlight serious but nonfatal side effects, such as permanent nerve damage or birth defects. Some warnings focus on strict prescribing rules to prevent misuse or abuse.

The FDA mandates black box warnings, and pharmaceutical companies draft them based on agency guidelines.

Black box warnings were first introduced by the FDA in 1979, starting with chloramphenicol, an antibiotic linked to a rare but fatal blood disorder.

“Black box warnings were initially rare, reserved for those that were considered most important,” Dr. Paul Axelsen, professor at the University of Pennsylvania Perelman School of Medicine, told The Epoch Times. “The first was a necessary alert about a drug that could be fatal. But over the years, these warnings have become far more common.”

A Growing Trend

As of 2022, more than 400 medications had black box warnings.

In 2023, the FDA issued more black box warnings than in any previous year, extending a decade-long increase. That year alone accounted for 40 percent of all black box warnings issued over the past decade, compared to 12 percent in 2022. Many of these warnings weren’t for newly developed drugs, but for widely used medications, including antidepressants, painkillers, and sleep aids.

Despite the sharp increase in black box warnings, the FDA has not conducted a formal analysis of the trend. In response to questions from The Epoch Times, the agency stated that determining the frequency and causes of these warnings over time would require manually reviewing more than 1,000 drug applications—an effort it does not consider an efficient use of resources.

What’s behind the surge? Some experts point to improved post-marketing surveillance, the FDA’s system for tracking drug safety after approval. Others worry that it means more high-risk drugs are making it to market.

Social media has transformed how drug safety concerns come to light. Patient forums and advocacy groups frequently highlight potential risks, sometimes prompting others to report side effects to the FDA.

A 2021 study in JMIR Public Health and Surveillance found that social media discussions often identify drug risks months or even years—up to nine years—before regulators take action. While these reports aren’t always reliable, online platforms have become a major influence on drug safety and could be fueling the rise in warnings.

Lawsuits have also become a driving force. More law firms now specialize in black box warning cases, holding drug manufacturers and health care providers accountable for failing to disclose risks.

“Litigation in this area has skyrocketed,” Axelsen said. “Many doctors don’t realize that not informing a patient about a black box warning can be used in court to imply that they did not inform a patient about any warnings.”

As lawsuits increase, so does pressure on regulators. Some argue that growing litigation pushes the FDA to issue warnings more aggressively, ensuring that risks are formally documented. Axelsen pointed out that black box warnings can shift duty to warn from drug manufacturers to doctors.

“If a drug has a black box warning, the question becomes, ‘Why didn’t the doctor warn the patient?’” he said.

Common Medications With Black Box Warnings

When Warnings Come Too Late

Even when issued, black box warnings often come after a drug has already reached millions of patients. A 2024 study published in Cureus found that approximately 80 percent of these warnings result from post-marketing studies—meaning serious risks often become evident only after widespread use. Since the FDA requires strong evidence before adding a warning, many patients are exposed to harm before the risks are formally recognized.

This delay means newly approved drugs often lack black box warnings—even if they pose serious risks. By the time enough adverse events accumulate to justify a warning, thousands—sometimes millions—of prescriptions have already been filled.

The FDA acknowledges this gap, explaining that pre-market clinical trials—while thorough—can’t always predict long-term risks. Trials typically include only a few thousand patients, so rare or delayed side effects may not appear until the drug is widely used. The agency told The Epoch Times that post-market surveillance is essential for uncovering these risks and adjusting warnings as needed.

Drug manufacturers have strong financial incentives to avoid black box warnings. These warnings restrict direct-to-consumer advertising, cutting into the billions of dollars spent on TV and online drug promotions—campaigns that drive sales and boost profits.

Yet a black box warning can also serve as a legal shield for drug makers. Once in place, it shifts liability to doctors, allowing manufacturers to argue that they disclosed the risks if a patient experiences serious side effects.

When Providers Miss the Warnings

Black box warnings are meant to improve safety, but they often fail to change how providers prescribe. In some cases, they introduce new risks.

One problem is awareness. Many doctors and pharmacists monitor black box warnings and discuss them with patients—this is especially true for specialist physicians who prescribe fewer types of medications than primary care physicians. However, with the sheer volume of medications they manage, other doctors may miss them entirely.

These alerts aren’t sent directly to physicians but are buried in lengthy drug inserts or electronic health record pop-ups that can easily be overlooked. A 2015 Journal of Medical Toxicology study found that emergency and pediatric doctors correctly identified medications with black box warnings only 36 percent of the time. Even when they knew that a drug carried a warning, just 13 percent could recall its details. Nearly one in three doctors admitted that they had no reliable way to stay updated.

“The information in a black box warning often does not reach the prescriber,” Axelsen said. As a result, some prescribe drugs with black box warnings without even realizing it.

Pharmacists, who receive drugs in bulk packaging from manufacturers, are often the only ones who see the printed black box warnings. But with the high volume of medications they handle, they have little reason to scrutinize each label for updates, according to Axelsen.

Patients, meanwhile, are asked if they have questions when picking up prescriptions—often via a touchscreen prompt—but most don’t know to ask about black box warnings in the first place.

Even when physicians see the warnings, how they respond can vary widely. A 2014 study of half a million patients found that after an FDA warning about a diabetes drug, prescribing rates dropped—but unevenly. Some doctors cut back sharply. Others barely changed. In fact, prescribing became more inconsistent after the warning, showing that FDA alerts alone aren’t enough. How hospitals and health systems enforce them determines whether they lead to real change.

The result? Many doctors unknowingly prescribe medications in violation of black box warnings—sometimes as often as 50 percent of the time. An Archives of Internal Medicine study found that seven in 1,000 outpatients received prescriptions that directly contradicted such warnings. While most cases resulted in no harm, the findings raise a critical question—if doctors don’t see the warnings, how effective can they really be?

Although prescription technology has advanced, newer studies on black box warnings are lacking, Axelsen said.

When Warnings Backfire

Black box warnings are meant to protect patients, but sometimes, they do the opposite.

One of the most debated black box warnings involves antidepressants. In 2004, the FDA required a warning on selective serotonin reuptake inhibitors (SSRIs) such as Prozac and Zoloft, citing studies that suggested an increased risk of suicidal thoughts in people younger than 24. The intent was to encourage closer monitoring, not to dissuade treatment.

That’s not what happened.

Many doctors pulled back, prescribing SSRIs less frequently. A 2024 study in Health Affairs found that after the warning, youth mental health care declined sharply—fewer depression diagnoses, fewer therapy visits, and fewer antidepressant prescriptions. Meanwhile, suicide deaths and psychotropic drug poisonings increased.

“The overwhelming evidence suggests that the ongoing use of these warnings may result in more harms than benefits,” the study authors wrote.

Some say the warning was necessary. A 2020 Frontiers in Psychiatry study argued that withholding safety data is irresponsible.

“When a clear body of evidence points to increased treatment-linked risk, patients and healthcare providers should be made aware,” the study states.

But the fallout exposed a deeper problem. When medication became a less viable option, many doctors had no alternative plan. Therapy didn’t replace lost prescriptions—treatment simply vanished.

The antidepressant controversy is not unique. Axelsen said some black box warnings deter doctors from prescribing beneficial treatments, even when the actual risk is low. Other warnings, however, go largely ignored.

Axelsen recalled a case in which an advanced practice nurse, wary of ciprofloxacin’s black box warning for tendon damage, prescribed Bactrim to an older, active patient instead. However, Bactrim carries a higher risk of severe allergic reactions, including Stevens-Johnson syndrome, a rare but severe skin reaction resulting in painful blisters. In avoiding one risk, she unknowingly introduced another, highlighting how black box warnings can distort clinical decision-making.

“The patient almost certainly did fine, but statistically, that was a bad trade,” Axelsen said. He noted that expecting every prescriber to weigh such risks accurately is unrealistic, especially when drug labels provide little context.

The fluoroquinolone warning did change prescribing habits, but inconsistently. A 2021 JAMA Network Open study found that fluoroquinolone prescriptions for upper respiratory infections and urinary tract infections declined after the 2016 FDA black box warning update, but the response varied by specialty. Primary care doctors were more likely to reduce prescribing, while specialists were slower to adjust. Researchers concluded that better systems are needed to ensure that FDA warnings lead to safer prescribing practices.

Is the FDA’s Warning System Broken?

Black box warnings are the FDA’s strongest caution, meant to flag life-threatening risks. But experts say the system is inconsistent, confusing, and in need of reform.

Yale School of Medicine research found that the FDA lacks standardized criteria for issuing black box warnings, leading to inconsistencies. Drug databases often disagree on what qualifies for the warning, and some high-risk medications have none at all. Meanwhile, other drugs carry a black box warning based on limited or inconclusive evidence.

Under pressure to act cautiously, the FDA sometimes issues black box warnings as a safeguard rather than as a final scientific conclusion, blurring the line between real danger and regulatory caution.

The FDA told The Epoch Times that it reviews and updates warnings when new safety data emerge, and some have been removed or modified over time. However, these changes often depend on drug companies submitting new evidence or regulators identifying risks on their own.

There are also no clear rules on when a warning should be revised or removed. Some remain indefinitely, even as newer data suggest lower risks. Others disappear with little public explanation. There’s no standard for how doctors should discuss these warnings with patients, leaving prescribers to navigate the risks—and the legal liability—on their own.

“Many black box warnings are merely expressions of concern about reported associations, and they lack the scientific backing to establish whether a drug truly deserves such a warning,” Axelsen said.

“The system is underfunded, understaffed, and, quite frankly, broken, so that once in place, black box warnings are nearly impossible to remove.”

According to experts such as Axelsen, for black box warnings to be effective, the system needs major reform. Without change, it will remain a mix of essential safety alerts, unnecessary fear, and regulatory red tape—leaving doctors and patients struggling to distinguish real dangers from legal disclaimers.

What Patients Need to Know

Black box warnings highlight serious risks, but only work if both doctors and patients engage with them. The Patient Safety Action Network, a nonprofit organization aimed at preventing medical harm, has noted that many patients remain unaware of black box warnings, even years after they are issued, because prescribers often fail to discuss them. Simply including a warning on a label is not enough—meaningful conversations between doctors and patients are essential to informed decision-making.

Protecting yourself starts with being proactive. Never assume that your provider is fully aware of a drug’s black box warning.

Always review the drug insert for any medication you take. The most serious warnings appear in a black box at the top. In addition, read the FDA-approved medication guide included with your prescription. Unlike the dense, jargon-filled inserts, these guides are written in plain language and offer a clearer explanation of real risks.

“These are your friends,” Axelsen said. “They tell you what you actually need to know.”

If your medication has a black box warning, ask your provider, “Why was this prescribed? What are the risks? Are there safer alternatives?”

A black box warning doesn’t necessarily mean you should avoid a medication—it means you should understand its risks. Every drug comes with trade-offs, and the goal is to make an informed choice, not to let fear dictate your decision.

For patients such as Alisa Mason, that balance was never explained. By the time she understood the risks of her antibiotic, the harm had already been done. Black box warnings exist to prevent these tragedies—but only if patients and providers pay attention.