Black Box Warning: What It Means and Which Drugs Have It

When a drug comes with a black box warning, the strongest safety alert the U.S. Food and Drug Administration (FDA) can require. Also known as a boxed warning, it’s printed in a bold black border on the drug’s label to grab attention—because the risks aren’t just possible, they’re serious, sometimes deadly. This isn’t a gentle reminder. It’s a red flag that says: "This medicine can kill you if used wrong, if you have certain conditions, or if you’re not monitored closely." You’ll find these warnings on drugs for depression, heart conditions, autoimmune diseases, and even some antibiotics.

The FDA, the federal agency responsible for approving and monitoring medications in the U.S. only adds a black box warning after clear evidence shows a pattern of severe harm—like liver failure, suicidal thoughts, or sudden heart rhythm problems. It’s not based on guesses or rare side effects. For example, antidepressants like fluoxetine carry this warning because young adults under 25 have a higher risk of suicidal behavior when starting treatment. Similarly, the diabetes drug rosiglitazone got one after studies linked it to heart attacks. These aren’t theoretical risks. They’re real, documented, and tracked.

What makes a black box warning different from other side effect lists? It’s not about mild nausea or dizziness. It’s about life-threatening outcomes: bone marrow failure, severe allergic reactions, or organ damage that can happen without warning. That’s why doctors don’t just prescribe these drugs—they monitor you closely. You might need regular blood tests, heart scans, or check-ins every few weeks. The warning doesn’t mean you can’t take the drug. It means you need to be smart about it. If you’re on a medication with this label, know the symptoms to watch for. Keep a journal. Ask your pharmacist what to do if something feels off. Don’t assume your doctor already knows everything you’re feeling.

You’ll see these warnings on drugs covered in our posts—like Baricitinib, a JAK inhibitor used for autoimmune diseases that carries a black box warning for serious infections and cancer risk, or Leukeran, a chemotherapy drug linked to leukemia risk after long-term use. Even older drugs like chlorambucil or certain antipsychotics have them. The Beers Criteria, a guide for unsafe medications in older adults, often overlaps with black box warnings because the same drugs that harm young people can be even more dangerous for seniors.

There’s no avoiding these drugs if you need them—many save lives. But understanding the warning means you’re not just a patient. You’re an active partner in your care. You know what to watch for. You know when to call your doctor. You know not to ignore symptoms that feel "off." Below, you’ll find detailed comparisons of medications that carry this warning, what alternatives exist, and how to manage the risks without giving up on treatment.