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

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 something serious could happen if you ignore it. This isn’t just a cautionary note. It’s a red flag that the drug has caused death, severe injury, or life-threatening side effects in real patients—sometimes even when used exactly as directed.

These warnings don’t appear randomly. They’re added after the FDA reviews reports from doctors, patients, and clinical studies. For example, antipsychotics, like ziprasidone, used to treat schizophrenia and bipolar disorder carry black box warnings for increased risk of death in elderly patients with dementia. Methotrexate, a common treatment for rheumatoid arthritis and some cancers, has one because it can cause severe liver damage or bone marrow failure if not monitored closely. Even isotretinoin, the powerful acne medication sold as Isofair, comes with a black box warning due to its link to severe birth defects.

What makes these warnings different from regular side effects? They’re not about mild nausea or dizziness. They’re about risks you can’t afford to overlook—like sudden heart problems, suicidal thoughts, organ failure, or death. That’s why doctors are required to discuss them with you before prescribing. And if you’re taking one of these drugs, you need to know the signs: unexplained bruising, chest pain, extreme fatigue, mood changes, or yellowing skin. Don’t wait. Call your provider immediately if something feels wrong.

The good news? These warnings exist to protect you. They don’t mean you can’t take the drug—they mean you need to be smart about it. Regular blood tests, careful dosing, avoiding alcohol or other meds, and open conversations with your doctor can make all the difference. Many people use these medications safely every day. But skipping checkups or ignoring symptoms? That’s when things go wrong.

Below, you’ll find real-world guides on drugs with black box warnings—what they are, why they’re risky, and what alternatives might work better. Whether you’re managing arthritis with methotrexate, treating acne with isotretinoin, or controlling heart rhythm with an antipsychotic, you’ll find clear, practical advice to help you stay safe and informed.