Black Box Warning

A black box warning (also known as a boxed warning) is the highest warning level issued by the US Food and Drug Administration ( FDA ) for prescription drugs. This warning is highlighted in a black box on the drug's packaging or package insert to indicate serious or potentially life-threatening side effects.

Features of a black box warning:

Highest FDA warning level:

• Issued only when there are significant risks that may be life-threatening.

Marked by a black box:

• The warning is visually highlighted to make the meaning clear to physicians and patients.

Target group:

• Doctors and pharmacists should be informed of serious risks to ensure safe use.
• Patients can also be warned, especially if the risk is not covered by normal safety instructions.

Reasons for a black box warning:

• The drug may have fatal or irreversible side effects.
• There is a high risk of serious drug interactions.
• The medication poses risks if used incorrectly (e.g. in the event of an overdose).

Examples of drugs with black box warnings:

• Opioids (e.g. oxycodone, fentanyl): Risk of respiratory depression and dependence.
• Antidepressants (e.g. SSRis): Increased risk of suicide in adolescents and young adults.
• Isotretinoin (for acne): Severe birth defects in pregnant women (Strauss JS et al. 1988)
• Topical calcineurin inhibitors (2006): Risk of malignant degeneration (Po-Chien Wu et al. 2021)

Why are black box warnings important?

• They help physicians to make an informed decision about the benefits and risks of a drug.
• Patients can be better informed about potential dangers.
• They help to avoid serious side effects by specifically pointing out risks.

Despite a black box warning, these drugs can be prescribed if their benefits outweigh the risks. However, doctors must be particularly careful and monitor patients carefully.

1. Po-Chien Wu et al (2021) Topical calcineurin inhibitors and the risk of lymphoma: a systematic review and meta-analysis. JDDG 19:1265-1270
2. Strauss JS et al (1988) Isotretinoin and teratogenicity. J Am Acad Dermatol 19:353-4.