What Is a Black Box Warning?

Black box warnings are labels on certain medications that carry severe side effects or warnings, such as injury or death. The labels intend to draw attention to the warning by displaying a black border with bolded font communicating essential instructions for safe drug use. Black box warnings can be found on the medication’s insert. 

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What is a Black Box Warning?

Black Box Warnings, also known as Boxed Warnings, is assigned by the Food and Drug Administration (FDA), indicating the highest safety-related warning that medications can have. Black box warnings typically apply to a particular drug class rather than one specific drug because the risk posed by the medication is generally associated with the mechanism - or the way the drug works within the body.

Currently, over 400 medications have a black boxed warning, but these labels can be added, taken away, or updated to any drug at any point during their time on the market. These labels aim to draw attention to risks associated with the medication for the consumer and prescriber. The warnings are not meant to say the prescription shouldn’t be used at all but instead used with an added level of caution. 

How a Medication Gets a Black Box Warning

The FDA labels medications with a Black Box warning depending on the safety concerns during clinical trial data or through “adverse events” reported to the agency by consumers and healthcare professionals on the FDA’s MedWatch site.

Often, evidence of adverse reactions occurs after the new drugs have already hit the market, so these medications will not yet have a black box warning. Should the FDA recommend these labels be added to the medication, the FDA will contact the drug manufacturer to add a warning to the label. The company then submits the label back to the FDA for approval, and the updated language will be added to the packaging and on the medication insert. 

Indications When a Black Box Warning is Necessary

The FDA will advise that a black box warning is necessary for labeling when the risks might outweigh the benefits. Consider the following situations when the FDA may enforce such labeling:

• Evidence shows a drug causes a severe adverse reaction (potentially fatal, life-threatening, or permanently disabling)
• A severe side effect can be avoided or reduced in severity or frequency by appropriate use of the drug, such as avoiding use in specific situations, observing patients, careful patient selection, or avoiding using the drug with certain medications.
• The FDA approved the drug only for restricted use to ensure public safety
• The drug is less effective or dangerous to populations such as the elderly, children, or pregnant women

Drugs With a Black Box Warning

Currently, over 400 medications have a black box warning indicating potentially severe adverse reactions if misused. Some of those medications include certain antibiotics, contraceptives, antidiabetics, antidepressants, and more.

If you are using any of these drug types and are experiencing symptoms of an adverse reaction, speak with your prescribing health care provider regarding alternatives or call 9-1-1 if your situation is emergent. Consider reporting your reaction to MedWatch. Below is a list of some of the types of drugs with a black box warning label. 

Fluoroquinolone Antimicrobials 

Fluoroquinolone antimicrobials or antibiotics are approved to treat and prevent certain bacterial infections. These drugs pose an increased risk of tendinitis, tendon rupture, and severe nerve damage. There are over 60 generic versions, but some common FDA-approved fluoroquinolone medications include: 

• Levofloxacin (Levaquin)
• Ciprofloxacin (Cipro)
• Moxifloxacin (Avelox)
• Oxacin
• Gemifloxacin (Factive)
• Delafloxacin (Baxdela)

Rosiglitazone

Rosiglitazone is also known as its brand name Avandia, an antidiabetic drug used in conjunction with diet and exercise to manage diabetes to treat Type 2 diabetes. The drug increases insulin sensitivity in the body’s cells. The black box warning on Avandia identifies the drug’s association with an increased risk of new or worsening congestive heart failure, including heart failure or heart attack.

Selective serotonin reuptake inhibitors (SSRIs)

In 2004, the FDA issued a black box warning for selective serotonin reuptake inhibitors (SSRIs) after clinical trials indicated an increased risk of suicidal thinking and behavior. SSRIs are used to treat depression. Some commonly prescribed SSRIs with black box warnings include: 

• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Fluvoxamine (Luvox)
• Paroxetine (Paxil)
• Fluoxetine (Prozac)
• Sertraline (Zoloft)
• Venlafaxine (Effexor)

Celecoxib

Celecoxib is a nonsteroidal anti-inflammatory drug (NSAIDs). Celecoxib relieves pain, tenderness, swelling, and stiffness caused by different forms of arthritis in the body. Celecoxib may also be used to treat short-term episodes of pain in menstrual periods, injuries, surgeries, or dental procedures. The medication has a black box label because of severe cardiovascular and gastrointestinal risks such as holes in the stomach or intestine, bloody stool, and heart attack or stroke.

Medroxyprogesterone

Medroxyprogesterone is a form of progesterone, a female hormone that helps regulate ovulation and menstrual periods. Medroxyprogesterone is often used as a method of contraception through intramuscular injection. This medication is used to treat absent or irregular menstrual periods or abnormal uterine bleeding, or other conditions related to menstruation and postmenopausal conditions. Medroxyprogesterone was issued a black box warning because of the association with a decrease in bone density in long-term use.

Effectiveness of Black Box Warnings

When it comes to the effectiveness of black box warnings, there are mixed reviews. SSRIs, a common type of antidepressant medication requiring a black box label, indicate the association with an increased risk of suicidal thinking, feeling, and behavior in young people on the black box warning. Many medical community members worried whether this would discourage patients from seeking help or physicians prescribing antidepressants when clinically indicated. 

In a 10-year clinical study of over 100,000 patients, it appeared that the black box warning posed no significant impact on the prescribing of SSRI antidepressants. A slight decline in prescription rates was observed within the years following the label being added to the medication. Consequently, pre-label prescription rates returned, and health professionals questioned whether the impact of the warning labels has dissipated over time. 

Black Box Warning Frequently Asked Questions (FAQs)

If you have been prescribed a medication with a black box warning, consider the following questions to help ensure safe use of your prescription. Speak with your healthcare provider for further questions you may have and use regarding your personal medical needs. 

What are the symptoms of an adverse reaction?

An adverse event or reaction is any undesirable experience associated with the use of a medical product. Adverse events are serious and should be reported to FDA when the patient outcome is:

• Death
• Life-threatening event
• Hospitalization (initial or prolonged)
• Disability or permanent damage
• Birth Defect
• Required intervention to prevent permanent impairment or damage
• Other serious medical event (difficulty breathing, blood disorders, seizures/convulsions, etc.)

Can a black box warning be removed from a medication’s label?

Clinical evidence proving the medication’s risk is less severe than previous studies had shown required for the FDA to consider removing the black box warning. Although once a drug has a warning label, they aren’t often removed.

Should I stop my medication because it has a black box warning?

According to the Cleveland Clinic, if a medication you are taking carries a risk that warrants a black box warning, that does not necessarily mean that you shouldn't take it. Understanding the risks and the benefits of medication is something your healthcare provider should discuss with you to determine whether this medication is necessary to help treat your condition.

Bottom Line

Black box warnings are put on the inserts of medications that pose serious risks and are to be used with caution and as specifically instructed. The black border and bolded text aim to draw attention to the patient and the prescriber to consider how the benefits of the medication compared to the potential risks. If you know someone or have experienced an adverse event related to a medication, report your experience to the FDA. 

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