FDA Black Box Warning

An FDA black box warning needs to be taken seriously and is explained here. A black box warning is the strongest form of all FDA warnings. It is a step just short of taking the drug off the market.

Not all pharmaceutical drugs are safe for all patients. A prescription drug may be safe for some patients, but dangerous to others. The FDA will require a warning about the adverse side effects. This will be printed on the package insert surrounded by a black border, hence, the name, black box warning.

An FDA black box warning means that clinical studies indicate that the drug poses a significant risk of serious or even life-threatening adverse effects. All literature about the pharmaceutical must contain the warning.

Black box warnings have been receiving increased media coverage since 2004. Some examples of the publicized stories are as follows.

• In 2004, the FDA required a black box warning on the contraceptive injection, Depo-Provera. There is a risk of significant bone density loss with long-term use.
• In 2006, The FDA added a black box warning to the anticoagulant, Warfarin, because of the risk of bleeding to death.
• Also in 2006, the FDA’s Drug Safety and Risk Management Advisory committee voted to put black box warnings on methylphenidate formulations, such as Ritalin, used to treat ADHD. This is because of possible cardiovascular side effects. Later, the FDA’s Pediatric Advisory Committee effectively rejected the black box warning for both cardiovascular and psychiatric adverse effects.
• In 2007, the FDA added a black box warning to the diabetes drug, Avandia. There is a risk of heart failure or heart attack for patients with underlying heart disease.
• Also in 2007, the FDA required a black box warning on all antidepressant medications citing increased risk of suicidal tendencies in children and adolescents.
• In 2008, the FDA ordered a back box warning on certain antibiotics containing fluoroquinolone, which is linked to tendon ruptures and tendinitis. The drugs include Cipro, Levaquin, Avelox, Noroxin and Floxin.
• FDA advisors recommended that Pfizer place a black box warning on celecoxib, Celebrex. There is a risk of serious cardiovascular thrombotic events, heart attack and stroke.
• In 2009, The FDA issued a black box warning for the drug metoclopramide, Reglan. Chronic use of the medication was linked to tardive dyskinesia. Tardive dyskinesia is involuntary, repetitive movements of the extremities. These symptoms are not reversible and there is no known treatment. There is an increased use of Regaln in neonatal units. The drug was never approved for use in infants. There are serious concerns about treating premature babies with metoclopramide.
• In 2010, the FDA added a black box warning to the label of Plavix. It says that mutations to the CYP2C19 gene render certain patients unable to respond to the drug. It places them at increased risk of heart attack and/or stroke. Because Plavix is such a widely used drug, this could lead to more gene-based metabolism assays of patients’ blood.

Of all the FDA warnings, the FDA black box warning is the most serious. They are based on research and clinical trials and should be heeded. Regulatory Affairs Associates can help you deal with the FDA.

Written by: Margaret Stenerson-Reynolds

September 25, 2010