In the United States, a boxed warning is a type of warning that appears on the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administration specifies that it is formatted with a 'box' or border around the text. The FDA can require a pharmaceutical company to place a boxed warning on the labeling of a prescription drug, or in literature describing it. It is the strongest warning that the FDA requires, and signifies that medical studies indicate that the drug carries a significant risk of serious or even life-threatening adverse effects. Economists and physicians have thoroughly studied the effects of FDA boxed warnings on prescription patterns. It is not necessarily true that a physician and patient will have a conversation about a drug's boxed warning after it is issued. For instance, an FDA-mandated boxed warning decreased rosiglitazone use by 70%, but that still meant 3.8 million people were given the drug. Later research indicated that after receiving an FDA advisory, there was a decrease in rosiglitazone use, due to a combined effect of media exposure, advisory, and scientific publications, whereas pioglitazone did not similarly decrease in use. In 2005, the FDA issued a boxed warning regarding the risk of atypical antipsychotics being prescribed among elderly patients with dementia. This advisory was associated with a decrease in use of antipsychotics, especially in elderly patients with dementia.
Examples
Boxed warnings on drugs have received increased media attention in the United States since 2004. Among some of the more widely covered stories:
The FDA has required that boxed warnings be placed on all antidepressant medications warning they may result in increased risk of suicidal tendencies in children, adolescents, and aged 18–24 years old.
FDA advisors have recommended that Pfizer be required to place a boxed warning on their non-steroidal anti-inflammatory drug Celebrex for cardiovascular and gastrointestinal risks.
, the FDA has required a boxed warning on the Depo-Provera contraceptive injection, due to the risk of significant loss of bone density with long-term use.
, natalizumab received a boxed warning on its packaging due to increased risk of developing progressive multifocal leukoencephalopathy. Tysabri was pulled from the market in 2004, shortly after its introduction, after three cases of the rare disease were linked to its use. PML has affected approximately 212 Natalizumab recipients in 2012. Tysabri is now distributed under a controlled prescription program called TOUCH.
On July 8, 2008, the FDA ordered a boxed warning on certain antibiotic medications containing fluoroquinolone, which has been linked to tendon ruptures and tendinitis. Included were the popular drugs Cipro, Levaquin, Avelox, Noroxin and Floxin.
, the FDA requires Chantix to carry a boxed warning due to public reports of side effects including depression, suicidal thoughts, and suicidal actions, the warning as of 2016 has now been removed due to updated evidence.
On October 27, 2010, the FDA issued a boxed warning regarding the use of Metacam oral suspension in cats in the United States. Meloxicam is a non-steroidal anti-inflammatory drug that is approved in the U.S. for a single post-operative injection in cats.
, the FDA issued a boxed warning regarding the use of thyroid hormone stimulating agents in treatment of obesity. Data does not indicate any benefits to using these agents for weight loss. Data does indicate an increased risk of life-threatening cardiovascular events when high levels of these agents are used in hypothyroid populations. Euthyroid populations demonstrate increased CV risk at clinical doses. Hypothyroid agents should not be used in combination with sympathomimetic agents including: stimulants, and diet pills, due to increased CV risks.
In July 2013, the FDA issued a boxed warning for the antimalarial drugmefloquine, noting the drug's adverse neuropsychiatric side effects, and emphasizing neurological effects from the drug could "occur at any time during drug use, and can last for months to years after the drug is stopped or can be permanent".
