Black box warning

In the United States, a black box warning (also sometimes called a black label warning or boxed warning^[1]) is a type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects. It is so named for the black border that usually surrounds the text of the warning.

A black box warning means that medical studies indicate that the drug carries a significant risk of serious or even life-threatening adverse effects. The U.S. Food and Drug Administration (FDA) can require a pharmaceutical company to place a black box warning on the labeling of a prescription drug, or in literature describing it. It is the strongest warning that the FDA requires.^[2]

Economists and physicians have thoroughly studied the effects of FDA black box warnings on prescription patterns. It is not necessarily true that a physician and patient will have a conversation about a drug's black box warning after it is issued.^[3] For instance, FDA black box warning decreased rosiglitazone use by 70% but that still means 3.8 million people were given the drug. Later research indicates 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 (with a similar advisory) did not similarly decrease in use.^[4] This challenges the idea that physicians and patients will have a conversation after a black box is issued. Throughout the country, black box warnings will be translated into prescription patterns differently by different physicians.

In 2005, the FDA issued a black box warning regarding the risk of atypical antipsychotics being prescribed among elderly patients with dementia. This advisory is associated with a decrease in use of antipsychotics, especially in elderly patients with dementia.^[5]

Examples

Black box 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 black box warnings be placed on all antidepressant medications warning they may result in increased risk of suicidal tendencies in children and adolescents.
FDA advisors have recommended that Pfizer be required to place a black box warning on their non-steroidal anti-inflammatory drug Celebrex (celecoxib) for cardiovascular and gastrointestinal risks.
As of 17 November 2004, the FDA has required a black box warning on the Depo-Provera contraceptive injection, due to the risk of significant loss of bone density with long-term use.^[6]
As of October 9, 2006, the FDA added a black box warning to the anticoagulant warfarin due to the risk of bleeding to death.^[7]
In February 2006, the FDA's Drug Safety and Risk Management Advisory Committee voted to include black box warnings on methylphenidate formulations used to treat attention deficit hyperactivity disorder, such as Ritalin (methylphenidate), due to possible cardiovascular side-effects.^[8] A month later, the agency's Pediatric Advisory Committee effectively rejected recommending boxed warnings for both cardiovascular and psychiatric adverse effects.^[9] Minutes and transcripts of the relevant meetings are available on the FDA website.^[10]^[11]
On November 14, 2007, the FDA added a black box warning to the diabetes medication Avandia (rosiglitazone), citing the risk of heart failure or heart attack to patients with underlying heart disease, or are at a high heart attack risk.^[12]
On July 8, 2008, the FDA ordered a black box warning on certain antibiotic medications containing fluoroquinolone, which has been linked to tendon ruptures and tendinitis. Included were the popular drugs Cipro (ciprofloxacin), Levaquin (levofloxacin), Avelox (moxifloxacin), Noroxin (norfloxacin) and Floxin (ofloxacin).^[13]
As of July 1, 2009, the FDA requires Chantix (varenicline) to carry a black box warning due to public reports of side effects including depression, suicidal thoughts, and suicidal actions.^[14]
On October 27, 2010, the FDA issued a black box warning regarding the use of Metacam (meloxicam) 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.^[15]

References

^ U.S. Food and Drug Administration. "Guidance for industry. Warnings and precautions, contraindications, and boxed warning sections of labeling for human prescription drug and biological products—content and format". http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm075096.pdf. Retrieved 2010-02-21.
^ National Institute of Mental Health, Antidepressant Medications for Children and Adolescents: Information for Parents and Caregivers."
^ Shah ND, Montori VM, Krumholz HM, Tu K, Alexander GC, Jackevicius CA. Geographic Variation in the Response to FDA Boxed Warnings for Rosiglitazone. N Engl J Med. 2010;22:2081-2084. [1]
^ Cohen A, Rabbani A, Shah N, Alexander GC. Changes in glitazone use among office-based physicians in the United States, 2003-2009. Diabetes care. 2010;33:823-825. [2]
^ Dorsey R, Rabbani A, Gallagher SA, Conti R, Alexander GC. The impact of black box warnings on the use of atypical antipsychotic medicines. Archives of Internal Medicine. 2010;170:96-103. [3]
^ "Black Box Warning Added Concerning Long-Term Use of Depo-Provera Contraceptive Injection". Archived from the original on 2007-08-09. http://web.archive.org/web/20070809090332/http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01325.html. Retrieved 2007-08-15.
^ "Black Box for Warfarin". http://www.medscape.com/viewarticle/545727. Retrieved 2007-08-15.
^ Associated Press (February 10, 2006). "Strongest warning suggested for ADHD drugs". CNN. http://www.cnn.com/2006/HEALTH/02/09/attention.deficit.ap. Retrieved 2007-08-15.
^ "'Black Box' ADHD Drug Warning Rejected". CBS News. March 22, 2006. http://www.cbsnews.com/stories/2006/03/22/health/main1429683.shtml. Retrieved 2007-08-15.
^ Pediatric Advisory Committee documentation available at: "2006 FDA Advisory Committees Meeting Documents by Center". U.S. Food and Drug Administration. February 5, 2007. http://www.fda.gov/ohrms/dockets/ac/oc06.htm. Retrieved 2007-08-15.
^ Drug Safety and Risk Management documentation available at: "CDER 2006 Meeting Documents". U.S. Food and Drug Administration. February 1, 2007. http://www.fda.gov/ohrms/dockets/ac/cder06.html#DrugSafetyRiskMgmt. Retrieved 2007-08-15.
^ "Glaxo's Avandia to carry heart-attack warning". MarketWatch. November 14, 2007. http://www.marketwatch.com/news/story/glaxos-avandia-carry-heart-attack/story.aspx?guid=%7B8819DDE2-9FD7-484E-A829-E73118A3E302%7D. Retrieved 2007-11-14.
^ "FDA orders 'black box' label on some antibiotics". CNN. 2008-07-08. http://www.cnn.com/2008/HEALTH/07/08/antibiotics.risk/index.html. Retrieved 2008-07-08.
^ FDA. "Public Health Advisory: FDA Requires New Boxed Warnings for the Smoking Cessation Drugs Chantix and Zyban". http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm169988.htm. Retrieved 2009-07-01.
^ "FDA Announces Addition of Boxed Warning to METACAM® (meloxicam) Labels". October 27, 2010. http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm231254.htm.

External links

Black Box Warnings by FormWeb.