Boxed warning
In the
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.[4] 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 (with a similar advisory but less media exposure) did not similarly decrease in use.[5]
Examples
Boxed warnings on drugs have received increased media attention in the United States since 2004. Among some of the more widely covered stories:
- In October 2004, the FDA began requiring that boxed warnings be placed on all adolescents. In May 2006, the black box warning was expanded to young adults aged 18–24 years old.[6][7]
- As of November 17, 2004[update], 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.[8]
- In April 2005, FDA advisors requested that
- 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.[11]
- As of 2006[update], natalizumab (marketed as Tysabri) received a boxed warning on its packaging due to increased risk of developing progressive multifocal leukoencephalopathy (PML). 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 (or 2.1 in every 1000 patients).[12] Tysabri is now distributed under a controlled prescription program called TOUCH (Tysabri Outreach: Unified Commitment to Health).[13]
- As of October 9, 2006[update], the FDA added a boxed warning to the anticoagulant warfarin due to the risk of bleeding to death.[14]
- In February 2006, the FDA's Drug Safety and Risk Management Advisory Committee voted to include boxed warnings on methylphenidate formulations used to treat attention deficit hyperactivity disorder, such as Ritalin (methylphenidate), due to possible cardiovascular side-effects.[15] A month later, the agency's Pediatric Advisory Committee effectively rejected recommending boxed warnings for both cardiovascular and psychiatric adverse effects.[16] (Minutes and transcripts of the relevant meetings are available on the FDA website.)[17][18]
- On November 14, 2007, the FDA added a boxed warning to the heart attack risk.[19]
- On July 8, 2008, the FDA ordered a boxed warning on certain antibiotic medications containing tendinitis. Included were the popular drugs Cipro (ciprofloxacin), Levaquin (levofloxacin), Avelox (moxifloxacin), Noroxin (norfloxacin) and Floxin (ofloxacin).[20]
- On July 1, 2009, the FDA required Chantix (varenicline) to carry a boxed warning due to public reports of side effects including depression, suicidal thoughts, and suicidal actions. As of 2016[update], the warning has been removed on the basis of updated evidence.[21]
- On October 27, 2010, the FDA issued a boxed warning regarding the use of Metacam (post-operative injection in cats.[22]
- As of May 2013[update], the FDA issued a boxed warning regarding the use of thyroid hormone stimulating agents in treatment of obesity.[23] 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 drug mefloquine, 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".[24]
In other jurisdictions
In China, a warning text (警示语) may be added to a package insert, either voluntarily by the manufacturer or at the request of
Health Canada terms its version of boxed warnings "
References
- ^ "The heading and the summary must be contained within a box and bolded." 21CFR201.57 Subpart B (a)(4)
- ^ a b "Warnings and Precautions, Contraindications, and Boxed Warning Sections of Labeling for Human Prescription Drug and Biological Products — Content and Format" (PDF). Guidance for industry. Even in the context of clinical research, human subjects are often not informed about the risks included in boxed warnings for drugs they are being given. For protocols involving drugs with boxed warnings, 63% of consent forms did not disclose 1 or more boxed warning risks. Warnings and precautions, contraindications, and boxed warning sections of labeling for human prescription drug and biological products—content and format. U.S. Food and Drug Administration. Retrieved February 21, 2010.
- ^ "Antidepressant Medications for Children and Adolescents: Information for Parents and Caregivers". National Institute of Mental Health. Archived from the original on March 1, 2010.
- PMID 21083379.
- PMID 20103549.
- PMID 31130881.
On October 2004, the FDA required a so-called black box warning for antidepressant drugs of any class. That warning became effective in January 2005. In 2006, the FDA warning extended to young adults aged up to 25 years, an announcement that followed a slew of media reports about the link between antidepressant drug use and suicide, possibly culminating in an exaggerated alarmist message.
- PMID 23351264.
- ^ "Black Box Warning Added Concerning Long-Term Use of Depo-Provera Contraceptive Injection". Food and Drug Administration. Archived from the original on August 9, 2007. Retrieved August 15, 2007.
- ^ "COX-2 Selective (includes Bextra, Celebrex, and Vioxx)". U.S. Food and Drug Administration. April 7, 2005. Retrieved January 2, 2024.
- ^ Corbett J (August 2, 2005). "Celebrex to Get 'Black Box' Label On Heart Risks". The Wall Street Journal. Retrieved January 2, 2024.
- PMID 20065205. Archived from the originalon July 27, 2011.
- PMID 22591293.
- ^ "TOUCH Program". TOUCH On-Line. Biogen Idec. Retrieved September 8, 2016.
- ^ "Black Box for Warfarin". Retrieved August 15, 2007.
- ^ "Strongest warning suggested for ADHD drugs". CNN. Associated Press. February 10, 2006. Archived from the original on August 18, 2007. Retrieved August 15, 2007.
- ^ "'Black Box' ADHD Drug Warning Rejected". CBS News. March 22, 2006. Retrieved August 15, 2007.
- ^ Pediatric Advisory Committee documentation available at: "2006 FDA Advisory Committees Meeting Documents by Center". U.S. Food and Drug Administration. February 5, 2007. Retrieved August 15, 2007.
- ^ Drug Safety and Risk Management documentation available at: "CDER 2006 Meeting Documents". U.S. Food and Drug Administration. February 1, 2007. Retrieved August 15, 2007.
- ^ "Glaxo's Avandia to carry heart-attack warning". MarketWatch. November 14, 2007. Retrieved November 14, 2007.
- ^ "FDA orders 'black box' label on some antibiotics". CNN. July 8, 2008. Retrieved July 8, 2008.
- ^ FDA. "Public Health Advisory: FDA Requires New Boxed Warnings for the Smoking Cessation Drugs Chantix and Zyban". Food and Drug Administration. Archived from the original on October 19, 2010. Retrieved July 1, 2009.
- ^ "FDA Announces Addition of Boxed Warning to METACAM® (meloxicam) Labels". October 27, 2010.
- ^ "Thyrolar (liotrix) dosing, indications, interactions, adverse effects, and more".
- ^ "FDA Drug Safety Communication: FDA approves label changes for antimalarial drug mefloquine hydrochloride due to risk of serious psychiatric and nerve side effects". July 29, 2013.
- doi:10.6039/j.issn.1001-0408.2014.33.29 (inactive January 31, 2024).)
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: CS1 maint: DOI inactive as of January 2024 (link - PMID 30166896.
- ^ "PAXLOVID". Pfizer Medical Information - Canada.
External links
- Black Box Warnings by FormWeb.