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Box Warning
Definition/Introduction
Boxed warnings (formerly known as Black Box Warnings) are the highest safety-related warning that medications can have assigned by the Food and Drug Administration. These warnings are intended to bring the consumer’s attention to the major risks of the drug. Medications can have a boxed warning added, taken away, or updated throughout their tenure on the market. Over 400 different medications currently have boxed warnings.[1]
Boxed warnings typically apply to a particular drug cohort rather than one specific drug; this is because, commonly, the severe risk is associated with the mechanism of action and its undesired effects on the body, therefore applying to several medications within a class.[2]
Issues of Concern
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Issues of Concern
Medications with boxed warnings associated with them may have adverse financial consequences as these warnings can affect the marketability of the drug and generate negative news reports.
Clinicians must use their clinical judgment on whether or not to prescribe medications with these warnings to their patients care. Boxed warnings are not meant to be absolute contraindications for drugs, but instead, to bring the attention to the clinician and pharmacist on potential severe side effects.[3][4]
In rare instances, a drug may be the subject of a recall from the market. The most serious type of recall (Class I) is when the use of a medication may cause severe health detriments or even possible death.
Clinical Significance
Examples of medications with boxed warnings[5][6][7][8][9]:
- Fluoroquinolone antimicrobials: increased risk of tendinitis and/or tendon rupture
- Rosiglitazone: increased risk of heart failure or myocardial infarction if the patient has current heart disease
- Selective serotonin reuptake inhibitors (SSRIs): increased risk of suicidal thinking and behavior in pediatric patients
- Celecoxib: cardiovascular and gastrointestinal risks
- Medroxyprogesterone: decreased bone density with long term use
Examples of medications with warnings that have been updated[10]
- Varenicline: the FDA removed the warning in 2009; original reports of depression, suicidal thoughts, and actions
The Food and Drug Administration uses a program, i.e., MedWatch, that helps to track adverse events associated with medications. There is an online program accessible to clinicians and patients to enter the adverse effects of a medicine.[1]
Nursing, Allied Health, and Interprofessional Team Interventions
The healthcare team, i.e., clinicians, nurses, and pharmacists, must work together to make sure that patients on pharmacotherapy correctly take their medications, e.g., ciprofloxacin, and importantly, to discuss any serious drug side effects they encounter, e.g., tendinitis, etc. This includes knowledge of any FDA-boxed warnings. A complete medication list for the patient is necessary before prescribing medications to prevent clinically significant drug interactions, and a pharmacist can perform medication reconciliation to answer any questions or address concerns other healthcare team members may have. [Level 5]
References
Buckley NA, Rossi S. Bringing greater transparency to "black box" warnings. Clinical toxicology (Philadelphia, Pa.). 2011 Jul:49(6):448-51. doi: 10.3109/15563650.2011.593523. Epub [PubMed PMID: 21824055]
Panagiotou OA, Contopoulos-Ioannidis DG, Papanikolaou PN, Ntzani EE, Ioannidis JP. Different black box warning labeling for same-class drugs. Journal of general internal medicine. 2011 Jun:26(6):603-10. doi: 10.1007/s11606-011-1633-9. Epub 2011 Feb 1 [PubMed PMID: 21286838]
O'Connor NR. FDA boxed warnings: how to prescribe drugs safely. American family physician. 2010 Feb 1:81(3):298-303 [PubMed PMID: 20112888]
Martin CM, Borgelt L. Black box warnings: what do they mean to pharmacists and patients. The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists. 2012 Jul:27(7):482-92. doi: 10.4140/TCP.n.2012.482. Epub [PubMed PMID: 22910129]
Tanne JH. FDA adds "black box" warning label to fluoroquinolone antibiotics. BMJ (Clinical research ed.). 2008 Jul 15:337(7662):a816. doi: 10.1136/bmj.a816. Epub 2008 Jul 15 [PubMed PMID: 18632714]
Tanne JH. FDA places "black box" warning on antidiabetes drugs. BMJ (Clinical research ed.). 2007 Jun 16:334(7606):1237 [PubMed PMID: 17569906]
Kondro W. FDA urges "black box" warning on pediatric antidepressants. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2004 Oct 12:171(8):837-8 [PubMed PMID: 15477614]
Lenzer J. FDA advisers warn: COX 2 inhibitors increase risk of heart attack and stroke. BMJ (Clinical research ed.). 2005 Feb 26:330(7489):440 [PubMed PMID: 15731142]
Green W. The FDA, contraceptive marketing approval and products liability litigation: Depo-Provera and the risk of osteoporosis. Food and drug law journal. 2013:68(2):115-35, i [PubMed PMID: 24640465]
Mohammadi D. Black-box warnings could be removed from varenicline. The Lancet. Respiratory medicine. 2016 Nov:4(11):861. doi: 10.1016/S2213-2600(16)30310-1. Epub 2016 Oct 11 [PubMed PMID: 27742352]