Black Box

Article Author:
Claire Delong

Article Editor:
Charles Preuss

Editors In Chief:
Jasleen Jhajj
Cliff Caudill
Evan Kaufman

Managing Editors:
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Orawan Chaigasame
Carrie Smith
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James Hughes
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Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi

2/6/2019 10:16:02 AM


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 its 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 usually 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

Medications with boxed warnings associated with them may suffer financially as these warnings can affect the marketability of the drug and generate negative news reports.

Physicians must use their clinical judgment on whether or to prescribe not 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 antibiotics: 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 complications with a medicine.[1]

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Black Box - Questions

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Which of the following is associated with a medication boxed warning?

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Black Box - References


Buckley NA,Rossi S, Bringing greater transparency to     [PubMed]
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;     [PubMed]
O'Connor NR, FDA boxed warnings: how to prescribe drugs safely. American family physician. 2010 Feb 1;     [PubMed]
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;     [PubMed]
Tanne JH, FDA adds     [PubMed]
Tanne JH, FDA places     [PubMed]
Kondro W, FDA urges     [PubMed]
Lenzer J, FDA advisers warn: COX 2 inhibitors increase risk of heart attack and stroke. BMJ (Clinical research ed.). 2005 Feb 26;     [PubMed]
Green W, The FDA, contraceptive marketing approval and products liability litigation: Depo-Provera and the risk of osteoporosis. Food and drug law journal. 2013;     [PubMed]
Mohammadi D, Black-box warnings could be removed from varenicline. The Lancet. Respiratory medicine. 2016 Nov;     [PubMed]


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