NAPLEX Question of the Week: Black Box Warnings

Black box warnings are one of the most stringent warnings issued by the FDA. Knowledge of these are critical when assessing and monitoring prescription medication therapy.

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Which of the following medications are appropriately matched with their correct Black Box Warning? Select all that apply.

A. Latuda- increased risk of mortality in elderly patients with dementia-related psychosis 

B. Tygacil- increased all cause mortality 

C. Uloric- increased risk of cardiovascular death

D. Zyloprim- increased risk of serious skin rashes 

E. Tegretol- aplastic anemia and agranulocytosis


The correct answers are A, B, C, and E


Black Box Warnings (BBWs) are important information to know for pharmacists who practice in all different types of settings. BBWs bring attention to serious and potentially fatal side effects of drugs that are commonly used both in the hospital and in the community. 

Latuda, or lurasidone, is an atypical antipsychotic commonly used in the treatment of bipolar disorder, major depressive disorder, and schizophrenia. Although lurasidone has an off-label indication for treating psychosis/agitation associated with dementia, there is a BBW for increased mortality when used in this patient population for dementia related psychosis, making Answer A correct. It is important to note that this is a class-wide BBW that can be found on all of the atypical antipsychotics such as aripiprazole, clozapine, ziprasidone, risperidone, quetiapine, and olanzapine. Lurasidone also has a BBW for increased risk of suicidal thoughts in patients taking the medication. 

Tygacil, or tigecycline, is a broad-spectrum IV antibiotic that can be used in the treatment of community-acquired pneumonia, complicated intra-abdominal infections, and complicated skin/skin structure infections. A meta-analysis of phase 3 and phase 4 clinical trials showed an increase in all-cause mortality in patients treated with tigecycline versus the comparator, making Answer B correct. Because of this BBW, tigecycline should be reserved for patients with no other alternative treatment options.  

Uloric, or febuxostat, is a xanthine oxidase inhibitor used to lower serum uric acid levels to prevent gout flares. Patients with established cardiovascular (CV) disease treated with febuxostat had higher rates of CV death compared to patients treated with allopurinol. This led to listing a BBW for cardiovascular death in the drug monograph of febuxostat, making Answer C correct. Because of the increased risk of CV disease when compared to another treatment option, febuxostat is only recommended in patients who have shown an inadequate response, are intolerant, or not a candidate for allopurinol treatment. 

Zyloprim, or allopurinol, is another xanthine oxidase inhibitor used to prevent gout flares. As discussed above, allopurinol is the preferred treatment regimen for patients with gout because of the BBW associated with febuxostat. Before prescribing allopurinol, prescribers should consider testing patients for the HLA-B*5801 allele for those at higher risk for developing severe cutaneous reactions (SCAR). Patients at high risk include Korean patients with Stage 3 or 4 CKD, and all patients of Han Chinese or Thai descent. Although SCAR is a concern for patients taking allopurinol, there is currently no BBW associated with this medication, making Answer D incorrect. Bonus: Allopurinol due to its uric acid lowering abilities is also used in the management of tumor lysis syndrome.

Lastly, Tegretol, or carbamazepine, is an antiepileptic drug commonly associated with severe rashes and the possibility of causing Stevens-Johnson syndrome (SJS). While there is a BBW for serious dermatologic reactions in patients with the HLA-B*1502 allele, there is also a BBW associated with carbamazepine for aplastic anemia and agranulocytosis, making Answer E correct. 

Black Box Warnings can be found in the package insert, or drug monograph, for each specific drug in question. 

Have a great week!

Dr. B

Christopher M. Bland

Clinical Professor, University of Georgia College of Pharmacy

Dr. Christopher M. Bland is a Clinical Professor at the University of Georgia College of Pharmacy at the Southeast GA campus in Savannah, GA. Dr. Bland has over 20 years of academic and clinical experience in a number of clinical areas. He is a Fellow of both the Infectious Diseases Society of America as well as the American College of Clinical Pharmacy. He is co-founder of the Southeastern Research Group Endeavor, SERGE-45, with over 80 practitioners across 14 states involved. Dr. Bland serves as Associate Editor for the NAPLEX Review Guide 4th edition as well as Editor-In-Chief for the Question of the Week. He has provided live, interactive reviews for more than 10 Colleges/Schools of Pharmacy over the course of his career.