Melissa Sammy, MDLinx, November 03 2019
In 2018, the FDA approved a record-breaking 59 emerging drugs for a miscellaneously diseases, bringing hope to scores of health sufferers around the globe. This range was more than twice enhanced from a previous decade, where 24 new drug were approved. Researchers have demonstrated that nearly one-third of all FDA-approved emerging therapeutics require new boxed warnings after hitting the market.
Researchers have shown a link between the increase in the number of novel therapeutic approvals and a rise in the incidence of black box warning labels – the FDA’s most strict safety labelling rules for prescription drugs, designed to inform prescribers and patients of the serious health risks correlated with a drug’s use. With more than 600 medications carrying boxed warnings and more than 40% of patients in the ambulatory care setting receiving at least one medication with a black box warning, it’s essential for healthcare providers to be conscious about commonly prescribed drugs that sustain these severe side effect warnings. Here, below is a compiled list of 10 black box warnings that every physician should know about when counselling patients on drug safety and treatment.
Aripiprazole (Abilify): This atypical antipsychotic is reported for the treatment of multiple mental health and mood disorders, including schizophrenia, depression, and bipolar disorder. However, aripiprazole enhances the risk of suicidal thoughts and behaviors in pediatric patients and young adults taking antidepressants, and raises the risk of death in elderly patients with dementia-related psychosis. Importantly, aripiprazole is not reported for the therapy of dementia-related psychosis, while has a past record of off-label use for the therapy of dementia. Additionally, even if not incorporated in the boxed warning, in May 2016 the FDA warned that the drug could induce impulse-control problems, such as binge eating and compulsive gambling. Over 2,700 patients who faced these intense compulsive behaviors have recorded lawsuits.
Dabigatran etexilate mesylate (Pradaxa): This generally prescribed anticoagulant is reported for the prevention of strokes in patients with atrial fibrillation, deep vein thrombosis, and pulmonary embolism. While during use, dabigatran has been proven to enhance the risk of serious bleeding, the drug’s boxed warning demonstrates that premature discontinuation may enhance the thrombotic events risk, which includes stroke or myocardial infarction (MI), due to blood clots.
Canagliflozin (Invokana): Canagliflozin, a third-line medication to metformin, is indicated to treat type 2 diabetes in addition with diet and exercise, and lower the risk of major adverse cardiovascular (CV) events in type 2 diabetes adults. However, a current boxed warning has indicated that patients with type 2 diabetes who have established CV disease (CVD) or are at risk for CVD may be at high risk for lower limb amputation, particularly the toe, midfoot, and leg. Until now, more than 1,000 lawsuits have been recorded.
Febuxostat (Uloric): Prescribed for the chronic management of hyperuricemia in adults with gout, Febuxostat has been given a black box warning in February 2019, warning prescribers and patients of the higher rate of CV mortality correlated with the drug’s use compared with allopurinol, its most common opponent.
Dextroamphetamine-amphetamine (Adderall): This CNS stimulant is commonly utilized for the therapy of Attention deficit hyperactivity disorder (ADHD). However, researchers have reported that it is commonly used for its effects on improved concentration/focus, recreationally by college students and other young adults, and also have showed a correlation of the drug’s use with obsessive behavior. Furthermore to the known side effects of sleep disruption and enhanced risk for mental health problems which includes depression, bipolar disorder, and aggressive or hostile behaviour – there are also CV risks such as high blood pressure and stroke, as well as the possibility for drug abuse and dependence, which have authorized a black box warning.
Alprazolam (Xanax): This sedative used initially for the therapy of anxiety disorders, is prohibited in patients with glaucoma, and should never be utilized in patients with a past record of drug abuse owing to its addictive possibility. Alprazolam’s boxed warning suggests that simultaneous use with opioids, alcohol, or other CNS depressants may induce major sedation, respiratory disorders, coma, and even mortality.
Hydrocodone and acetaminophen (Vicodin). This schedule II drug is used for the treatment of moderate to severe pain, largely after surgery. It earned a black box warning due to its highly addictive potential, as well as the increased risk of respiratory depression and significantly increased risk of liver damage/failure associated with its use.
Sertraline hydrochloride (Zoloft): Prescribed for the therapy of major depressive disorder, Obsessive-compulsive disorder (OCD), Post-traumatic stress disorder (PTSD), panic disorder, and social anxiety disorder, this selective serotonin reuptake inhibitor antidepressant has been given a black box warning owing to the higher risk of suicide correlated with its use in various demographics, including children, adolescents, and young adults.
Ticagrelor (Brilinta): This antiplatelet medication has been given FDA approval in 2011, and is indicated to lower the risk of CV death, MI, and stroke in patients with acute coronary syndrome or a history of MI. However, it protected its black box warning for inducing significant and sometimes fatal bleeding. Ticagrelor should not be indicated for patients with active pathological bleeding or a history of intracranial hemorrhage, and should not be initiated in patients experiencing urgent coronary artery bypass graft surgery. Also included in the black box warning – Ticagrelor enhance the risk of sequential CV events upon premature termination; thus, managing bleeding events without treatment discontinuation is recommeded. Ticagrelor’s labelling also warns that maintenance doses of aspirin greater than 100 mg can lower the potency of ticagrelor and should thus be eliminated.
Tigecycline (Tygacil). An injectable antibiotic, tigecycline is prescribed for the therapy of complicated skin structure infections, complicated intra-abdominal infections, and community-acquired bacterial pneumonia in patients aged 18 years and older. Although, the tetracycline class antibacterial carries a black box warning for rising all-cause mortality compared with comparators. Therefore, it should only be utilized for infections that cannot be treated with any other medications.
This evidence encourages to warn the FDA of side effects that may not be included in a drug’s package insert, important safety information, or medication guide, and can lead to the inclusion of new boxed warnings.
Source: Aripiprazole – https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-new-impulse-control-problems-associated-mental-health ;Dabigatran etexilate mesylate (Pradaxa) – https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-safety-review-post-market-reports-serious-bleeding-events ; Canagliflozin (Invokana) – https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-confirms-increased-risk-leg-and-foot-amputations-diabetes-medicine; Febuxostat (Uloric) – https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-increased-risk-death-gout-medicine-uloric-febuxostat ; Dextroamphetamine-amphetamine (Adderall) – https://www.ncbi.nlm.nih.gov/books/NBK507808/ ; Alprazolam (Xanax) – https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-serious-risks-and-death-when-combining-opioid-pain-or ; Hydrocodone and acetaminophen (Vicodin) – https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-prescription-acetaminophen-products-be-limited-325-mg-dosage-unit ; Sertraline hydrochloride (Zoloft) – https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/suicidality-children-and-adolescents-being-treated-antidepressant-medications; Ticagrelor (Brilinta) – https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf ; Tigecycline (Tygacil) – https://www.medsafe.govt.nz/Profs/Datasheet/t/Tygacilinj.pdf
