Introduction
Boxed warnings were previously known as black box warnings. They are the greatest safety-related warning drugs the Food and Drug Administration assigns. These black box warnings are done to bring to the attention of the consumer the major risks and health concerns of the particular drug. Such medications usually have a black-boxed warning mentioned, taken away, or updated throughout their market term. Currently, about 400 different medications have these black-boxed warnings.
Boxed warnings apply to a drug cohort in particular rather than one specific drug because the severe health risk is usually associated with the drug’s mechanism of action and its harmful effects on the body. Therefore, it applies to several medications within a class.
FDA black box warnings derive their name from the black border around the drug warning information. These warnings were first labeled on medications in the 1970s. While pharmaceutical drug companies are responsible for providing information on a certain drug label, only the Food and Drug Administration can create a black box warning.
What Are the Major Issues of Concern?
Drugs with boxed warnings related to them may have detrimental financial consequences as these labeled warnings might affect the drug's marketability and generate negative news among the people. Boxed warnings do not suggest absolute drug contraindications; instead, they are intended to bring the attention of the doctor and pharmacist to the potentially harmful side effects of these drugs.
In rare cases, a drug may be withdrawn from the market. This usually occurs when drug use may pose severe health hazards or even death.
What Is the FDA’s Black Box Warning Process?
Before labeling the drug with a boxed warning, sufficient evidence is required by the FDA suggesting the significant risk of the drug. Several observations and studies are conducted after the drug release in the market to collect sufficient data and evidence.
However, this suggests that newer drugs that have recently hit the market will not have these warnings in particular, and people who consume these drugs may be at a higher risk for an unknown side effect.
Once the drug is determined, the drug company is contacted by the FDA to add a warning to its drug labeling. The language is submitted by the drug company for FDA approval. Once the language is approved by FDA, it is printed on the package of the drug and the medication insert.
The FDA assigns boxed warnings to highlight health hazards in the following situations:
-
If a drug poses a serious life-threatening or fatal adverse reaction where the number of risks might outweigh the health benefits.
-
If a drug has a fatal side effect that can be minimized in severity or frequency by diligent use of the drug, such as avoiding its usage in certain situations, patient observation, careful selection of patients, or avoiding usage of the drug with certain medicines.
-
If the drug is only for restricted use for public safety. The drug is dangerous to certain populations, such as aged people, young children, or pregnant women.
What Are the Clinical Significance of Black Box Warnings?
There are several examples of medications having black box warnings.
-
Antipsychotics - These include medicines like Quetiapine, Haloperidol, Olanzapine, and Risperidone.
Warning issued by the FDA: Increased mortality in aged people who are suffering from dementia-related psychosis.
-
Atypical Antipsychotics - These include medicines such as Clozapine.
The warning issued in the context of this drug is agranulocytosis.
-
Fluoroquinolones - These include medications such as Ciprofloxacin, Moxifloxacin, and Levofloxacin.
Warning issued is increased risk of damage to the tendon causing rupture. The risk is high in aged patients and people who consume corticosteroids.
-
Selective Serotonin Reuptake Inhibitors (SSRIs)- These are commonly recommended antidepressants. These include drugs like Paroxetine, Fluoxetine, Sertraline, Fluvoxamine, etc.
Warning assigned to these drugs include a higher risk of suicidal tendencies, typically in the younger generation.
-
Antiarrhythmic Drugs- Drugs like Amiodarone.
The warning includes a higher risk of pulmonary toxicity, liver toxicity, and heart failure.
-
Antimalarials - Drugs like Mefloquine.
Warning issued to these drugs includes a higher risk of neuro psychopathic effects such as depression, anxiety, epileptic fits, imbalance, delusions, and hallucinations.
-
Monoclonal Antibody Drugs - Drugs such as Natalizumab.
The warning assigned to this medicine is progressive multifocal leukoencephalopathy (PML).
-
Progestins - Drugs like Medroxyprogesterone.
Warning issued in relation to this drug includes a reduced density of bone, primarily in premenopausal females. However, the effect is reversible if the offending drug is discontinued.
-
Fatty Acids - Drugs like Valproic acid.
The drug is associated with warnings like hepatotoxicity and pancreatitis.
-
Opioids - Drugs like Morphine, Hydrocodone, Fentanyl, etc.
Warnings issued include the increased risk of addiction, drug abuse, and misuse. Fatal respiratory depression can also occur.
-
Long-acting Beta-2 Agonists - Drugs like Formoterol and Salmeterol.
These drugs are associated with an increased risk of asthma, which can lead to death. Therefore, it should be used in association with an inhaled corticosteroid.
-
Sodium Blockers - Drugs like Carbamazepine and Lamotrigine.
The warning assigned to these drugs includes fatal, severe skin reactions like Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN).
-
Direct Thrombin Inhibitors - Drugs like Dabigatran.
Warning linked to this drug includes the formation of a blood clot that can lead to permanent paralysis of the spinal region if the drug is injected in that area, or the patient might have a spinal puncture.
-
Tetracyclines- Drugs such as Tigecycline.
These drugs are labeled by FDA under black box warnings as there is an increased risk of mortality when given intravenously for serious infections like abdominal infections.
Therefore, these black box warnings, or boxed warnings, generate awareness and warn the general public and healthcare professionals of life-threatening severe side effects, such as injury or even death.
Conclusion
To conclude, the black box warning is the FDA’s highest safety-related stringent warning for the drugs and medical devices available in the market. Healthcare clinicians, nurses, and pharmacists should therefore collaborate together to ensure that patients on drug therapy correctly take their medicines. It is also crucial to discuss any severe drug side effects which they may encounter while consuming those drugs. Knowledge of any FDA-boxed warnings should be included. A complete pharmacological drug list for the patient is crucial before prescribing medicines to prevent potentially significant drug interactions.
