Journal of Psychosocial Nursing and Mental Health Services

Psychopharmacology 

Medication Safety: What Nurses Should Know About Black Box Warnings

Laura G. Leahy, DrNP, APRN, PMH-CNS/FNP, BC

Abstract

“Safety first” has always been a nursing priority—just as medication education has been an essential nursing function. Approximately 79 million individuals of all ages, birth-to-death, were prescribed psychotropic medications in 2013. Nurses of all disciplines and who work in all practice settings must be aware of the potential safety concerns related to medications patients may be taking. Black Box Warnings (BBWs) are the strictest labeling requirements that the U.S. Food and Drug Administration can mandate. Risks of increased suicidality, mortality in older adults, potential for abuse and drug dependence, and life-threatening hepatic failure are among the most significant BBWs attributed to psychotropic medications. As such, nurses must be aware of not only how medications will benefit patients in relieving symptoms of or preventing their disease but also the potential risks, adverse reactions, and BBWs. [Journal of Psychosocial Nursing and Mental Health Services, 55(6), 11–15.]

Abstract

“Safety first” has always been a nursing priority—just as medication education has been an essential nursing function. Approximately 79 million individuals of all ages, birth-to-death, were prescribed psychotropic medications in 2013. Nurses of all disciplines and who work in all practice settings must be aware of the potential safety concerns related to medications patients may be taking. Black Box Warnings (BBWs) are the strictest labeling requirements that the U.S. Food and Drug Administration can mandate. Risks of increased suicidality, mortality in older adults, potential for abuse and drug dependence, and life-threatening hepatic failure are among the most significant BBWs attributed to psychotropic medications. As such, nurses must be aware of not only how medications will benefit patients in relieving symptoms of or preventing their disease but also the potential risks, adverse reactions, and BBWs. [Journal of Psychosocial Nursing and Mental Health Services, 55(6), 11–15.]

Exploring psychotherapeutic issues and agents in clinical practice

“Safety first” has always been a nursing priority—just as medication education has been an essential nursing function. Whether a licensed practical nurse, RN, or advanced practice registered nurse (APRN), it is imperative to understand and advise patients about medication safety related to contraindications, drug–drug interactions, and adverse drug reactions (ADR) or side effects. Approximately 79 million individuals of all ages, birth-to-death, were prescribed psychotropic medications in 2013 (Citizens Commission on Human Rights International, 2014). Nurses of all disciplines and who work in all practice settings must be aware of the potential safety concerns related to medications patients may be taking.

Safe Prescribing with Steps

Sheldon Preskorn, MD, first introduced the STEPS pneumonic in 1994 as criteria for selecting antidepressant therapy (Table 1) (Preskorn, 1994). The STEPS criteria can be applied to prescribing any medication and should be used by physicians and APRNs when determining appropriate drug therapy for patients.


Steps Criteria for Medication Therapy Selectiona

Table 1:

Steps Criteria for Medication Therapy Selection

Prescribing practitioners must review the contraindications, potential side effects, black box warnings (BBWs), risks, and benefits with patients when determining medication therapy. If a patient is prescribed more than one medication or is taking over-the-counter medications, herbal supplements, or even vitamins, it is essential for the prescriber to review the risks and weigh the benefits prior to prescribing a medication. Safety, efficacy, tolerability, pricing, and simplicity (STEPS) must all be taken into consideration for purposes of patient adherence and, most importantly, patient safety.

Understanding the U.S. Food and Drug Administration's Warnings

The U.S. Food and Drug Administration (FDA) has a system of warnings to alert prescribers, health care professionals, and patients regarding the potential safety concerns related to every medication on the market. Although patients who entrust nurses with their care are to be informed of the potential for ADRs by the prescriber and pharmacist, many learn of potential drug side effects through television commercials, magazine advertisements, or word-of-mouth from friends and family members. Patients may present with a predetermined drug in mind to relieve their symptoms or a stance that they will not take a certain drug based on these considerations. As nurses, it is our duty to provide education and information to patients so that they can make informed decisions regarding their health care, treatments, and medication therapies.

The FDA includes warnings and precautions on all medication product labeling. This section of the prescription drug labeling insert is intended to alert prescribers to potential adverse reactions and safety hazards that may be serious or clinically significant so they can make informed decisions when prescribing the medication and managing patients' responses (FDA, 2011). The two most common warnings and precautions include ADRs and BBWs.

According to “A Guide to Drug Safety Terms at FDA” (FDA, 2012, p. 1):

An Adverse Drug Reaction (ADR), also called a side effect, is any undesirable experience associated with the use of a medicine in a patient. Adverse events can range from mild to severe. Serious adverse events are those that can cause disability, are life-threatening, result in hospitalization or death, or are birth defects.

A Boxed Warning (BBW) is also commonly referred to as a “black box warning.” It appears on a prescription drug's label and is designed to call attention to serious or life-threatening risks.

BBWs are “the strictest labeling requirements that the FDA can mandate” (O'Shea, 2016, p. 1). They are “more than a precaution [and] less than a contraindication” (Martin, 2014, p. 8). BBWs highlight three particular situations: (a) a random ADR so serious in proportion to the benefit that risk versus benefit must be weighed, (b) a serious ADR that is preventable or whose frequency or severity can be reduced given appropriate use of the drug, and (c) the FDA approved the drug with specific restrictions to ensure safe use for eligible patients (FDA, 2011). So what do these warnings and precautions mean for nurses and patients who are prescribed psychotropic medications?

Black Box Warnings and Psychotropic Medications

The prescribing clinician determining the most appropriate use of the medication in relation to the patient's symptoms, medical history, family history, and concurrent medications must weigh the risks and benefits related to the BBWs carefully. As nurses encounter patients who have been prescribed psychotropic medications in all practice settings, it is essential that they be informed about the BBWs related to such medications. In addition to potential drug–drug interactions and bothersome side effects, BBWs for psychotropic medications listed in Table 2 must be reviewed with patients prescribed such medications.


Black Box Warnings for Psychotropic Drugsa

Table 2:

Black Box Warnings for Psychotropic Drugs

Nurses are part of the system of “checks and balances” to maintain patient safety. Although the first line of education related to medications should be a discussion between the patient and prescribing practitioner, pharmacists and nurses also have an obligation to review medication safety and potential for adverse reactions/side effects with the patient. Nurses working in hospitals and primary care settings are often challenged to reconcile patients' medications. This process aids in the identification of drug–drug interactions and drugs with BBWs for serious and potentially life-threatening reactions. In addition, nurses are often the health care professionals to whom patients report side effects and adverse reactions. Being educated regarding the BBWs related to psychotropic medications may mean the difference between life and death for certain patients.

Risks of increased suicidality, mortality in older adults, potential for abuse and drug dependence, and life-threatening hepatic failure are among the most significant BBWs attributed to psychotropic medications. With these risks in mind, it is a wonder patients are willing to take these medications. Thus, partnering with patients and offering medication education is important not only for them and family members to monitor for potential adverse reactions but also for nurses to improve safety and adherence. The FDA offers up-to-date medication guides for hundreds of prescription medications (access https://www.fda.gov/Drugs/DrugSafety/ucm085729.htm).

Although the current article primarily focuses on BBWs related to psychotropic medications, some potential serious adverse reactions are also worth mentioning. Antipsychotic medications may contribute to increased risk of heat exhaustion/heat stroke and photosensitivity/sun burn. When patients are prescribed antipsychotic medications, it is important to advise them to (a) maintain a cool environment using air conditioning and fans; (b) maintain hydration by drinking cool, clear liquids such as water; and (c) apply sunscreen, even on darker skin (State of New Jersey Division of Mental Health & Addiction Services, 2015).

In addition, in December 2016, the FDA released the BBW related to neuropsychiatric symptoms and suicidality for the smoking cessation drugs varenicline (Chantix®) and bupropion (Zyban®), as the risks were found to be lower than previously suspected (FDA, 2016). These drugs still maintain a warning, but not at the highest level (i.e., BBW). Finally, the question of whether BBWs are truly a safety measure is revealed in more recent studies exploring the risk of suicidality in children, adolescents, and adults related to antidepressant medications. Friedman (2014) cited declines in depression diagnoses and prescribing of antidepressant medications for children, adolescents, and young adults since the BBW for increased risk of suicidality was issued in 2004. Friedman (2014) also reported an alarming statistically significant increase in suicide attempts and gradual increase in suicide completions since the BBW was issued for this population. These trends draw into question whether this advisory has adversely contributed to the lack of effective treatment for young individuals experiencing depression.

Conclusion

Nurses are experts in providing education to patients regarding their disease state, treatments, and medications. As such, nurses must be aware of how medications will benefit patients in relieving the symptoms of or preventing their disease and the potential risks, adverse reactions, and BBWs. As of 2014, more than 10 million Americans were prescribed medications to treat attention-deficit/hyperactivity disorder, more than 41 million were prescribed antidepressant medications, approximately 7 million were prescribed antipsychotic medications, and approximately 36.5 million were prescribed medications to treat anxiety (Citizens Commission on Human Rights International, 2014). These numbers all but ensure that every nurse will eventually work with a patient prescribed at least one psychotropic medication; therefore, it is essential that all nurses have a working knowledge of the BBWs related to psychotropic medications.

It is also important for patients and health care practitioners, including nurses of all levels of practice, to monitor for and voluntarily report any adverse events related to medication therapy. Both health care professionals and patients can report adverse events via the MedWatch Online Voluntary Reporting Form (FDA, 2017b). Reporting adverse events will provide another layer of safety for the medications available to patients and also allow the FDA to reduce warnings if the risks are lower than previously established.

References

Steps Criteria for Medication Therapy Selectiona

SafetyDrug–drug interactions
Toxicity and therapeutic index
Risk of long-term adverse drug reactions
Pharmacokinetics and pharmacodynamics
Tolerability“Nuisance” side-effect profile
Acute versus long term
EfficacyOverall rate and maintenance of response
Unique spectrum of activity
Short-term versus long-term use/safety
Improvement in quality of life
PricingCost effectiveness
Cost of drug monitoring, if any
Affordability (insurance coverage, insurance tier, out-of-pocket costs)
SimplicityEase of use (route of administration, titration, monitoring)
Frequency of dosing
Drug delivery system

Black Box Warnings for Psychotropic Drugsa

WarningPsychotropic Drug
Increased risk of suicidality (suicidal thinking and behavior) in children, adolescents, and young adults with major depressive disorderSelective serotonin reuptake inhibitor antidepressant medications

citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vilasidone

Tri- and heterocyclic antidepressant medications

amitriptyline, desipramine, clomipramine, doxepin, trazodone, imipramine, nortriptyline

Monoamine oxidase inhibitor antidepressant medications

tranylcypromine, selegiline, phenelzine, isocarboxazid

Other antidepressant medications

bupropion Hcl, bupropion hydrobromide, duloxetine, venlafaxine, desvenlafaxine, mirtazapine, nefazodone, atomoxetine

Atypical antipsychotic medications

aripiprazole, quetiapine, olanzapine/fluoxetine, lurasidone, brexpiprazole

Increased risk of mortality in older adults with dementia-related psychosisAll typical (1st generation) antipsychotic medications

haloperidol, chlorpromazine, fluphenazine, loxapine, thioridazine, thiothixene, pimozide, perphenazine, trifluoperazine

All atypical (2nd and 3rd generation) antipsychotic medications

aripiprazole, clozapine, iloperidone, ziprasidone, paliperidone, lurasidone, olanzapine, risperidone, asenapine, quetiapine, brexpiprazole, pimavanserin, cariprazine

High potential for abuse and drug dependenceAll formulations of psychostimulant medications

dextroamphetamine/amphetamine, methylphenidate, dextroamphetamine, dexmethylphenidate, lisdexamfetamine, amphetamine, methamphetamine

Risk from concomitant opioid drug useAll benzodiazepine medications

lorazepam, clonazepam, diazepam, oxazepam, alprazolam, triazolam, estazolam, temazepam, chlordiazepoxide, flurazepam, clobazam, clorazepate

Life-threatening hepatic failure/potential for severe liver injury

nefazodone and valproic acid/valproate

atomoxetine, duloxetine, and pemoline (bolded, not Black Box Warning)

Serious dermatological reaction including toxic epidermal necrolysis and Stevens-Johnson syndrome

carbamazepine and lamotrigine

Aplastic anemia and agranulocytosis

carbamazepine and clozapine

Orthostatic hypotension, bradycardia, syncope, severe neutropenia, myocarditis, cardiomyopathy, mitral valve incompetence, and seizures

clozapine

Teratogenicity/fetal risk, pancreatitis

valproic acid/valproate

Neuropsychiatric symptoms and suicidality

bupropion and varenicline (reduced from Black Box Warning to warning [U.S. Food and Drug Administration, 2016])

Authors

Dr. Leahy is Family Psychiatric Advanced Practice Nurse and Master Clinician in Psychopharmacology, APNSolutions, LLC, Sewell, New Jersey.

The author has disclosed no potential conflicts of interest, financial or otherwise.

Address correspondence to Laura G. Leahy, DrNP, APRN, PMH-CNS/FNP, BC, Family Psychiatric Advanced Practice Nurse and Master Clinician in Psychopharmacology, APNSolutions, LLC, 123 Egg Harbor Road, Suite 703, Sewell, NJ 08080; e-mail: lgleahy@apnsolutions.com.

10.3928/02793695-20170519-01

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