Cardiotoxic safety communications after FDA approval of novel cancer therapies.

e18629 Background: Proliferation of novel anticancer therapies has dramatically improved survival. However, in practice, cardiovascular disease (CVD) events have become an increasing concern. Post-market safety communications by the US Food and Drug Administration (FDA) are a primary source of new safety information for patients and providers. Yet, the prevalence and factors associated with the issuance of CVD warnings among cancer therapies are unknown. Methods: Leveraging the Drugs@FDA database and publicly available FDA drug reviews, we identified all anticancer drugs given new-drug applications from 1998-2018. Characteristics related to approval, including drug class, therapeutic area, priority review status, accelerated approval status, orphan product status, regulatory review times, near-regulatory deadline approval status, and post-market safety events were evaluated. Post-market safety communications were defined as the composite of safety-related drug withdrawals and the issuance of black box label warnings or precautions. CVD was defined as heart failure, hypertension (HTN), coronary disease, myocardial infarction, stroke, thromboembolic disease, arrhythmia/electrocardiographic change, or sudden cardiac death. Multivariable logistic regression was used to assess for characteristics associated with the need for CVD safety communications. Results: Overall, there were 125 novel anticancer therapies, including 24 biologics, 10 immunotherapies, and 48 targeted drugs. There were 177 safety communications (41 black box warnings, 7 withdrawals, 4 dose adjustments, and 84 general warnings). Cardiac safety warnings were issued for 63 (51.2%) of therapies, including 23 (36.5% of all) black box warnings. CVD was the most common reason for a black box warning; Table. Among all CVD warnings, arrhythmias (21.6%) followed by heart failure (13.9%), thromboembolic disease (13.9%), uncontrolled HTN (11.8%), sudden CVD death (9.0%), ischemic disease (6.9%), stroke (4.9%), and other CVD events (12.5%) were found. In a multivariable model, only therapeutic class and prior in-class cardiotoxicity were associated with the issuance of CVD safety communications. Conclusions: Among novel cancer therapies, cardiac safety communications are prevalent.[Table: see text]

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The Influence of FDA Advisory Information and Black Box Warnings on Consumer Use of Prescription Antidepressants

SSRN Electronic Journal ◽

10.2139/ssrn.1292082 ◽

2008 ◽

Cited By ~ 3

Author(s):

Kristy Parkinson ◽

Joseph Price ◽

Kosali Ilayperuma Simon ◽

Sharon L. Tennyson

Keyword(s):

Black Box ◽

Black Box Warnings

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Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies

Acta Haematologica ◽

10.1159/000500229 ◽

2019 ◽

Vol 143 (1) ◽

pp. 73-77

Author(s):

Anat Gafter-Gvili ◽

Ariadna Tibau ◽

Pia Raanani ◽

Daniel Shepshelovich

Keyword(s):

Hematological Malignancies ◽

New Drugs ◽

Priority Review ◽

Regulatory Review ◽

Regulatory Pathways ◽

The Us ◽

Black Box Warnings ◽

Accelerated Approval ◽

Drug Approvals ◽

Approved Drugs

The prevalence of safety-related postmarketing label modifications of medications for hematological malignancies is unknown. We identified 35 new drugs indicated for hematological malignancies approved by the US Food and Drug Administration between January 1999 and December 2014. Characteristics of supporting trials and safety-related label modifications from approval to December 2017 were collected from drug labels. Regulatory review and approval pathways were also collected. New drug approvals were supported by trials with a median of 167 patients (interquartile range 115–316). All drugs were approved based on surrogate endpoints. Twenty-seven drug approvals (77%) were not supported by randomized controlled trials. All drugs received orphan drug designation, and most were granted fast track designation, priority review, and accelerated approval (83, 74, and 60%, respectively). A total of 28 drugs (80%) had postmarketing safety-related label modifications. Additions to black box warnings, contraindications, warnings and precautions, and common adverse reactions were identified in 31, 11, 77, and 46% of drugs, respectively. Five drugs (14%) were permanently or temporarily withdrawn from the US market. Drugs for hematological malignancies are often approved based on limited evidence through expedited regulatory pathways with incomplete safety profiles. Hematologists should be vigilant for unrecognized side effects when prescribing newly approved drugs.

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Cardiovascular, Dermatological, Gastrointestinal, Hematological, Hormonal, and Immunosuppressant Agents

Hospital Pharmacy ◽

10.1177/001857870203701001 ◽

2002 ◽

Vol 37 (10) ◽

pp. 1113-1126 ◽

Cited By ~ 1

Author(s):

Joyce A. Generali

Keyword(s):

At Risk ◽

Adverse Events ◽

Drug Interactions ◽

Prescription Drugs ◽

Hospital Pharmacy ◽

Safety Data ◽

Black Box ◽

Information Monitoring ◽

Black Box Warnings ◽

Wall Chart

“Black-box” warnings report valuable postmarketing safety data about prescription drugs, keeping practitioners informed about potential adverse events, drug interactions, key dosing information, monitoring and administration requirements, and at-risk patient populations. They are especially crucial for newly approved agents. A list of agents with black-box warnings does not currently exist; however Hospital Pharmacy will be publishing comprehensive lists by drug category in this column until November 2002. At that time, a complete list in wall chart form will be released. Hospital Pharmacy will update the data as salient information becomes available.

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Effect of the FDA Black Box Suicidality Warnings for Antidepressants on Suicide Rates in the USA

Crisis ◽

10.1027/0227-5910/a000843 ◽

2021 ◽

Author(s):

Martin Plöderl ◽

Michael Pascal Hengartner

Keyword(s):

Young Adults ◽

Young Adult ◽

Detrimental Effect ◽

Black Box ◽

Adolescent And Young Adult ◽

Ecological Data ◽

Suicide Rates ◽

Black Box Warnings ◽

The Usa ◽

Random Fluctuations

Abstract. Background: Some authors claimed that the US Food and Drug Administration (FDA) black box warning on treatment-emergent suicidality with antidepressants in adolescents (issued 2004) and young adults (issued 2006) led to an increase of suicides, based on the analyses of ecological data with debatable assumptions about putative changes in suicide rates. Aims: To explore if putative changes in suicide rates in adolescents and young adults at the time of the FDA warnings is a detectable signal in the data or compatible with random fluctuations. Method: We applied different changepoint analyses for adolescent and young adult suicide rates from 1981 to 2019 in the USA. Results: Changepoint analysis did not support a detrimental effect of the FDA black box warnings. The downward trend of suicides reversed several years after the warning in adolescents (2007–2009) and many years before in young adults (1999–2001). Limitations: Our analyses cannot rule out detrimental effects of the FDA warnings. However, even if there was such an effect, it was likely small and indistinguishable from random fluctuations in the available suicide data. Conclusion: There is no detectable change of trend in adolescent or young adult suicide rates in line with a detrimental effect of the FDA black box warnings on treatment-emergent suicidality.

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Treatments for Substance Use Disorders

Psychopharmacology ◽

10.1093/med/9780197537046.003.0007 ◽

2020 ◽

pp. 267-324

Author(s):

Arash Ansari ◽

David N. Osser

Keyword(s):

Substance Use ◽

Substance Use Disorders ◽

Clinical Characteristics ◽

Black Box ◽

Brand Names ◽

Opioid Use ◽

Childbearing Age ◽

Black Box Warnings ◽

Amphetamine Use ◽

Opioid Use Disorders

The chapter on treatments for substance use disorders discusses and reviews the use of medication-assisted treatments with (a) methadone, buprenorphine/naloxone, and naltrexone for opioid use disorders; (b) disulfiram, acamprosate, naltrexone, and several off-label medications for alcohol use disorders; and (c) nicotine replacement therapies, bupropion, and varenicline for tobacco use disorders. The chapter reviews the mechanisms of action, clinical characteristics, potential medication interactions, and adverse effects of these medications, followed by an in-depth discussion of their clinical use in these disorders. The chapter also briefly reviews several non-Food and Drug Administration (FDA)-approved medicines studied for cocaine, cannabis, and amphetamine use disorders. It also briefly discusses complementary and alternative pharmacotherapies, such as the use of cannabinoids. It also discusses the use of these medicines in women of childbearing age, notably for pregnancy and breastfeeding considerations. Finally, the chapter includes a table of approved substance use disorder medicines that includes each medicine’s generic and brand names, usual adult doses, pertinent clinical comments, black box warnings, and FDA indications.

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Stimulants and Other ADHD Medicines

Psychopharmacology ◽

10.1093/med/9780197537046.003.0006 ◽

2020 ◽

pp. 231-266

Author(s):

Arash Ansari ◽

David N. Osser

Keyword(s):

Eating Disorder ◽

Clinical Characteristics ◽

Mechanisms Of Action ◽

Black Box ◽

Brand Names ◽

Clinical Use ◽

Childbearing Age ◽

Hyperactivity Disorder ◽

Medical Disorders ◽

Black Box Warnings

The chapter on adult attention-deficit/hyperactivity disorder (ADHD) medicines discusses and reviews the use of psychostimulants (such as methylphenidate and amphetamines), and nonstimulants (such as atomoxetine, guanfacine, and clonidine). It reviews their mechanisms of action, clinical characteristics, potential medication interactions, and adverse effects. It further reviews stimulants’ risk of misuse and dependence. The chapter also briefly discusses complementary and alternative pharmacotherapies. It includes an in-depth review of the clinical use of these medications for ADHD (particularly in college students) and for other psychiatric disorders (such as binge-eating disorder) and other medical disorders. It also discusses the use of ADHD medicines in women of childbearing age, notably for pregnancy and breastfeeding considerations. Finally, the chapter includes a table of ADHD medicines that includes each medicine’s generic and brand names, usual adult doses, pertinent clinical comments, black box warnings, and Food and Drug Administration indications.

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Mood Stabilizers

Psychopharmacology ◽

10.1093/med/9780197537046.003.0005 ◽

2020 ◽

pp. 185-230

Author(s):

Arash Ansari ◽

David N. Osser

Keyword(s):

Clinical Characteristics ◽

Bipolar Depression ◽

Black Box ◽

Brand Names ◽

Mood Stabilizers ◽

Clinical Use ◽

Omega 3 ◽

Childbearing Age ◽

Second Generation Antipsychotics ◽

Black Box Warnings

The chapter on mood stabilizers discusses and reviews the use of available treatments for bipolar disorder, including lithium, selected anticonvulsants (such as valproate, carbamazepine, oxcarbazepine, and lamotrigine) and second-generation antipsychotics. It reviews each medication’s mechanism of action, clinical characteristics, potential medication interactions, and adverse effects. The chapter also reviews emerging pharmacotherapies such as the use of ketamine. It also briefly discusses complementary and alternative pharmacotherapies and the use of omega-3 fatty acids. The chapter includes an in-depth review of the clinical use of the previously listed medications for bipolar depression, mania, mixed episodes, and bipolar maintenance. It also reviews the risks of using antidepressants for bipolar depression. It also discusses the use of mood stabilizers in women of childbearing age, notably for pregnancy and breastfeeding considerations. Finally, the chapter includes a table of mood stabilizers that includes each medication’s generic and brand names, usual adult doses, pertinent clinical comments, black box warnings and Food and Drug Administration indications.

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Antipsychotics

Psychopharmacology ◽

10.1093/med/9780197537046.003.0004 ◽

2020 ◽

pp. 121-184

Author(s):

Arash Ansari ◽

David N. Osser

Keyword(s):

Clinical Characteristics ◽

First Generation ◽

Black Box ◽

Brand Names ◽

Clinical Use ◽

Childbearing Age ◽

Medical Disorders ◽

Second Generation Antipsychotics ◽

Black Box Warnings ◽

Potential Risks

The chapter on antipsychotics discusses and reviews the use of first-generation antipsychotics, including haloperidol and chlorpromazine, as well as the use of second-generation antipsychotics, including risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, clozapine, paliperidone, iloperidone, asenapine, lurasidone, brexpiprazole, and cariprazine. Pimavanserin is also discussed. The chapter reviews each medication’s mechanism of action, clinical characteristics, potential medication interactions, and potential risks including neuroleptic side effects such as acute dystonias, parkinsonian symptoms, akathisia, and tardive dyskinesia. Metabolic syndrome (which includes risks of weight gain, hyperglycemia, and hyperlipidemias) and cardiac risks are also discussed. The chapter also briefly discusses complementary and alternative pharmacotherapies. It then provides an in-depth review of the clinical use of antipsychotics for psychotic and behavioral disorders, as well as for other nonpsychotic psychiatric and medical disorders. It also discusses the use of antipsychotics in women of childbearing age, notably in regard to pregnancy and breastfeeding considerations. Finally, the chapter includes a table of antipsychotics that includes each medication’s generic and brand names, usual adult doses, pertinent clinical comments, black box warnings, and Food and Drug Administration indications.

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