Download Boxed Warnings Adverse Drug Reactions Poster

PRESENTED BY: Christine M. Cheng, PharmD, Colleen DeLizza, BSPharm, Joan Kapusnik-Uner, PharmD
A Survey Of Boxed Warning Adverse Reaction Content From U.S. Prescription Drug Labeling
BACKGROUND
• Boxed warnings describe serious, potentially life-threatening
adverse reactions associated with use of a drug 1, 2
RESULTS
6%
INGREDIENT EXAMPLES
7
2%
OBJECTIVE
295
93
22%
NUMBER OF
GROUPS (%)
70%
TO REPORT CATEGORIES OF ADVERSE REACTIONS
• Assign labels to drug groups based on boxed warning
content
• Drug groups may be based on drug class or ingredient
and further qualified by additional attributes (e.g., dose
form, strength) if needed
• Identify subset of drug groups with boxed warnings that
describe ≥ 1 adverse reaction
•C
ategorize boxed warning adverse reactions using
hierarchical concepts
DRUG CLASS EXAMPLES
2%
Dermatologic
Disorders
Systemic fluoroquinolones
Nonsteroidal anti-inflammatory drugs
Endocrine
Disorders
INGREDIENT + STRENGTH
WARNING: SERIOUS PULMONARY OIL MICROEMBOLISM (POME) REACTIONS
AND ANAPHYLAXIS
• Serious POME reactions, involving urge to cough, dyspnea, throat tightening, chest
pain, dizziness, and syncope; and episodes of anaphylaxis, including life-threatening
reactions, have been reported to occur during or immediately after the administration
of testosterone undecanoate injection. These reactions can occur after any injection
of testosterone undecanoate during the course of therapy, including after the first
dose [see Warnings and Precautions (5.1)].
•F
ollowing each injection of Aveed, observe patients in the healthcare setting for 30
minutes in order to provide appropriate medical treatment in the event of serious
POME reactions or anaphylaxis [see Warnings and Precautions (5.1)].
• Because of the risks of serious POME reactions and anaphylaxis, Aveed is available
only through a restricted program under a Risk Evaluation and Mitigation Strategy
(REMS) called the Aveed REMS Program [see Warnings and Precautions (5.2)].
ANDROGEL (testosterone) gel
AbbVie Inc.
WARNING: SECONDARY EXPOSURE TO TESTOSTERONE
• Virilization has been reported in children who were secondarily exposed to
testosterone gel [see Warnings and Precautions (5.2) and Adverse Reactions 6.2)].
•C
hildren should avoid contact with unwashed or unclothed application sites in
men using testosterone gel [see Dosage and Administration (2.2) Warnings and
Precautions (5.2)].
• Healthcare providers should advise patients to strictly adhere to recommended
instructions for use [see Dosage and Administration (2.2) Warnings and Precautions
(5.2) and Patient Counseling Information (17)].
MIFEPREX® (mifepristone) tablet, 200 mg
Danco Labs LLC
Serious and sometimes fatal infections and bleeding occur very rarely following
spontaneous, surgical, and medical abortions, including following Mifeprex* use. No
causal relationship between the use of Mifeprex and misoprostol and these events
has been established. Before prescribing Mifeprex, inform the patient about the
risk of these serious events and discuss the MEDICATION GUIDE and the PATIENT
AGREEMENT. Ensure that the patient knows whom to call and what to do, including
going to an Emergency Room if none of the provided contacts are reachable, if
she experiences sustained fever, severe abdominal pain, prolonged heavy bleeding,
or syncope, or if she experiences abdominal pain or discomfort or general malaise
(including weakness, nausea, vomiting or diarrhea) more than 24 hours after taking
misoprostol.
• Atypical Presentation of Infection. Patients with serious bacterial infections (e.g.
Clostridium sordellii) and sepsis can present without fever, bacteremia or significant
findings on pelvic examination following an abortion. Very rarely, deaths have been
reported in patients who presented without fever, with or without abdominal pain,
but with leukocytosis with a marked left shift, tachycardia, hemoconcentration, and
general malaise. A high index of suspicion is needed to rule out serious infection
and sepsis (see WARNINGS).
• Bleeding. Prolonged heavy bleeding may be a sign of incomplete abortion or other
complications and prompt medical or surgical intervention may be needed. Advise
patients to seek immediate medical attention if they experience prolonged heavy
vaginal bleeding (see WARNINGS).
Patients should be advised to take their MEDICATION GUIDE with them if they visit
an emergency room or another health care provider who did not prescribe Mifeprex,
so that provider will be aware that the patient is undergoing a medical abortion.
KORLYM (mifepristone) tablet, 300 mg
Corcept Therapeutics Inc.
ADVERSE
EVENTS
Fetal
Disorders
Hematologic
Abnormalities
Immune System
Disorders
Neoplasms
Infection
Hepatic
Disorders
Metabolic and
Nutritional Disorders
Neoplasms
EXAMPLE DRUG GROUP
103 (27%)
Bone marrow suppression
Thrombotic disorders
Hemolytic anemia
clozapine
tamoxifen
fludarabine
72 (19%)
Suicidal ideation
antidepressants
Abuse potential
amphetamines
Congestive heart failure
thiazolidinediones
Capillary leak syndrome
aldesleukin
Hepatic failure
valproic acid and derivatives
Peliosis hepatis
danazol
T cell lymphoma
metreleptin
Medullary thyroid carcinoma
liraglutide
Interstitial pneumonitis
nilutamide
Pulmonary oil microembolism reaction
testosterone undecanoate
Anaphylaxis
carboplatin
Infusion reactions
trastuzumab
Progressive multifocal leukoencephalopathy
brentuximab
Opportunistic infection
belatacept
61 (16%)
58 (15%)
50 (13%)
42 (11%)
41 (11%)
37 (10%)
restricted distribution program for the drug (e.g., TOUCH prescribing
program for natalizumab).
Neurologic Disorders
Subcategories
5 There were 32 drug groups not associated with an adverse reaction.
Botulinum Toxin
Spread
Central Nervous
System Depression
Post-injection
Delirium & Sedation
Chemical
Arachnoiditis
Myasthenia Gravis
Exacerbation
Respiratory System
Disorders
Neurotoxicity
Fluoroquinolones, including CIPRO®, are associated with an increased risk of tendinitis
and tendon rupture in all ages. This risk is further increased in older patients usually
over 60 years of age, in patients taking corticosteroid drugs, and in patients with
kidney, heart or lung transplants (see WARNINGS).
Urinary System
Disorders
Seizure
Fluoroquinolones, including CIPRO, may exacerbate muscle weakness in persons with
myasthenia gravis. Avoid CIPRO in patients with known history of myasthenia gravis
(see WARNINGS).
Vision
Disorders
Mifepristone is a potent antagonist of progesterone and cortisol via the progesterone
and glucocorticoid (GR-II) receptors, respectively. The antiprogestational effects will
result in the termination of pregnancy. Pregnancy must therefore be excluded before
the initiation of treatment with Korlym and prevented during treatment and for one
month after stopping treatment by the use of a non-hormonal medically acceptable
method of contraception unless the patient has had a surgical sterilization, in which
case no additional contraception is needed. Pregnancy must also be excluded if
treatment is interrupted for more than 14 days in females of reproductive potential.
Hepatic disorders
EXAMPLE SUBCATEGORIES
4 Boxed warnings for 33/387 (9%) of drug groups referenced a
Psychiatric
Disorders
WARNING
Psychiatric disorders
Infection
WARNING: TERMINATION OF PREGNANCY
CIPRO® (ciprofloxacin hydrochloride) TABLETS
CIPRO® (ciprofloxacin) ORAL SUSPENSION
Hematologic abnormalities
Immune system disorders
Intracranial
Hypertension
CIPRO (ciprofloxacin hydrochloride) tablet, film coated
CIPRO (ciprofloxacin) kit
Bayer HealthCare Pharmaceuticals Inc.
CATEGORY
NUMBER OF DRUG GROUPS (% OF
DRUG GROUPS WITH BXW ADR)
Respiratory system disorders
Gastrointestinal
System Disorders
Neurologic
Disorders
DRUG CLASS
described at least one adverse reaction (range 1 to 10 ADR concepts per drug group).
Cardiovascular disorders
Mifepristone 200 mg
Mifepristone 300 mg
INGREDIENT + DOSE FORM
Main Categories of Adverse Events
(partial listing)
Cardiac Rhythm
Disorders
Testosterone transdermal gel solution
22% Testosterone undecanoate (intramuscular injection solution)
INGREDIENT + STRENGTH EXAMPLES
AVEED (testosterone undecanoate) injection
Endo Pharmaceuticals Solutions Inc.
•R
eview collection of prescription drug labels with boxed
warnings on DailyMed and the FDA websites that were
previously identified 3
Cardiovascular
Disorders
INGREDIENT + DOSE FORM EXAMPLES
6%
3 The majority (n=387/419, 92%) of the drug groups had a boxed warning that
Top Boxed Warning Adverse Drug Reaction Categories
70% Warfarin, adalimumab, bupropion
•A
dverse drug reactions (ADRs) described within boxed
warnings have not been well characterized
METHODS
included 25 main categories and > 150 subcategories.
24
• More than 1/3 of drug labels for human prescription drugs
have a boxed warning 3
described within boxed warnings in FDA-approved prescription
drug labels available on the National Library of Medicine
DailyMed website and the FDA website between July 2013
and March 2014.
2 Hierarchical representation of boxed warning adverse reactions
1 There were a total of 419 boxed warning drug groups.
• Most prevalent clinical issues described were:
• Need for experienced physician supervision during use of
the drug (n= 16/32, 50% of drug groups).
• Precautions surrounding appropriate patient selection
criteria for use of the drug (n= 15/32, 47% of drug groups).
DISCLOSURES:
Author(s) of this presentation have the following to disclose concerning possible
financial or personal relationships with commercial entities that may have a direct or
indirect interest in the subject matter of this presentation:
Christine M. Cheng: Employee, First Databank, Inc.
Colleen DeLizza: Employee, First Databank, Inc.
Joan-Kapusnik Uner: Employee, First Databank, Inc.
REFERENCES:
1. Code of Federal Regulations, Title 21, Part 201, subpart B, section 201.57 (21CFR201.57)
2. Guidance for Industry on Warnings and Precautions, Contraindications, and Boxed Warning Sections of Labeling for Human Prescription Drug and
Biological Products—Content and Format; October 2011. Accessed 5/19/2014 at http://www.fda.gov/downloads/Drugs/Guidances/ucm075096.pdf.
3. Cheng CM, DeLizza C, Kapusnik-Uner J. Prevalence and therapeutic classifications of FDA-approved prescription drugs with boxed warnings.
Therapeutic Innovation and Regulatory Science, 2014;48:165-172.
4. Thompson CA. Hospital inspectors eye black-box warnings. American Journal of Health System Pharmacists, 2008;65:890-4. © 2014 First Databank, Inc. Part of the Hearst Health network. All trademarks mentioned herein belong to their respective holders
DISCUSSION /CONCLUSION
Neuromuscular
Blockade
Osmotic Demyelination
Syndrome
Peripheral
Neuropathy
Tardive Dyskinesia
• Knowledge of boxed warning adverse reaction content can help guide safe and appropriate use of
high-risk drugs
• Boxed warning adverse reactions are diverse but can be organized into an adverse reaction
classification schema
• When integrated within health information systems, hierarchical classification of boxed warning adverse
reactions may help facilitate
• Identification of patients at risk for a serious reaction from a boxed warning drug
• Development of specific monitoring/surveillance programs for boxed warning drugs and adverse reactions
• Retrospective evaluation for quality improvement initiatives related to boxed warning drugs
• Fulfillment of regulatory requirements for boxed warning drugs
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