Drug Safety-related Labeling Changes (SrLC)
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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
ZYBAN (NDA-020711)
(BUPROPION HYDROCHLORIDE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
07/19/2019 (SUPPL-48)
05/04/2017 (SUPPL-45)
05/04/2017 (SUPPL-46)
05/04/2017 (SUPPL-47)
5 Warnings and Precautions
5.1 Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults(additions underlined)
Although ZYBAN is not indicated for treatment of depression, it contains the same active ingredient as the antidepressant medications WELLBUTRIN, WELLBUTRIN SR, and WELLBUTRIN XL. Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials.
Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.
…
(subsection revised, additions underlined)
Serious neuropsychiatric adverse events have been reported in patients taking ZYBAN for smoking cessation. These postmarketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. However, some of these adverse events occurred in patients taking ZYBAN who continued to smoke.
Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illness. Observe patients for
the occurrence of neuropsychiatric adverse events.
Advise patients and caregivers that the patient should stop taking ZYBAN and
contact a healthcare provider immediately if agitation, depressed mood, or
changes in behavior or thinking that are not typical for the patient are
observed, or ifthe patient develops suicidal ideation or suicidal behavior. The
healthcare provider should evaluate the severity of the adverse events and the extent
to which the patient is benefiting from treatment, and consider options
including continued treatment under closer monitoring or discontinuing
treatment. In many postmarketing cases, resolution of symptoms after
discontinuation of ZYBAN was reported. However, the symptoms persisted in some
cases; therefore, ongoing monitoring and supportive care should be provided
until symptoms resolve.
The neuropsychiatric safety of ZYBAN was evaluated in a randomized, double-blind, active- and placebo-controlled study that included patients without a history of psychiatric disorder (non- psychiatric cohort, n = 3,912) and patients with a history of psychiatric disorder (psychiatric cohort n = 4,003). In the non-psychiatric cohort, ZYBAN was not associated with an increase composite of the following neuropsychiatric (NPS) adverse events: severe events of anxiety, depression, feeling abnormal, or hostility, and moderate or severe events of agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, and irritability. In the psychiatric cohort, there were more events reported in each treatment group compared with the non- psychiatric cohort and the incidence of events in the composite endpoint was higher for ZYBAN compared with placebo: Risk Difference (95% CI) vs. placebo was 2.2% (-0.5, 4.9) for ZYBAN.
In the non-psychiatric cohort, neuropsychiatric adverse events of a serious nature were reported in 0.5% of patients treated with ZYBAN and 0.4% of placebo-treated patients. In the psychiatric cohort, neuropsychiatric events of a serious nature were reported in 0.8% of patients treated with ZYBAN, all involving psychiatric hospitalization. In placebo-treated patients, serious neuropsychiatric events occurred in 0.6%, with 0.2% requiring psychiatric hospitalization.
(additions underlined)
Antidepressant treatment can precipitate a manic, mixed, or hypomanic episode. The risk appears to be increased in patients with bipolar disorder or who have risk factors for bipolar disorder. There were no reports of activation of psychosis or mania in premarketing clinical trials with ZYBAN conducted in nondepressed smokers. However, events of this nature were seen in patients with pre-existing psychiatric diagnoses in a smoking cessation trial. Bupropion is not approved for use in treating bipolar depression.
(addition underlined)
Depressed patients treated with bupropion in depression trials have had a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. Some of these patients had a diagnosis of bipolar disorder. In some cases, these symptoms abated upon dose reduction and/or withdrawal of treatment. Instruct patients to contact a healthcare professional if such reactions occur.
In premarketing clinical trials with ZYBAN conducted in non-depressed smokers, the incidence of neuropsychiatric side effects was generally comparable to placebo. However, in the postmarketing experience, patients taking ZYBAN to quit smoking have reported similar types of neuropsychiatric symptoms to those reported by patients in the clinical trials of bupropion for depression.
6 Adverse Reactions
6.1 Clinical Trials Experience(additions underlined)
…
In the trial of patients without or with a history of psychiatric disorder, the most common adverse events in subjects treated with ZYBAN were broadly similar to those observed in premarketing studies. Adverse events reported in >10% of subjects treated with ZYBAN in the entire study population were nausea, insomnia, and anxiety disorders. Additionally, the following psychiatric adverse events were reported in >2% of patients in either treatment group (ZYBAN vs. placebo) by cohort. For the non-psychiatric cohort, these adverse events were anxiety, nervousness, abnormal dreams, and insomnia. For the psychiatric cohort, these adverse events were agitation, anxiety, panic, abnormal dreams, insomnia, and crying.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(extensive additions and revisions, please refer to label)