Drug Safety-related Labeling Changes (SrLC)

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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.

FORFIVO XL (NDA-022497)

(BUPROPION HYDROCHLORIDE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

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11/05/2025 (SUPPL-18)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

…

Nervous System: abnormal coordination, depersonalization, emotional lability, hyperkinesia, hypertonia, hypesthesia, vertigo, amnesia, ataxia, derealization, abnormal electroencephalogram (EEG), aggression, akinesia, aphasia, coma, dysarthria, dyskinesia, dystonia, euphoria, extrapyramidal syndrome, hypokinesia, increased libido, neuralgia, neuropathy, paranoid ideation, restlessness, suicide attempt, and unmasking tardive dyskinesia and aseptic meningitis.

…

05/07/2024 (SUPPL-15)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

…

Cardiovascular: postural hypotension, hypertension, stroke, vasodilation, syncope, complete atrioventricular block, extrasystoles, myocardial infarction, phlebitis, pulmonary embolism, and Brugada pattern/syndrome.

…

Skin and subcutaneous tissue disorders: maculopapular rash, alopecia, angioedema, exfoliative dermatitis, hirsutism, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS).

…

12/10/2019 (SUPPL-8)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Neuropsychiatric Adverse Events and Suicide Risk in Smoking Cessation Treatment

(additions underlined)

…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 bupropion was reported. However, the symptoms persisted in some cases; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion, please refer to label for complete information)

8.2 Lactation

(PLLR conversion)

Risk Summary

Data from published literature report the presence of bupropion and its metabolites in human milk (see Data). There are no data on the effects of bupropion or its metabolites on milk production. Limited data from postmarketing reports have not identified a clear association of adverse reactions in the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for FORFIVO XL and any potential adverse effects on the breastfed child from FORFIVO XL or from the underlying maternal condition.

Data

In a lactation study of ten women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily infant exposure (assuming 150 mL/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. Postmarketing reports have described seizures in breastfed infants. The relationship of bupropion exposure and these seizures is unclear.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(additions underlined)

IMPORTANT: Be sure to read the three sections of this Medication Guide. The first section is about the risk of suicidal thoughts and actions with antidepressant medicines; the second section is about the risk of changes in thinking and behavior, depression and suicidal thoughts or actions with medicines used to quit smoking; and the third section is entitled “What Other Important Information Should I Know About FORFIVO XL?”

…

Who should not take FORFIVO XL?

Do not take FORFIVO XL if you:

…

drink a lot of alcohol and abruptly stop drinking, or take medicines called sedatives (these make you sleepy), benzodiazepines, or anti-seizure medicines, and you stop taking them all of a sudden.

…

What should I tell my healthcare provider before taking FORFIVO XL?

…

Tell your healthcare provider about your other medical conditions, including if you:

are pregnant or plan to become pregnant. Talk to your healthcare provider about the risk to your unborn baby if you take FORFIVO XL during pregnancy.

Tell your healthcare provider if you become pregnant or think you are pregnant during treatment with FORFIVO XL.
If you become pregnant during treatment with FORFIVO XL, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants. You can register by calling 1-844-405-6185. o

are breastfeeding or plan to breastfeed during treatment with FORFIVO XL. FORFIVO XL passes into your milk. Talk to your healthcare provider about the best way to feed your baby during treatment with FORFIVO XL.

…

How should I take FORFIVO XL?

…

If you are taking FORFIVO XL for the treatment of major depressive disorder, it may take several weeks for you to feel that FORFIVO XL is working. Once you feel better, it is important to keep taking FORFIVO XL exactly as directed by your healthcare provider. Call your healthcare provider if you do not feel FORFIVO XL is working for you.

What should I avoid while taking FORFIVO XL?

Avoid using alcohol during treatment with FORFIVO XL. If you usually drink a lot of alcohol, talk with your healthcare provider before suddenly stopping. If you suddenly stop drinking alcohol, you may increase your chance of having seizures.

…

What are the ingredients in FORFIVO XL?

Active ingredient: bupropion hydrochloride

Inactive ingredients: carboxymethyl cellulose sodium, colloidal silicon dioxide, hydrochloric acid, hydroxypropyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer, polyethylene glycol 8000, polyethylene oxide, polyvinyl pyrrolidone and polyvinyl acetate blend, stearic acid, talc, titanium dioxide and triacetin. The tablets are printed with edible black ink.

…

PATIENT COUNSELING INFORMATION

(additions underlined)

…

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy with FORFIVO XL. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to FORFIVO XL during pregnancy.

05/04/2017 (SUPPL-4)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Neuropsychiatric Adverse Events and Suicide Risk in Smoking Cessation Treatment

(additions underlined)

FORFIVO XL is not approved for smoking cessation treatment, but bupropion hydrochloride sustained-release is approved for this use. Serious neuropsychiatric adverse events have been reported in patients taking bupropion 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 bupropion who continued to smoke.

Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses. Observe patients for the occurrence of neuropsychiatric adverse events. Advise patients and caregivers that the patient should stop taking FORFIVO XL 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 if the patient develops suicidal ideation or suicidal behavior. In many postmarketing cases, resolution of symptoms after discontinuation of bupropion was reported. However, the symptoms persisted in some cases; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

(additions underlined)

…

Neuropsychiatric Adverse Events and Suicide Risk in Smoking Cessation Treatment

FORFIVO XL is not indicated for smoking cessation treatment, it contains the same active ingredient as ZYBAN® which is approved for this use. Inform patients that some patients have experienced changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation and suicide when attempting to quit smoking while taking bupropion. Instruct patients to discontinue FORFIVO XL and contact a healthcare professional if they experience such symptoms.

MEDICATION GUIDE

(additions and revisions, please refer to label)