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.

GRALISE (NDA-022544)

(GABAPENTIN)

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

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04/25/2025 (SUPPL-31)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Suicidal Behavior and Ideation

Additions and/or revisions underlined:

Antiepileptic drugs (AEDs), including gabapentin, the active ingredient in GRALISE, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Suicidal behavior and ideation have also been reported in patients after discontinuation of gabapentin [see Warnings and Precautions (5.3)]. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

. . .

5.2 Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation

Newly added subsection

After discontinuation of short-term and long-term treatment with gabapentin, withdrawal symptoms have been observed in some patients [see Adverse Reactions (6.2) and Drug Abuse and Dependence (9.3)]. Suicidal behavior and ideation have also been reported in patients after discontinuation of gabapentin [see Warnings and Precautions (5.1)]. If GRALISE is discontinued, this should be done gradually over a minimum of 1 week or longer (at the discretion of the prescriber).

6 Adverse Reactions

Additions and/or revisions underlined:

The following adverse reactions are described elsewhere in the labeling:

Suicidal Behavior and Ideation [see Warnings and Precautions (5.1)]
Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation [see Warnings and Precautions (5.2)]
Respiratory Depression [see Warnings and Precautions (5.3)]
Tumorigenic Potential [see Warnings and Precautions (5.4)]
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.5)]

Laboratory Tests [see Warnings and Precautions (5.6)]

6.2 Postmarketing and Other Experience with other Formulations of Gabapentin

Additions and/or revisions underlined:

. . .

There are postmarketing reports of withdrawal symptoms after discontinuation of gabapentin. Reported adverse reactions include, but are not limited to, seizures, depression, suicidal ideation and behavior, agitation, confusion, disorientation, psychotic symptoms, anxiety, insomnia, nausea, pain, sweating, tremor, headache, dizziness, and malaise [see Warnings and Precautions (5.2)].

. . .

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

. . .

Postmarketing data suggest that extended gabapentin use with opioids close to delivery may increase the risk of neonatal withdrawal versus opioids alone [see Clinical Considerations]. Although there is at least one report of neonatal withdrawal syndrome in an infant exposed to gabapentin alone during pregnancy, there are no comparative epidemiologic studies evaluating this association. Therefore, it is not known whether exposure to gabapentin alone late in pregnancy may cause withdrawal signs and symptoms.

. . .

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Neonatal withdrawal syndrome has been reported in newborns exposed to gabapentin in utero for an extended period of time when also exposed to opioids close to delivery. Neonatal withdrawal signs and symptoms reported have included tachypnea, vomiting, diarrhea, hypertonia, irritability, sneezing, poor feeding, hyperactivity, abnormal sleep pattern, and tremor. Reported signs and symptoms that may also be related to withdrawal include tongue thrusting, wandering eye movements while awake, back arching, and continuous extremity movements. Observe neonates exposed to GRALISE and opioids for signs and symptoms of neonatal withdrawal and manage accordingly.

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

. . .

Suicidal Thoughts and Behavior

Counsel patients, their caregivers, and families that AEDs, including gabapentin, the active ingredient in GRALISE, may increase the risk of suicidal thoughts and behavior and of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Instruct patients, caregivers, and families to report behaviors of concern immediately to healthcare providers. Also inform patients who plan to or have discontinued GRALISE that suicidal thoughts and behavior can appear even after the drug is stopped [see Warnings and Precautions (5.1)].

. . .

Use in Pregnancy

Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with GRALISE, and to notify their physician if they are breast feeding or intend to breast feed during therapy [see Use in Specific Populations (8.1) and (8.2)].

Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233- 2334 [see Use in Specific Populations (8.1)].

04/02/2020 (SUPPL-26)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Respiratory Depression

(Newly added subsection)

There is evidence from case reports, human studies, and animal studies associating gabapentin with serious, life-threatening, or fatal respiratory depression when co-administrated with central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment. When the decision is made to co-prescribe GRALISE with another CNS depressant, particularly an opioid, or to prescribe GRALISE to patients with underlying respiratory impairment, monitor patients for symptoms of respiratory depression and sedation, and consider initiating GRALISE at a low dose. The management of respiratory depression may include close observation, supportive measures, and reduction or withdrawal of CNS depressants (including GRALISE).

6 Adverse Reactions

6.2 Postmarketing and Other Experience with other Formulations of Gabapentin

(Additions and/or revisions underlined)

In addition to the adverse experiences reported during clinical testing of gabapentin, the following adverse experiences have been reported in patients receiving other formulations of marketed gabapentin. These adverse experiences have not been listed above and data are insufficient to support an estimate of their incidence or to establish causation. The listing is alphabetized: angioedema, blood glucose fluctuation, breast enlargement, bullous pemphigoid, elevated creatine kinase, elevated liver function tests, erythema multiforme, fever, hyponatremia, jaundice, movement disorder, Stevens-Johnson syndrome.

Adverse events following the abrupt discontinuation of gabapentin immediate release have also been reported. The most frequently reported events were anxiety, insomnia, nausea, pain and sweating.

There are postmarketing reports of life-threatening or fatal respiratory depression in patients taking gabapentin with opioids or other central nervous system (CNS) depressants, or in the setting of underlying respiratory impairment.

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

17 PATIENT COUNSELING INFORMATION

17.1 Suicidal Thoughts and Behavior

(Additions and/or revisions underlined)

Advise patients, their caregivers, and families that AEDs, including gabapentin, the active ingredient in GRALISE, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.

17.2 Respiratory Depression

(Additions and/or revisions underlined)

Inform patients about the risk of respiratory depression. Include information that the risk is greatest for those using concomitant central nervous system (CNS) depressants (such as opioid analgesics) or in those with underlying respiratory impairment. Teach patients how to recognize respiratory depression and advise them to seek medical attention immediately if it occurs.

17.3 Dosing and Administration

(Additions and/or revisions underlined)

GRALISE is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration.

The safety and effectiveness of GRALISE in patients with epilepsy has not been studied.

MEDICATION GUIDE

(Extensive changes; please refer to label)