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.

SUBVENITE (NDA-218879)

(LAMOTRIGINE)

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

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07/17/2026 (SUPPL-1)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: SERIOUS SKIN RASHES

. . .

In addition to age, factors that may increase the risk of occurrence or the severity of rash caused by lamotrigine include (1) coadministration of lamotrigine with valproate (includes valproic acid and divalproex sodium), (2) exceeding the recommended initial dose of SUBVENITE, (3) exceeding the recommended dose escalation for SUBVENITE, or (4) the presence of the HLA-B*1502 allele. However, cases have occurred in the absence of these factors.

. . .

5 Warnings and Precautions

5.1 Serious Skin Rashes [see Boxed Warning]

Additions and/or revisions underlined:

. . .

Risk Factors

Concomitant Use of Valproate

There is evidence that the inclusion of valproate in a multidrug regimen increases the risk of serious, potentially life-threatening rash in adults. Specifically, of 584 patients administered lamotrigine with valproate in epilepsy clinical trials, 6 (1%) were hospitalized in association with rash; in contrast, 4 (0.16%) of 2,398 clinical trial patients and volunteers administered lamotrigine in the absence of valproate were hospitalized.

Patients with History of Allergy or Rash to Other Antiepileptic Drugs

The risk of rash may be increased in patients with a history of allergy or rash to other AEDs.

Not Adhering to the Recommended Dosage

The risk of rash is increased by both exceeding the recommended initial dose of SUBVENITE and exceeding the recommended dose escalation for SUBVENITE.

Patients with Genetic Variant Human Leukocyte Antigen (HLA)-B*1502 Allele

Retrospective case-control studies in patients of certain Asian ancestry (e.g., Han Chinese and Thai) suggest that the HLA-B*1502 allele is associated with an increased risk (approximately 2-3 times higher) of developing Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) in patients using lamotrigine. The risks and benefits of therapy should be weighed when considering use of SUBVENITE in patients known to be positive for HLA-B*1502. Application of HLA genotyping as a screening tool has important limitations and must never substitute for appropriate clinical vigilance and patient management. Many HLA-B*1502-positive patients treated with SUBVENITE will not develop SJS/TEN or other hypersensitivity reactions, and these reactions can still occur in HLA-B*1502-negative patients of any ethnicity.

6 Adverse Reactions

6.3 Postmarketing Experience

Additions and/or revisions underlined:

. . .

Skin and Subcutaneous Tissue Disorders

Photosensitivity reaction.

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

. . .

Disease-associated Maternal and/or Embryofetal Risk

Epilepsy, with or without exposure to antiepileptic drugs, has been associated with several adverse outcomes during pregnancy, including preeclampsia, preterm labor, antepartum and postpartum hemorrhage, placental abruption, poor fetal growth, prematurity, fetal death, and maternal mortality. The risk of maternal or fetal injury may be greatest for patients with untreated or poorly controlled convulsive seizures. Women with epilepsy who become pregnant should not abruptly discontinue antiepileptic drugs, including SUBVENITE, due to the risk of status epilepticus or severe seizures, which may be life-threatening [see Warnings and Precautions (5.10)].

Dose Adjustments During Pregnancy and the Postpartum Period

As with other AEDs, physiological changes during pregnancy may affect lamotrigine concentrations and/or therapeutic effect. There have been reports of decreased lamotrigine concentrations during pregnancy and restoration of pre-pregnancy concentrations after delivery. Dose adjustments may be necessary to maintain clinical response.

. . .

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

MEDICATION GUIDE

Additions and/or revisions underlined:

What is the most important information I should know about SUBVENITE?

1. SUBVENITE may cause a serious skin rash that may cause you to be hospitalized or even cause death.

. . .

The risk of serious skin reactions may be associated with a variant in genes called HLA-B*1502 in people from Asian origin (mainly of Han Chinese and Thai origin). See, “Before taking SUBVENITE, tell your healthcare provider about all of your health conditions”.

. . .

Before taking SUBVENITE, tell your healthcare provider about all of your health conditions, including if you:

have had a rash or allergic reaction to another antiseizure medicine.
are of Asian origin, have had HLA testing before, and know you are carrying the genetic variant, HLA-B*1502.

. . .