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.

GLIADEL (NDA-020637)

(CARMUSTINE)

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

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12/05/2018 (SUPPL-29)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Impaired Neurosurgical Wound Healing

(addition underlined)

Impaired neurosurgical wound healing including wound dehiscence, delayed wound healing, and subdural, subgleal, or wound effusions occur with GLIADEL Wafer treatment. In Study 1, 16% of GLIADEL Wafer-treated patients with newly diagnosed glioma experienced impaired intracranial wound healing and 5% had cerebrospinal fluid leaks. In Study 2, 14% of GLIADEL Wafer-treated patients with recurrent high-grade glioma experienced wound healing abnormalities.Monitor patients post-operatively for impaired neurosurgical wound healing.

5.6 Embryo-Fetal Toxicity

(subsection revised, additions underlined)

GLIADEL Wafers can cause fetal harm when administered to a pregnant woman. Carmustine, the active component of GLIADEL Wafer, is embryotoxic and teratogenic in rats at exposures less than the exposure at the recommended human dose based on body surface area (BSA) and embryotoxic in rabbits at exposures similar to the exposure at the recommended human dose based on BSA.

Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception for 6 months after implantation of GLIADEL Wafer. Advise males with female partners of reproductive potential to use effective contraception for 3 months following implantation of GLIADEL Wafers.

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

GLIADEL Wafer can cause fetal harm when administered to a pregnant woman. There are no available data on GLIADEL use in pregnant women. There have been no animal reproductive studies with GLIADEL Wafer; however, carmustine, the active component of GLIADEL Wafer, is embryotoxic and teratogenic in rats at exposures less than the exposure at the recommended human dose based on body surface area (BSA) and embryotoxic in rabbits at exposures similar to exposures at the recommended human dose based on BSA (see Data). Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

There are no studies assessing the reproductive toxicity of GLIADEL Wafer; however, carmustine, the active component of GLIADEL Wafer, is embryotoxic and teratogenic in rats at intraperitoneal doses of

0.5 mg/kg/day or greater when given on gestation days 6 through 15. Carmustine caused fetal malformations (anophthalmia, micrognathia, omphalocele) at 1 mg/kg/day (about 0.12 times the recommended human dose, eight wafers of 7.7 mg carmustine/wafer, based on BSA). Carmustine was embryotoxic in rabbits at intravenous doses of 4 mg/kg/day (about 1.2 times the recommended human dose based on BSA). Embryotoxicity was characterized by increased embryo-fetal deaths, reduced numbers of litters, and reduced litter sizes.

8.2 Lactation

(PLLR conversion)

Risk Summary

No data are available regarding the presence of carmustine, the active component of GLIADEL Wafer, or its metabolites in human milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children from GLIADEL Wafers, advise women not to breastfeed following implantation with GLIADEL Wafers and for at least 7 days after implantation.

8.3 Females and Males of Reproductive Potential

(PLLR conversion)

Pregnancy Testing

Verify pregnancy status of females of reproductive potential prior to implantation with GLIADEL Wafer.

Contraception

GLIADEL Wafer can cause fetal harm when administered to a pregnant woman.

Females

Advise females of reproductive potential to use effective contraception for 6 months after implantation of GLIADEL Wafer.

Males

Based on its mechanism of action, advise males with female partners of reproductive potential to use effective contraception for 3 months following implantation of GLIADEL Wafer.

Infertility

Males

Carmustine caused testicular degeneration in animals. Advise male patients of the potential risk of infertility.

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

17 PATIENT COUNSELING INFORMATION

(additions underlined)

…

Embryo-Fetal Toxicity

Advise patients of the potential risk to a fetus. Advise women to inform their healthcare provider of a known or suspected pregnancy.

Advise females of reproductive potential to use effective contraception for at least 6 months after implantation of GLIADEL Wafer.

Advise males with female partners of reproductive potential to use effective contraception for 3 months following implantation of GLIADEL Wafer.

Lactation

Advise women not to breastfeed following implantation with GLIADEL Wafers and for at least 7 days after implantation.

Infertility

Advise males of reproductive potential that GLIADEL Wafer may impair fertility.