Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | 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.

LOREEV XR (NDA-214826)

(LORAZEPAM)

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

Download Data

Expand all

01/13/2023 (SUPPL-3)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.8 Neonatal Sedation and Withdrawal Syndrome

Additions and/or revisions underlined:

Use of LOREEV XR late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate [see Use in Specific Populations (8.1)]. Monitor neonates exposed to LOREEV XR during pregnancy or labor for signs of sedation and monitor neonates exposed to LOREEV XR during pregnancy for signs of withdrawal; manage these neonates accordingly.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions (5.8)]

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LOREEV XR during pregnancy. Health care providers are encouraged to register patients by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or by visiting online at https://womensmentalhealth.org/pregnancyregistry.

Risk Summary

Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see Warnings and Precautions (5.8), Clinical Considerations]. Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects (see Data). In animal studies, administration of lorazepam during the organogenesis period of pregnancy resulted in increased incidences of fetal malformations at doses greater than those used clinically. Data for benzodiazepines suggest the possibility of increased neuronal cell death and long-term effects on neurobehavioral function based on findings in animals following prenatal or early postnatal exposure at clinically relevant doses (see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia and sedation in neonates. Monitor neonates exposed to LOREEV XR during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to LOREEV XR during pregnancy for signs of withdrawal. Manage these neonates accordingly [see Warnings and Precautions (5.8)].

…

8.2 Lactation

Newly added information:

Because of the potential for serious adverse reactions, including sedation and withdrawal symptoms in breastfed infants, advise patients that breastfeeding is not recommended during treatment with LOREEV XR.

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

MEDICATION GUIDE

Additions and/or revisions underlined:

…

Before taking LOREEV XR, tell your healthcare provider about all of your medical conditions, including if you:

have or have had depression, mood problems, or suicidal thoughts or behavior
have a history of drug or alcohol abuse or addiction
have lung disease or breathing problems (such as COPD, sleep apnea syndrome)
have liver or kidney problems
have or have had seizures
are pregnant or plan to become pregnant.
- Taking LOREEV XR late in pregnancy may cause your baby to have symptoms of sedation (breathing problems, sluggishness, low muscle tone), and/or withdrawal symptoms (jitteriness, irritability, restlessness, shaking, excessive crying, feeding problems).
- Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with LOREEV XR.
- There is a pregnancy registry for women who take LOREEV XR during pregnancy. The purpose of the registry is to collect information about the health of you and your baby. If you become pregnant during treatment with LOREEV XR, talk to your healthcare provider about registering with the National Pregnancy Registry for Psychiatric Medications. You can register by calling 1-866-961-2388 or visiting https://womensmentalhealth.org/pregnancyregistry/.
are breastfeeding or plan to breastfeed. LOREEV XR passes into your breast milk.

Talk to your healthcare provider about the best way to feed your baby if you take LOREEV XR.
Breastfeeding is not recommended during treatment with LOREEV XR.

…

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Advise pregnant females that use of LOREEV XR late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns [see Warnings and Precautions (5.8), Use in Specific Populations (8.1)]. Instruct patients to inform their healthcare provider if they are pregnant.

Advise pregnant women that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to LOREEV XR [see Use in Specific Populations (8.1)].

Lactation

Advise patients that breastfeeding is not recommended during treatment with LOREEV XR [see Use in Specific Populations (8.2)].