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.

BYFAVO (NDA-212295)

(REMIMAZOLAM BESYLATE)

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

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01/13/2023 (SUPPL-3)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4 Neonatal Sedation and Withdrawal Syndrome

Subsection title revised

Additions and revisions underlined:

Receiving benzodiazepines 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. Monitor neonates exposed to benzodiazepines, including BYFAVO, during pregnancy or labor for signs of sedation and monitor neonates exposed to benzodiazepines during pregnancy for signs of withdrawal and manage these neonates accordingly [see Use in Specific Populations (8.1)].

6 Adverse Reactions

ADVERSE REACTIONS

Newly added information:

The following serious adverse reactions are discussed in greater detail in other sections:

Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)]

8 Use in Specific Populations

8.1 Pregnancy

Additions and revisions underlined:

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 (5.4), 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).

. . .

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. Monitor neonates exposed to BYFAVO during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to BYFAVO during pregnancy for signs of withdrawal. Manage these neonates accordingly [see Warnings and Precautions (5.4)].

8.2 Lactation

Additions and revisions underlined:

Risk Summary

There are reports of sedation, poor feeding, and poor weight gain in infants exposed to benzodiazepines through breast milk. There are no data on the effects of remimazolam in human milk, the effects on the breastfed infant or the effects on milk production. Remimazolam is present in animal milk (see Data). When a drug is present in animal milk, it is likely that it will be present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BYFAVO and any potential adverse effects on the breastfed child from BYFAVO or from the underlying maternal condition.

Clinical Considerations

Infants exposed to BYFAVO through breast milk should be monitored for sedation, poor feeding, and poor weight gain.

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

PATIENT COUNSELING INFORMATION

Additions and revisions underlined:

Alcohol and Current Medications

Advise patients to notify their healthcare provider about alcohol or medication use. Alcohol and other CNS depressants, such as opioid analgesics and benzodiazepines, can have an additive effect when administered with BYFAVO [see Warnings and Precautions (5.1), Drug Interactions (7.1)].

Pregnancy

Advise pregnant females that receiving BYFAVO 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. Instruct patients to inform their healthcare provider if they are pregnant during treatment with BYFAVO [see Warnings and Precautions (5.4, 5.5), Use in Specific Populations (8.1)].

. . .

Lactation

Instruct patients to notify their healthcare provider if they are breastfeeding or intend to breastfeed. Instruct breastfeeding patients receiving BYFAVO to monitor infants for excessive sedation, poor feeding and poor weight gain, and to seek medical attention if they notice these signs. A lactating woman may consider pumping and discarding breast milk for 5 hours after receiving BYFAVO during procedural sedation to minimize drug exposure to the breastfed infant [see Use in Specific Populations (8.2)].

04/08/2021 (SUPPL-2)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Following Table 3: Common Adverse Reactions in Colonoscopy Study 2 (Incidence >2%), ASA III and IV, additions and/or revisions underlined:

† Hypertension defined as an increase in systolic BP to greater than or equal to180 mmHg or in diastolic BP to greater than or equal to 100 mmHg, or an increase of systolic or diastolic BP of 20% or more over baseline or necessitating medical intervention.