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.

BELEODAQ (NDA-206256)

(BELINOSTAT)

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

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11/19/2024 (SUPPL-6)

Approved Drug Label (PDF)

7 Drug Interactions

Additions and/or revisions underlined:

Avoid concomitant administration of Beleodaq with UGT1A1inhibitors. If concomitant use of a UGT1A1 inhibitor is unavoidable, modify the Beleodaq dose [see Dosage and Administration (2.6)]. Belinostat is primarily metabolized by UGT1A1. Concomitant use with a UGT1A1 inhibitor increases belinostat exposure [see Clinical Pharmacology (12.3)], which may increase the risk of Beleodaq adverse reactions.

8 Use in Specific Populations

8.3 Females and Males of Reproductive Potential

Additions and/or revisions underlined:

Beleodaq can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

…

8.6 Use in Patients with Hepatic Impairment

Additions and/or revisions underlined:

No dosage adjustment is recommended for patients with mild hepatic impairment (total bilirubin less than or equal to 1.5 x ULN, any AST). Reduce the Beleodaq dosage in patients with moderate hepatic impairment (total bilirubin > 1.5 to 3 x ULN, any AST) [see Dosage and Administration (2.3)]. Avoid use of Beleodaq in patients with severe hepatic impairment (total bilirubin > 3 x ULN, any AST) [see Clinical Pharmacology (12.3)].

Belinostat is metabolized in the liver, moderate hepatic impairment (total bilirubin > 1.5 to 3 x ULN, any AST) and severe hepatic impairment (total bilirubin > 3 x ULN, any AST) increases belinostat exposure [see Clinical Pharmacology (12.3)], which may increase the risk of Beleodaq adverse reactions.

8.7 Use in Patients with Renal Impairment

Additions and/or revisions underlined:

No dosage adjustment is recommended for patients with mild renal impairment (CLcr 60 to < 90 mL/min). Reduce the Beleodaq dosage in in patients with moderate renal impairment (CLcr 30 to <60 mL/min) [see Dosage and Administration (2.4)]. Avoid use of Beleodaq in patients with severe renal impairment (CLcr < 30 mL/min). Moderate renal impairment (CLcr 30 to <60 mL/min) increases belinostat exposure [see Clinical Pharmacology (12.3)], which may increase the risk of Beleodaq adverse reactions. The effect of severe renal impairment (CLcr < 30 mL/min) on belinostat pharmacokinetics is unknown [see Clinical Pharmacology (12.3)].

01/08/2020 (SUPPL-3)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.6 Embryo-Fetal Toxicity

Additions and/or revisions underlined:

Based on its mechanism of action and findings of genotoxicity, Beleodaq can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1)]. Advise pregnant women of the risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with Beleodaq and for 6 months after the last dose [see Use in Specific Populations (8.1, 8.3)]. Advise males with female partners of reproductive potential to use effective contraception during treatment with Beleodaq and for 3 months after the last dose.

6 Adverse Reactions

‘clinically significant’ replaces ‘serious’ in first sentence.

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion, additions and/or revisions underlined:

Risk Summary

Based on its mechanism of action, Beleodaq can cause teratogenicity and/or embryo-fetal lethality because it is genotoxic and targets actively dividing cells [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1)]. There are no available data on Beleodaq use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. No animal reproduction studies were conducted with Beleodaq. Advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) 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 2-4% and 15-20%, respectively.

8.2 Lactation

PLLR conversion, additions and/or revisions underlined:

Risk Summary

There are no data on the presence of belinostat in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with Beleodaq, and for 2 weeks after the last dose.

8.3 Females and Males of Reproductive Potential

PLLR conversion, newly added subsection:

Pregnancy Testing

Pregnancy testing is recommended for females of reproductive potential prior to initiating Beleodaq. Contraception

Females

Beleodaq can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with Beleodaq and for 6 months after the last dose.

Males

Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with Beleodaq and for 3 months after the last dose [see Nonclinical Toxicology (13.1)].

Infertility

Males

Based on findings from animal studies, Beleodaq may impair male fertility. The reversibility of the effect on fertility is unknown [see Nonclinical Toxicology (13.1)].

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Of the potential risk to the fetus and for women to avoid pregnancy and use effective contraception while receiving Beleodaq and for 6 months after the last dose [see Warnings and Precautions (5.6)]. Advise males with female partners of reproductive potential to use effective contraception during treatment with Beleodaq and for 3 months after the last dose.
To avoid breastfeeding while receiving Beleodaq and for 2 weeks after the last dose [see Use in Specific Populations (8.2)].