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.

DECITABINE (NDA-205582)

(DECITABINE)

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

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09/16/2020 (SUPPL-15)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions underlined)

…

Interstitial lung disease

05/21/2020 (SUPPL-14)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Embryo-Fetal Toxicity

(Additions and/or revisions underlined)

Based on findings from human data, animal studies and its mechanism of action, Decitabine for Injection can cause fetal harm when administered to a pregnant woman. In preclinical studies in mice and rats, decitabine caused adverse developmental outcomes including embryo-fetal lethality and malformations. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception while receiving Decitabine for Injection and for 6 months following the last dose. Advise males with female partners of reproductive potential to use effective contraception while receiving treatment with Decitabine for Injection and for 3 months following the last dose.

6 Adverse Reactions

(Addition of the following)

The following clinically significant adverse reactions are described elsewhere in the labeling:

Myelosuppression

6.1 Clinical Trials Experience

(Subsection title revised)

(Extensive changes; please refer to label)

8 Use in Specific Populations

8.1 Pregnancy

(Additions and/or revisions underlined)

Risk Summary

Based on findings from human data, animal studies, and the mechanism of action, Decitabine for Injection can cause fetal harm when administered to a pregnant woman. Limited published data on decitabine use throughout the first trimester during pregnancy describe adverse developmental outcomes including major birth defects (structural abnormalities). In animal reproduction studies, administration of decitabine to pregnant mice and rats during organogenesis caused adverse developmental outcomes including malformations and embryo-fetal lethality starting at doses approximately 7% of the recommended human dose on a mg/m2 basis. Advise pregnant women of the potential risk to a fetus.

…

8.2 Lactation

(Additions and/or revisions underlined)

Risk Summary

There are no data on the presence of decitabine or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions from decitabine in a breastfed child, advise women not to breastfeed while receiving Decitabine for Injection and for at least 2 weeks after the last dose.

8.3 Females and Males of Reproductive Potential

(Additions and/or revisions underlined)

Pregnancy Testing

Conduct pregnancy testing of females of reproductive potential prior to initiating Decitabine for Injection.

Contraception

Females

Decitabine for Injection can cause fetal harm when administered to pregnant women. Advise females of reproductive potential to use effective contraception while receiving Decitabine for Injection and for 6 months following the last dose.

Males

Advise males with female partners of reproductive potential to use effective contraception while receiving treatment with Decitabine for Injection and for 3 months following the last dose.

Infertility

Based on findings of decitabine in animals, male fertility may be compromised by decitabine. The reversibility of the effect on fertility is unknown.

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

PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Myelosuppression

Advise patients of the risk of myelosuppression and to report any symptoms of infection, anemia, or bleeding to their healthcare provider as soon as possible. Advise patients for the need for laboratory monitoring.

Embryo-Fetal Toxicity

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

Advise females of reproductive potential to use effective contraception while receiving Decitabine for Injection and for 6 months after last dose.

Advise males with female partners of reproductive potential to use effective contraception while receiving treatment with Decitabine for Injection and for 3 months after the last dose.

Lactation

Advise women to avoid breastfeeding while receiving Decitabine for Injection and for at least 2 weeks after the last dose.

02/03/2020 (SUPPL-12)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during post-approval use of decitabine for injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Sweet’s syndrome (acute febrile neutrophilic dermatosis)

Differentiation syndrome

05/22/2019 (SUPPL-9)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Myelosuppression

(additions underlined)

Fatal and serious myelosuppression occurs in decitabine for injection-treated patients. Myelosuppression (anemia, neutropenia, and thrombocytopenia) is the most frequent cause of decitabine for injection dose reduction, delay, and discontinuation. Neutropenia of any grade occurred in 90% of decitabine for injection treated patients with grade 3 or 4 occurring in 87% of patients. Thrombocytopenia of any grade occurred in 89% of patients with grade 3 or 4 occurring in 85% of patients. Grade 3 or 4 febrile neutropenia occurred in 23% of patients. Anemia of any grade occurred in 82% of patients.

Perform complete blood count with platelets at baseline, prior to each cycle, and as needed to monitor response and toxicity. Manage toxicity using dose-delay, dose-reduction, growth factors, and anti- infective therapies as needed . Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles, and may not necessarily indicate progression of underlying MDS.

5.2 Embryo-fetal Toxicity

(subsection revised, additions underlined)

Decitabine for injection can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action, decitabine for injection alters DNA synthesis and is expected to result in adverse reproductive effects. In preclinical studies in mice and rats, decitabine was teratogenic, fetotoxic, and embryotoxic. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Advise women of childbearing potential to avoid becoming pregnant while taking decitabine for injection and for 6 months following the last dose. Advise men with female partners of childbearing potential to avoid fathering a child while receiving treatment with decitabine for injection, and for 3 months following the last dose. Counsel patients of childbearing potential to use effective contraception during this time.

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion, please refer to label for more information)

8.2 Lactation

(PLLR conversion)

Risk Summary

There are no data on the presence of decitabine or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions from decitabine for injection in a nursing child, advise lactating women to avoid breastfeeding during treatment with decitabine for injection and for at least 1 week after the last dose.

8.3 Females and Males of Reproductive Potential

(PLLR conversion)

Pregnancy Testing

Conduct pregnancy testing of females of reproductive potential prior to initiating decitabine for injection.

Contraception

Females

Advise females of reproductive potential to avoid pregnancy and use effective contraception while receiving decitabine for injection and for 6 months following the last dose. Males Advise males with female partners of reproductive potential to use effective contraception while receiving treatment with decitabine for injection and for 3 months following the last dose.

Infertility

Based on findings of decitabine in animals, male fertility may be compromised by treatment with decitabine for injection.

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

PATIENT COUNSELING INFORMATION

(additions underlined)

Advise women of childbearing potential to avoid pregnancy and to use effective contraception while receiving decitabine for injection and for 6 months after last dose.

Advise men not to father a child while receiving treatment with decitabine for injection, and for 3 months after the last dose. Advise men with female partners of childbearing potential to use effective contraception .

Advise patients to avoid breastfeeding while receiving decitabine for injection and for at 1 week after the last dose. Advise patients of the risk of myelosuppression and to report any symptoms of infection, anemia, or bleeding to their healthcare provider as soon as possible. Advise patients for the need for laboratory monitoring.