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.

DUAVEE (NDA-022247)

(BAZEDOXIFENE ACETATE; ESTROGENS, CONJUGATED)

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

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03/04/2024 (SUPPL-10)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Malignant Neoplasms

Additions and revisions underlined:

The WHI substudy of daily conjugated estrogens (0.625 mg)-alone provided information about breast cancer in estrogen-alone users.

12/06/2022 (SUPPL-7)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

…

Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile.

…

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

PATIENT INFORMATION

Additions and or revisions underlined:

…

What is the most important information I should know about DUAVEE?

…

Using estrogen-alone may increase your chances of getting strokes or blood clots.
Using estrogen-alone may increase your chances of getting dementia, based on a study of women 65 years of age or older.
The risks listed above are based on a study of an estrogen-alone oral product. Since other products and doses have not been studied in the same way, it is not known how the use of DUAVEE will affect your chances of getting these conditions. You and your healthcare provider should talk regularly about whether you still need treatment with DUAVEE.
…

12/18/2019 (SUPPL-6)

Approved Drug Label (PDF)

5 Warnings and Precautions

Premenopausal Women

(Newly added information)

Additionally, there is concern regarding inadvertent drug exposure in pregnancy in women of reproductive potential who become pregnant, due to risk of fetal harm [see Use in Specific Populations (8.1)].

8 Use in Specific Populations

Females and Males of Reproductive Potential

(PLLR Conversion, as below)

Infertility

Bazedoxifene

Based on animal data, bazedoxifene administration may adversely affect female fertility. However, clinical fertility studies with bazedoxifene have not been conducted [see Nonclinical Toxicology (13.1)].

Lactation

(PLLR Conversion, as below)

Risk Summary

DUAVEE is not indicated for use in females of reproductive potential [see Warnings and Precautions (5.15)].

Conjugated Estrogens

Estrogens are present in human milk and can reduce milk production in breast-feeding females.

This reduction can occur at any time but is less likely to occur once breast-feeding is well-established.

Bazedoxifene

There are no data on the presence of bazedoxifene in either human or animal breast milk, the effect on the breastfed infant, or the effects on milk production. Based on mechanism of action, bazedoxifene may block the important functions that estrogen has in mammary tissue during lactation [see Clinical Pharmacology (12.1)].

Pregnancy

(PLLR Conversion, as below)

Risk Summary

DUAVEE is contraindicated for use in pregnant women and is not indicated for use in females of reproductive potential [see Contraindications (4), Warnings and Precautions (5.15)].

Conjugated Estrogens (CE)

There are no data with the use of conjugated estrogens in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital and non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives before conception or during early pregnancy.

Bazedoxifene

There are no available data on bazedoxifene use in pregnant women to inform a drug associated risk of adverse developmental outcomes. Animal studies have shown that oral bazedoxifene administered during the period of organogenesis to pregnant rats or rabbits at 0.3 and 2 times, respectively, the exposure at the maximum recommended dose, can cause fetal harm [see Data]. Based on mechanism of action, bazedoxifene may block the important functions that estrogen has during all stages of pregnancy [see Clinical Pharmacology (12.1)].

11/01/2017 (SUPPL-4)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Malignant Neoplasms

Ovarian Cancer

Additions and/or revisions underlined:

… A meta-analysis of 17 prospective and 35 retrospective epidemiology studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer. The primary analysis, using case-control comparisons, included 12,110 cancer cases from the 17 prospective studies. The relative risks associated with current use of hormonal therapy was 1.41 (95% confidence interval [CI] 1.32 to 1.50); there was no difference in the risk estimates by duration of the exposure (less than 5 years [median of 3 years] vs. greater than 5 years [median of 10 years] of use before the cancer diagnosis). The relative risk associated with combined current and recent use (discontinued use within 5 years before cancer diagnosis) was 1.37 (95% CI 1.27 to 1.48), and the elevated risk was significant for both estrogen-alone and estrogen plus progestin products. The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown.