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.

ALORA (NDA-020655)

(ESTRADIOL)

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

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05/05/2025 (SUPPL-22)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Malignant Neoplasms

Additions and/or revisions underlined:

…

Clinical surveillance of all women taking estrogen/progestin combinations is important. Undertake adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding with unknown etiology.

…

5.3 Probable Dementia

Additions and/or revisions underlined:

…

In the WHIMS estrogen plus progestin ancillary study, a population of, 4,532 postmenopausal women 65 to 79 years of age was randomized to daily CE (0.625 mg) plus MPA (2.5 mg) or placebo. After an average follow-up of 4 years, 40 women in the CE plus MPA group and 21 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE plus MPA versus placebo was 2.05 (95% confidence interval 1.21 – 3.48). The absolute risk of probable dementia for CE plus MPA versus placebo was 45 versus 22 cases per 10,000 women-years8 [see Use in Specific Populations (8.5), and Clinical Studies (14.5)].

…

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

PATIENT INFORMATION

Additions and/or revisions underlined:

…

Before you use ALORA, tell your healthcare provider about all of your medical conditions, including if you:

…

are pregnant or think you may be pregnant.
Alora is not for pregnant women.
…
What Are the Possible Side Effects of ALORA?
Side effects are grouped by how serious they are and how often they happen when you are treated. Serious, but less common side effects include:
…

fluid retention
changes in certain laboratory test results

…

These are not all the possible side effects of ALORA. For more information, ask your healthcare provider or pharmacist for advice about side effects. Tell your healthcare provider if you have any side effects that bother you or do not go away.

…

General information about the safe and effective use of ALORA.

…

This leaflet provides a summary of the most important information about Alora. If you would like more information, talk with your healthcare provider for information about ALORA that is written for health professionals. For more information, call Allergan at 1-800-678-1605.

…

02/15/2024 (SUPPL-23)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Malignant Neoplasms

Additions and/or revisions underlined:

Breast Cancer

…

Consistent with the WHI clinical trial, observational studies have also reported an increased risk of breast cancer with estrogen plus progestin therapy, and a smaller increase in the risk for breast cancer with estrogen- alone therapy, after several years of use. One large meta-analysis of prospective cohort studies reported increased risks that were dependent upon duration of use and could last up to >10 years after discontinuation of estrogen plus progestin therapy and estrogen-alone therapy. Extension of the WHI trials also demonstrated increased breast cancer risk associated with estrogen plus progestin therapy.

…

11/01/2017 (SUPPL-20)

Approved Drug Label (PDF)

5 Warnings and Precautions

PRECAUTIONS

Ovarian Cancer

Additions and/or revisions underlined:

… The absolute risk for CE/MPA vs. placebo was 0.774.2 vs. 2.7 cases per 10,000 women-years.

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 1.27-1.48) 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.

WARNINGS

Additions and/or revisions underlined:

Cardiovascular Disorders

… Risk factors for arterial vascular disease

Dementia

In the estrogen plus progestin WHIMS, a population of 4,532 postmenopausal women aged 65 to 79 years was randomized to CE/MPA or placebo …

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

PATIENT INFORMATION

Additions and/or revisions underlined:

How should I store Alora?

Store at 20-25°C (68-77°F). [See USP controlled room temperature.] Do not store patches outside of their pouches. Apply the patch as soon as you take it out of the protective pouch.

Discard used Alora in household trash in a manner that prevents accidental application or ingestion by children, pets, or others.