Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

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.

LOESTRIN 21 1.5/30 (NDA-017875)

(ETHINYL ESTRADIOL; NORETHINDRONE ACETATE)

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

Download Data

Expand all

01/04/2023 (SUPPL-41)

Approved Drug Label (PDF)

4 Contraindications

(Additions and/or revisions underlined)

Oral contraceptives are contraindicated in women who currently have the following conditions:
Thrombophlebitis or thromboembolic disorders
A past history of deep vein thrombophlebitis or thromboembolic disorders
Cerebral vascular or coronary artery disease
Current diagnosis of, or history of, breast cancer, which may be hormone sensitive
Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia

5 Warnings and Precautions

WARNINGS

3. Malignant Neoplasms

(Additions and/or revisions underlined)

Cervical Cancer

Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women (42-45).

4. Hepatic Neoplasia

(Additions and/or revisions underlined)

Benign hepatic adenomas are associated with oral contraceptive use, although the incidence of benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/100,000 for users, a risk that increases after four or more years of use (46). Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage (47,48).

Studies from Britain have shown an increased risk of developing hepatocellular carcinoma (49-51) in long-term (greater than 8 years) oral contraceptive users. However, these cancers are extremely rare in the U.S., and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users.

7. Oral Contraceptive Use Before and During Early Pregnancy

(Additions and/or revisions underlined)

Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy (52-54). Studies also do not suggest a teratogenic effect, particularly insofar as cardiac anomalies and limb reduction defects are concerned (52, 53, 55, 56), when taken inadvertently during early pregnancy.

8. Gallbladder Disease

(Additions and/or revisions underlined)

Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens (57,58). More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal (59-61). The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens.

9. Carbohydrate And Lipid Metabolic Effects

(Additions and/or revisions underlined)

Oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users (23). Oral contraceptives containing greater than 75 mcg of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance (62). Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents (23,63). However, in the non-diabetic woman, oral contraceptives appear to have no effect on fasting blood glucose (64). Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking oral contraceptives.

…

10. Elevated Blood Pressure

(Additions and/or revisions underlined)

An increase in blood pressure has been reported in women taking oral contraceptives (65) and this increase is more likely in older oral contraceptive users (66) and with continued use (65). Data from the Royal College of General Practitioners (18) and subsequent randomized trials have shown that the incidence of hypertension increases with increasing concentrations of progestogens.

Women with a history of hypertension or hypertension-related diseases or renal disease (67) should be encouraged to use another method of contraception. If women elect to use oral contraceptives, they should be monitored closely, and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping oral contraceptives (66), and there is no difference in the occurrence of hypertension among ever and never users (65,67,68).

13. Hereditary Angioedema

(Newly added subsection)

In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.

14. Depression

(Newly added subsection)

Carefully observe women with a history of depression and discontinue LOESTRIN if depression recurs to a serious degree.

PRECAUTIONS

7. Drug Interactions

(Additions and/or revisions underlined)

Effects of Other Drugs on Oral Contraceptives (69)

Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Co-administration of LOESTRIN with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir is contraindicated due to

Potential for ALT elevations (see Warnings, RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT). Co-administration of LOESTRIN and glecaprevir/pibrentasvir is not recommended due to potential for ALT elevations.

10. Pregnancy

(Additions and/or revisions underlined)

Discontinue LOESTRIN if pregnancy occurs because there is no reason to use COCs in pregnancy. See WARNINGS section.

6 Adverse Reactions

(Additions and/or revisions underlined)

Post Marketing Experience

Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 1) (70-74).

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1) (70,73,75). One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use.

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

PATIENT COUNSELING INFORMATION

(Extensive changes; please refer to label for complete information)

05/02/2022 (SUPPL-40)

Approved Drug Label (PDF)

4 Contraindications

Addition of the following to the bulleted line listing:

Current diagnosis of, or history of, breast cancer, which may be hormone sensitive

5 Warnings and Precautions

WARNINGS

Additions underlined

…

3. Malignant Neoplasms

Breast Cancer

Loestrin is contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive (see CONTRAINDICATIONS).

Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer. However, some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use (see ADVERSE REACTIONS, Postmarketing Experience).

…

6 Adverse Reactions

Postmarketing Experience

New subsection added

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1). One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use.

Please refer to label to view Figure 1.

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

PATIENT INFORMATION

BRIEF SUMMARY PATIENT PACKAGE INSERT

Addotions underlined

…

There may be slight increases in the risk of breast cancer among current users of hormonal birth control pills with longer duration of use of 8 years or more. Some studies have found an increase in the risk of developing cancer of the cervix in women taking the pill, but this finding may be related to differences in sexual behavior or other factors not related to use of the pill.

DETAILED PATIENT PACKAGE INSERT

Additions underlined

…

5.Risk of Cancer

It is not known if hormonal birth control pills cause breast cancer. Some studies, but not all, suggest that there could be a slight increase in the risk of breast cancer among current users with longer duration of use.

If you have breast cancer now, or have had it in the past, do not use hormonal birth control because some breast cancers are sensitive to hormones.

…

08/09/2017 (SUPPL-37)

Approved Drug Label (PDF)

4 Contraindications

(Additions and/or revisions are underlined)

Oral contraceptives should not be used in women who currently have the following conditions:

Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations.

5 Warnings and Precautions

WARNINGS

(Additions and/or revisions are underlined)

5. Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment

During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications such as COCs. Discontinue LOESTRIN prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. LOESTRIN can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen.

7 Drug Interactions

(Additions and/or revisions are underlined)

Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer LOESTRIN with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations.

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

Patient Information

(Additions and/or revisions are underlined)

DETAILED PATIENT PACKAGE INSERT

WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES

Some women should not use the pill. For example, you should not take the pill if you are pregnant or think you may be pregnant. You should also not use the pill if you have any of the following conditions:

Take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme “alanine aminotransferase” (ALT) in the blood.