Drug Safety-related Labeling Changes (SrLC)

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NORDETTE-28 (NDA-018782)

(ETHINYL ESTRADIOL; LEVONORGESTREL)

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

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04/29/2022 (SUPPL-41)

Approved Drug Label (PDF)

4 Contraindications

Additions underlined

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

5 Warnings and Precautions

WARNINGS

Additions underlined

  1. Malignant Neoplasms

    Breast Cancer

    NORDETTE-28 is contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive [see Contraindications (4)].

    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

Additions 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 2).

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2). 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.

Figure 2: Relevant Studies of Risk of Breast Cancer with Combined Oral Contraceptives

Please refer to label to view Figure 2.

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

PATIENT INFORMATION

Additions underlined

Do birth control pills cause cancer?

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.

05/07/2021 (SUPPL-40)

Approved Drug Label (PDF)

5 Warnings and Precautions

PRECAUTIONS

(Additions and/or revisions underlined)

4.3 Concomitant Use with Hepatitis C Virus (HCV) Combination Therapy-Liver Enzyme Elevation

Do not co-administer NORDETTE-28 with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, [see Warnings (5)], and glecaprevir/pibrentasvir due to potential for ALT elevations.

6 Pregnancy

Risk Summary

Discontinue NORDETTE-28 if pregnancy occurs because there is no reason to use COCs in

pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to COCs before conception or during early pregnancy. Animal studies to evaluate embryo/fetal toxicity were not conducted.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.

10 PATIENT COUNSELING INFORMATION

  • Counsel patients that cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs (see BOXED WARNING and CONTRAINDICATIONS).

  • Counsel patients that this product does not protect against HIV-infection (AIDS) and other sexually transmitted infections.

  • Counsel patients to take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event pills are missed (see DOSAGE AND ADMINISTRATION).

  • Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs [see PRECAUTIONS (4.1)].

  • Counsel patients who are breastfeeding or who desire to breastfeed that COCs may reduce breast milk production. This is less likely to occur if breastfeeding is well established [see PRECAUTIONS (7)].

  • Counsel any patient who starts NORDETTE-28 postpartum, and who has not yet had a period, to use an additional method of contraception until she has taken a light-orange tablet for 7 consecutive days (see DOSAGE AND ADMINISTRATION).

  • Counsel patients that amenorrhea may occur. Pregnancy should be considered in the event of amenorrhea, and should be ruled out if amenorrhea is associated with symptoms of pregnancy, such as morning sickness or unusual breast tenderness [see WARNINGS (9)].

  • Depression may occur. Women should contact their healthcare provider if depression occurs, including shortly after initiating the treatment [see WARNINGS (10)].

03/13/2019 (SUPPL-39)

Approved Drug Label (PDF)

Other

(Extensive changes; please refer to labeling)

08/09/2017 (SUPPL-38)

Approved Drug Label (PDF)

4 Contraindications

(Additions and/or revisions are underlined)

Combination oral contraceptives should not be used in women with any of 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 Nordette-28 prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. Nordette-28 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 Hepatitis C Virus (HCV) Combination Therapy – Liver Enzyme Elevation

Do not co-administer Nordette-28 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 LABELING

WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES

Or, if you have any of the following:

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

Questions related to the drug data in these files should be directed to the Center for Drug Evaluation and Research, Division of Drug Information
druginfo@fda.hhs.gov.

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