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.

ORTHO TRI-CYCLEN (NDA-019697)

(ETHINYL ESTRADIOL; NORGESTIMATE)

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

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06/15/2023 (SUPPL-56)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

Immune System Disorders: Anaphylactic reaction, hypersensitivity;

7 Drug Interactions

7.1 Effects of Other Drugs on Combined Oral Contraceptives

Additions and/or revisions underlined:

…

Human immunodeficiency virus (HIV)/Hepatitis C virus (HCV) protease inhibitors, non- nucleoside reverse transcriptase inhibitors, and HIV/AIDS medications containing strong inhibitors or inducers of CYP3A

Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir])/HCV protease inhibitors (decrease [e.g., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]) or with HIV/AIDS medications containing strong inhibitors (e.g., cobicistat and ritonavir) or inducers of CYP3A.

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

There is no use for contraception in pregnancy, therefore, ORTHO-CYCLEN and ORTHO TRI- CYCLEN should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb reduction defects) following exposure to CHCs before conception or during early pregnancy.

8.2 Lactation

Additions and/or revisions underlined:

Risk Summary

Contraceptive hormones and/or metabolites are present in human milk. CHCs can reduce milk production in breastfeeding females. This reduction can occur at any time but is less likely to occur once breastfeeding is well-established. When possible, advise the nursing female to use other forms of contraception until she discontinues breast-feeding. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for ORTHO- CYCLEN and ORTHO TRI-CYCLEN and any potential adverse effects on the breast-fed child from ORTHO-CYCLEN and ORTHO TRI-CYCLEN or from the underlying maternal condition.

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

PATIENT INFORMATION

Additions and/or revisions underlined:

Other serious side effects include:

…

severe allergic reactions that may include swelling of your skin especially around your mouth, eyes, and in your throat (angioedema).

06/15/2023 (SUPPL-57)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

Immune System Disorders: Anaphylactic reaction, hypersensitivity;

7 Drug Interactions

7.1 Effects of Other Drugs on Combined Oral Contraceptives

Additions and/or revisions underlined:

…

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

8.2 Lactation

Additions and/or revisions underlined:

Risk Summary

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

PATIENT INFORMATION

Additions and/or revisions underlined:

Other serious side effects include:

…

severe allergic reactions that may include swelling of your skin especially around your mouth, eyes, and in your throat (angioedema).

04/29/2022 (SUPPL-58)

Approved Drug Label (PDF)

4 Contraindications

Additions underlined

…

ORTHO-CYCLEN and ORTHO TRI-CYCLEN are contraindicated in females who are known to have or develop the following conditions:

…

Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.11)]

…

5 Warnings and Precautions

5.11 Malignant Neoplasms

Additions underlined

Breast Cancer

ORTHO-CYCLEN and ORTHO TRI-CYCLEN are 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 Postmarketing Experience (6.2)].

…

6 Adverse Reactions

6.2 Postmarketing Experience

Additions underlined

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).

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.

…

The following additional adverse drug reactions have been reported from worldwide

postmarketing experience with norgestimate/ethinyl estradiol. Because these reactions are…

Vascular Events: Deep vein thrombosis, pulmonary embolism, retinal vascular thrombosis, hot flush, venous thrombosis (including Budd Chiari Syndrome and hepatic vein thrombosis);

…

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

PATIENT INFORMATION

Additions underlined

…

Do birth control pills cause 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

…

08/09/2017 (SUPPL-54)

Approved Drug Label (PDF)

4 Contraindications

(Additions and/or revisions are underlined)

Do not prescribe ORTHO-CYCLEN or ORTHO TRI-CYCLEN to women who are known to have the following conditions:

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

5 Warnings and Precautions

5.3 Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment

(Newly added subsection)

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 ORTHO-CYCLEN or ORTHO TRI-CYCLEN prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. ORTHO-CYCLEN or ORTHO TRI-CYCLEN can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.

7 Drug Interactions

7.4 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation

(Newly added subsection)

Do not co-administer ORTHO-CYCLEN or ORTHO TRI-CYCLEN 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)

Who should not take ORTHO-CYCLEN or ORTHO TRI-CYCLEN?

Do not take ORTHO-CYCLEN or ORTHO TRI-CYCLEN if you:

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.