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.

IMPLANON (NDA-021529)

(ETONOGESTREL)

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

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01/16/2026 (SUPPL-27)

Approved Drug Label (PDF)

Boxed Warning

Newly added section:

WARNING: RISK OF COMPLICATIONS DUE TO IMPROPER INSERTION and REMOVAL

Improper insertion of NEXPLANON increases the risk of complications [see Warnings and Precautions (5.1)].
Proper training prior to first use of NEXPLANON can minimize the risk of improper NEXPLANON insertion [see Warnings and Precautions (5.1)].
Because of the risk of complications due to improper insertion and removal NEXPLANON is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the NEXPLANON REMS [see Warnings and Precautions (5.2)].

4 Contraindications

Additions and/or revisions underlined:

NEXPLANON should not be used in women who have

…

Undiagnosed abnormal uterine bleeding

…

5 Warnings and Precautions

5.1 Risk of Complications Due to Improper Insertion and Removal

Subsection title revised

Additions and/or revisions underlined:

…

NEXPLANON is available only through a restricted program under a REMS [see Warnings and Precautions (5.2)].

5.2 NEXPLANON REMS

Newly added subsection:

NEXPLANON is only available through a restricted program under a REMS called NEXPLANON REMS because of the risk of complications due to improper insertion and removal [see Warnings and Precautions (5.1)].

Notable requirements of the NEXPLANON REMS include the following:

Healthcare providers must be certified with the program by enrolling and completing training on the proper insertion and removal of NEXPLANON prior to first use.
Pharmacies must be certified with the program and must only dispense NEXPLANON to certified healthcare providers who dispense NEXPLANON for insertion.
Wholesalers and distributors must be registered with the program and must only distribute to certified pharmacies and certified healthcare providers.

Further information is available at www.NEXPLANONREMS.com and 1-833-697-7367.

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

Adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice, because clinical trials are conducted under widely varying conditions.

In clinical trials of three years duration involving 942 women who were evaluated for safety, change in menstrual bleeding patterns (irregular menses) was the most common adverse reaction causing discontinuation of use of the non-radiopaque etonogestrel implant (IMPLANON) (11.1% of women).

Adverse reactions that resulted in a rate of discontinuation of greater than or equal to 1% are shown in Table 3.

Table 3: Adverse Reactions Leading to Discontinuation of Treatment in 1% or More of Subjects in 3-Year Clinical Trials of the Non-Radiopaque Etonogestrel Implant (IMPLANON)

…

Table 4: Common Adverse Reactions Reported by greater than or equal to 5% of Subjects in 3-Year Clinical Trials with the Non-Radiopaque Etonogestrel Implant (IMPLANON)

…

In a separate clinical trial to assess contraceptive efficacy and safety of NEXPLANON beyond 3 years, up to 5 years, where a total of 498 women were evaluated for safety, a similar adverse reaction profile was observed as in Years 1 through 3.The most frequently reported adverse reaction >5% related to NEXPLANON was intermenstrual bleeding (5.4%), Changes in menstrual bleeding patterns were the most frequently reported adverse reaction leading to discontinuation occurring in 4.0% of participants.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of NEXPLANON have been established in women of reproductive potential. Safety and effectiveness of NEXPLANON are expected to be the same in postpubertal adolescents as in adult women.

NEXPLANON is not indicated before menarche.

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

PATIENT INFORMATION

Additions and/or revisions underlined:

…

What is NEXPLANON?

NEXPLANON is a hormone-releasing birth control implant for prevention of pregnancy for up to 5 years. The implant is a flexible plastic rod about the size of a matchstick that contains a progestin hormone called etonogestrel. It contains a small amount of barium sulfate (15 mg), so that the implant can be seen by X-ray, an ethylene vinyl acetate (EVA) copolymer (28% vinyl acetate, 43 mg) core, and magnesium stearate (0.1 mg). Your healthcare professional will insert the implant just under the skin of the inner side of your upper arm. You can use a single NEXPLANON implant for up to 5 years. NEXPLANON does not contain estrogen.

…

03/14/2016 (SUPPL-13)

Approved Drug Label (PDF)

5 Warnings and Precautions

Complications of Insertion and Removal

There have been reports of migration of the implant within the arm from the insertion site, which may be related to deep insertion. There also have been postmarketing reports of implants located within the vessels of the arm and the pulmonary artery, which may be related to deep insertions or intravascular insertion. In cases where the implant has migrated to the pulmonary artery, endovascular or surgical procedures may be needed for removal.
If at any time the implant cannot be palpated, it should be localized and removal is recommended.
Exploratory surgery without knowledge of the exact location of the implant is strongly discouraged.
Removal of deeply inserted implants should be conducted with caution in order to prevent injury to deeper neural or vascular structures in the arm and be performed by healthcare providers familiar with the anatomy of the arm. If the implant is located in the chest, healthcare providers familiar with the anatomy of the chest should be consulted. Failure to remove the implant may result in continued effects of etonogestrel, such as compromised fertility, ectopic pregnancy, or persistence or occurrence of a drug related adverse event.

6 Adverse Reactions

Postmarketing Experience

Expulsion or migration of the implant have been reported, including to the chest wall. In some cases, implants have been found within the vasculature, including the pulmonary artery. Some cases of implants found within the pulmonary artery reported chest pain and/or dyspnea; others have been reported as asymptomatic. Surgical intervention might be necessary when removing the implant.