Selected Safety Information

CONTRAINDICATIONS

• NEXPLANON should not be used in women who have known or suspected pregnancy; current or past history of thrombosis or thromboembolic disorders; liver tumors, benign or malignant, or active liver disease; undiagnosed abnormal genital bleeding; known or suspected breast cancer, personal history of breast cancer, or other progestin-sensitive cancer, now or in the past; and/or allergic reaction to any of the components of NEXPLANON.

WARNINGS AND PRECAUTIONS

Complications of Insertion and Removal

• NEXPLANON should be inserted subdermally so that it will be palpable after insertion, and this should be confirmed by palpation immediately after insertion. Failure to insert NEXPLANON properly may go unnoticed unless it is palpated immediately after insertion. Undetected failure to insert the implant may lead to an unintended pregnancy. 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.
• Complications related to insertion and removal procedures, such as pain, paresthesias, bleeding, hematoma, scarring, or infection, may occur. If NEXPLANON is inserted deeply (intramuscular or in the fascia), neural or vascular injury may occur. Implant removal may be difficult or impossible if the implant is not inserted correctly, inserted too deeply, not palpable, encased in fibrous tissue, or has migrated. If at any time the implant cannot be palpated, it should be localized and removal is recommended.
• There 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 insertions. Endovascular or surgical procedures may be needed for removal.

Changes in Menstrual Bleeding Patterns

• After starting NEXPLANON, women are likely to have changes in their menstrual bleeding pattern. These may include changes in frequency, intensity, or duration. Abnormal bleeding should be evaluated as needed to exclude pathologic conditions or pregnancy. In clinical studies of the non-radiopaque etonogestrel implant, reports of changes in bleeding pattern were the most common reason for stopping treatment (11.1%). Women should be counseled regarding bleeding pattern changes that they may experience.

Ectopic Pregnancies

• Be alert to the possibility of an ectopic pregnancy in women using NEXPLANON who become pregnant or complain of lower abdominal pain.

Thrombotic and Other Vascular Events

• The use of combination hormonal contraceptives increases the risk of vascular events, including arterial events (strokes and myocardial infarctions) or deep venous thrombotic events (venous thromboembolism, deep venous thrombosis, retinal vein thrombosis, and pulmonary embolism). It is recommended that women with risk factors known to increase the risk of venous and arterial thromboembolism be carefully assessed. There have been postmarketing reports of serious arterial thrombotic and venous thromboembolic events, including cases of pulmonary emboli (some fatal), deep vein thrombosis, myocardial infarction, and strokes, in women using etonogestrel implants. NEXPLANON should be removed in the event of a thrombosis. Due to the risk of thromboembolism associated with pregnancy and immediately following delivery, NEXPLANON should not be used prior to 21 days postpartum. Women with a history of thromboembolic disorders should be made aware of the possibility of a recurrence. Consider removal of the NEXPLANON implant in case of long-term immobilization due to surgery or illness.

Ovarian Cysts

• If follicular development occurs, atresia of the follicle is sometimes delayed, and the follicle may continue to grow beyond the size it would attain in a normal cycle. Generally, these enlarged follicles disappear spontaneously. Rarely, surgery may be required.

Carcinoma of the Breast and Reproductive Organs

• Some studies suggest that the use of combination hormonal contraceptives might increase the incidence of breast cancer, and increase the risk of cervical cancer or intraepithelial neoplasia. Women with a family history of breast cancer or who develop breast nodules should be carefully monitored.

Liver Disease

• NEXPLANON should be removed if jaundice occurs.

Elevated Blood Pressure

• The NEXPLANON implant should be removed if blood pressure rises significantly and becomes uncontrolled.

Gallbladder Disease

• Studies suggest a small increased relative risk of developing gallbladder disease among combination hormonal contraceptive users. It is not known whether a similar risk exists with progestin-only methods like NEXPLANON.

Carbohydrate and Lipid Metabolic Effects

• Prediabetic and diabetic women using NEXPLANON should be carefully monitored.

Depressed Mood

• Women with a history of depressed mood should be carefully observed. Consideration should be given to removing NEXPLANON in patients who become significantly depressed.

Return to Ovulation

• In clinical trials with the non-radiopaque etonogestrel implant (IMPLANON), the etonogestrel levels in blood decreased below sensitivity of the assay by one week after removal of the implant. In addition, pregnancies were observed to occur as early as 7 to 14 days after removal. Therefore, a woman should re-start contraception immediately after removal of the implant if continued contraceptive protection is desired.

Fluid Retention

• Hormonal contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. It is unknown if NEXPLANON causes fluid retention.

Contact Lenses

• Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.

Broken or Bent Implant

• There have been reports of broken or bent implants, which may be related to external forces (e.g., manipulation of the implant or contact sports) while in the patient’s arm. There have also been reports of migration of a broken implant fragment within the arm. Based on in vitro data, when an implant is broken or bent, the release rate of etonogestrel may be slightly increased. When an implant is removed, it is important to remove it in its entirety.

ADVERSE REACTIONS

Clinical Trial Experience

• The most common adverse reaction causing discontinuation of use of the implant in clinical trials was change in menstrual bleeding patterns, specifically irregular menses (11.1%).The most common adverse reactions (≥10%) reported in clinical trials were headache (24.9%), vaginitis (14.5%), weight increase (13.7%), acne (13.5%), breast pain (12.8%), abdominal pain (10.9%), and pharyngitis (10.5%).

Effects of Other Drugs on Hormonal Contraceptives

Substances decreasing the plasma concentrations of hormonal contraceptives and potentially diminishing the efficacy of hormonal contraceptives:

• Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of hormonal contraceptives and potentially diminish the effectiveness of hormonal contraceptives or increase breakthrough bleeding. Women should use an alternative non-hormonal method of contraception or a back-up method when enzyme inducers are used with hormonal contraceptives, and to continue back-up non-hormonal contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.

Substances increasing the plasma concentrations of hormonal contraceptives:

• Co-administration of certain hormonal contraceptives and strong or moderate CYP3A4 inhibitors may increase the serum concentrations of progestins, including etonogestrel.

Human Immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors:

• Significant changes (increase or decrease) in the plasma concentrations of progestin have been noted in cases of co-administration with HIV protease inhibitors, HCV protease inhibitors, or with non-nucleoside reverse transcriptase inhibitors. These changes may be clinically relevant.

Effects of Hormonal Contraceptives on Other Drugs

• Hormonal contraceptives may affect the metabolism of other drugs. Consequently, plasma concentrations may either increase (for example, cyclosporine) or decrease (for example, lamotrigine).

USE IN SPECIFIC POPULATIONS

Pregnancy

• Rule out pregnancy before inserting NEXPLANON.

Lactation

• Small amounts of contraceptive steroids and/or metabolites, including etonogestrel are present in human milk. No significant adverse effects have been observed in the production or quality of breast milk, or on the physical and psychomotor development of breastfed infants.
• Hormonal contraceptives, including etonogestrel, can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women.

Pediatric Use

• Safety and efficacy of NEXPLANON have been established in women of reproductive age and are expected to be the same for postpubertal adolescents. However, no studies have been conducted in women less than 18 years of age. Use of this product before menarche is not indicated.

Overweight Women

• The efficacy of NEXPLANON in women who weighed more than 130% of their ideal body weight has not been defined because such women were not studied in clinical trials. Serum concentrations of etonogestrel are inversely related to body weight and decrease with time after implant insertion. Therefore, NEXPLANON may be less effective in overweight women.

PATIENT COUNSELING INFORMATION

• Counsel women to contact their health care provider immediately if, at any time, they are unable to palpate the implant.
• NEXPLANON does not protect against HIV or other STDs.

Before prescribing NEXPLANON, please read the accompanying Prescribing Information. The Patient Information also is available.