Etonogestrel (NEXPLANON)

1. Health Canada Product Monograph — Etonogestrel

• NEXPLANON is used for prevention of pregnancy for up to 3 years.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• NEXPLANON is contraindicated in known or suspected pregnancy, since there is no need for pregnancy prevention in a woman who is already pregnant.
• Epidemiologic studies and meta-analyses have not shown an increased risk of genital or non-genital birth defects, including cardiac anomalies and limb-reduction defects, following exposure to low-dose hormonal contraceptives before conception or in early pregnancy.
• NEXPLANON should be removed if the woman wishes to maintain a pregnancy that occurs while the implant is in place.

• NEXPLANON may be used while breastfeeding, starting after the fourth postpartum week; in women at greater risk of unintended pregnancy or loss to follow-up, it may be inserted immediately postpartum.
• Small amounts of etonogestrel pass into breast milk, but no significant adverse effects on milk production or quality, or on the physical and psychomotor development of breastfed infants, have been observed.
• Hormonal contraceptives, including etonogestrel, can reduce milk production in some breastfeeding mothers, though this is less likely once breastfeeding is well established.

• NEXPLANON has not been studied in women over 65 years of age and is not indicated for postmenopausal women.

• NEXPLANON has not been studied in women under 18 years of age and is not indicated for use before menarche.
• Safety and efficacy are expected to be similar in post-pubertal adolescents as in adult women of reproductive age.

• A single NEXPLANON implant is inserted subdermally in the inner side of the non-dominant upper arm and provides contraception for up to 3 years; it must be removed no later than three years after insertion.
• Timing of insertion depends on the woman's recent contraceptive history: if no hormonal contraceptive was used in the preceding month, insert between Day 1 and Day 5 of the menstrual cycle; different timing rules apply when switching from a combined hormonal method, a progestin-only method, or after abortion, miscarriage, or childbirth.
• After removal, a new implant may be inserted immediately in the same or a different arm to maintain continuous contraceptive protection.
• Overweight women may require earlier replacement of the implant, since serum etonogestrel concentrations are inversely related to body weight and decrease over time, so effectiveness may be reduced, especially with concomitant use of hepatic enzyme inducers.
• The implant must only be inserted and removed by a healthcare professional trained in the specific insertion and removal technique, using the preloaded applicator under aseptic conditions.
• The presence of the implant must be verified by palpation immediately after insertion; if it cannot be felt, imaging such as ultrasound, X-ray, CT, or MRI, or blood etonogestrel testing, should be used to confirm its location before the woman relies on it for contraception.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• There is no data available on overdose with the etonogestrel implant.
• Overdose of contraceptives in general has not been associated with serious harmful effects.
• An implant should always be removed before a new one is inserted, to avoid excess exposure.

• Headache may occur.
• Weight increase may occur.
• Acne may occur.
• Breast pain may occur.
• Emotional lability (mood swings) may occur.
• Dizziness may occur.
• Abdominal pain may occur.
• Irregular vaginal bleeding patterns, including spotting, prolonged, frequent, or absent bleeding, are very common, especially in the first three months.
• Nausea may occur.
• Flatulence may occur.
• Dysmenorrhea (painful periods) may occur, though it tends to improve with use.
• Ovarian cysts may occur, usually resolving spontaneously without surgery.
• Hot flushes may occur.
• Insertion site pain or reaction may occur, particularly during and shortly after the procedure.
• Decreased libido may occur.
• Vaginitis may occur.
• Alopecia (hair thinning) may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis, have been reported, some fatal; NEXPLANON should be removed if a thrombosis occurs.
• Arterial thromboembolic events, including stroke and myocardial infarction, have been reported.
• Ectopic pregnancy can occur if pregnancy occurs during use; seek prompt evaluation for lower abdominal pain.
• Deep or incorrect insertion can cause neural or vascular injury, including postmarketing reports of implants migrating into blood vessels or the pulmonary artery, sometimes requiring surgical or endovascular removal.
• Implant migration within the arm can occur, occasionally making the implant difficult to locate or remove.
• Broken or bent implants have been reported, which may be related to external forces such as manipulation, tourniquet use, or trauma at the implant site.
• Depression, including significant worsening of mood, has been reported; consideration should be given to removing the implant in affected patients.
• Severe hypersensitivity reactions, including anaphylaxis, urticaria, and angioedema (including aggravation of hereditary angioedema), have been reported.
• Sustained hypertension or worsening blood pressure control can occur; the implant should be removed if blood pressure does not adequately respond to antihypertensive therapy.
• Idiopathic intracranial hypertension has been reported post-marketing.
• Liver tumours, benign or malignant, and disturbances of liver function, including jaundice, have been reported.
• Seek urgent medical attention for calf pain or swelling, sudden chest pain or shortness of breath, sudden severe headache, vision changes, or signs of a severe allergic reaction.

• Use with caution in women with a history of thrombosis or risk factors for thromboembolic disease.
• Use with caution in women with hypertension; blood pressure should be closely monitored, and the implant removed if hypertension becomes poorly controlled.
• Use with caution in women with diabetes or prediabetes, since etonogestrel may cause mild insulin resistance and small changes in glucose concentrations.
• Use with caution in women being treated for hyperlipidemia, as some progestins may elevate LDL cholesterol and make lipid control more difficult.
• Use with caution in women with a history of chloasma (melasma), and advise avoiding sun or ultraviolet exposure.
• Use with caution in women with a history of depressed mood, and consider removal if significant depression develops.
• Use with caution in women with conditions that might be aggravated by fluid retention.
• Use with caution in women who weigh more than 130% of their ideal body weight, since effectiveness may be reduced over time.
• Use with caution during long-term immobilization due to surgery or illness, where removal of the implant should be considered.
• Counsel women that NEXPLANON does not protect against sexually transmitted infections, including HIV, and that condoms should be used in combination for STI protection.

• Contraindicated in women with known or suspected pregnancy.
• Contraindicated in women with current or past history of thrombosis or thromboembolic disorders.
• Contraindicated in women with benign or malignant liver tumours or active liver disease.
• Contraindicated in women with undiagnosed abnormal genital bleeding.
• Contraindicated in women with known or suspected breast cancer, a personal history of breast cancer, or other progestin-sensitive cancer.
• Contraindicated in patients with known hypersensitivity to etonogestrel or to any ingredient in the formulation, including any non-medicinal ingredient or component of the container.

• Enzyme-inducing drugs, including barbiturates, carbamazepine, oxcarbazepine, phenytoin, rifampicin, rifabutin, topiramate, felbamate, griseofulvin, bosentan, and aprepitant, may decrease etonogestrel plasma concentrations and reduce contraceptive efficacy; a back-up non-hormonal method is advised during and for 28 days after use of the inducer.
• Strong or moderate CYP3A4 inhibitors, such as itraconazole, voriconazole, fluconazole, and ketoconazole, may increase progestin plasma concentrations.
• HIV protease inhibitors such as nelfinavir can significantly decrease progestin plasma concentrations, while indinavir and ritonavir-boosted protease inhibitors can significantly increase them.
• Hepatitis C protease inhibitors, including boceprevir and telaprevir, can significantly decrease progestin plasma concentrations.
• Non-nucleoside reverse transcriptase inhibitors have variable effects: nevirapine and efavirenz can significantly decrease progestin plasma concentrations, while etravirine can significantly increase them.
• NEXPLANON may affect the metabolism of other drugs, increasing plasma concentrations of some (such as cyclosporine) and decreasing others (such as lamotrigine); prescribing information of concurrently used drugs should be consulted.

• Grapefruit or grapefruit juice can inhibit CYP3A4 and may increase serum concentrations of progestins, including etonogestrel.

• NEXPLANON is not taken on a daily schedule; timing relates only to the day of insertion relative to the menstrual cycle or prior contraceptive method, as directed by a healthcare professional.

• Store at 2°C to 30°C, and do not insert the implant after the expiry date printed on the primary package.

• NEXPLANON is a single-rod contraceptive implant inserted under the skin of the upper arm that prevents pregnancy for up to 3 years.
• Changes in menstrual bleeding patterns are common and expected, especially in the first three months, and do not necessarily indicate a problem.
• NEXPLANON does not protect against sexually transmitted infections; use condoms for STI protection.
• Seek prompt medical attention for calf swelling or pain, sudden chest pain or breathlessness, severe headache or vision changes, significant mood changes, or if the implant becomes difficult to feel under the skin.