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Pronunciation: e-TOE-noe-jes-trel
Class: Contraceptive hormone

Trade Names

- Implant, subdermal 68 mg

- Implant, subdermal 68 mg


Suppresses ovulation, increases viscosity of the cervical mucus, and alters the endometrium.

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Bioavailability is approximately 100%. Mean C max ranges from 781 to 894 pg/mL ( Implanon ) and 1,200 pg/mL ± 604 ( Nexplanon ), and is reached within a few weeks after insertion. Concentration decreases gradually over time to 156 to 177 pg/mL ( Implanon ) and 138 pg/mL ( Nexplanon ) at 36 mo.


Vd averages 201 L. 66% bound to plasma albumin.


Etonogestrel is metabolized in the liver by CYP3A4.


Elimination half-life is approximately 25 h. Etonogestrel is excreted mainly in the urine as free steroid or as conjugates. After removal of the implant, concentrations decrease below assay sensitivity by 1 wk.

Special Populations

Renal Function Impairment

No formal pharmacokinetic studies were conducted to evaluate the effect of renal disease.

Hepatic Function Impairment

No formal pharmacokinetic studies were conducted to evaluate the effect of hepatic disease.


No formal pharmacokinetic studies were conducted to evaluate the effect of race.


The etonogestrel implant may be less effective in overweight women, especially in the presence of other factors that decrease etonogestrel concentrations, such as concomitant use of hepatic enzyme inducers.

Indications and Usage

Prevention of pregnancy.

Unlabeled Uses

Male contraceptive agent.


Known or suspected pregnancy; current or history of thrombosis or thromboembolic disorders; hepatic tumors (benign or malignant) or active liver disease; undiagnosed abnormal genital bleeding; known or suspected carcinoma of the breast or personal history of breast cancer or other progestin-sensitive cancer; hypersensitivity to any component of the product.

Dosage and Administration


Subdermal implant One etonogestrel implant inserted subdermally in the upper arm.

General Advice

  • Insertion and removal of the etonogestrel implant are performed by a health care provider.
  • Rule out pregnancy before inserting the etonogestrel implant.
  • Insert etonogestrel so that it is palpable.
  • Insert implant subdermally in the inner side of the nondominant upper arm about 8 to 10 cm (3 to 4 in) above the medial epicondyle of the humerus.
  • Timing of insertion depends on the patient's recent history. See manufacturer's prescribing information for more information.
  • The implant must be removed by the end of the third year and replaced by a new implant at the time of removal if continued contraception is desired.
  • If inserted as recommended, back up contraception is not necessary. If deviating from the recommended timing of insertion, rule out pregnancy and advise patient to use back up nonhormonal contraception for 7 days after insertion.


Store between 59° and 86°F. Protect from light.

Drug Interactions

Aprepitant, azole antifungals (eg, itraconazole, ketoconazole), barbiturates (eg, phenobarbital), carbamazepine, efavirenz, felbamate, griseofulvin, hepatitis C virus protease inhibitors (eg, boceprevir), hydantoins (eg, phenytoin), modafinil, nevirapine, oxcarbazepine, phenylbutazone, rifamycins (eg, rifampin), rufinamide, St. John's wort, thiazolidinediones (eg, pioglitazone), topiramate

Breakthrough bleeding or unintended pregnancy may occur. Consider use of an additional nonhormonal contraceptive method. Use with nevirapine is not recommended.


Hormonal contraceptives may increase lamotrigine metabolism, decreasing the therapeutic effect. Larger doses of lamotrigine may be needed. Additional plasma concentration and clinical monitoring are warranted.

Protease inhibitors (eg, atazanavir, ritonavir)

Safety and efficacy of oral contraceptives may be affected. It is unknown whether this applies to the etonogestrel implant. Refer to the labeling of the individual HIV protease inhibitors for further drug interaction information.


Hormonal contraceptives may inhibit the metabolism of selegiline, causing a loss of selective inhibition of monoamine oxidase type B and increasing the risk of adverse reactions. Close clinical monitoring is warranted.


Plasma concentrations of theophyllines may be elevated, increasing the pharmacologic effects and risk of toxicity. Monitor theophylline plasma concentrations; adjust the dose accordingly.

Tranexamic acid

The antifibrinolytic effects of tranexamic acid may further increase the thrombotic risk associated with etonogestrel.


Coadministration may be associated with a high frequency of cholestatic jaundice. Avoid coadministration.

Valproic acid

Valproic acid plasma concentrations may be reduced, decreasing the pharmacologic effects. Monitor valproic acid serum concentrations and clinical effects. Adjust the valproic acid dosage as needed.

Laboratory Test Interactions

Sex hormone–binding globulin may be decreased for the first 6 mo after etonogestrel insertion, followed by gradual recovery; initially, thyroxine concentrations may be decreased slightly, followed by gradual recovery.

Adverse Reactions


Hot flushes, hypertension, varicose vein (less than 5%).


Headache (25%); dizziness, emotional lability (7%); depression, nervousness (6%); abnormal crying, anxiety, asthenia, decreased libido, fatigue, hypoesthesia, insomnia, migraines, somnolence (less than 5%); convulsions (postmarketing).


Acne (14%); alopecia, hypertrichosis, pruritus, rash (less than 5%); aggravation of angioedema and/or hereditary angioedema, chloasma, seborrhea, urticaria (postmarketing).


Pharyngitis (11%); abnormal vision, otitis media, rhinitis (less than 5%).


Abdominal pain (11%); nausea (6%); anorexia, constipation, diarrhea, dyspepsia, flatulence, gastritis, vomiting (less than 5%).


Vaginitis (15%); breast pain (13%); vaginal bleeding (11%); leukorrhea (10%); dysmenorrhea (7%); abnormal sexual function, breast discharge, breast enlargement, breast fibroadenosis, dysuria, genital pruritus, nonpuerperal lactation, ovarian cyst, pelvic cramping, positive cervical smear test, premenstrual tension, vaginal discomfort (less than 5%); ectopic pregnancy, UTI, vulvovaginal discomfort (postmarketing).


Implant-site reactions (9%); insertion-site pain (5%); injection-site reaction (less than 5%); implant-site complications (4%); hematoma, implant-site erythema, pain (3%); implant-site bruising (2%), implant-site swelling (1%); implant insertion or removal complications (eg, abscess, bruising, local irritation, fibrosis, itching, pain, paresthesia or paresthesia-like events, scarring) (postmarketing).


Increased weight (14%); decreased weight, increased appetite (less than 5%); weight gain.


Back pain (7%); arthralgia, myalgia, skeletal pain (less than 5%).


Upper respiratory tract infection (13%); sinusitis (6%); asthma, coughing (less than 5%).


Influenza-like symptoms (8%); pain (6%); hypersensitivity (5%); allergic reaction, edema, fever, generalized edema (less than 5%).



Perform a complete medical evaluation prior to implantation and carefully monitor women with a family history of breast cancer or those who have breast nodules. In case of undiagnosed, persistent, or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Monitor patient closely for loss of vision, sudden onset of proptosis, diplopia, papilledema, or retinal vascular lesions. Monitor patient for an increase in blood pressure, signs and symptoms of thromboembolic disorders, signs or symptoms of depression, glycemic control in patients with diabetes, lipid profiles in patients being treated for hyperlipidemia, and patients with conditions that may be aggravated by fluid retention.


Category X . Not indicated for use during pregnancy.


Small amounts excreted in breast milk. May be used during lactation after postpartum wk 4.


Safety and efficacy expected to be the same for post pubertal adolescents. Use of this product before menarche is not indicated.


Not indicated in this population.

Hepatic Function

Use in women with active liver disease or liver cancer is contraindicated. Etonogestrel may be poorly metabolized in patients with impaired liver function.

Bleeding irregularities

Changes in vaginal bleeding pattern, such as amenorrhea, or bleeding frequency, duration, or intensity, may occur.

Breast cancer

Women with breast cancer should not use hormonal contraceptives because breast cancer may be hormonally sensitive.

Contact lenses

Consider ophthalmologic examination in contact lens wearers who develop visual changes or lens intolerance.


Carefully observe patients with a history of depression. If patients become severely depressed, consider removing the implant.

Ectopic pregnancy

Be alert for ectopic pregnancy after insertion.

Fluid retention

Because steroid contraceptives cause some degree of fluid retention, use them with caution in patients with conditions that may be aggravated by fluid retention.

Gallbladder disease

The risk of gallbladder disease may be increased slightly with use of combined oral contraceptives.

Glucose tolerance

Mild insulin resistance and small changes in glucose concentrations may occur.

Hepatic neoplasm

Benign hepatic adenomas have been associated with use of combined oral contraceptives.


Incidence of hypertension increases with increasing doses of progestin.

Lipid metabolic effects

Progestins may elevate LDL levels and render the control of hyperlipidemia more difficult.

Ovarian cysts

Atresia of the follicle may be delayed and follicle may continue to grow beyond the size attained in a normal cycle.

Return to ovulation

Pregnancies occurred as early as 1 wk after removal of the implant.


This product does not protect against infection from HIV or other STDs.


Cigarette smoking increases the risk of serious CV adverse reactions from use of combined hormonal contraceptives. It is not known if a similar risk exists with progestin-only methods.


Serious thromboembolic reactions have been reported, including cases of fatal pulmonary emboli, deep vein thrombosis, MI, and stroke.

Weight gain

May occur.



None well documented.

Patient Information

  • Provide patients with a copy of the patient information leaflet and ensure they understand the information before etonogestrel insertion or removal.
  • Inform patients that etonogestrel implant does not protect against HIV infection or other STDs.
  • Inform patients that they must have the etonogestrel implant removed after 3 y and that, if they want to continue using the etonogestrel implant, a health care provider can put a new etonogestrel implant under their skin after taking out the old one.
  • Counsel patients to expect their menstrual period to be irregular and unpredictable throughout the time they are using the etonogestrel implant. Warn patients that they may have more bleeding, less bleeding, or no bleeding, that the time between periods may vary, and in between periods they may have spotting.
  • Advise patients to not use the etonogestrel implant if they are pregnant or think they may be pregnant; have, or have had serious blood clots, such as blood clots in their legs (deep venous thrombosis), lungs (pulmonary embolism), eyes (retinal thrombosis), heart (heart attack), or head (stroke); have unexplained vaginal bleeding; or have liver disease or have breast cancer, now or in the past.
  • Inform patients that the risk of thrombosis is increased in women who smoke. Advise patients who smoke to quit.
  • Advise patients to tell their health care provider at least 4 wk before if they are going to have surgery or will need to be on bed rest. Inform patients that there is an increased risk of getting thrombosis during surgery or bed rest.
  • Inform patients that a few women who use birth control that contains hormones may get high blood pressure, gallbladder problems, or rare cancerous or noncancerous liver tumors.

Copyright © 2009 Wolters Kluwer Health.