U.S. Brand Names

• Implanon™

Generic Available

No

Pharmacologic Categories

• Contraceptive
• Progestin

Related Terms

• 3-Keto-desogestrel
• ENG

Available Products

Image	Description
	Brand Name Implanon™ Strength 68 mg Labeler Organon Inc Class Rx Route subdermal NDC 000520272

Restrictions on Use

Only healthcare providers who have undergone training in the insertion and removal procedures will be able to order Implanon™. Materials related to the insertion and removal of Implanon™ are available from the manufacturer (877-467-5266).

Indications

Prevention of pregnancy; for use in women who request long-acting (up to 3 years) contraception

Hypersensitivity to etonogestrel or any component of the formulation; undiagnosed abnormal uterine bleeding; active hepatic disease or tumors; active thrombophlebitis or thromboembolic disorders (current or history of); known/suspected or history of carcinoma of the breast; pregnancy

Concerns related to adverse effects:

• Bleeding irregularities: Changes in bleeding patterns are likely to occur. Abnormal bleeding should be evaluated as required to exclude pathologic conditions or pregnancy.
• Ectopic pregnancy: Ectopic pregnancy (rare) may occur more commonly than in women using no contraception.
• Thromboembolism: May increase the risk of thromboembolism. Consider removal during periods of prolonged immobilization.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment. Women with renal disease should be encouraged to use a nonhormonal form of contraception.
• Hepatic disease: Use in contraindicated with hepatic disease; remove implant if jaundice develops.

Concurrent drug therapy issues:

• Hepatic enzyme inducers: Etonogestrel serum levels and contraceptive efficacy may be significantly decreased by potent hepatic enzyme inducer; the manufacturer does not recommend use in women chronically taking hepatic enzyme inducers.

Special populations:

• Overweight: Use with caution in overweight women (may be less effective); women >130% of ideal body weight were not included in clinical studies.
• Pediatrics: Not for use prior to menarche.

Other warnings/precautions:

• Appropriate use: Insert intradermally; should be palpable after implanted. Improper insertion may lead to unintended pregnancy or may cause difficult or impossible removal. Failure to properly remove may lead to infertility, ectopic pregnancy, or continued adverse reactions. Menstrual bleeding patterns are likely to be altered; patients should be counseled prior to implant insertion.
• HIV infection protection: Use does not protect against HIV infection or other sexually-transmitted diseases.

Additional concerns reported with combination oral contraceptives:

• Breast cancer: Use has been associated with a slight increase in frequency of breast cancer, however, studies are not consistent.
• Carbohydrate intolerance: May have adverse effects on glucose tolerance; use caution in women with diabetes.
• Cardiovascular disease: Use with caution in patients with risk factors for coronary artery disease; may lead to increased risk of myocardial infarction. May have a dose-related risk of vascular disease and hypertension; women with hypertension should be encouraged to use a nonhormonal form of contraception. May increase the risks of stroke, pulmonary emboli, and deep vein thrombosis.
• Depression: Use with caution in patients with depression.
• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including asthma, epilepsy, migraine, diabetes or renal dysfunction.
• Gallbladder disease: May have a dose-related risk of gallbladder disease.
• Hepatic adenomas: Extremely rare adenomas and focal nodular hyperplasia resulting in fatal intra-abdominal hemorrhage have been reported in association with long-term oral contraceptive use. Presentation of an abdominal mass, acute abdominal pain, or intra-abdominal bleeding warrants further evaluation to rule out source.
• Lipid effects: May effect serum triglyceride and lipoprotein levels. Estrogen compounds are generally associated with lipid effects such as increased HDL-cholesterol and decreased LDL-cholesterol. Triglycerides may also be increased; use with caution in patients with familial defects of lipoprotein metabolism.
• Migraine: Use with caution in patients with a history of migraine.
• Retinal vascular thrombosis: Estrogens may cause retinal vascular thrombosis (has been reported rarely with combination hormonal contraceptives); discontinue permanently if papilledema or retinal vascular lesions are observed on examination.
• Smokers: The risk of cardiovascular side effects increases in women who smoke cigarettes, especially those who are >35 years of age; women who use combination hormonal contraceptives should be strongly advised not to smoke.
• Surgical patients: Whenever possible, therapy should be discontinued at least 4 weeks prior to and for 2 weeks following elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.

>10%:

• Central nervous system: Headache (25%)
• Dermatologic: Acne (14%)
• Endocrine & metabolic: Infrequent menstrual bleeding (<3 episodes/90 days: 34%), amenorrhea (no bleeding in 90 days: 22%), prolonged menstrual bleeding (lasting >14 days: 18%), breast pain (13%), menstrual bleeding irregularities requiring discontinuation (11%)
• Gastrointestinal: Weight gain (14%), abdominal pain (11%)
• Genitourinary: Vaginitis (15%)
• Respiratory: Upper respiratory tract infection (13%), pharyngitis (11%)

5% to 10%:

• Central nervous system: Dizziness (7%), emotional lability (7%), depression (6%), nervousness (6%), pain (6%)
• Endocrine & metabolic: Dysmenorrhea (7%), frequent menstrual bleeding (>5 episodes/90 days: 7%)
• Gastrointestinal: Nausea (6%)
• Genitourinary: Leukorrhea (10%)
• Local: Insertion site pain (5%)
• Neuromuscular & skeletal: Back pain (7%)
• Respiratory: Sinusitis (6%)
• Miscellaneous: Flu-like syndrome (8%)

<5% (Limited to important or life-threatening): Allergic reaction, alopecia, anorexia, anxiety, appetite increased, arthralgia, asthma, breast discharge, breast enlargement, breast fibroadenosis, cervical smear test positive, constipation, coughing, crying, diarrhea, dyspepsia, dysuria, edema, fatigue, fever, flatulence, gastritis, hot flushes, hypertension, hypoesthesia, injection site reaction, insomnia, lactation nonpuerperal, libido decreased, migraine, myalgia, otitis media, ovarian cyst, pelvic cramping, premenstrual tension, pruritus, rash, rhinitis, sexual function abnormal, skeletal pain, somnolence, vaginal discomfort, varicose vein, vision abnormal, vomiting, weakness, weight loss

Drug Interactions

Acitretin: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Given the potential for progestin-only preparations to fail to prevent pregnancy during acitretin therapy, such products should not be relied upon. Alternative, nonhormonal forms of contraception must be employed during acitretin therapy. Risk D: Consider therapy modification

Aminoglutethimide: May increase the metabolism of Progestins. Management: Progestin-containing contraceptives are not recommended; consider the use of alternative, nonhormonal contraceptives. Risk D: Consider therapy modification

Aprepitant: May decrease the serum concentration of Contraceptives (Progestins). Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Risk D: Consider therapy modification

Artemether: May decrease the serum concentration of Contraceptives (Progestins). Management: Consider the use of an alternative (i.e., non-hormonal) means of contraception in all women of childbearing potential who are using artemether. Risk D: Consider therapy modification

Barbiturates: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Risk D: Consider therapy modification

Benzodiazepines (metabolized by oxidation): Contraceptives (Progestins) may increase the serum concentration of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the serum concentration of Contraceptives (Progestins). Management: Administer oral progestin-containing contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Risk D: Consider therapy modification

Bosentan: May decrease the serum concentration of Contraceptives (Progestins). Management: Use an alternative (i.e., non-hormonal) means of contraception for all women of childbearing potential who are using bosentan, and do not rely on hormonal contraceptives alone. Risk D: Consider therapy modification

CarBAMazepine: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Risk D: Consider therapy modification

Efavirenz: May diminish the therapeutic effect of Etonogestrel. Management: Use a reliable barrier contraceptive if efavirenz is used in combination with etonogestrel. Continue using barrier contraception for 12 weeks after discontinuation of efavirenz. Risk D: Consider therapy modification

Felbamate: May decrease the serum concentration of Contraceptives (Progestins). Management: Contraceptive failure is possible. Use of an alternative, nonhormonal method of contraception is recommended. Risk D: Consider therapy modification

Fosaprepitant: May decrease the serum concentration of Contraceptives (Progestins). The active metabolite aprepitant is likely responsible for this effect. Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Risk D: Consider therapy modification

Griseofulvin: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Risk X: Avoid combination

Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the adverse/toxic effect of Progestins. Risk C: Monitor therapy

LamoTRIgine: May decrease the serum concentration of Contraceptives (Progestins). Management: Women using progestin-only “minipill” products may be at risk for contraceptive failure; it is unclear if other progestin-containing products would be significantly impacted. Alternative, non-hormonal, means of contraception are recommended. Risk D: Consider therapy modification

Mycophenolate: May decrease the serum concentration of Contraceptives (Progestins). Management: Use of an additional or alternative (nonhormonal) method of contraception should be considered. Risk D: Consider therapy modification

OXcarbazepine: May decrease the serum concentration of Contraceptives (Progestins). Management: Contraceptive failure is possible. Use of an additional or alternative, nonhormonal method of contraception is recommended. Risk D: Consider therapy modification

Phenytoin: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Risk D: Consider therapy modification

Retinoic Acid Derivatives: May diminish the therapeutic effect of Contraceptives (Progestins). Retinoic Acid Derivatives may decrease the serum concentration of Contraceptives (Progestins). Management: Two forms of effective contraception should be used in patients receiving retinoic acid derivatives. Particularly, microdosed progesterone-only preparations may be inadequately effective. Risk D: Consider therapy modification

Rifamycin Derivatives: May decrease the serum concentration of Contraceptives (Progestins). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Risk D: Consider therapy modification

Selegiline: Contraceptives (Progestins) may increase the serum concentration of Selegiline. Risk C: Monitor therapy

St Johns Wort: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Consider using a product other than St John's wort. Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Risk D: Consider therapy modification

Topiramate: May decrease the serum concentration of Contraceptives (Progestins). Management: Caution patients that this combination may be associated with reduced contraceptive effectiveness. Consider adding an additional (non-hormonal) contraceptive method. Risk D: Consider therapy modification

Tranexamic Acid: Contraceptives (Progestins) may enhance the thrombogenic effect of Tranexamic Acid. Management: Ensure that the potential benefits of concurrent therapy outweigh the increased risk of potential thrombosis that accompanies use of tranexamic acid with hormonal contraceptives. Risk D: Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Contraceptives (Progestins) may diminish the anticoagulant effect of Vitamin K Antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. Management: When possible, concomitant hormonal contraceptives and coumarin derivatives should be avoided in order to eliminate the risk of thromboembolic disorders. Consider using an alternative, nonhormonal contraceptive. Risk D: Consider therapy modification

Voriconazole: May increase the serum concentration of Contraceptives (Progestins). Contraceptives (Progestins) may increase the serum concentration of Voriconazole. Risk C: Monitor therapy

Ethanol/Nutrition/Herb Interactions

Herb/Nutraceutical: St John's wort (an enzyme inducer) may decrease serum levels of etonogestrel. Concomitant use is not recommended. Bloodroot, chasteberry, damiana, oregano, and yucca may enhance the adverse/toxic effect of progestins.

Lab Test Interactions

Sex hormone-binding globulin: Serum concentrations may be decreased for first 6 months following implantation.

Thyroxine: Serum concentrations may be slightly decreased initially.

Dosing: Adults

Contraception: Subdermal: Implant 1 rod in the inner side of the upper, nondominant arm. Remove no later than 3 years after the date of insertion. After ruling out pregnancy, timing of insertion is based on the patient's contraceptive history:

• No hormonal contraceptives within the past month: Insert between days 1 through 5 of menstruation, even if woman is still bleeding
• Switching from combination hormonal contraceptive:
  • Oral tablet: Insert anytime within 7 days after the last active tablet
  • Vaginal ring: Insert anytime during the 7-day ring-free period
  • Transdermal system: Insert anytime during the 7-day patch-free period
• Switching from a progestin-only contraceptive:
  • Oral pill: Any day during the month; do not skip days between the last pill and implant insertion
  • Implant: Insert on same day as removal of implant
  • IUD: Insert on same day as removal of IUD
  • Injection: Insert on day next injection is due
• First trimester abortion or miscarriage: Insert immediately. If not inserted within first 5 days follow directions for “no hormonal contraception within the past month”
• Following delivery or second trimester abortion: May insert between 21 and 28 days (if not exclusively breast-feeding) or after 4 weeks (if exclusively breast-feeding). Patients should use a second form of contraception for the first 7 days if insertion occurs at >4 weeks.
• Note: If following above insertion schedule, no back-up contraception needed. If deviating, use back-up method for 7 days postinsertion.

Dosing: Elderly

Not for use after menopause

Dosing: Pediatric

Not for use prior to menarche

Dosing: Renal Impairment

Use with caution; formal studies have not been conducted.

Dosing: Hepatic Impairment

Use is contraindicated.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Rod, subdermal:

• Implanon™: 68 mg [latex free]

Administration, Other

Subdermal: For insertion under local anesthesia by healthcare providers trained in the insertion and removal procedure. Rod must be palpable after insertion. Deep insertion may require surgery to remove. If rod is impalpable, ultrasound should be used to locate the rod; MRI may also be useful if ultrasound is not successful. A pressure bandage should be applied and left in place for 24 hours after insertion to decrease bruising; a small bandage placed over the insertion site should remain in place for 3-5 days.

Pregnancy Implications

Teratogenic effects were not observed in animal studies. Not for use during pregnancy; rule out pregnancy prior to insertion. Remove implant if pregnancy is detected during use. Ovulation may return within 1 week of implant removal; alternate forms of contraception may be required. In a multicenter clinical trial, 11 out of 46 women no longer using contraception became pregnant between 1 and 18 weeks following removal of the implant. Do not insert <21 days postpartum. Women weighing >130% of their ideal body weight were not included in clinical studies. With oral combination hormonal contraceptives, an increase in contraceptive failure was noted in women with a BMI >27.3. Similar findings were noted in patients weighing ≥90 kg (198 lb) using the contraceptive patch.

Lactation

Enters breast milk/use caution

Breast-Feeding Considerations

Etonogestrel was not found to affect the quality or quantity of breast milk. Do not insert <21 days postpartum. Levels of etonogestrel are highest during the first month following insertion (~2.2% of the weight-adjusted maternal daily dose).

Mechanism of Action

Etonogestrel is the active metabolite of desogestrel. It prevents pregnancy by suppressing ovulation, increasing the viscosity of cervical mucous, and inhibiting endometrial proliferation.

Pharmacodynamics/Kinetics

Onset of action: Serum levels sufficient to inhibit ovulation: ≤8 hours of implant

Duration: Implant: Each rod maintains etonogestrel levels sufficient to inhibit ovulation for 3 years

Distribution: V_d: ~201 L

Protein binding: Albumin (66%) and sex hormone-binding globulin (32%)

Metabolism: Hepatic via CYP3A4; forms metabolites (activity not known)

Bioavailability: Implant: 100%

Half-life, elimination: ~25 hours

Excretion: Urine (primarily); feces

Monitoring Parameters

Before starting therapy, a physical exam with reference to the breasts and pelvis are recommended, including a Papanicolaou smear. Exam may be deferred if appropriate; pregnancy should be ruled out prior to use. Monitor patient closely for loss of vision, sudden onset of proptosis, diplopia, migraine; 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 hyperlipidemias. Adequate diagnostic measures, including endometrial sampling, if indicated, should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.

Reference Range

Etonogestrel: A release rate of 25-30 mcg/day is required to inhibit ovulation

Inform prescriber of all prescription medications, OTC medications, or herbal products you are taking. Do not take any new medications without consulting prescriber. Does not protect against HIV or other sexually transmitted diseases. Regular (as directed by prescriber) gynecological and regular self-breast exams are important. Changes in menstrual periods may occur (change in frequency, length, or spotting between periods). Use of a backup method of birth control (ie, condom) is recommended for 7 days after insertion. Periodically check for the presence of the device. If the device cannot be felt, use an alternative form of birth control until your prescriber confirms its presence. You will be given a user card to document the insertion of the device. Keep with your health records and keep track of the removal date. You may experience acne, breast pain, weight gain, vaginal discharge, back pain, dizziness (use caution when driving or engaging in tasks requiring alertness until response to drug is known), or nausea (small, frequent meals, frequent oral care, sucking lozenges, or chewing gum may help). Report excessive vaginal bleeding, depression or severe mood swings, persistent or severe headaches, chest pain, coughing up blood, shortness of breath, pain in legs, or abdominal pain. Pregnancy/breast-feeding precautions: Inform prescriber if you become pregnant. Consult prescriber if breast-feeding.

Storage

Store at controlled room temperature of 25°C (77°F); excursions permitted to 15°C to 30˚C (59˚F to 86˚F). Protect from light.

For subdermal insertion by healthcare providers trained on the insertion and removal procedure. For use in women who request long-acting (up to 3 years) contraception. A User Card (to give to the patient), consent form (to keep on file), and a medication guide (for the patient) are provided with the device. Materials related to the insertion and removal of Implanon™ are available from the manufacturer (877-467-5266).

The rod releases etonogestrel at a rate of 60-70 mcg/day, decreasing to 35-45 mcg/day after the first year, 30-40 mcg/day after the second year, and 25-30 mcg/day at the end of the third year. Following removal of rod, levels decrease rapidly and are less than the level of detection within 1 week.

• Croxatto HB and Makarainen L, "The Pharmacodynamics and Efficacy of Implanon™. An Overview of the Data," Contraception, 1998, 58(6 Suppl):91-7.
• Croxatto HB, Urbancsek J, Massai R, et al, "A Multicentre Efficacy and Safety Study of the Single Contraceptive Implant Implanon™. Implanon Study Group," Hum Reprod, 1999, 14(4):976-81. [PMID:10221230]
• Funk S, Miller MM, Mishell DR Jr, et al, "Safety and Efficacy of Implanon™, a Single-Rod Implantable Contraceptive Containing Etonogestrel," Contraception, 2005, 71(5):319-26. [PMID:15854630]
• Merki-Feld GS, Brekenfeld C, Migge B, et al, "Nonpalpable Ultrasonographically Not Detectable Implanon™ Rods Can be Localized by Magnetic Resonance Imaging," Contraception, 2001, 63(6):325-8. [PMID:11672555]