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Precautions
General
Women should be informed that this product does not protect against infection from HIV (the virus that causes AIDS) or other sexually transmitted diseases.
IMPORTANT: Pregnancy must be excluded before inserting IMPLANON® (etonogestrel implant).
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Physical Examination and Follow-up
A complete medical evaluation, including history and physical examination and relevant laboratory tests, should be performed prior to IMPLANON® insertion or reinsertion. It is good medical practice for patients using IMPLANON® to have regular physical examinations. In case of undiagnosed, persistent, or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a family history of breast cancer or who have breast nodules should be monitored with particular care.
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Information for the Patient
Provide your patient with a copy of the Patient Labeling and ensure that she understands the information in the Patient Labeling before insertion and removal. A USER CARD and consent form are included in the packaging. Have the patient complete a consent form and retain it in your records. The USER CARD should be filled out and given to the patient after IMPLANON® insertion so that she will have a record of the location of IMPLANON® and when IMPLANON® should be removed.
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Weight Gain
In clinical studies, mean weight gain in US IMPLANON® users was 2.8 pounds after one year and 3.7 pounds after two years. How much of the weight gain was related to IMPLANON® is unknown. In studies, 2.3% of IMPLANON® users reported weight gain as the reason for having IMPLANON® removed.
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Carbohydrate and Lipid Metabolic Effects
IMPLANON® may induce mild insulin resistance and small changes in glucose concentrations of unknown clinical significance. Women with diabetes or impaired glucose tolerance should be carefully observed while using IMPLANON®.
Women who are being treated for hyperlipidemias should be followed closely if they elect to use hormonal contraceptives. Some progestins may elevate LDL levels and may render the control of hyperlipidemias more difficult.
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Liver Function
If jaundice develops in any patient using IMPLANON®, remove IMPLANON®. The hormone in IMPLANON® may be poorly metabolized in patients with impaired liver function.
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Depression
Women with a history of depression should be carefully observed. Consideration should be given to removing IMPLANON® in patients who become significantly depressed.
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Contact Lenses
Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.
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Drug Interactions
Changes in Contraceptive Effectiveness Associated with Co-Administration of Other Drugs
a. Anti-Infective Agents and Anticonvulsants
IMPLANON® is not recommended for women who require chronic use of drugs that are potent inducers of hepatic enzymes because IMPLANON® is likely to be less effective for these women.
Contraceptive effectiveness may be reduced when hormonal contraceptives are co-administered with some antibiotics, antifungals, anticonvulsants, and other drugs that increase the metabolism of contraceptive steroids. This could result in an unintended pregnancy or breakthrough bleeding. Examples include: barbiturates, griseofulvin, rifampin, phenylbutazone, phenytoin, carbamazepine, felbamate, oxcarbazepine, topiramate, and modafinil. Patients should use an additional non-hormonal contraceptive method when taking medications that may decrease the efficacy of hormonal contraceptives.
b. Anti-HIV Protease Inhibitors
Several of the anti-HIV protease inhibitors have been studied with co-administration of combination oral contraceptives; significant changes (increase and decrease) in the mean area under the curve (AUC) of the estrogen and progestin have been noted in some cases. The efficacy and safety of combination oral contraceptive products may be affected with coadministration of anti-HIV protease inhibitors; it is unknown whether this applies to IMPLANON®. Healthcare providers should refer to the labeling of the individual anti-HIV protease inhibitors for further drug-drug interaction information.
c. Herbal Products
Herbal products containing St. John’s Wort (Hypericum perforatum) may induce hepatic enzymes and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids.
Increase in Plasma Hormone Levels Associated with Co-Administered Drugs
Inhibitors of hepatic enzymes such as itraconazole or ketoconazole may increase plasma hormone levels.
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Interactions with Laboratory Tests
Certain endocrine tests may be affected by IMPLANON® use
a. Sex hormone-binding globulin concentrations may be decreased for the first six months after IMPLANON® insertion followed by a gradual recovery.
b. Thyroxine concentrations may initially be slightly decreased followed by gradual recovery to baseline.
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Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 24-month carcinogenicity study in rats with subdermal implants releasing 10 and 20 µg etonogestrel (ENG) per day (equal to approximately 1.8-3.6 times the systemic steady state exposure of women using IMPLANON®), no drug-related carcinogenic potential was observed. ENG was not genotoxic in the in vitro Ames/Salmonella reverse mutation assay, the chromosomal aberration assay in Chinese hamster ovary cells or in the in vivo mouse micronucleus test. Fertility returned after withdrawal from treatment.
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Pregnancy
IMPLANON® is not indicated for use during pregnancy.
Teratology studies have been performed in rats and rabbits, respectively, using oral administration up to 390 and 790 times the human IMPLANON® dose (based upon body surface) and revealed no evidence of fetal harm due to ENG exposure.
Studies have revealed no increased risk of birth defects in women who have used combination oral contraceptives before pregnancy or during early pregnancy. There is no evidence that the risk associated with IMPLANON® is different from that of combination oral contraceptives. IMPLANON® should be removed if maintaining a pregnancy.
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Nursing Mothers
Based on limited data, IMPLANON® may be used during lactation after the 4th postpartum week. Use of IMPLANON® before the 4th postpartum week has not been studied.
Small amounts of ENG are excreted in breast milk. During the first months after IMPLANON® insertion, when maternal blood levels of ENG are highest, about 100 ng of ENG may be ingested by the child per day based on an average daily milk ingestion of 658 mL. Based on daily milk ingestion of 150 mL/kg, the mean daily infant ENG dose one month after insertion of IMPLANON® is about 2.2% of the weight-adjusted maternal daily dose, or about 0.2% of the estimated absolute maternal daily dose. The health of breast-fed infants whose mothers began using IMPLANON® during the 4th to 8th week postpartum (n=38) was evaluated in a comparative study with infants of mothers using a non-hormonal IUD (n=33). They were breast-fed for a mean duration of 14 months and followed up to 36 months of age. No significant effects and no differences between the groups were observed on the physical and psychomotor development of these infants. No differences between groups in the production or quality of breast milk were detected.
Healthcare providers should discuss both hormonal and nonhormonal contraceptive options, as steroids may not be the initial choice for these patients.
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Return to Ovulation
In clinical trials, pregnancies occurred as early as during the first week after removal of IMPLANON®. Therefore, a patient should re-start contraception immediately after removal of IMPLANON® if she still needs to prevent pregnancy.
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Fluid Retention
Steroid 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 IMPLANON® causes fluid retention.
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Pediatric Use
Safety and efficacy of IMPLANON® have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents. However, no clinical studies have been conducted in women less than 18 years of age. Use of this product before menarche is not indicated.
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Geriatric Use
This product has not been studied in women over 65 years of age and is not indicated in this population.
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Indication
IMPLANON® (etonogestrel implant) is indicated for women for the prevention of pregnancy.
IMPLANON® must be removed by the end of the third year and may be replaced by a new IMPLANON® at the time of removal, if continued contraceptive protection is desired.
Important Safety Information
Women should be informed that this product does not protect against infection from HIV (the virus that causes AIDS) or other sexually transmitted diseases.
Serious consequences may be associated with the insertion and removal of IMPLANON®. IMPLANON® should be inserted subdermally so that it is palpable after insertion. Failure to insert IMPLANON® properly may go unnoticed unless the implant is palpated immediately after insertion. Deep insertions may lead to difficult or impossible removals. Failure to remove IMPLANON® may result in infertility, ectopic pregnancy, or inability to stop a drug-related adverse event. Undetected failure to insert IMPLANON® may lead to an unintended pregnancy.
In clinical trials, 1.0% of patients had complications at implant insertion and 1.7% had complications at implant removal. Deep insertions may result in the need for a surgical procedure in an operating room in order to remove IMPLANON®. When IMPLANON® is inserted too deeply, this may cause neural or vascular damage. Too deep insertions have been associated with paraesthesia and migration of the implant and, in rare cases, with intravascular insertion. In postmarketing use, there have been cases of failure to localize and remove the implant, probably due to deep insertion. All healthcare providers performing insertions and/or removals of IMPLANON® must receive instruction and training and, where appropriate, supervision prior to inserting or removing IMPLANON®.
IMPLANON® should not be used in women who have the following conditions: known or suspected pregnancy, current or past history of thrombosis or thromboembolic disorders, hepatic tumors (benign or malignant), active liver disease, undiagnosed abnormal genital bleeding, known or suspected carcinoma of the breast (or a personal history of breast cancer), or hypersensitivity to any of the components of IMPLANON®.
Pregnancy must be excluded before inserting IMPLANON®.
The use of IMPLANON® and other progestin-only hormonal contraceptives have been associated with ectopic pregnancy, bleeding irregularities, and ovarian cysts. The use of hormonal contraceptives is associated with increased risks of several serious cardiovascular conditions including myocardial infarction, stroke, venous thromboembolism, deep venous thrombosis, retinal vein thrombosis, and pulmonary embolism. There have been postmarketing reports of serious thromboembolic events, including cases of pulmonary emboli (some fatal) and strokes, in patients using IMPLANON®. IMPLANON® should be removed in the event of a thrombosis. Consider removal of IMPLANON® in case of long-term immobilization due to surgery or illness. Women with a history of thromboembolic disorders should be made aware of the possibility of a recurrence.
Cigarette smoking increases the risk of serious cardiovascular side effects from the use of hormonal contraceptives. This risk increases with age (women over 35 years of age) and with heavy smoking. Women who use hormonal contraceptives should be advised not to smoke.
In clinical trials including 942 patients, bleeding irregularities (11%) were the most common adverse event causing discontinuation of IMPLANON®. Adverse events reported in >5% of subjects include headache, vaginitis, weight increase, acne, breast pain, upper respiratory tract infection, abdominal pain, pharyngitis, leukorrhea, influenza-like symptoms, dizziness, dysmenorrhea, back pain, emotional lability, nausea, pain, nervousness, sinusitis, depression, and insertion site pain.
Please see full Prescribing Information.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
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