Implanon® (etonogestrel implant) 68 mg

Precautions

General

Women should be informed that IMPLANON (etonogestrel implant) 68 mg does not protect against infection from HIV (the virus that causes AIDS) or other sexually transmitted diseases.

Important: Pregnancy must be excluded before inserting this product.

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.

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.

Weight gain

In clinical studies, mean weight gain in U.S. 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.

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.

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.

Depression

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

Contact lenses

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

Drug interactions

Changes in contraceptive effectiveness associated with coadministration of other drugs

  1. 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.

  2. 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.

  3. 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 coadministered drugs

Inhibitors of hepatic enzymes such as itraconazole or ketoconazole may increase plasma hormone levels.

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.

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.

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.

Nursing mothers

Based on limited data, IMPLANON may be used during lactation after the fourth postpartum week. Use of IMPLANON before the fourth 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 fourth to eighth 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.

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.

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.

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.

Geriatric use

This product has not been studied in women over 65 years of age and is not indicated in this population.

IMPLANON (etonogestrel implant) is indicated for use by women to prevent pregnancy.

SELECTED SAFETY INFORMATION

  • IMPLANON 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; or allergic reaction to any of the components of IMPLANON.
  • IMPLANON 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 IMPLANON 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. Occasionally in post-marketing use, implant insertions have failed because the implant fell out of the needle or remained in the needle during insertion. If IMPLANON is inserted too 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. Deep insertions may lead to difficult localization of the implant and may also result in the need for a surgical procedure in an operating room in order to remove the implant.
  • After starting IMPLANON, 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 IMPLANON, 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.
  • Be alert to the possibility of an ectopic pregnancy in women using IMPLANON who become pregnant or complain of lower abdominal pain.
  • 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 and venous thromboembolic events, including cases of pulmonary emboli (some fatal), deep vein thrombosis, myocardial infarction, and stroke, in women using IMPLANON. IMPLANON should be removed in the event of a thrombosis. Due to the risk of thromboembolism associated with pregnancy and immediately following delivery, IMPLANON 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 IMPLANON implant in case of long-term immobilization due to surgery or illness.
  • 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.
  • 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.
  • IMPLANON should be removed if jaundice occurs.
  • The IMPLANON implant should be removed if blood pressure rises significantly and becomes uncontrolled.
  • 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 IMPLANON.
  • Prediabetic and diabetic women using IMPLANON should be carefully monitored.
  • Women with a history of depressed mood should be carefully observed. Consideration should be given to removing IMPLANON in patients who become significantly depressed.
  • In clinical trials, 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.
  • 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 IMPLANON causes fluid retention.
  • Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.
  • 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%).
  • Drugs or herbal products that induce enzymes, including CYP3A4, that metabolize progestins may decrease the plasma concentrations of progestins and may decrease the effectiveness of IMPLANON. In women on long-term treatment with hepatic enzyme inducing drugs, it is recommended to remove the implant and to advise a contraceptive method that is unaffected by the interacting drug. Significant changes (increase or decrease) in the plasma levels of progestin have been noted in some cases of coadministration with HIV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors.
  • CYP3A4 inhibitors, such as itraconzaole or ketoconazole, may increase plasma concentrations of etonogestrel.
  • Hormonal contraceptives may affect the metabolism of other drugs. Consequently, plasma concentrations may either increase (for example, cyclosporin) or decrease (for example, lamotrigine).
  • Rule out pregnancy before inserting IMPLANON.
  • Based on limited clinical data, IMPLANON may be used during breast-feeding after the fourth postpartum week. Use of IMPLANON before the fourth postpartum week has not been studied. Small amounts of etonogestrel are excreted in breast milk. The health of breast-fed infants whose mothers began using IMPLANON during the fourth to eighth 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.
  • Safety and efficacy of IMPLANON 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.
  • The efficacy of IMPLANON 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, IMPLANON may be less effective in overweight women.
  • IMPLANON does not protect against HIV infection (AIDS) or other sexually transmitted diseases.

Before prescribing IMPLANON, please read the Prescribing Information.