"The U.S. Food and Drug Administration today announced that it has approved an amended application submitted by Teva Women's Health, Inc. to market Plan B One-Step (active ingredient levonorgestrel) for use without a prescription by women 15 years"...
The following information is based on experience with either IMPLANON, other progestin-only contraceptives, or experience with combination (estrogen plus progestin) oral contraceptives.
Complications Of Insertion And Removal
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. 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. To reduce the risk of neural or vascular injury, IMPLANON should be inserted at the inner side of the non-dominant upper arm about 8-10 cm (3-4 inches) above the medial epicondyle of the humerus. IMPLANON should be inserted subdermally just under the skin to avoid the large blood vessels and nerves that lie deeper in the subcutaneous tissues in the sulcus between the triceps and biceps muscles. Deep insertions of IMPLANON have been associated with paraesthesia (due to neural injury) and migration of the implant (due to intramuscular or fascial insertion), and in a very few cases with intravascular insertion. If infection develops at the insertion site, start suitable treatment. If the infection persists, the implant should be removed. Incomplete insertions or infections may lead to expulsion. In postmarketing use there have been cases of failure to localize and remove the implant, probably due to deep insertion. There has been 1 case of an intravascular insertion reported post-marketing which led to inability to remove the implant.
Implant removal may be difficult or impossible if the implant is not inserted correctly, is 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. Exploratory surgery without knowledge of the exact location of the implant is strongly discouraged. Removal of deeply inserted implants should be conducted with caution in order to prevent injury to deeper neural or vascular structures in the arm and be performed by healthcare providers familiar with the anatomy of the arm. 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.
Changes In Menstrual Bleeding Patterns
After starting IMPLANON, women are likely to have a change from their normal menstrual bleeding pattern. These may include changes in bleeding frequency (absent, less, more frequent or continuous), intensity (reduced or increased) or duration. In clinical trials, bleeding patterns ranged from amenorrhea (1 in 5 women) to frequent and/or prolonged bleeding (1 in 5 women). The bleeding pattern experienced during the first three months of IMPLANON use is broadly predictive of the future bleeding pattern for many women. Women should be counseled regarding the bleeding pattern changes they may experience so that they know what to expect. 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%). Irregular bleeding (10.8%) was the single most common reason women stopped treatment, while amenorrhea (0.3%) was cited less frequently. In these studies, women had an average of 17.7 days of bleeding or spotting every 90 days (based on 3,315 intervals of 90 days recorded by 780 patients). The percentages of patients having 0, 1-7, 8-21, or > 21 days of spotting or bleeding over a 90-day interval while using the IMPLANON implant are shown in Table 1.
Table 1: Percentages of Patients with 0, 1 - 7, 8 -
21, or > 21 Days of Spotting or Bleeding Over a 90-Day Interval While Using
|Total Days of Spotting or Bleeding||Percentage of Patients|
|Treatment Days 91-180
(N = 745)
|Treatment Days 271-360
(N = 657)
|Treatment Days 631-720
(N = 547)
|> 21 Days||35%||33%||35%|
Bleeding patterns observed with use of IMPLANON for up to 2 years, and the proportion of 90-day intervals with these bleeding patterns, are summarized in Table 2.
Table 2: Bleeding Patterns
Using IMPLANON during the First 2 Years of Use*
|Infrequent||Less than three bleeding and/or spotting episodes in 90 days (excluding amenorrhea)||33.6|
|Amenorrhea||No bleeding and/or spotting in 90 days||22.2|
|Prolonged||Any bleeding and/or spotting episode lasting more than 14 days in 90 days||17.7|
|Frequent||More than 5 bleeding and/or spotting episodes in 90 days||6.7|
|Based on 3,315 recording
periods of 90 day's duration in 780 women, excluding the first 90 days after
† % = Percentage of 90-day intervals with this pattern
In case of undiagnosed, persistent, or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy.
As with all progestin-only contraceptive products, be alert to the possibility of an ectopic pregnancy among women using IMPLANON who become pregnant or complain of lower abdominal pain. Although ectopic pregnancies are uncommon among women using IMPLANON, a pregnancy that occurs in a woman using IMPLANON may be more likely to be ectopic than a pregnancy occurring in a woman using no contraception.
Thrombotic And Other Vascular Events
The use of combination hormonal contraceptives (progestin plus estrogen) 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). IMPLANON is a progestin-only contraceptive. It is unknown whether this increased risk is applicable to etonogestrel alone. It is recommended, however, 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 strokes, 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. On rare occasion, surgery may be required.
Carcinoma Of The Breast And Reproductive Organs
Women who currently have or have had breast cancer should not use hormonal contraception because breast cancer may be hormonally sensitive [see CONTRAINDICATIONS]. Some studies suggest that the use of combination hormonal contraceptives might increase the incidence of breast cancer; however, other studies have not confirmed such findings.
Some studies suggest that the use of combination hormonal contraceptives is associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there is controversy about the extent to which such findings are due to differences in sexual behavior and other factors.
Women with a family history of breast cancer or who develop breast nodules should be carefully monitored.
Disturbances of liver function may necessitate the discontinuation of hormonal contraceptive use until markers of liver function return to normal. Remove IMPLANON if jaundice develops.
Hepatic adenomas are associated with combination hormonal contraceptives use. An estimate of the attributable risk is 3.3 cases per 100,000 for combination hormonal contraceptives users. It is not known whether a similar risk exists with progestin-only methods like IMPLANON.
In clinical studies, mean weight gain in US IMPLANON users was 2.8 pounds after 1 year and 3.7 pounds after 2 years. How much of the weight gain was related to the implant is unknown. In studies, 2.3% of the users reported weight gain as the reason for having the implant removed.
Elevated Blood Pressure
Women with a history of hypertension-related diseases or renal disease should be discouraged from using hormonal contraception. For women with well-controlled hypertension, use of IMPLANON can be considered. Women with hypertension using IMPLANON should be closely monitored. lf sustained hypertension develops during the use of IMPLANON, or if a significant increase in blood pressure does not respond adequately to antihypertensive therapy, IMPLANON should be removed.
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.
Carbohydrate And Lipid Metabolic Effects
Use of IMPLANON may induce mild insulin resistance and small changes in glucose concentrations of unknown clinical significance. Carefully monitor prediabetic and diabetic women using IMPLANON.
Women who are being treated for hyperlipidemia should be followed closely if they elect to use IMPLANON. Some progestins may elevate LDL levels and may render the control of hyperlipidemia more difficult.
Women with a history of depressed mood should be carefully observed. Consideration should be given to removing IMPLANON in patients who become significantly depressed.
Return To Ovulation
In clinical trials with IMPLANON, 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.
A woman who is using IMPLANON should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated health care.
Drug-Laboratory Test Interactions
Sex hormone-binding globulin concentrations may be decreased for the first 6 months after IMPLANON insertion followed by a gradual recovery. Thyroxine concentrations may initially be slightly decreased followed by gradual recovery to baseline.
Patient Counseling Information
“See FDA-Approved Patient Labeling (PATIENT INFORMATION)”
- Counsel women about the insertion and removal procedure of the IMPLANON implant. Provide the woman 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 woman complete a consent form and retain it in your records. The USER CARD should be filled out and given to the patient after insertion of the IMPLANON implant so that she will have a record of the location of the implant in the upper arm and when it should be removed.
- Counsel women that IMPLANON does not protect against HIV infection (AIDS) or other sexually transmitted diseases.
- Counsel women that the use of IMPLANON may be associated with changes in their normal menstrual bleeding patterns so that they know what to expect.
FDA-Approved Patient Labeling
See the full PATIENT INFORMATION for IMPLANON.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In a 24-month carcinogenicity study in rats with subdermal implants releasing 10 and 20 mcg etonogestrel per day (equal to approximately 1.8-3.6 times the systemic steady state exposure in women using IMPLANON), no drug-related carcinogenic potential was observed. Etonogestrel 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.
Use In Specific Populations
IMPLANON is not indicated for use during pregnancy [see CONTRAINDICATIONS].
Teratology studies have been performed in rats and rabbits 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 etonogestrel 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.
Based on limited clinical data, IMPLANON may be used during breastfeeding 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. During the first months after insertion of IMPLANON, when maternal blood levels of etonogestrel are highest, about 100 ng of etonogestrel 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 etonogestrel 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 non-hormonal contraceptive options, as steroids may not be the initial choice for these patients.
Safety and efficacy of IMPLANON have been established in women of reproductive age. Safety and efficacy of IMPLANON 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.
This product has not been studied in women over 65 years of age and is not indicated in this population.
No studies were conducted to evaluate the effect of hepatic disease on the disposition of IMPLANON. The use of IMPLANON in women with active liver disease is contraindicated [see CONTRAINDICATIONS].
No studies were conducted to evaluate the effect of renal disease on the disposition of IMPLANON.
The effectiveness 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. It is therefore possible that IMPLANON may be less effective in overweight women, especially in the presence of other factors that decrease serum etonogestrel concentrations such as concomitant use of hepatic enzyme inducers.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 11/21/2014
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