Nexaplanon
(Etonogestrel)Dosage & Administration
The efficacy of NEXPLANON does not depend on daily, weekly, or monthly administration.
All healthcare professionals should receive instruction and training prior to performing insertion and/or removal of NEXPLANON.
A single NEXPLANON implant is inserted subdermally just under the skin at the inner side of the non-dominant upper arm. The insertion site is overlying the triceps muscle about 8-10 cm (3-4 inches) from the medial epicondyle of the humerus and 3-5 cm (1.25-2 inches) posterior to (below) the sulcus (groove) between the biceps and triceps muscles. This location is intended to avoid the large blood vessels and nerves lying within and surrounding the sulcus (see
 |
Figure 2a P – Proximal (toward the shoulder) D – Distal (toward the elbow) |
Before initiating the removal procedure, the healthcare professional should assess the location of the implant and carefully read the instructions for removal. The exact location of the implant in the arm should be verified by palpation. If the implant is not palpable, consult the medical record to verify the arm which contains the implant. If the implant cannot be palpated, it may be deeply located or have migrated. Consider that it may lie close to vessels and nerves. Removal of non-palpable implants should only be performed by a healthcare professional experienced in removing deeply placed implants and familiar with localizing the implant and the anatomy of the arm. Call 1-844-674-3200 for further information.
Before removal of the implant, the healthcare professional should confirm that:
The following equipment is needed for removal of the implant:
Step 1. Have the woman lie on her back on the table. The arm should be positioned with the elbow flexed and the hand underneath the head (or as close as possible). (See Figure 1.)
Mark the distal end (end closest to the elbow), for example, with a surgical marker.
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Figure 10 P – Proximal (toward the shoulder) D – Distal (toward the elbow) |
Step 3. Clean the site with an antiseptic solution.
Step 4. Anesthetize the site, for example, with 0.5 to 1 mL 1% lidocaine, where the incision will be made . Be sure to inject the local anesthetic
 |
Figure 11 |
Step 5. Push down the end of the implant closest to the shoulder to stabilize it throughout the procedure. Starting over the tip of the implant closest to the elbow, make a longitudinal (parallel to the implant) incision of 2 mm towards the elbow. Take care not to cut the tip of the implant.
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Figure 12 |
Step 6. The tip of the implant should pop out of the incision. If it does not, gently push the implant towards the incision until the tip is visible. Grasp the implant with forceps and, if possible, remove the implant . If needed, gently remove adherent tissue from the tip of the implant using blunt dissection. If the implant tip is not exposed following blunt dissection, make an incision into the tissue sheath and then remove the implant with the forceps .
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Figure 13 |
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Figure 14 | Figure 15 |
Step 7. If the tip of the implant does not become visible in the incision, insert forceps (preferably curved mosquito forceps, with the tips pointed up) superficially into the incision . Gently grasp the implant and then flip the forceps over into your other hand .
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Figure 16 | Figure 17 |
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Figure 18 |
Step 9. Confirm that the entire implant, which is 4 cm long, has been removed by measuring its length. There have been reports of broken implants while in the patient's arm. In some cases, difficult removal of the broken implant has been reported. If a partial implant (less than 4 cm) is removed, the remaining piece should be removed by following the instructions in section 2.3. If the woman would like to continue using NEXPLANON, a new implant may be inserted immediately after the old implant is removed using the same incision as long as the site is in the correct location
Step 10. After removing the implant, close the incision with a sterile adhesive wound closure.
Step 11. Apply a pressure bandage with sterile gauze to minimize bruising. The woman may remove the pressure bandage in 24 hours and the sterile adhesive wound closure in 3 to 5 days.
There have been reports of migration of the implant; usually this involves minor movement relative to the original position
A non-palpable implant should always be located prior to attempting removal. Given the radiopaque nature of the implant, suitable methods for localization include two-dimensional X-ray and X-ray computer tomography (CT). Ultrasound scanning (USS) with a high-frequency linear array transducer (10 MHz or greater) or magnetic resonance imaging (MRI) may be used. Once the implant has been localized in the arm, the implant should be removed by a healthcare professional experienced in removing deeply placed implants and familiar with the anatomy of the arm
If the implant cannot be found in the arm after comprehensive localization attempts, consider applying imaging techniques to the chest as events of migration to the pulmonary vasculature have been reported. If the implant is located in the chest, surgical or endovascular procedures may be needed for removal; healthcare professionals familiar with the anatomy of the chest should be consulted.
If at any time these imaging methods fail to locate the implant, etonogestrel blood level determination can be used for verification of the presence of the implant. For details on etonogestrel blood level determination, call 1-844-674-3200 for further instructions.
If the implant migrates within the arm, removal may require a minor surgical procedure with a larger incision or a surgical procedure in an operating room. Removal of deeply-inserted implants should be conducted with caution to help prevent injury to deeper neural or vascular structures in the arm. Non-palpable and deeply-inserted implants should be removed by healthcare professionals familiar with the anatomy of the arm and removal of deeply-inserted implants.
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 professionals familiar with the anatomy of the arm. If the implant is located in the chest, healthcare professionals familiar with the anatomy of the chest should be consulted. 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.
NEXPLANON must be inserted by the expiration date stated on the packaging. NEXPLANON is a long-acting (up to 3 years), reversible, hormonal contraceptive method. The implant must be removed by the end of the third year and may be replaced by a new implant at the time of removal, if continued contraceptive protection is desired.
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Nexaplanon Prescribing Information
Dosage and Administration, Insertion of NEXPLANON (The basis for successful use and subsequent removal of NEXPLANON is a correct and carefully performed subdermal insertion of the single, rod-shaped implant in accordance with the instructions . Both the healthcare professional and the woman should be able to feel the implant under the skin after placement.All healthcare professionals performing insertions and/or removals of NEXPLANON should receive instructions and training prior to inserting or removing the implant. Preparation Before inserting NEXPLANON, carefully read the instructions for insertion as well as the full prescribing information. If you are unsure of the necessary steps to safely insert and/or remove NEXPLANON, do not attempt the procedure. Call the Organon Service Center at 1-844-674-3200 if you have any questions. Videos demonstrating insertion and removal are available online for trained healthcare professionals (www.nexplanontraining.com). Before insertion of NEXPLANON, the healthcare professional should confirm that:
Insert NEXPLANON under aseptic conditions. The following equipment is needed for the implant insertion:
Insertion Procedure To help make sure the implant is inserted just under the skin, the healthcare professionals should be positioned to see the advancement of the needle by viewing the applicator from the side and not from above the arm. From the side view, the insertion site and the movement of the needle just under the skin can be clearly visualized. For illustrative purposes, Figures depict the left inner arm. Step 1. Have the woman lie on her back on the examination table with her non-dominant arm flexed at the elbow and externally rotated so that her hand is underneath her head (or as close as possible) .
[See Warnings and Precautions (5.1).] Step 3. Make two marks with a surgical marker: first, mark the spot where the etonogestrel implant will be inserted, and second, mark a spot at 5 centimeters (2 inches) proximal (toward the shoulder) to the first mark . This second mark (guiding mark) will later serve as a direction guide during insertion.
Step 4. After marking the arm, confirm the site is in the correct location on the inner side of the arm. Step 5. Clean the skin from the insertion site to the guiding mark with an antiseptic solution. Step 6. Anesthetize the insertion area (for example, with anesthetic spray or by injecting 2 mL of 1% lidocaine just under the skin along the planned insertion tunnel). Step 7. Remove the sterile preloaded disposable NEXPLANON applicator containing the implant from its blister packaging. Prior to use, visually inspect the packaging for breaches of integrity or damage (e.g., torn, punctured, etc.). If the packaging has any visual damage that could compromise sterility, do not use the product. Step 8. Hold the applicator just above the needle at the textured surface area. Remove the transparent protection cap by sliding it horizontally in the direction of the arrow away from the needle . If the cap does not come off easily, the applicator should not be used. You should see the white colored implant by looking into the tip of the needle. Do not touch the purple slider until you have fully inserted the needle subdermally, as doing so will retract the needle and prematurely release the implant from the applicator. Step 9. If the purple slider is released prematurely, restart the procedure with a new applicator.
Step 10. With your free hand, stretch the skin around the insertion site towards the elbow .
Step 11. The implant should be inserted subdermally just under the skin [see Warnings and Precautions (5.1)] .To help make sure the implant is inserted just under the skin, you should position yourself to see the advancement of the needle by viewing the applicator from the side and not from above the arm. From the side view (see Figure 6), you can clearly see the insertion site and the movement of the needle just under the skin. Step 12. Puncture the skin with the tip of the needle slightly angled less than 30° .
Step 14. Lower the applicator to a nearly horizontal position. To facilitate subdermal placement, lift the skin with the needle while sliding the needle to its full length . You may feel slight resistance but do not exert excessive force. If the needle is not inserted to its full length, the implant will not be inserted properly. If the needle tip emerges from the skin before needle insertion is complete, the needle should be pulled back and be readjusted to subdermal position before completing the insertion procedure.
Step 15. Keep the applicator in the same position with the needle inserted to its full length . If needed, you may use your free hand to stabilize the applicator. Unlock the purple slider by pushing it slightly down . Move the slider fully back until it stops. Do not move the applicator while moving the purple slider . The implant is now in its final subdermal position, and the needle is locked inside the body of the applicator. The applicator can now be removed .
If the applicator is not kept in the same position during this procedure or if the purple slider is not moved fully back until it stops, the implant will not be inserted properly and may protrude from the insertion site. If the implant is protruding from the insertion site, remove the implant and perform a new procedure at the same insertion site using a new applicator. Do not push the protruding implant back into the incision. Step 16. Apply a small adhesive bandage over the insertion site. Step 17. Always verify the presence of the implant in the woman's arm immediately after insertion by palpation. By palpating both ends of the implant, you should be able to confirm the presence of the 4 cm rod . See " If the rod is not palpable after insertion" below.
Step 18. Request that the woman palpate the implant. Step 19. Apply a pressure bandage with sterile gauze to minimize bruising. The woman may remove the pressure bandage in 24 hours and the small adhesive bandage over the insertion site after 3 to 5 days. Step 20. Complete the PATIENT CHART LABEL and affix it to the woman's medical record. Step 21. The applicator is for single use only and should be disposed in accordance with the Center for Disease Control and Prevention guidelines for handling of hazardous waste. If the rod is not palpable after insertion: If you cannot feel the implant or are in doubt of its presence, the implant may not have been inserted or it may have been inserted deeply:
Until the presence of the implant has been verified, the woman should be advised to use a non-hormonal contraceptive method, such as condoms. Deeply-placed implants should be localized and removed as soon as possible to avoid the potential for distant migration [see Warnings and Precautions (5.1)] .Figure 1 Figure Figure 2a Figure 2b Figure 2c Figure 3 Figure 4 Figure 5a Figure Figure 5b Figure 6 Figure 7 Figure 8a Figure 8b Figure 8c Figure 9 | 09/2023 | ||||||||||||||||||||||||||||||||||||
Warnings and Precautions, Complications of Insertion/Removal and Broken/Bent Implants (5.1 Complications of Insertion/Removal and Broken/Bent Implants Complications of Insertion and Removal NEXPLANON 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 NEXPLANON 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 may occur, e.g., pain, paresthesia, bleeding, hematoma, scarring, or infection. If NEXPLANON is inserted deeply (intramuscular or intrafascial), neural or vascular injury may occur. To help reduce the risk of neural or vascular injury, NEXPLANON should be inserted subdermally just under the skin at the inner side of the non-dominant upper arm overlying the triceps muscle, about 8-10 cm (3-4 inches) from the medial epicondyle of the humerus, and 3-5 cm (1.25-2 inches) posterior to (below) the sulcus (groove) between the biceps and triceps muscles. This location is intended to avoid the large nerves and blood vessels lying within and surrounding the sulcus. Deep insertions of NEXPLANON have been associated with paresthesia (due to neural injury), migration of the implant (due to intramuscular or fascial insertion), and 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. Reports of implant migration within the arm may have been related to deep insertion. Postmarketing reports of implants located within the vessels of the arm and the pulmonary artery also may have been related to deep insertions or intravascular insertions. Some cases of implants found within the pulmonary artery were associated with chest pain and/or respiratory disorders (such as dyspnea, cough, or hemoptysis); others were asymptomatic. In cases where the implant has migrated to the pulmonary artery, endovascular or surgical procedures may be needed for removal. 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. If at any time the implant cannot be palpated, it should be localized, and removal is recommended. When an implant is removed, it is important to remove it in its entirety [see Dosage and Administration (2.3)]. 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 professionals familiar with the anatomy of the arm. If the implant is located in the chest, healthcare professionals familiar with the anatomy of the chest should be consulted. 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. Broken or Bent Implants Cases of breakage or bending of implants while inserted within a patient’s arm have been reported. Cases of migration of a broken implant fragment within the arm have also occurred. These cases may be related to external forces, e.g., manipulation of the implant or contact sports. The release rate of etonogestrel may be slightly increased in a broken or bent implant, based on in vitro data. As noted previously, when an implant is removed, it is important to remove it in its entirety[see Dosage and Administration (2.3)] . | 09/2023 |
Step 2. Identify the insertion site, which is at the inner side of the non-dominant upper arm. The insertion site is overlying the triceps muscle about 8-10 cm (3-4 inches) from the medial epicondyle of the humerus and 3-5 cm (1.25-2 inches) posterior to (below) the sulcus (groove) between the biceps and triceps muscles (Figures 2a, 2b and 2c). This location is intended to avoid the large blood vessels and nerves lying within and surrounding the sulcus. If it is not possible to insert the implant in this location (e.g., in women with thin arms), it should be inserted as far posterior from the sulcus as possible.
Step 13. Insert the needle until the bevel (slanted opening of the tip) is just under the skin (and no further) . If you inserted the needle deeper than the bevel, withdraw the needle until only the bevel is beneath the skin.
NEXPLANON® is indicated for use by women to prevent pregnancy.
The efficacy of NEXPLANON does not depend on daily, weekly, or monthly administration.
All healthcare professionals should receive instruction and training prior to performing insertion and/or removal of NEXPLANON.
A single NEXPLANON implant is inserted subdermally just under the skin at the inner side of the non-dominant upper arm. The insertion site is overlying the triceps muscle about 8-10 cm (3-4 inches) from the medial epicondyle of the humerus and 3-5 cm (1.25-2 inches) posterior to (below) the sulcus (groove) between the biceps and triceps muscles. This location is intended to avoid the large blood vessels and nerves lying within and surrounding the sulcus (see
|
Figure 2a P – Proximal (toward the shoulder) D – Distal (toward the elbow) |
Before initiating the removal procedure, the healthcare professional should assess the location of the implant and carefully read the instructions for removal. The exact location of the implant in the arm should be verified by palpation. If the implant is not palpable, consult the medical record to verify the arm which contains the implant. If the implant cannot be palpated, it may be deeply located or have migrated. Consider that it may lie close to vessels and nerves. Removal of non-palpable implants should only be performed by a healthcare professional experienced in removing deeply placed implants and familiar with localizing the implant and the anatomy of the arm. Call 1-844-674-3200 for further information.
Before removal of the implant, the healthcare professional should confirm that:
- The woman does not have allergies to the antiseptic or anesthetic to be used.
The following equipment is needed for removal of the implant:
- An examination table for the woman to lie on
- Sterile surgical drapes, sterile gloves, antiseptic solution, surgical marker
- Local anesthetic, needles, and syringe
- Sterile scalpel, forceps (straight and curved mosquito)
- Skin closure, sterile gauze, and pressure bandage
Step 1. Have the woman lie on her back on the table. The arm should be positioned with the elbow flexed and the hand underneath the head (or as close as possible). (See Figure 1.)
Mark the distal end (end closest to the elbow), for example, with a surgical marker.
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Figure 10 P – Proximal (toward the shoulder) D – Distal (toward the elbow) |
Step 3. Clean the site with an antiseptic solution.
Step 4. Anesthetize the site, for example, with 0.5 to 1 mL 1% lidocaine, where the incision will be made . Be sure to inject the local anesthetic
|
Figure 11 |
Step 5. Push down the end of the implant closest to the shoulder to stabilize it throughout the procedure. Starting over the tip of the implant closest to the elbow, make a longitudinal (parallel to the implant) incision of 2 mm towards the elbow. Take care not to cut the tip of the implant.
|
Figure 12 |
Step 6. The tip of the implant should pop out of the incision. If it does not, gently push the implant towards the incision until the tip is visible. Grasp the implant with forceps and, if possible, remove the implant . If needed, gently remove adherent tissue from the tip of the implant using blunt dissection. If the implant tip is not exposed following blunt dissection, make an incision into the tissue sheath and then remove the implant with the forceps .
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Figure 13 |
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Figure 14 | Figure 15 |
Step 7. If the tip of the implant does not become visible in the incision, insert forceps (preferably curved mosquito forceps, with the tips pointed up) superficially into the incision . Gently grasp the implant and then flip the forceps over into your other hand .
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Figure 16 | Figure 17 |
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Figure 18 |
Step 9. Confirm that the entire implant, which is 4 cm long, has been removed by measuring its length. There have been reports of broken implants while in the patient's arm. In some cases, difficult removal of the broken implant has been reported. If a partial implant (less than 4 cm) is removed, the remaining piece should be removed by following the instructions in section 2.3. If the woman would like to continue using NEXPLANON, a new implant may be inserted immediately after the old implant is removed using the same incision as long as the site is in the correct location
Step 10. After removing the implant, close the incision with a sterile adhesive wound closure.
Step 11. Apply a pressure bandage with sterile gauze to minimize bruising. The woman may remove the pressure bandage in 24 hours and the sterile adhesive wound closure in 3 to 5 days.
There have been reports of migration of the implant; usually this involves minor movement relative to the original position
A non-palpable implant should always be located prior to attempting removal. Given the radiopaque nature of the implant, suitable methods for localization include two-dimensional X-ray and X-ray computer tomography (CT). Ultrasound scanning (USS) with a high-frequency linear array transducer (10 MHz or greater) or magnetic resonance imaging (MRI) may be used. Once the implant has been localized in the arm, the implant should be removed by a healthcare professional experienced in removing deeply placed implants and familiar with the anatomy of the arm
If the implant cannot be found in the arm after comprehensive localization attempts, consider applying imaging techniques to the chest as events of migration to the pulmonary vasculature have been reported. If the implant is located in the chest, surgical or endovascular procedures may be needed for removal; healthcare professionals familiar with the anatomy of the chest should be consulted.
If at any time these imaging methods fail to locate the implant, etonogestrel blood level determination can be used for verification of the presence of the implant. For details on etonogestrel blood level determination, call 1-844-674-3200 for further instructions.
If the implant migrates within the arm, removal may require a minor surgical procedure with a larger incision or a surgical procedure in an operating room. Removal of deeply-inserted implants should be conducted with caution to help prevent injury to deeper neural or vascular structures in the arm. Non-palpable and deeply-inserted implants should be removed by healthcare professionals familiar with the anatomy of the arm and removal of deeply-inserted implants.
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 professionals familiar with the anatomy of the arm. If the implant is located in the chest, healthcare professionals familiar with the anatomy of the chest should be consulted. 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.
NEXPLANON must be inserted by the expiration date stated on the packaging. NEXPLANON is a long-acting (up to 3 years), reversible, hormonal contraceptive method. The implant must be removed by the end of the third year and may be replaced by a new implant at the time of removal, if continued contraceptive protection is desired.
Single, white/off-white, soft, radiopaque, flexible, ethylene vinyl acetate (EVA) copolymer implant, 4 cm in length and 2 mm in diameter containing 68 mg etonogestrel, 15 mg of barium sulfate, and 0.1 mg of magnesium stearate.
- Pregnancy: Discontinue if maintaining a pregnancy. ()
8.1 PregnancyRisk SummaryNEXPLANON is contraindicated during pregnancy because there is no need for pregnancy prevention in a woman who is already pregnant
[see Contraindications (4)]. Epidemiologic studies and meta-analyses have not shown an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following maternal exposure to low dose CHCs prior to conception or during early pregnancy. No adverse development outcomes were observed in pregnant rats and rabbits with the administration of etonogestrel during organogenesis at doses of 315 or 781 times the anticipated human dose (60 µg/day) (seeData).NEXPLANON should be removed if maintaining a pregnancy.
DataAnimal DataTeratology studies have been performed in rats and rabbits using oral administration up to 315 and 781 times the human etonogestrel dose (based upon body surface) and revealed no evidence of fetal harm due to etonogestrel exposure.
- Overweight women: NEXPLANON may become less effective in overweight women over time, especially in the presence of other factors that decrease etonogestrel concentrations, such as concomitant use of hepatic enzyme inducers. ()
8.7 Overweight WomenThe effectiveness of the etonogestrel implant 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 NEXPLANON 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.
NEXPLANON 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
- Allergic reaction to any of the components of NEXPLANON [see]
6 ADVERSE REACTIONSThe following adverse reactions reported with the use of hormonal contraception are discussed elsewhere in the labeling:
- Changes in Menstrual Bleeding Patterns[see Warnings and Precautions (5.2)]
- Ectopic Pregnancies[see Warnings and Precautions (5.3)]
- Thrombotic and Other Vascular Events[see Warnings and Precautions (5.4)]
- Liver Disease[see Warnings and Precautions (5.7)]
Most common (≥10%) adverse reactions reported in clinical trials were change in menstrual bleeding pattern, headache, vaginitis, weight increase, acne, breast pain, abdominal pain, and pharyngitis.
To report SUSPECTED ADVERSE REACTIONS, contact Organon USA LLC, a subsidiary of Organon & Co., at 1-844-674-3200 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.6.1 Clinical Trials ExperienceAdverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice, because clinical trials are conducted under widely varying conditions.
In clinical trials involving 942 women who were evaluated for safety, change in menstrual bleeding patterns (irregular menses) was the most common adverse reaction causing discontinuation of use of the non-radiopaque etonogestrel implant (IMPLANON) (11.1% of women).
Adverse reactions that resulted in a rate of discontinuation of ≥1% are shown in Table 3.
Table 3: Adverse Reactions Leading to Discontinuation of Treatment in 1% or More of Subjects in Clinical Trials of the Non-Radiopaque Etonogestrel Implant (IMPLANON) Adverse Reactions All Studies
N = 942Bleeding IrregularitiesIncludes "frequent", "heavy", "prolonged", "spotting", and other patterns of bleeding irregularity. 11.1% Emotional LabilityAmong US subjects (N=330), 6.1% experienced emotional lability that led to discontinuation. 2.3% Weight Increase 2.3% Headache 1.6% Acne 1.3% DepressionAmong US subjects (N=330), 2.4% experienced depression that led to discontinuation. 1.0% Other adverse reactions that were reported by at least 5% of subjects in the non-radiopaque etonogestrel implant clinical trials are listed in Table 4.
Table 4: Common Adverse Reactions Reported by ≥5% of Subjects in Clinical Trials with the Non-Radiopaque Etonogestrel Implant (IMPLANON) Adverse Reactions All Studies
N = 942Headache 24.9% Vaginitis 14.5% Weight increase 13.7% Acne 13.5% Breast pain 12.8% Abdominal pain 10.9% Pharyngitis 10.5% Leukorrhea 9.6% Influenza-like symptoms 7.6% Dizziness 7.2% Dysmenorrhea 7.2% Back pain 6.8% Emotional lability 6.5% Nausea 6.4% Pain 5.6% Nervousness 5.6% Depression 5.5% Hypersensitivity 5.4% Insertion site pain 5.2% In a clinical trial of NEXPLANON, in which investigators were asked to examine the implant site after insertion, implant site reactions were reported in 8.6% of women. Erythema was the most frequent implant site complication, reported during or shortly after insertion, occurring in 3.3% of subjects. Additionally, hematoma (3.0%), bruising (2.0%), pain (1.0%), and swelling (0.7%) were reported.
6.2 Postmarketing ExperienceAdverse Reactions and Events from Postmarketing StudyNexplanon Observational Risk Assessment Study (NORA)A postmarketing prospective active surveillance study was conducted among 7,364 patients in the United States to characterize the frequency of insertion-, localization-, and removal-related events.
Implant InsertionInsertion difficulty or an insertion-related event occurred in 2.6% of the study participants. The overall incidence of incorrect insertion (unrecognized non-insertion, partial insertion, and deep insertion), reported by healthcare professionals was 12.6 per 1,000 insertions (95% CI, 10.2, 15.5). Table 5summarizes the types and frequencies of these incorrect insertions.
Table 5: Incorrect Insertion Types and Incidence Reported by Healthcare Professionals Type of Incorrect Insertion Event Number of EventsTotal Insertion Procedures = 7,364 Incidence per 1,000 Insertions (95% CI) (Initially) Unrecognized Non-insertions1 0.1 (0.0-0.8) Partial Insertions27 3.7 (2.4-5.3) Deep Insertions65 8.8 (6.8-11.2) Injury to nerve or blood vessel 1 0.1 (0.0-0.8) Implant located within muscle 2 0.3 (0.0-1.0) Implant located adjacent to fascial tissue 56 7.6 (5.8-9.9) Implant not palpable 6 0.8 (0.3-1.8) Implant RemovalImplant removal information from both healthcare professionals and patients was collected for 5,159 patients (70% of the study population). Of these patients, data were available from healthcare professionals regarding 4,373 removal procedures. Healthcare professionals reported removal-related difficulties or complications in 1.5% of removal procedures. Table 6provides a summary.
Table 6: Removal-related Events Reported by Healthcare Professionals Removal Related Events Number of EventsTotal Removal Procedures: N= 4,373 Incidence per 1,000 Removals (95% CI) Any EventLimited to one event per removal procedure 60 13.7 (10.5-17.6) Encased in Fibrotic Tissue 29 6.6 (4.4-9.5) Implant Too Deep 11 2.5 (1.3-4.5) Implant MigratedOnly local migrations within the arm reported 6 1.4 (0.5-3.0) Multiple Attempts Required 13 3.0 (1.6-5.1) OtherOther included fragmented or bent implants, patient-related issues, wound care required, two incisions required, and difficulty identifying end of device. 14 3.2 (1.8-5.4) At the time of implant removal, eighteen implants (0.4% of all localizations or removals) were not palpable by the healthcare professionals. Of these eighteen, eleven were localized and removed, and one was localized but left in situ. Removal was not attempted for six non-palpable implants due to underlying health conditions, administrative problems, or unspecified reasons.
There were no reports of implants having migrated more than a few centimeters from the insertion site and no reports of implants localized at a site other than the arm. No neurovascular injuries were reported by healthcare professionals.
Adverse Reactions Reported by PatientsTable 7provides a summary of adverse reactions reported by patients at the time of implant insertion and after removal.
Table 7: Adverse Reactions Reported by Patients at Implant Insertion and after Removal Patient Reported Adverse Reactions At Insertion After Removal NTotal Insertion Procedures: N = 7,364 Incidence per 1000 insertions (95% CI) N Incidence per 1000 insertions (95% CI) Any EventLimited to one event per woman 49 6.7 (4.9-8.8) 42Based on 3,447 questionnaires 5.7 (4.1-7.7) Pins and Needles/Numbness (arm/hand/fingers) 17 2.3 (1.4-3.7) 24 3.3 (2.1-4.9) Severe Pain 10 1.4 (0.7-2.5) 11 1.5 (0.8-2.7) Altered Strength/Movement 3 0.4 (0.1-1.2) 8 1.1 (0.5-2.1) Injury to Blood Vessels or Blood Clots in ArmNo blood clots were observed during the study 2 0.3 (0-1.0) -- -- Other“Other” included localized or insertion site pain, soreness, tenderness, dermatological changes, itching, bruising, and infection, local migrations within the arm, and physical damage to the implant (e.g., fractured or bent implant). 22 3.0 (1.9-4.5) 18 2.4 (1.5-3.9) In summary, this prospective active surveillance study showed that the frequency of insertion-, localization-, and removal-related events is consistent with results previously reported from clinical trials.
Adverse Reactions from Postmarketing Spontaneous ReportsThe following additional adverse reactions have been identified during post-approval use of IMPLANON and NEXPLANON. It is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure because these reactions are reported voluntarily from a population of uncertain size.
Gastrointestinal disorders:constipation, diarrhea, flatulence, vomiting.General disorders and administration site conditions:edema, fatigue, implant site reaction, pyrexia.Immune system disorders:anaphylactic reactions.Infections and infestations:rhinitis, urinary tract infection.Investigations:clinically relevant rise in blood pressure, weight decreased.Metabolism and nutrition disorders:increased appetite.Musculoskeletal and connective tissue disorders:arthralgia, musculoskeletal pain, myalgia.Nervous system disorders:convulsions, migraine, somnolence.Pregnancy, puerperium and perinatal conditions:ectopic pregnancy.Psychiatric disorders:anxiety, insomnia, libido decreased.Renal and urinary disorders:dysuria.Reproductive system and breast disorders:breast discharge, breast enlargement, ovarian cyst, pruritus genital, vulvovaginal discomfort.Skin and subcutaneous tissue disorders:angioedema, aggravation of angioedema and/or aggravation of hereditary angioedema, alopecia, chloasma, hypertrichosis, pruritus, rash, seborrhea, urticaria.Vascular disorders:hot flush.Reported complications related to insertion or removal of the etonogestrel implants include vasovagal reactions (e.g., hypotension, dizziness, or syncope), bruising, slight local irritation, pain, itching, fibrosis at the implant site, paresthesia or paresthesia-like events, scarring, and abscesses. Implant expulsions and migrations also have been reported. In some cases, implants have migrated to the chest wall or into the vasculature, including the pulmonary artery. Some cases of implants migrating to the pulmonary artery presented with symptoms of chest pain and/or respiratory disorders (e.g., dyspnea, cough, or hemoptysis); other cases have been reported as asymptomatic. In-patient surgical interventions might be necessary when removing implants associated with complications
[see Warnings and Precautions (5.1)]. - Changes in Menstrual Bleeding Patterns