Nexplanon (etonogestrel) contraceptive implants: new insertion site to reduce rare risk of neurovascular injury and implant migration

Amended advice on the insertion site for Nexplanon contraceptive implants following concerns regarding reports of neurovascular injury and implants migrating to the vasculature (including the pulmonary artery).

Advice for healthcare professionals:

  • an implant should be inserted subdermally by a healthcare professional who has been appropriately trained and accredited – correct insertion of the implant just under the skin is essential to reduce the risk of neurovascular injury and the implant migrating through the vasculature
  • review the updated guidance for how to correctly insert the implant, including an amended diagram that illustrates:
    • the new insertion site
    • the correct position of the arm for insertion (flexed at the elbow with the woman’s hand underneath her head)
    • how to view the needle (by sitting and viewing it from the side) to avoid deep insertion
  • show the woman how to locate the implant and advise her to do this occasionally; if she has any concerns, she should return promptly to the clinic for advice
  • localise any implant that cannot be palpated (for example, by imaging the arm) and remove it at the earliest opportunity – perform chest imaging if it cannot be located in the arm
  • implants inserted at the previous site that can be palpated should not pose a risk and do not need to be moved to the new site; only replace implants if you have concerns regarding their location or if routine replacement is due
  • report any suspected side effects to Nexplanon on a Yellow Card, including difficulties with insertion or adverse incidents from migration of the implant or related to its removal

Risk of neurovascular injury and implant migration

Nexplanon is a highly effective, long-acting contraceptive implant containing etonogestrel, a synthetic progestogen. Nexplanon acts by preventing ovulation and is usually effective for 3 years. Safety and efficacy have been established in women between 18 and 40 years of age. For maximum effectiveness and safety, Nexplanon needs to be correctly implanted by someone who is trained to fit it.

There have been reports of neurovascular injury and migration of the contraceptive implant from the insertion site and in rare cases into the pulmonary artery. Some cases have reported haematoma and excessive bruising at the insertion site and dyspnoea.

Although this risk has been known since 2016 (see Drug Safety Update, June 2016), reports continue to be received with Nexplanon. Up to June 2019, the MHRA is aware of 126 reports of implant migration. Of these reports 18 mention migration to the lung, with some mentioning multiple instances of implants that have migrated to the lung. Worldwide, a total of 107 cases of migration to the pulmonary artery and lung have been identified by the marketing authorisation holder since Nexplanon was launched (between 28 August 1998 to 3 September 2019).

Although no specific risk factors have been identified, potential risk factors include:

  • deep insertion

  • insertion in an inappropriate site

  • insertion in thin arms

Updated advice for insertion of the implant

Following continued receipt of reports, the manufacturer of Nexplanon has further explored the anatomy of the arm to identify an insertion site with the lowest number of vascular/neurological structures.

The recommended site for insertion is just under the skin at the inner side of the non-dominant upper arm about 8–10 cm from the medial epicondyle of the humerus and 3–5 cm posterior to the sulcus (groove) between the biceps and triceps muscles. The updated instructions have been added to the product information for Nexplanon and a letter has been sent to healthcare professionals. The Faculty of Sexual and Reproductive Healthcare (FSRH) has also issued a statement.

Subdermal insertion of the implant is the best way to avoid injury, and use of the new site is thought to minimise the risk of migration to the lung and neurovascular injury in case of inadvertent deep insertion. The insertion site is located in an area overlying the triceps muscle, a location generally free of major blood vessels and nerves.

The woman’s arm should be flexed at the elbow with her hand underneath her head (or as close as possible) during insertion and removal of the implant. This increased flexion should deflect the ulnar nerve away from the insertion site, potentially further reducing the risk of ulnar nerve injury during implant insertion and removal. On insertion, it is essential to view the needle and tenting of the skin to ensure subdermal insertion.

Evidence from the literature shows that implants found in the vasculature can become endothelised into the pulmonary artery.[footnote 1] [footnote 2] [footnote 3] If they are located early enough it is possible to remove them by endovascular procedure.[footnote 4] [footnote 5] Women should be shown how to locate the implant immediately following insertion and advised to check the position of the implant occasionally to ensure it has not migrated.

Expert removers’ network

There is a network of healthcare professionals who are experienced in implant localisations and difficult removals and who are available for consultation. To request additional information on implant insertion and removal, contact the network by calling 01992 467 272.

Report any suspected adverse reactions on a Yellow Card

Healthcare professionals and patients should continue to report any suspected adverse drug reactions to Nexplanon to the Yellow Card Scheme.

Clarification - March 2020

Please note, the 107 cases of migration mentioned in the article were located in the pulmonary artery and chest (including but not limited to the lung).

Article citation: Drug Safety Update volume 13, issue 7: February 2020: 4.

  1. D’Journo XB, et al. Intravascular pulmonary migration of a subdermal contraceptive implant. Ann Thorac Surg 2015; 99: 1828. 

  2. Patel A, et al. Contraceptive implant embolism into the pulmonary artery. Ann Thorac Surg 2014; 97: 1452. 

  3. O’Brien A, et al. Subdermal contraceptive implant embolism to a pulmonary artery. Ann Thorac Surg 2015; 2254: 2255. 

  4. Heudes P-M, et al. Migration of a contraceptive subcutaneous device into the pulmonary artery. Report of a case. Case Rep Womens Health 2015; 8: 6–8. 

  5. Maroteix P, et al. Embolie pulmonaire par implant progestatif [Pulmonary embolus with a progestogen implant]. Ann Fr Med Urgence 2015; 5: 332–33. 

Published 12 February 2020