This is a long-acting reversible contraceptive (LARC).
Nexplanon® is the only contraceptive implant on the UK market. From October 2010, it replaced the bio-equivalent Implanon®. It offered an improved insertion device and added barium sulfate to enable location of lost devices on X-ray.
Nexplanon® is a 4 cm flexible rod containing 68 mg etonogestrel (a progestogen) which is released slowly into the systemic circulation following subdermal insertion in the upper arm. It must be removed after three years when it can be replaced immediately.
Norplant®, which consists of six small rods, was previously available in the UK, along with Norplant-2® (also called Jadelle®), which is still used in some countries.
Mechanism of action
The main mechanism of action of Nexplanon® is to inhibit ovulation. It also thickens the cervical mucus, inhibiting the passage of sperm to the uterus, and thins the endometrium, preventing implantation were an egg to be fertilised.
Statistics on contraceptive use in the UK are sparse. The use of LARCs as a primary method of contraception amongst women has been slowly increasing and in 2013/14 accounted for 31% of all women making contact with sexual and reproductive health services. This compares to 18% in 2003-04. 16% of the women in contact with sexual and reproductive health services, using LARCs in England in 2017/18, have the implant.
Progestogen-only subdermal implants (POSDIs) such as Nexplanon® are suitable for:
- Those who want a reliable but reversible form of contraception which does not require daily vigilance or action at the time of intercourse.
- Women who have contra-indications to oestrogen therapy (another alternative is the injectable progestogen-only contraception, Depo-Provera®).
- Diabetes - it is not a contra-indication to using Nexplanon®.
- Breast-feeding - it is not a contra-indication to using Nexplanon®.
- Migraine (with or without aura) - it is not a contra-indication to using Nexplanon®.
- Body mass index (BMI) >30 kg/m2- higher body weight is not a not contra-indication to using Nexplanon®, indeed it has many advantages over the combined oral contraceptive (COC) pill for women at increased risk of VTE due to BMI. Because blood levels of etonogestrel are lower in the third year of use in women with a BMI >35 kg/m2, the SPC suggests 'earlier than usual removal/replacement in heavier women'. However, there is no evidence to support this requirement and the Faculty of Sexual and Reproductive Healthcare (FSRH) recommends only that women be informed of the manufacturer's recommendation but advised that there is no evidence to support it. It recommends taking into account other factors such as bleeding patterns and previous fertility when considering early replacement, and that a cut-off of 70 kg is a reasonable one. Some authors suggest a pragmatic response is to have early replacement in patients of higher body weight, who begin to cycle regularly.
All patients should be carefully counselled before insertion - supplemented by a suitable patient information leaflet.
This is very low; most studies show no failures. The National Institute for Health and Care Excellence (NICE) quotes a failure rate of less than 1 in 1,000 women in three years of use. Pregnancies which have occurred related to incorrect timing of insertion, conception prior to insertion and failure of insertion. No studies have demonstrated increased pregnancy rates attributable to high body weight up to 149 kg.
- Exclude pregnancy before insertion; a history of recent normal menstruation or reliable use of another contraceptive is adequate.
- If there is any doubt, suggest a urine pregnancy test pre-insertion.
- Unexplained vaginal bleeding.
- Progesterone-dependent cancers.
- Current hydatidiform mole or choriocarcinoma (until human chorionic gonadotrophin (hCG) is undetectable).
- Current severe impairment of liver function (with abnormal LFTs) or history of liver adenoma or steroid-induced cholestatic jaundice.
- History of severe arterial disease or very high-risk factors: Although there is no evidence of increased risk with Nexplanon®, the manufacturer advises that it be avoided in those with current active venous thromboembolism (VTE).
- Hypersensitivity to any components of Nexplanon®.
- POSDIs share the contra-indications of oral progestogen-only contraceptives.
- Acute porphyria, even if there is no history of active disease: there is evidence that both oestrogen and progesterone can precipitate attacks and 1% are fatal.
- Liver adenoma.
- Previous breast cancer - the progestogen-only contraceptive implant can be used for >5 years provided there is no evidence of recurrence.
- Liver enzyme-inducing drugs - eg, anti-epileptic drugs: The Summary of Product Characteristics (SPC) states that hepatic enzyme inducers may lower the blood levels of etonogestrel, which may explain some observed failures. Advice is therefore as follows:
- Women on short-term treatment with these drugs are advised to use a barrier method whilst taking the drug and for 28 days afterwards.
- Women on long-term treatment with liver enzyme inducers are advised instead to consider using intrauterine system (IUS)/intrauterine contraceptive device (IUCD), depot medroxyprogesterone acetate (DMPA) or other non-hormonal methods of contraception. A further effective option would be to add Cerazette® once daily to the Nexplanon®, but there is no published evidence for this.
- Antiretroviral drugs for HIV - there have been reports that the efficacy of both may be reduced, although the evidence on this is inconclusive.
- Safety and convenience, steady dosing without an initial peak dose to the liver (as with injectables) or fluctuating hormone levels - as with the contraceptive progestogen-only pill (POP).
- Dysmenorrhoea and pain associated with ovulation but with no identifiable cause may be improved or resolved by methods - including the implant - which suppress ovulation .
- No demonstrable effect on systolic or diastolic blood pressure.
- Studies of women using Norplant® show very low rates of ectopic pregnancy. There are no studies of the effect of Nexplanon® on rates of ectopic pregnancy but because it inhibits ovulation it is presumed that the rates are very low. It is therefore suitable for women who have a history of ectopic pregnancy.
- Dysmenorrhoea usually improves while using Nexplanon®.
- There is no evidence of delay in return to fertility on removal of Nexplanon®. Etonogestrel levels are undetectable four days following removal.
- There is no evidence of reduced bone mineral density with Nexplanon®, unlike the contraceptive injection.
- There is no evidence (as for other progestogen-only contraceptives) of increased VTE risk.
- Women may experience worsening of, improvement to or new onset of, acne as a result of using the implant.
- Local adverse effects can occur (infection, expulsion or migration of the device).
- No protection is provided against sexually transmitted infections.
- Unlike many methods of contraception, women cannot stop using an implant without the involvement of a properly trained healthcare professional.
- Removal of Nexplanon® is usually a straightforward minor operation under local anaesthetic but discomfort is possible.
- Possible complications include difficulty finding the rod and broken implants.
- Women may experience worsening of, improvement to or new onset of, acne as a result of using the implant.
- Fewer than one-quarter of women using the progestogen-only implant will have regular bleeds. Infrequent bleeding is the most common pattern (approximately one third); around one fifth of women experience no bleeding; and approximately one quarter of women have prolonged or frequent bleeding. These changes do NOT settle with time.
- 33% of women have Nexplanon® removed early because of a change in bleeding pattern. This is the most common reason for removal.
- If there are no contra-indications, short-term cyclical oestrogens (either as a COC pill or as ethinylestradiol), mefenamic acid and mifepristone may be of use in treating irregular or heavy bleeding. Counselling prior to insertion is important in decreasing discontinuation rates.
- Loss of libido and altered mood are rare side-effects of Nexplanon®. The NICE guidelines recommend that these should not be cited as side-effects when counselling women.
- Acne may improve or worsen while using Nexplanon®.
- If pregnancy occurs during use of hormonal contraception (including COC pills), there is no evidence of increased risk of congenital malformation. There is, however, a theoretical risk of virilisation of the fetus, so the implant should be removed as soon as possible.
- Nausea, vomiting, dizziness and mastalgia. Breast pain may be caused by Nexplanon®.
- Breast cancer incidence is slightly raised during and for up to 10 years after use of injectable contraceptives.
There is no evidence that Nexplanon® causes headaches, weight gain, increased blood pressure, increased risk of VTE or changes in lipids or glucose. There is also no evidence that it has a clinically significant adverse effect on bone mineral density.
Whilst there is no scientific evidence of a causal link between these symptoms and the device, including weight gain, patients should be met 'where they are' and if they remain convinced that the device is no longer acceptable due to symptoms they attribute to it then the device should be removed and they will need help to find an acceptable alternative method.
- Always take a full medical history (family, menstrual, contraceptive and sexual).
- Always give full counselling about risks and benefits of the implant:
- Method of insertion and removal of device, including possible adverse effects; women should be advised to expect some discomfort and bruising at the site of insertion.
- Duration of action.
- Timing of removal.
- Return to fertility after removal.
- Possible adverse effects of progestogen-only contraception.
- Always complete a sexual health risk assessment and include discussion of protection against sexually transmitted diseases.
- Day 1-5 is the usual timing for immediate effect, with a recommendation of additional contraception for seven days after insertion if doing so at any other time in the menstrual cycle. However, implants may be inserted at any time in the menstrual cycle as long as the woman is 'reasonably certain' that she is not pregnant. This includes those switching from another hormonal method of contraception. Therefore, if a woman is using DMPA or the COC pill then the implant may be inserted at any time without additional precautions.
- When switching from a levonorgestrel intrauterine system (LNG-IUS), the implant can be inserted immediately if the IUS was used correctly (or if the clinician is reasonably certain that the woman is not pregnant). The LNG-IUS should be continued for at least seven days.
- When switching from a copper intrauterine contraceptive device (Cu-IUCD), the implant may be inserted immediately if the Cu-IUCD was used correctly (or if the clinician is reasonably certain that the woman is not pregnant). The Cu-IUCD should be continued for at least seven days.
- If the patient is amenorrhoeic or if insertion occurs after day 5 of the menstrual cycle, extra, non-hormonal contraceptive precautions should be taken for seven days.
- After termination of pregnancy (TOP) in the first or second trimester, insertion may take place immediately. If implanted >5 days after abortion or miscarriage, additional contraception is required for seven days.
- After pregnancy, Nexplanon® should be inserted 21-28 days after delivery or TOP. It may be inserted immediately but this may lead to an increase in irregular or heavy bleeding. If insertion takes place after day 28, additional contraception should be used for seven days.
Although the insertion technique is straightforward, it is a minor surgical procedure which cannot be learned from any book. Practical training (model arm plus supervised live patient training) is essential.
- After injection of local anaesthetic, Nexplanon® is inserted into the subdermal tissue of the upper arm (flexor surface).
- After insertion, both the health professional and the patient should examine the arm and be satisfied that the implant is in place, thus reducing the risk of insertion failures.
- To replace a previous Nexplanon®, the new one may be inserted through the same removal incision, with additional local anaesthetic and ensuring that the needle is inserted to its full length.
- Technically difficult insertions are unusual (<1 in 100).
- Removal is usually simple and contraceptive effect is lost immediately.
- Under local anaesthetic, digital pressure is applied to the proximal end of the device where it is felt under the skin. A 2 mm incision over the distal end then leads to delivery of the rod, which is grasped with mosquito forceps. Formal practical training in the procedure is essential (model arm and supervised live patients).
- Good training minimises removal difficulties, including discomfort.
- Difficult removals usually relate to too-deep insertion. This is particularly a risk in thin or muscular woman who lack much subcutaneous tissue. The device can be localised on X-ray but ultrasound guidance is needed for removal in these cases.
Unless the woman experiences problems, no follow-up is required until removal is due three years after insertion.
St John's wort
St John's wort is a liver enzyme inducer available without prescription from health food shops and pharmacies, and is often used for premenstrual syndrome, headaches and anxiety and low mood.
There have been concerns for some years that St John's wort reduced the effectiveness of hormonal contraception, although at first there was uncertainty as to whether the theoretical risk translated into unplanned pregnancies. In March 2014 the Medicines and Healthcare products Agency (MHRA) issued guidance on St John's wort and hormonal contraception, stating categorically that St John's wort reduces the effectiveness of these contraceptives and increases the risk of unplanned pregnancy. This applies to all hormonal contraceptives except intrauterine devices, for which there are currently no data. MHRA stated that four reports of suspected interactions between St John's wort and contraceptive implants resulting in unplanned pregnancy had been received through the Yellow Card Scheme since 2000.
There are warnings about these interactions and their consequences in the product information provided with all contraceptives and the authorised St John's wort products. Some unlicensed products on the UK market or available online do not include the appropriate warnings regarding possible interactions.
Advise women who are using combined and progestogen-only hormonal contraceptives that herbal products containing St John's wort can decrease the effect of this contraceptive cover. Therefore, women taking hormonal contraception for pregnancy prevention should not take herbal products that contain St John's wort.
Further reading and references
Trends in Contraceptive Use Worldwide; United Nations (2015)
Summary of Product Characteristics (SPC) - Nexplanon® 68 mg implant for subdermal use; Merck Sharp & Dohme Limited, electronic Medicines Compendium, March 2019
NHS contraceptive services: England Community Contraceptive Clinics 2013-14; Health and Social Care Information Centre (HSCIC), 30 October 2014
Contraception - assessment; NICE CKS, Dec 2017 (UK access only)
Progestogen-only implants; Faculty of Sexual and Reproductive Healthcare (Feb 2014)
Manufacturer's PIL, Nexplanon® 68 mg implant for subdermal use; Merck Sharp & Dohme Limited, The electronic Medicines Compendium. Dated October 2016.
Long-acting reversible contraception; NICE Clinical Guideline (September 2014)
UK Medical Eligibility Criteria for Contraceptive Use; Faculty of Sexual and Reproductive Healthcare (2016)
Leticee N, Viard JP, Yamgnane A, et al; Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz. Contraception. 2012 Apr85(4):425-7. doi: 10.1016/j.contraception.2011.09.005. Epub 2011 Oct 27.
Contraception - progestogen-only methods; NICE CKS, December 2017 (UK access only)
Campodonico J, Wolfrey J, Buchanan J; Reports of Two Broken Nexplanon(R) Rods. J Am Board Fam Med. 2019 Mar-Apr32(2):269-271. doi: 10.3122/jabfm.2019.02.180222.
St John’s wort: interaction with hormonal contraceptives, including implants - reduced contraceptive effect; Drug Safety Update, Medicines and Healthcare products Regulatory Agency (MHRA), March 2014