Drugs List

Therapeutic Indications

Uses

Contraception - injectable

Administration

To be administered by a healthcare professional who has been appropriately trained and accredited in the procedure.

One implant is inserted subdermally (subcutaneously) according to manufacturer's instructions in the inner aspect of the upper non-dominant arm approximately 8 to 10 cm from the medial epicondyle of the humerus and 3 to 5 cm posterior to the sulcus (groove) between the biceps and triceps muscles, under local anaesthesia and using aseptic technique. Care should be taken to avoid the sulcus between the biceps and triceps muscle where the large blood vessels and nerves lie in the neurovascular bundle.

It is recommended that the healthcare professional is positioned to view the applicator from the side and not above the arm in order to see the advancement of the needle. In this position the insertion site and the movement of the needle just under the skin can be clearly seen.

Immediately after insertion, verify the presence of the implant by palpation. If it cannot be palpated, or its presence is doubtful, confirm its presence with ultrasound imaging or by magnetic resonance imaging after consulting the manufacturer of the implant.
Barrier methods of contraception must be used until the presence of the implant is confirmed.

When removing the implant verify the location by palpation of the arm and ensure the entire rod, which is 4 cm long has been removed. There have been reports of broken implants while in the patients arm.
An implant that has been deeply inserted or has migrated may not be palpable and therefore imaging procedures may be required to confirm its location. If the implant cannot be located in the arm, consider applying imaging techniques to the chest as extremely rare cases of migration to the pulmonary vasculature have been reported. Should imaging methods fail to locate the implant, etonogestrel blood level determination can be used for verification of the presence of the implant after consulting with the manufacturer of the implant.

The applicator is for single-use only and must be disposed of in accordance with the local regulations for biohazardous waste.

Contraindications

Children under 18 years
Patients over 40 years
Abnormal liver function test
Hepatic neoplasm
History of hepatic neoplasm
History of severe hepatic disorder
Porphyria
Pregnancy
Progestogen-dependent neoplasm
Severe hepatic disorder
Thromboembolic disorder
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Obesity
Predisposition to venous thromboembolism
Prolonged immobilisation
Recent surgery
Breast cancer
Breastfeeding
Diabetes mellitus
Disorder of lipid metabolism
Hepatic impairment
History of breast cancer
History of chloasma
History of pregnancy-related deterioration in otosclerosis
History of pruritus during pregnancy
History of thromboembolic disorder
History of thrombosis
Hypertension

May decrease glucose tolerance in patients with diabetes mellitus
Assess family medical history prior to commencing treatment
Long term effectiveness may be reduced in overweight patients
Expulsion may occur if inserted incorrectly
Record name and batch number of administered product
Do breast & pelvic exam. before & during treatment if clinically indicated
Exclude pregnancy prior to initiation of treatment
Monitor blood pressure pre-treatment and periodically thereafter
Breastfeeding: Monitor infant for systemic effects of treating the mother
Check up recommended 3 months after insertion
May induce insulin resistance
Refer if hepatic function disturbed to a specialist
Consider ectopic pregnancy if abdominal and menstrual disturbances occur
Increased risk of VTE during travel involving >5hr immobilisation
Irregular vaginal bleeding may occur
May affect results of some laboratory tests
Advise patient to seek advice at first indications of pregnancy
Consider early replacement in overweight women (BMI >35kg/sq,metre)
Discontinue if persistent hypertension unresponsive to therapy occurs
Discontinue if thromboembolism occurs
Possibly discontinue treatment before surgery/immobilisation
Advise patient concurrent St John's wort may reduce contraceptive effect
Advise patient of possible recurrence of thromboembolic disorders
Advise patient of slight increased risk of breast cancer
Advise patient to check device location regularly for the first few months
Women with a history of chloasma should avoid exposure to sun/UV light

The use of oral contraceptives slightly increases the risk of having breast cancer diagnosed. The risks with progestogen-only contraceptives such as etonogestrel implant may be similar.

With all low dose hormonal contraceptives, follicular development occurs and occasionally the follicle may continue to grow beyond the size it would attain in a normal cycle. Usually these disappear spontaneously but rarely require surgical intervention. Often they are asymptomatic, but may be associated with mild abdominal pain.

Irregular vaginal bleeding may occur. Information, counselling and the use of a bleeding diary can improve the woman's perception of their bleeding pattern. Vaginal bleeding may be evaluated and can include examinations to exclude gynaecological pathology or pregnancy.

Pregnancy and Lactation

Pregnancy

Etonogestrel is contraindicated in pregnancy.

The implant should be removed if pregnancy occurs during treatment.

Animal studies have shown that very high dose of progestogenic substances may cause masculinisation of female foetuses.

Extensive epidemiological studies have revealed neither an increased risk of birth defects in children born to women who used oral contraceptives before pregnancy nor of a teratogenic effect when inadvertently used during pregnancy. Although this applies to oral contraceptives, this may not be the case for etonogestrel implant. Pharmacovigilance data with various desogestrel-containing combined oral contraceptives did not demonstrate an increased risk (etonogestrel is a metabolite of desogestrel).

Inadvertent use of combined hormonal contraceptives during pregnancy is not cause for termination or invasive diagnostic procedures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use etonogestrel with caution in breastfeeding.

Etonogestrel implant may be used during breastfeeding. However, if used, manufacturer advises that the growth and development of the child must be carefully monitored.

Studies on the effects of etonogestrel on breastfeeding report no statistically significant differences in infant illness or growth rates. No difference was found in milk volume, or in the content of lactose, protein or fat. Etonogestrel is excreted in milk in small amounts.

The use of non-hormonal contraceptive methods are preferred during breastfeeding. Hormonal contraception should not be initiated until at least 4 weeks post partum. Progestogen-only contraceptives are preferred over combined hormonal contraceptives during breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acne
Alopecia
Amenorrhoea
Anaphylactic reaction
Angioedema
Anxiety
Arthralgia
Back pain
Breast enlargement
Breast pain
Breast tenderness
Bruising at injection site
Constipation
Depression
Diarrhoea
Dizziness
Dysmenorrhoea
Dysuria
Emotional lability
Fatigue
Fever
Fibrosis at injection site
Flatulence
Galactorrhoea
Genital pruritus
Headache
Hepatic impairment
Hot flushes
Hypersensitivity reactions
Hypertension
Hypertrichosis
Increased appetite
Increased risk of ectopic pregnancy
Influenza-like syndrome
Injection site reactions
Insomnia
Irregular menstruation
Irritation (injection site)
Itching (injection site)
Local pain (injection site)
Migraine
Musculoskeletal pain
Myalgia
Nausea
Nervousness
Oedema
Ovarian cysts
Pain
Paraesthesia
Pharyngitis
Pruritus
Rash
Reduced libido
Rhinitis
Somnolence
Urinary tract infections
Urticaria
Vaginal discharge
Vaginal discomfort
Vomiting
Vulvovaginal infections
Weight changes

Presentation

Subdermal (subcutaneous) implant containing etonogestrel

Drugs List

Therapeutic Indications

Uses

Contraception - injectable

Dosage

Adults

Administration

To be administered by a healthcare professional who has been appropriately trained and accredited in the procedure.

One implant is inserted subdermally (subcutaneously) according to manufacturer's instructions in the inner aspect of the upper non-dominant arm approximately 8 to 10 cm from the medial epicondyle of the humerus and 3 to 5 cm posterior to the sulcus (groove) between the biceps and triceps muscles, under local anaesthesia and using aseptic technique. Care should be taken to avoid the sulcus between the biceps and triceps muscle where the large blood vessels and nerves lie in the neurovascular bundle.

It is recommended that the healthcare professional is positioned to view the applicator from the side and not above the arm in order to see the advancement of the needle. In this position the insertion site and the movement of the needle just under the skin can be clearly seen.

Immediately after insertion, verify the presence of the implant by palpation. If it cannot be palpated, or its presence is doubtful, confirm its presence with ultrasound imaging or by magnetic resonance imaging after consulting the manufacturer of the implant.
Barrier methods of contraception must be used until the presence of the implant is confirmed.

When removing the implant verify the location by palpation of the arm and ensure the entire rod, which is 4 cm long has been removed. There have been reports of broken implants while in the patients arm.
An implant that has been deeply inserted or has migrated may not be palpable and therefore imaging procedures may be required to confirm its location. If the implant cannot be located in the arm, consider applying imaging techniques to the chest as extremely rare cases of migration to the pulmonary vasculature have been reported. Should imaging methods fail to locate the implant, etonogestrel blood level determination can be used for verification of the presence of the implant after consulting with the manufacturer of the implant.

The applicator is for single-use only and must be disposed of in accordance with the local regulations for biohazardous waste.

Contraindications

Children under 18 years
Patients over 40 years
Abnormal liver function test
Hepatic neoplasm
History of hepatic neoplasm
History of severe hepatic disorder
Porphyria
Pregnancy
Progestogen-dependent neoplasm
Severe hepatic disorder
Thromboembolic disorder
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Obesity
Predisposition to venous thromboembolism
Prolonged immobilisation
Recent surgery
Breast cancer
Breastfeeding
Diabetes mellitus
Disorder of lipid metabolism
Hepatic impairment
History of breast cancer
History of chloasma
History of pregnancy-related deterioration in otosclerosis
History of pruritus during pregnancy
History of thromboembolic disorder
History of thrombosis
Hypertension

May decrease glucose tolerance in patients with diabetes mellitus
Assess family medical history prior to commencing treatment
Long term effectiveness may be reduced in overweight patients
Expulsion may occur if inserted incorrectly
Record name and batch number of administered product
Do breast & pelvic exam. before & during treatment if clinically indicated
Exclude pregnancy prior to initiation of treatment
Monitor blood pressure pre-treatment and periodically thereafter
Breastfeeding: Monitor infant for systemic effects of treating the mother
Check up recommended 3 months after insertion
May induce insulin resistance
Refer if hepatic function disturbed to a specialist
Consider ectopic pregnancy if abdominal and menstrual disturbances occur
Increased risk of VTE during travel involving >5hr immobilisation
Irregular vaginal bleeding may occur
May affect results of some laboratory tests
Advise patient to seek advice at first indications of pregnancy
Consider early replacement in overweight women (BMI >35kg/sq,metre)
Discontinue if persistent hypertension unresponsive to therapy occurs
Discontinue if thromboembolism occurs
Possibly discontinue treatment before surgery/immobilisation
Advise patient concurrent St John's wort may reduce contraceptive effect
Advise patient of possible recurrence of thromboembolic disorders
Advise patient of slight increased risk of breast cancer
Advise patient to check device location regularly for the first few months
Women with a history of chloasma should avoid exposure to sun/UV light

The use of oral contraceptives slightly increases the risk of having breast cancer diagnosed. The risks with progestogen-only contraceptives such as etonogestrel implant may be similar.

With all low dose hormonal contraceptives, follicular development occurs and occasionally the follicle may continue to grow beyond the size it would attain in a normal cycle. Usually these disappear spontaneously but rarely require surgical intervention. Often they are asymptomatic, but may be associated with mild abdominal pain.

Irregular vaginal bleeding may occur. Information, counselling and the use of a bleeding diary can improve the woman's perception of their bleeding pattern. Vaginal bleeding may be evaluated and can include examinations to exclude gynaecological pathology or pregnancy.

Pregnancy and Lactation

Pregnancy

Etonogestrel is contraindicated in pregnancy.

The implant should be removed if pregnancy occurs during treatment.

Animal studies have shown that very high dose of progestogenic substances may cause masculinisation of female foetuses.

Extensive epidemiological studies have revealed neither an increased risk of birth defects in children born to women who used oral contraceptives before pregnancy nor of a teratogenic effect when inadvertently used during pregnancy. Although this applies to oral contraceptives, this may not be the case for etonogestrel implant. Pharmacovigilance data with various desogestrel-containing combined oral contraceptives did not demonstrate an increased risk (etonogestrel is a metabolite of desogestrel).

Inadvertent use of combined hormonal contraceptives during pregnancy is not cause for termination or invasive diagnostic procedures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use etonogestrel with caution in breastfeeding.

Etonogestrel implant may be used during breastfeeding. However, if used, manufacturer advises that the growth and development of the child must be carefully monitored.

Studies on the effects of etonogestrel on breastfeeding report no statistically significant differences in infant illness or growth rates. No difference was found in milk volume, or in the content of lactose, protein or fat. Etonogestrel is excreted in milk in small amounts.

The use of non-hormonal contraceptive methods are preferred during breastfeeding. Hormonal contraception should not be initiated until at least 4 weeks post partum. Progestogen-only contraceptives are preferred over combined hormonal contraceptives during breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Advise the user that she may request removal of the implant at any time.

Instruct the patient on how to locate the implant and advise her to do this frequently for the first few months. If she has any concerns she should return to the clinic for advice.

Remind the patient that hormonal contraceptives do not protect against HIV infection or other sexually transmitted diseases.

Warn women with a history of thromboembolic disorders of the possibility of a recurrence.

Women with an increased risk of developing chloasma should be warned to avoid exposure to sunlight and ultraviolet radiation during therapy.

Advise patient of the slight increased risk of breast cancer.

Advise patient to seek advice at the first indications of pregnancy.

Advise patient concurrent St John's wort may reduce contraceptive effect.

Side Effects

Abdominal pain
Acne
Alopecia
Amenorrhoea
Anaphylactic reaction
Angioedema
Anxiety
Arthralgia
Back pain
Breast enlargement
Breast pain
Breast tenderness
Bruising at injection site
Constipation
Depression
Diarrhoea
Dizziness
Dysmenorrhoea
Dysuria
Emotional lability
Fatigue
Fever
Fibrosis at injection site
Flatulence
Galactorrhoea
Genital pruritus
Headache
Hepatic impairment
Hot flushes
Hypersensitivity reactions
Hypertension
Hypertrichosis
Increased appetite
Increased risk of ectopic pregnancy
Influenza-like syndrome
Injection site reactions
Insomnia
Irregular menstruation
Irritation (injection site)
Itching (injection site)
Local pain (injection site)
Migraine
Musculoskeletal pain
Myalgia
Nausea
Nervousness
Oedema
Ovarian cysts
Pain
Paraesthesia
Pharyngitis
Pruritus
Rash
Reduced libido
Rhinitis
Somnolence
Urinary tract infections
Urticaria
Vaginal discharge
Vaginal discomfort
Vomiting
Vulvovaginal infections
Weight changes

Effects on Laboratory Tests

Contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, serum levels of carrier proteins, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. The changes generally remain in the normal range. It is not known to what extent these changes apply to progestogen-only contraceptives.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: January 2015

Reference Sources

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 25 September 2014.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Nexplanon 68 mg implant for subdermal use. Merck Sharp & Dohme Ltd. Revised May 2016.

MHRA Drug Safety Update February 2020
Available at: https://www.mhra.gov.uk
Last accessed: 16 April 2020

UK Drugs in Lactation Advisory Service.
Available at: https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Last accessed: 25 September 2014

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Etonogestrel Last revised: 16 January 2014
Last accessed: 25 September 2014

The Drug Database for acute Porphyria (NAPOS).
Available at: https://www.drugs-porphyria.com/languages/UnitedKingdom/index2.php?l=gbr
Etonogestrel Last revised: October 1, 2004
Last accessed: 24 September 2014