Etonogestrel

Etonogestrel is not indicated during pregnancy. If pregnancy occurs during use of etonogestrel, the implant should be removed. Animal studies have shown that very high doses of progestagenic 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 OCs prior to pregnancy, nor of a teratogenic effect when OCs were inadvertently used during pregnancy. Although this probably applies to all OCs, it is not clear whether this is also the case for etonogestrel.

Pharmacovigilance data with various etonogestrel- and desogestrel-containing products (etonogestrel is a metabolite of desogestrel) do not indicate an increased risk.

Clinical data indicate that etonogestrel does not influence the production or the quality (protein, lactose or fat concentrations) of breast milk. However, small amounts of etonogestrel are excreted in breast milk. Based on an average daily milk ingestion of 150 ml/kg, the mean daily infant etonogestrel dose calculated after one month of etonogestrel release is approximately 27 ng/kg/day. This corresponds to approximately 2.2% of the weight-adjusted maternal daily dose and to approximately 0.2% of the estimated absolute maternal daily dose. Subsequently the milk etonogestrel concentration decreases with time during the lactation period.

Limited long-term data are available on 38 children, whose mothers had an implant inserted during the 4^th to 8^th week postpartum. They were breast-fed for a mean duration of 14 months and followed-up to 36 months of age. Evaluation of growth, and physical and psychomotor development did not indicate any differences in comparison to nursing infants whose mothers used an IUD (n=33). Nevertheless, development and growth of the child should be carefully followed. Based on the available data, etonogestrel may be used during lactation and should be inserted after the 4th postpartum week.

On the basis of the pharmacodynamic profile, etonogestrel is expected to have no or negligible influence on the ability to drive or use machines.

During the use of etonogestrel, women are likely to have changes in their menstrual bleeding pattern which are unpredictable beforehand. These may include the occurrence of an irregular bleeding pattern (absent, less frequent, more frequent or continuous), and changes in bleeding intensity (reduced or increased) or duration. Amenorrhoea was reported in about 1 of 5 women while another 1 of 5 women reported frequent and/or prolonged bleeding. Occasionally, heavy bleeding has been reported. In clinical trials, bleeding changes were the most common reason for stopping treatment (about 11%). The bleeding pattern experienced during the first three months is broadly predictive of future bleeding patterns for many women.

Possibly related undesirable effects reported in clinical trials have been listed below¹:

Very Common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100)

Infections and Infestations

Very Common: vaginal infection;

Uncommon: pharyngitis, rhinitis; urinary tract infection;

Immune system disorders

Uncommon: Hypersensitivity;

Metabolism and nutrition disorders

Common: increased appetite;

Psychiatric disorders

Common: affect lability; depressed mood; nervousness; libido decreased;

Uncommon: Anxiety; insomnia;

Nervous system disorders

Very Common: Headache;

Common: Dizziness;

Uncommon: Migraine; somnolence;

Vascular disorders

Common: hot flush;

Gastrointestinal disorders

Common: abdominal pain; nausea; flatulence;

Uncommon: Vomiting; constipation; diarrhoea;

Skin and subcutaneous tissue disorders

Very Common: Acne;

Common: Alopecia;

Uncommon: hypertrichosis, rash; pruritus;

Musculoskeletal and connective tissue disorders

Uncommon: back pain; arthralgia; myalgia; musculoskeletal pain;

Renal and urinary disorders

Uncommon: Dysuria;

Reproductive system and breast disorders

Very Common: breast tenderness; breast pain; menstruation irregular;

Common: Dysmenorrhoea; ovarian cyst;

Uncommon: genital discharge; vulvovaginal discomfort; galactorrhoea; breast enlargement; pruritus genital;

General disorders and administration site condition

Common: implant site pain; implant site reaction; fatigue; influenza like illness; pain;

Uncommon: Pyrexia; oedema;

Investigations

Very Common: weight increased;

Common: weight decreased;

¹ The most appropriate MedDRA term (version 10.1) to describe a certain adverse reaction is listed. Synonyms or related conditions are not listed, but should be taken into account as well.

During post marketing surveillance, a clinically relevant rise in blood pressure has been observed in rare cases. Seborrhoea has also been reported. Anaphylactic reactions, urticaria, angioedema, aggravation of angioedema and/or aggravation of hereditary angioedema may occur. Insertion or removal of the implant may cause some bruising, including haematoma in some cases, slight local irritation, pain or itching.

Fibrosis at the implant site may occur, a scar may be formed or an abscess may develop. Paraesthesia or paraesthesia-like events may occur. Expulsion or migration of the implant have been reported, including rarely to the chest wall. In rare cases, implants have been found within the vasculature including the pulmonary artery. Some cases of implants found within the pulmonary artery reported chest pain and/or respiratory disorders (such as dyspnoea, cough, haemoptysis); others have been reported as asymptomatic. If instructions are not followed, incorrect insertions, difficult localisations and difficult removals of the implant may occur. Surgical intervention might be necessary when removing the implant.

On rare occasions, ectopic pregnancies have been reported.

In women using (combined oral) contraceptives a number of (serious) undesirable effects have been reported. These include venous thromboembolic disorders, arterial thromboembolic disorders, hormone-dependent tumours (e.g. liver tumours, breast cancer) and chloasma.