Desogestrel

Substances increasing the clearance of contraceptive hormones (diminished contraceptive efficacy by enzyme induction) e.g.:

Barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, efavirenz and possibly also felbamate, griseofulvin, oxcarbazepine, topiramate, rifabutin and products containing the herbal remedy St. John’s Wort (hypericum perforatum).

Concomitant administration of strong (e.g. ketoconazole, itraconazole, clarithromycin) or moderate (e.g. fluconazole, diltiazem, erythromycin) CYP3A4 inhibitors may increase the serum concentrations of progestins, including etonogestrel, the active metabolite of desogestrel.

When co-administered with hormonal contraceptives, many combinations of HIV protease inhibitors (e.g. ritonavir, nelfinavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and/or combinations with Hepatitis C virus (HCV) medicinal products (e.g. boceprevir, telaprevir), can increase or decrease plasma concentrations of progestins. The net effect of these changes may be clinically relevant in some cases.

Therefore, the prescribing information of concomitant HIV/HCV medications should be consulted to identify potential interactions and any related recommendations. In case of any doubt, an additional barrier contraceptive method should be used by women on protease inhibitor or non-nucleoside reverse transcriptase inhibitor therapy.

If a sustained hypertension develops during the use of desogestrel, or if a significant increase in blood pressure does not adequately respond to antihypertensive therapy, the discontinuation of desogestrel should be considered.

Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking desogestrel.

Although progestogens may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for a need to alter the therapeutic regimen in diabetics using progestogen-only pills. However, diabetic patients should be carefully observed during the first months of use.

Desogestrel is not indicated during pregnancy. If pregnancy occurs during treatment with desogestrel, further intake should be stopped.

Animal studies have shown that very high doses 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 COCs prior to pregnancy, nor a teratogenic effect when COCs were taken inadvertently during early pregnancy. Pharmacovigilance data collected with various desogestrel-containing COCs also do not indicate an increased risk.

Desogestrel does not influence the production or the quality (protein, lactose, or fat concentrations) of breast milk. However, small amounts of etonogestrel are excreted in the breast milk. As a result, 0.01-0.05 microgram etonogestrel per kg body weight per day may be ingested by the child (based on an estimated milk ingestion of 150 ml/kg/day).

Limited long-term follow-up data are available on children, whose mothers started using desogestrel during the 4^th to 8^th week post-partum. They were breast-fed for 7 months and followed up to 1.5 years (n=32) or to 2.5 years (n=14) of age. Evaluation of growth and physical and psychomotor development did not indicate any differences in comparison to nursing infants, whose mother used a copper-IUD. Based on the available data desogestrel may be used during lactation. The development and growth of a nursing infant, whose mother uses desogestrel, should, however, be carefully observed.

Fertility

Desogestrel is indicated for the prevention of pregnancy.

Desogestrel has no or negligible influence on the ability to drive and use machines.

The most commonly reported undesirable effect in the clinical trials is bleeding irregularity. Some kind of bleeding irregularity has been reported in up to 50% of women using desogestrel. Since desogestrel causes ovulation inhibition close to 100%, in contrast to other progestogen-only pills, irregular bleeding is more common than with other progestogen-only pills. In 20-30% of the women, bleeding may become more frequent, whereas in another 20% bleeding may become less frequent or totally absent. Vaginal bleeding may also be of longer duration. After a couple of months of treatment, bleedings tend to become less frequent. Information, counselling, and a bleeding diary can improve the woman’s acceptance of the bleeding pattern.

The most commonly reported other undesirable effects in the clinical trials with desogestrel (>2.5%) were acne, mood changes, breast pain, nausea and weight increase. The undesirable effects are mentioned below.

All undesirable effects are listed by system organ class and frequency; common (≥1/100), uncommon (1/1,000 to <1/100) and rare (<1/1,000).

Infections and infestations

Uncommon: Vaginal infection

Psychiatric disorders

Common: Mood altered, Depressed mood, Libido decreased

Nervous system disorders

Common: Headache

Eye disorders

Uncommon: ontact lens intolerance

Gastrointestinal disorders

Common: Nausea

Uncommon: Vomiting

Skin and subcutaneous tissue disorders

Common: Acne

Uncommon: Alopecia

Rare: Rash, Urticaria, Erythema nodosum

Reproductive system and breast disorders

Common: Breast pain, Menstruation irregular, Amenorrhoea

Uncommon: Dysmenorrhoea, Ovarian cyst

General disorders and administration site condition

Uncommon: Fatigue

Investigations

Common: Weight increased

* MedDRA version 9.0

Breast discharge may occur during use of desogestrel. On rare occasions, ectopic pregnancies have been reported. In addition, (aggravation of) angioedema and/or aggravation of hereditary angioedema may occur.

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.

Breakthrough bleeding and/or contraceptive failure may result from interactions of other drugs (enzyme inducers) with hormonal contraceptives.