Serious side effects of combined oral contraceptives containing desogestrel may include venous thromboembolism, arterial thromboembolism, hormone-dependent tumors (e.g., liver tumors, breast cancer), and melasma. Overdose
No serious harmful effects have been reported with overdose of desogestrel. Symptoms may include nausea, vomiting, and, in young girls, slight vaginal bleeding. In safety studies, dosages of up to 750 μg/day desogestrel in women showed no adverse effects on laboratory and various other parameters and produced no reported subjective side effects. There is no antidote to desogestrel overdose and treatment should be based on symptoms. Interactions
Inducers of liver enzymes can increase the metabolism of desogestrel and etonogestrel and reduce their circulating levels. This may result in contraceptive failure. Examples of liver enzyme inducers include barbiturates (e.g., phenobarbital), bosentan, carbamazepine, efavirenz, phenytoin, primidone, rifampicin, and possibly also felbamate, griseofulvin, oxcarbazepine, rifabutin, St. Johns Wort, and topiramate. Many antivirals for HIV/AIDS and HCV, such as boceprevir, nelfinavir, nevirapine, ritonavir, and telaprevir, may increase or decrease levels of desogestrel and etonogestrel. CYP3A4 inhibitors including strong inhibitors like clarithromycin, itraconazole, and ketoconazole and moderate inhibitors like diltiazem, erythromycin, and fluconazole may increase levels of desogestrel and etonogestrel. Hormonal contraceptives may interfere with the metabolism of other drugs, resulting in increased levels (e.g., ciclosporine) or decreased levels (e.g., lamotrigine). Pharmacology
Pharmacodynamics
Desogestrel is a prodrug of etonogestrel (3-ketodesogestrel), and, via this active metabolite, it has progestogenic activity, antigonadotropic effects, very weak androgenic activity, very weak glucocorticoid activity, and no other hormonal activity. Progestogenic activity
Desogestrel is a progestogen, or an agonist of the progesterone receptor (PR).
Clinical studies with norethisterone even at very high dosages (e.g., 10 to 60 mg/day) have observed only mild androgenic effects in a minority of women including acne, increased sebum production, hirsutism, and slight virilization of female fetuses.In accordance with its very weak androgenic activity, desogestrel has minimal effects on lipid metabolism and the blood lipid profile, although there may still be some significant changes. Desogestrel also reduces sex hormone-binding globulin (SHBG) levels by 50% when given to women alone, but when combined with 30 μg/day ethinylestradiol, which in contrast strongly activates SHBG production, there is a 200% increase in SHBG concentrations. Desogestrel may slightly reduce ethinylestradiol-induced increases in SHBG levels. However, at the dosages used in oral contraceptives and in combination with ethinylestradiol, which has potent functional antiandrogenic effects mainly due to increased SHBG levels, the androgenic activity of desogestrel is said to be essentially without any clinical relevance. Indeed, combined oral contraceptives containing ethinylestradiol and desogestrel have been found to significantly decrease free concentrations of testosterone and to possess overall antiandrogenic effects, significantly reducing symptoms of acne and hirsutism in women with hyperandrogenism. Glucocorticoid activity
Desogestrel has no affinity for the glucocorticoid receptor, but etonogestrel has about 14% of the affinity of dexamethasone for this receptor. Hence, desogestrel and etonogestrel have weak glucocorticoid activity. At typical clinical dosages, the glucocorticoid activity of desogestrel is said to be negligible or very weak and hence not clinically relevant.