Azalia Mechanism of Action

Pharmacotherapeutic group: Hormonal contraceptives for systemic use, Progestogens. ATC code: G03AC09.
Pharnacology: Pharmacodynamics: Mechanism of action: Azalia is a progestogen-only pill, which contains the progestogen desogestrel. Like other progestogen-only pills, Azalia is best suited for use during breast feeding and for women who may not or do not want to use oestrogens. In contrast to traditional progestogen-only pills, the contraceptive effect of Azalia is achieved primarily by inhibition of ovulation. Other effects include increased viscosity of the cervical mucus.
The Pearl-Index for desogestrel is comparable to the one historically found for COCs in the general COC-using population.
Treatment with desogestrel leads to decreased estradiol levels, to a level corresponding to the early follicular phase. No clinically relevant effects on carbohydrate metabolism, lipid metabolism and haemostasis have been observed.
Paediatric population: No clinical data on efficacy and safety are available in adolescents below 18 years.
Pharmacokinetics: Absorption: After oral dosing of Azalia desogestrel (DSG) is rapidly absorbed and converted into etonogestrel.
Under steady-state conditions, peak serum levels are reached 1.8 hours after tablet-intake and the absolute bioavailability of etonogestrel is approximately 70%.
Distribution: Etonogestrel is 95.5-99% bound to serum proteins, predominantly to albumin and to a lesser extent to sex hormone binding globuline (SHBG).
Biotransformation: Desogestrel is metabolised via hydroxylation and dehydrogenation to the active metabolite etonogestrel. Etonogestrel is metabolised via sulphate and glucuronide conjugation.
Elimination: Etonogestrel is eliminated with a mean half-life of approximately 30 hours, with no difference between single and multiple dosing. Steady-state levels in plasma are reached after 4-5 days. The serum clearance after i.v. administration of etonogestrel is approximately 10 L per hour. Excretion of etonogestrel and its metabolites either as free steroid or as conjugates, is with urine and faeces (ratio 1.5:1). In lactating women, etonogestrel is excreted in breast milk with a milk/serum ratio of 0.37-0.55. Based on these data and an estimated milk intake of 150 ml/kg/day, 0.01-0.05 microgram etonogestrel may be ingested by the infant.
Special populations: Effect of renal impairment: No studies were performed to evaluate the effect of renal disease on the pharmacokinetics of DSG.
Effect of hepatic impairment: No studies were conducted to evaluate the effect of hepatic disease on the pharmacokinetics of DSG. However, steroid hormones may be poorly metabolized in women with impaired liver function.
Ethnic groups: No studies were performed to assess pharmacokinetics in ethnic groups.
Toxicology: Preclinical safety data: No effects are expected other than those, which can be explained from the hormonal properties of desogestrel.