Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: hormonal contraceptives for systemic use, ATC code: G03AC09.

Mechanism of action
Cerazette is a progestogen-only pill, which contains the progestogen desogestrel. Like other progestogen-only pills, Cerazette can be used for women who may not or do not want to use oestrogens. In contrast to traditional progestogen-only pills, the contraceptive effect of Cerazette is achieved primarily by inhibition of ovulation. Other effects include increased viscosity of the cervical mucus.

Clinical efficacy and safety
When studied for 2 cycles, using a definition of ovulation as a progesterone level greater than 16 nmol/L for 5 consecutive days, the ovulation incidence was found to be 1% (1/103) with a 95% confidence interval of 0.02% - 5.29% in the ITT group (user and method failures). Ovulation inhibition was achieved from the first cycle of use. In this study, when Cerazette was discontinued after 2 cycles (56 continuous days), ovulation occurred on average after 17 days (range 7-30 days).

In a comparative efficacy trial (which allowed a maximum time of 3 hours for missed pills) the overall ITT Pearl-Index found for Cerazette was 0.4 (95% confidence interval 0.09-1.20), compared to 1.6 (95 % confidence interval 0.42-3.96) for 30 µg levonorgestrel.

The Pearl-Index for Cerazette is comparable to the one historically found for COCs in the general COC-using population.

Treatment with Cerazette 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.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
Absorption
After oral dosing of Cerazette desogestrel (DSG) is rapidly absorbed and converted into etonogestrel (ENG). Under steady-state conditions, peak serum levels are reached 1.8 hours after tablet-intake and the absolute bioavailability of ENG is approximately 70%.

Distribution
ENG is 95.5-99% bound to serum proteins, predominantly to albumin and to a lesser extent to SHBG.

Biotransformation
DSG is metabolised via hydroxylation and dehydrogenation to the active metabolite ENG. ENG is primarily metabolised by the cytochrome P450 3A (CYP3A) isoenzyme and subsequently conjugated with sulphate and glucuronide.

Elimination
ENG 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 ENG is approximately 10 l per hour. Excretion of ENG and its metabolites either as free steroid or as conjugates, is with urine and faeces (ratio 1.5:1). In lactating women, ENG 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 maybe 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.