Gracial ProdMonograph_cover - epgonline.org

More documents

Recommendations

Info

Pharmacodynamics In vitro receptor-binding studies are useful in predicting the hormonal characteristics of progestogens. Such studies have shown that desogestrel has very little affinity for progesterone, estrogen or androgen receptors (Bergink et al 1981; Breiner et al 1986; Juchem and Pollow 1990). However, its active metabolite etonogestrel exhibits: • significantly stronger affinity for the progesterone receptor than levonorgestrel or norethisterone •very low affinity for the androgen receptor (considerably lower than levonorgestrel or gestodene) • negligible binding to the estrogen receptor (Bergink et al 1981, 1983; Hoppen and Hammann 1987; Juchem and Pollow 1990; Kloosterboer et al 1988) 3.2 Selectivity index The hormonal characteristics of a progestogen can be assessed by its binding affinity for progesterone and androgen receptors in in vitro receptor-binding studies as well as by in vivo bioassay techniques in animal models. In addition, progestogenic activity can also be assessed in women by employing clinical endpoints such as the dose needed for complete ovulation inhibition and effects on the endometrium and cervical mucus. Low risk of adverse androgenic events The receptor-binding affinity studies have indicated that etonogestrel has a high affinity for the progesterone receptor, only a low affinity for the androgen receptor and no significant binding affinity for the estrogen and glucocorticoid receptors. Figure 7 shows the selectivity index (relative binding affinity to progesterone versus androgen receptors) of etonogestrel, the active metabolite of DSG, and the progestogens norethisterone, levonorgestrel and gestodene. (Kloosterboer et al 1987). 11
Pharmacodynamics 40 30 20 10 0 norethisterone levonorgestrel etonogestrel gestodene Fig. 7: Selectivity index of various progestogens Kloosterboer et al 1987 Suppression of LH and FSH secretion The selectivity index was higher for etonogestrel than for the other progestogens, norethisterone, levonorgestrel or gestodene. Receptor-binding studies do have certain limitations because the pharmacokinetics and pharmacodynamics of each compound are not considered. Nevertheless, they give an indication of the intrinsic properties of a progestogen and may contribute to the evaluation of animal and human data. This can be useful when comparing OCs with similar hormone doses and dose regimens. 3.3 Effects on the pituitary ovarian axis The contraceptive efficacy of combined oral contraceptives is primarily due to the ovulation-inhibiting effect of the progestogen component at the level of the hypothalamus and pituitary gland. Gonadotrophin (LH and FSH) secretion is suppressed and as a result follicular maturation and ovulation are inhibited. Etonogestrel has been shown to have strong ovulationinhibiting properties when given in a daily oral dose of 60 µg (Skouby 1976; Cullberg et al 1982). Gracial contains a daily dose of desogestrel of 25 µg for seven days and 125 µg for the consecutive 15 days. The 22-day regimen permits an extremely low progestogen dose in the first seven days of the cycle, without compromising contraceptive reliability. 12
Page 1 and 2: ® indicates trademark(s) registere
Page 3 and 4: © 2000 N.V. Organon All rights res
Page 5 and 6: Contents Page 8. SUMMARY 42 9. REFE
Page 7 and 8: Introduction Since all the current
Page 9 and 10: Introduction 1.1 Rationale for Grac
Page 11 and 12: 2. Pharmacokinetics • After oral
Page 13 and 14: Pharmacokinetics ENG mainly bound t
Page 15: 3. Pharmacodynamics •Etonogestrel
Page 19 and 20: Pharmacodynamics mIU/ml 7 6 5 4 3 2
Page 21 and 22: 4. Contraceptive efficacy • The P
Page 23 and 24: Acceptability Effect of Gracial on
Page 25 and 26: Acceptability % of women 35 30 25 2
Page 27 and 28: 6. Gracial and mild to moderate acn
Page 29 and 30: Gracial and mild to moderate acne G
Page 31 and 32: Gracial and mild to moderate acne R
Page 33 and 34: Safety aspects Gracial not included
Page 35 and 36: Safety aspects The incidence of VTE
Page 37 and 38: Safety aspects Table 5: Relative ri
Page 39 and 40: Safety aspects Oral contraceptives
Page 41 and 42: Safety aspects Stroke With regard t
Page 43 and 44: Safety aspects Influence of adjustm
Page 45 and 46: Safety aspects On balance, this stu
Page 47 and 48: 8. Summary The most recent area of
Page 49 and 50: References Falsetti L. Acne treatme
Page 51 and 52: References Lunsen HW van. Recent or
Page 53 and 54: 10. Summary of product characterist
Page 55 and 56: Summary of product characteristics

Gracial ProdMonograph_cover - epgonline.org

Create successful ePaper yourself

Delete template?

Save as template?