Gracial ProdMonograph_cover - epgonline.org

More documents

Recommendations

Info

Introduction Estrogen dominance 7 days Progestogen dominance 15 days Excellent cycle control Gracial, the first combiphasic oral contraceptive, has an estrogen-dominant phase of seven days (25 µg DSG + 40 µg EE), which is followed by a progestogen-dominant phase of 15 days (125 µg DSG + 30 µg EE). The relative estrogenic dominance during the first seven days controls irregular bleeding in the first part of the cycle. From day 8 onwards, the shift to progestogen dominance controls irregular bleeding during the middle and latter part of the cycle. Theoretically, this makes Gracial an ideal OC for women with unacceptable irregular bleeding. It has been clearly demonstrated that Gracial has exceptionally good cycle control characteristics (Dieben, Op ten Berg et al 1994). Table 1: Estrogen/progestogen balance of DSG-containing OCs EE dose Desogestrel dose E/P (µg/cycle) (µg/cycle) balance Mercilon 420 3150 1:7.5 Marvelon 630 3150 1:5.0 Laurina 665 2100 1:3.2 Gracial 730 2050 1:2.8 The new regimen allows a reduction of one third of the total progestogen dose compared to Mercilon and Marvelon and a completely different estrogen/progestogen balance compared to other OCs containing EE and DSG (Newton 1994). Conclusion Gracial is a unique combiphasic oral contraceptive that is particularly suitable for women who wish to switch to a different OC because of unacceptable irregular bleeding or subjective side effects. Gracial has also been shown to have beneficial effects on androgenic skin disorders such as acne. 5
2. Pharmacokinetics • After oral administration, desogestrel is rapidly transformed into its active metabolite, etonogestrel • Approximately 96–99% of circulating etonogestrel is bound to plasma proteins, predominantly albumin and SHBG • EE undergoes rapid absorption after oral administration, with peak plasma levels being reached after approximately 1.5 hours Etonogestrel 2.1 Desogestrel Absorption Desogestrel (DSG) itself is relatively inactive and most of its pharmacological activity is attributed to its active metabolite etonogestrel. In humans, oral doses of DSG are rapidly and almost completely absorbed, mostly from the duodenum. Following oral administration, DSG is rapidly and adequately biotransformed into the active progestogen etonogestrel (Hasenack et al 1986). In vitro studies indicate that biotransformation occurs in both the liver and the intestinal mucosa (Madden et al 1989;1990), the bioavailability being 62–81% after multiple dosing (Timmer et al 1990). Metabolism The biotransformation of DSG into etonogestrel takes place in gastrointestinal and hepatic tissues within 30 minutes following ingestion. Potential drug interactions The main route of DSG metabolism is a cytochrome P450- catalyzed hydroxylation followed by a dehydrogenation. The hepatic cytochrome P450 enzyme system involved in the metabolism of contraceptive steroids may be induced by rifampicin, griseofulvin and a number of anticonvulsant drugs (hydantoins, barbiturates, primidone, carbamazepine) (Geurts et al 1993). Interactions with oxcarbazepine, rifabutin, troglitazone and felbamate are also suspected. Animal studies with phenobarbitone have shown that it induces the metabolism of desogestrel and etonogestrel. Therefore, there is a theoretical risk that the effectiveness of Gracial may be reduced in women taking the specified enzyme-inducing drugs. 6
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: Introduction 1.1 Rationale for Grac
Page 13 and 14: Pharmacokinetics ENG mainly bound t
Page 15 and 16: 3. Pharmacodynamics •Etonogestrel
Page 17 and 18: Pharmacodynamics 40 30 20 10 0 nore
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

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?