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Safety aspects Safety aspects Negligible effect on lipid metabolism The effects of Cerazette® on lipid metabolism were compared with those of levonorgestrel 30 µg/day in a double-blind, randomized, multicenter study over 7 treatment periods in 98 women (Barkfeldt et al. 2001). Similar, generally slight, reductions in the main lipid parameters were observed with both Cerazette® and levonorgestrel, the only significant intergroup difference being a smaller reduction in HDL 3 -cholesterol with Cerazette® than with levonorgestrel (Table 12). None of the changes was considered to be clinically important. It can be concluded, therefore, that Cerazette® has a negligible effect on lipid metabolism. Despite the higher progestogen dose, the effect of Cerazette® is similar to that of levonorgestrel 30 µg/day, a finding that can be explained by the lower androgenicity of Cerazette®. TABLE 12. The effects on parameters of lipid metabolism (% change treatment period 7 vs. baseline) Parameter Cerazette ® Levonorgestrel 30 µg/day Triglycerides –9.6 –11.1 Total cholesterol –5.9 –6.5 LDL-cholesterol –0.8 –3.6 HDL-cholesterol –12.7 –12.5 HDL 3 -cholesterol –1.9 –12.3* Lipoprotein (a) –14.0 –18.6 Apolipoprotein A-I –9.6 –10.9 Apolipoprotein A-II –3.9 –7.4 Apolipoprotein B 0.0 0.0 Abbreviations and symbols: HDL= high-density lipoprotein; LDL= low-density lipoprotein; * p
Safety aspects Safety aspects Hemostatic effects are slight Concern regarding a possible causal relationship between newer progestogens, including desogestrel, and VTE was raised when several epidemiological studies (Jick et al. 1995; Spitzer et al. 1996; Farley et al. 1995) observed differences in the risk of VTE between users of COCs containing second- and third-generation progestogens. However, subsequent studies (Farmer and Lawrenson 1996; Heinemann et al. 1996; Jamin and de Mouzon 1996; Lewis et al. 1996; Lidegaard 1997; Lidegaard and Milsom 1996; van Lunsen 1996; Westhoff 1996) demonstrated the existence of, and relevance of, major sources of bias and confounding in these studies. More recent epidemiological studies (Farmer et al. 1997, 1998; Lidegaard et al. 2000) and advanced analyses of two earlier studies that corrected more appropriately for these newly recognized confounding factors (Lewis et al. 1998a, 1998b; Suissa et al. 1997) observed no difference in the risk of VTE between COCs containing the same low estrogen dose and a progestogen of the second- or third-generation. The limited epidemiological data indicate that if there is any increased risk of VTE with POPs, it is confined to high-risk patients (McCann and Potter 1994). Changes in hemostatic parameters may indicate a tendency of a new agent to predispose to thromboembolic disorders. Since changes in hemostatic variables are related to the estrogen dose, minimal effects would be expected with POPs. However, published data on the hemostatic effects of progestogens alone are limited (Kluft and Lansink 1997). The effect of Cerazette® on hemostatic factors has been compared with that of levonorgestrel 30 µg/day over 7 treatment periods and a post-treatment assessment (between days 15 and 28) (Winkler et al. 1998). Extensive investigations included newer assays, which reflect the in vivo activity of the hemostatic system and are considered to be more predictive of a prethrombotic state (Winkler et al. 1995), as well as conventional measurements of clotting factors, fibrinogen and plasminogen. The changes from baseline seen with both POPs mostly indicated a tendency toward reduced coagulation and increased fibrinolysis. Parameters showing a statistically significant change from baseline and/or a statistically significant difference between Cerazette® and levonorgestrel are shown in Table 13. TABLE 13. Changes from baseline in hemostatic parameters a Hemostatic parameter Treatment Treatment Treatment Postperiod 3 period 7 treatment Procoagulatory factors Factor VII activity Cerazette ® –4.8 –8.1* –8.7 Levonorgestrel –7.6 –6.9** +2.2 Prothrombin Cerazette ® –7.8 –14.0* –7.1 fragment 1+2 Levonorgestrel +0.6 –6.7 –10.1* Anticoagulatory factors Protein S Cerazette ® +9.1 +10.0*** † +7.7** † Profibrinolytic factors Levonorgestrel –2.3 –1.8 –1.8 Plasminogen activity Cerazette ® –2.0 –7.7 –7.8* Levonorgestrel –4.0 –8.1** –6.6*** Tissue plasminogen Cerazette ® +21.1 +12.5 +10.5* activator Levonorgestrel –3.5 +23.9* +28.0*** Plasmin-antiplasmin Cerazette ® +4.5 +4.3 † –6.0 † complex Levonorgestrel –0.4 –17.4 –12.9 a Values are median percentage changes from baseline values. A positive value indicates an increase and a negative value a decrease. Symbols: * p
Page 1 and 2: Product Monograph ® indicates trad
Page 3 and 4: Contents Product Monograph 1 2 Intr
Page 5 and 6: Introduction A reliable alternative
Page 7 and 8: Pharmacodynamics Pharmacodynamics T
Page 9 and 10: Pharmacodynamics Pharmacodynamics a
Page 11 and 12: Contraceptive efficacy Contraceptiv
Page 13 and 14: 5 Acceptability ■ ■ ■ ■ The
Page 15 and 16: Acceptability Acceptability Trends
Page 17 and 18: Acceptability Acceptability TABLE 9
Page 19 and 20: 6 Use during lactation ■ ■ ■
Page 21: 7 Safety aspects ■ ■ ■ Ceraze
Page 25 and 26: 8 Summary The estrogen component of
Page 27 and 28: References References Coutinho EM,
Page 29 and 30: References References Rekers H. Mul
Page 31 and 32: Summary of Product Characteristics
Page 33: Summary of Product Characteristics

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