Marketing Authorisation Holder Invented name Strength Pharmaceutical Form. Postinor 1500 Mikrogramm-Tablette

Transcription

1 Annex I List of the names, pharmaceutical form, strengths of the medicinal products, route of, marketing authorisation holders in the Member States 1

2 Levonorgestrel-containing emergency contraceptive medicinal products Member State Austria Austria Austria Austria Austria Belgium 15. rue Béranger Velvian Germany GmbH Carl-Zeiss-Ring Ismaning Germany Velvian Germany GmbH Carl-Zeiss-Ring Ismaning Germany Sandoz N.V. Telecom Gardens Medialaan Vilvoorde Belgium Postinor 1500 Mikrogramm-Tablette 1.5 mg Tablet Oral use Vikela 750 Mikrogramm mg Tablet Oral use Tabletten Vikela 1,5 Milligramm- 1.5 mg Tablet Oral use Tablette Velafam 1,5 mg Tabletten 1.5 mg Tablet Oral use Velafam 750 Mikrogramm 0.75 mg Tablet Oral use Tabletten Levodonna 1.5 mg Tablet Oral use 2

3 Belgium Belgium Belgium Belgium Bulgaria Bulgaria Bulgaria 15. rue Béranger Norlevo 0.75 mg Tablet Oral use Norlevo 1.5 mg Tablet Oral use Postinor 1.5 mg Tablet Oral use Postinor 0.75 mg Tablet Oral use Escapelle 1.5 mg Tablet Oral use Ramonna 1.5 mg Tablet Oral use Postinor-Duo 0.75 mg Tablet Oral use 3

4 Bulgaria Bulgaria Croatia Croatia Cyprus Cyprus Laboratorios Leon Farma SA Poligono Industrial Navatejera, La Vallina s/n, Villaquilambre,Leon Spain Laboratorios Leon Farma SA Poligono Industrial Navatejera, La Vallina s/n, Villaquilambre,Leon Spain Arenda d.o.o., Medarska ulica 56b Zagreb Croatia Sandoz d.o.o. Maksimirska 120 Zagreb Croatia Etiyone 1.5 mg Tablet Oral use Melkidos 0.75 mg Tablet Oral use Vikela 1,5 mg tableta 1.5 mg Tablet Oral use Escapelle 1.5 mg Tablet Oral use Norlevo 0.75 mg Tablet Oral use Norlevo 1.5 mg Tablet Oral use 4

5 Czech Republic Czech Republic Czech Republic Czech Republic Czech Republic Denmark Denmark Egis Pharmaceuticals PLC Keresztúri út H-1106 Budapest Laboratorios León Farma S.A. Calle La Vallina s/n Polígono Industrial Navatejera Navatejera - León Spain Escapelle 1.5 mg Tablet Oral use Postinor mg Tablet Oral use Ramonna 1.5 mg Tablet Oral use Egianti 0,75 mg 0.75 mg Tablet Oral use Nopregy 1,5 mg tablety 1.5 mg Tablet Oral use Norlevo 0.75 mg Tablet Oral use Norlevo 1.5 mg Tablet Oral use 5

6 Denmark Estonia Estonia Estonia Estonia Estonia Estonia Sandoz A/S Edvard Thomsens Vej 14 DK-2300 København S Denmark Orivas UAB J.Jasinskio 16B LT Vilnius Sandoz Pharmaceuticals Verovškova Ljubljana Slovenia Actavis Group PTC ehf Reykjavikurvegi Hafnarfjördur Iceland Orivas UAB J.Jasinskio 16B LT Vilnius Levodonna 1.5 mg Tablet Oral use RAMONNA 1.5 mg Tablet Oral use ESCAPELLE 1.5 mg Tablet Oral use LEVIDON 0.75 mg Tablet Oral use LEVODONNA 1.5 mg Tablet Oral use LEVONORGESTREL 0.75 mg Tablet Oral use ACTAVIS ELISTREL 1.5 mg Tablet Oral use 6

7 Finland Finland MYLAN SAS 117, allée des Parcs Saint-Priest Norlevo 0.75 mg Tablet Oral use Norlevo 1.5 mg Tablet Oral use ANTHIA mg Tablet Oral use microgrammes, comprimé LEVONORGESTREL 1.5 mg Tablet Oral use BIOGARAN 1500 microgrammes, comprimé LEVONORGESTREL MYLAN 1.5 mg Tablet Oral use 1,5 mg, comprimé NORLEVO 1,5 mg, 1.5 mg Tablet Oral use comprimé NORLEVO mg Tablet Oral use microgrammes, comprimé 7

8 Germany Germany Germany Germany Germany VELVIAN Germany GmbH Carl-Zeiss-Ring Ismaning Germany VELVIAN Germany GmbH Carl-Zeiss-Ring Ismaning Germany Hexal Aktiengesellschaft Industriestr Holzkirchen Germany VIKELA 1,5 mg, comprimé 1.5 mg Tablet Oral use VIKELA mg Tablet Oral use microgrammes, comprimé Navela 0,75 mg Tabletten 0.75 mg Tablet Oral use Navela 1,5 mg Tabletten 1.5 mg Tablet Oral use PiDaNa 1,5 mg Tablette 1.5 mg Tablet Oral use Postinor mg Tablet Oral use Mikrogramm Tablette unofem HEXAL 1,5 mg 1.5 mg Tablet Oral use Tabletten 8

9 Germany Greece Greece Greece Laboratorios Leon Farma, SA Poligono Industrial Navatejera C/La Vallina s/n Navatejera - Villaquilambre Spain Egis Pharmaceuticals PLC Keresztúri út H-1106 Budapest Actavis Group PTC ehf Reykjavikurvegi Hafnarfjördur Iceland Etiyone 1500 Mikrogramm Tabletten 1.5 mg Tablet Oral use NORLEVO 0.75 mg Tablet Oral use NORLEVO 1.5 mg Tablet Oral use POSTINOR 1.5 mg Tablet Oral use Escapelle 1.5 mg Tablet Oral use Empil 0,75 mg tabletta 0.75 mg Tablet Oral use Helibona 1.5 mg Tablet Oral use 9

10 Iceland Iceland Iceland Ireland Ireland Ireland Rigesoft 0.75 mg Tablet Oral use Norlevo 1.5 mg Tablet Oral use Norlevo 0.75 mg Tablet Oral use Postinor 1.5 mg Tablet Oral use Levonelle 1500 microgram 1.5 mg Tablet Oral use Tablet NORLEVO mg Tablet Oral use micrograms tablet NORLEVO 1.5 mg tablet 1.5 mg Tablet Oral use 10

11 Ireland Italy Italy Italy Latvia Latvia Latvia Laboratorios Leon Farma, S.A. C/ Roa de la Vega 15, Leon Spain Tyedra 1500 micrograms tablet 1.5 mg Tablet Oral use NORLEVO 0.75 mg Tablet Oral use NORLEVO 1.5 mg Tablet Oral use LONEL 1.5 mg Tablet Oral use Escapelle 1,5 mg tablets 1.5 mg Tablet Oral use Ramonna mg Tablet Oral use micrograms tablets Postinor-Duo mg Tablet Oral use micrograms tablets 11

12 Latvia Latvia Latvia UAB Orivas J. Jasinskio g. 16B LT Vilnius UAB Orivas J. Jasinskio g. 16B LT Vilnius Actavis Group PTC ehf Reykjavikurvegi Hafnarfjördur Iceland UAB Orivas J. Jasinskio g. 16B LT Vilnius UAB Orivas J. Jasinskio g. 16B LT Vilnius Elistrel 1500 micrograms tablets 1.5 mg Tablet Oral use Levidon 750 micrograms 0.75 mg Tablet Oral use tablets Levonorgestrel Actavis 0.75 mg Tablet Oral use 750 micrograms tablets ESCAPELLE 1.5 mg Tablet Oral use RAMONNA 1.5 mg Tablet Oral use Elistrel 1.5 mg Tablet Oral use Levidon 0.75 mg Tablet Oral use 12

13 Luxembourg Luxembourg Luxembourg Luxembourg UAB Inteli Generics Nord Šeimyniškių 3 LT Vilnius UAB Inteli Generics Nord Šeimyniškių 3 LT Vilnius Avodele 0.75 mg Tablet Oral use Avodele 1.5 mg Tablet Oral use POSTINOR-DUO 0.75 mg Tablet Oral use Norlevo 0.75 mg Tablet Oral use Norlevo 1.5 mg Tablet Oral use Postinor 0.75 mg Tablet Oral use Postinor 1.5 mg Tablet Oral use 13

14 Norway Norway Norway Norway Poland Poland Portugal Sandoz A/S Edvard Thomsens Vej 14 DK-2300 København S Denmark Gedeon Richter Polska Sp. z o.o. 5 Ks. J. Poniatowskiego Street Grodzisk Mazowiecki Poland NORLEVO 0.75 mg Tablet Oral use NORLEVO 1.5 mg Tablet Oral use POSTINOR 1.5 mg Tablet Oral use Isteranda 1.5 mg Tablet Oral use Escapelle tabletka mg Tablet Oral use mikrogramów Ramonna 1.5 mg Tablet Oral use Norlevo 0.75 mg Tablet Oral use 14

15 Portugal Portugal Romania Romania Romania Slovak Republic Slovak Republic Gedeon Richter Romania S.A. Str. Cuza-Vodă nr Târgu Mureş Romania Norlevo 1.5 mg Tablet Oral use Postinor 1.5 mg Tablet Oral use ESCAPELLE 1.5 mg Tablet Oral use RAMONNA 1.5 mg Tablet Oral use POSTINOR mg Tablet Oral use micrograme ESCAPELLE 1.5 mg Tablet Oral use Ramona 1.5 mg Tablet Oral use 15

16 Slovak Republic Slovak Republic Slovenia Slovenia Slovenia Spain Egis Pharmaceuticals PLC Keresztúri út H-1106 Budapest Actavis Group PTC ehf Reykjavikurvegi Hafnarfjördur Iceland Gyömrői út H-1103 Budapest Gyömrői út H-1103 Budapest CHIESI ESPAÑA, S.A. Plaça d Europa, planta L Hospitalet de Llobregat (Barcelona) Spain EGIANTI 0,75 mg tablety 0.75 mg Tablet Oral use Helibona 1,5 mg 1.5 mg Tablet Oral use Escapelle 1,5 mg tableta 1.5 mg Tablet Oral use NORLEVO 1,5 mg tableta 1.5 mg Tablet Oral use Ramonna 1,5 mg tableta 1.5 mg Tablet Oral use Norlevo 750 microgramos 0.75 mg Tablet Oral use comprimidos 16

17 Spain Spain Spain Sweden Sweden Sweden Sweden CHIESI ESPAÑA, S.A. Plaça d Europa, planta L Hospitalet de Llobregat (Barcelona) Spain Actavis Group PTC ehf Reykjavikurvegi Hafnarfjördur Iceland Sandoz A/S Edvard Thomsens Vej 14 DK-2300 København S Denmark Norlevo 1500 microgramos comprimido 1.5 mg Tablet Oral use Postinor mg Tablet Oral use microgramos comprimido Julirona 1,5 mg 1.5 mg Tablet Oral use comprimido EFG NorLevo 0.75 mg Tablet Oral use NorLevo 1.5 mg Tablet Oral use Levodonna 1.5 mg Tablet Oral use Postinor 1.5 mg Tablet Oral use 17

18 The Netherlands The Netherlands The Netherlands The Netherlands United Kingdom United Kingdom United Kingdom Perryment Ltd High street Esher, KT10 9QY Surrey Sandoz Limited Frimley Business Park Frimley, Camberley Surrey GU16 7SR NorLevo, tabletten 0,75 mg 0.75 mg Tablet Oral use NorLevo 1,5 mg, tabletten 1.5 mg Tablet Oral use Postinor 1500 microgram, 1.5 mg Tablet Oral use tablet Vikela, tabletten mg Tablet Oral use microgram Isteranda 1.5mg Tablets 1.5 mg Tablet Oral use Upostelle 1500 Microgram 1.5 mg Tablet Oral use Tablets Levonelle mg Tablet Oral use Microgram Tablet 18

19 United Kingdom Levonelle 1500 Microgram Tablet 1.5 mg Tablet Oral use United Kingdom Levonelle One Step 1500 Microgram Tablet / Boots Emergency Contraceptive 1.5 mg Tablet 1.5 mg Tablet Oral use United Kingdom Laboratorios Leon Farma SA Calle La Vallina S/N Poligono Industrial Navatejera Navatejera, Leon E Spain Melkine 1.5mg Tablet 1.5 mg Tablet Oral use 19

20 Annex II Scientific conclusions and grounds for variation to the terms of the marketing authorisations 20

21 Scientific conclusions Overall summary of the scientific evaluation of emergency contraceptives medicinal products containing levonorgestrel or ulipristal acetate Emergency contraceptives can be used to prevent an unintended pregnancy following an unprotected sexual intercourse or in case of failure of a contraceptive method. The emergency contraceptives can be divided into levonorgestrel (LNG)- and ulipristal acetate (UPA)-containing emergency contraceptives and they act by inhibiting and/or delaying ovulation. The use of emergency contraception is an occasional method that is far less effective compared with most contraceptive products used on a regular basis, e.g. combined hormonal contraceptives, gestagen-only pills and various long-acting methods like intra-uterine devices and implants. On 16 January 2014 the Swedish Agency sent a notification for a referral under Article 31 of directive 2001/83 EC regarding all emergency contraceptives containing LNG or UPA asking the CHMP to give its opinion on whether the marketing authorisations should be maintained, varied, suspended or withdrawn. The CHMP was requested to assess whether the efficacy of emergency contraceptives is affected in relation to body weight and/or body mass index (BMI) of the women. The CHMP reviewed all data from clinical studies, published literature, post-marketing experience, including responses submitted by the marketing authorisation holders (MAHs), on the efficacy of emergency contraceptive medicinal products containing LNG or UPA, in particular with regards to the relation of high weight/bmi of women. Levonorgestrel (LNG) LNG is a synthetic progestagen. For emergency contraception one tablet of 1.5 mg LNG needs to be taken, or two tablets of 0.75 mg LNG at once. The products are indicated for emergency contraception within 72 hours (3 days) of unprotected sexual intercourse or contraceptive failure, and have been approved in more than 100 countries worldwide and used for more than 30 years. Eight relevant studies with LNG-containing emergency contraceptives are available in public literature. During the data submission an analysis was provided on three WHO studies (Von Hertzen et al., and ; Dada et al., ) as well as an analysis on two other studies (Creinin et al., ; Glasier et al., ). The rest of the studies have been submitted in the form of published literature. There are limited and inconclusive data from clinical trials that evaluated the effect of high body weight/high BMI on the contraceptive efficacy. In the meta-analysis including the three WHO studies, primarily including African and Asian women, no trend for a reduced efficacy with increasing body weight/bmi was observed (Table 1). In contrast, in the two comparative studies of Creinin and colleagues (2006) and Glasier and colleagues (2010), primarily including Caucasian women, a reduced contraceptive efficacy was observed with increasing body weight or BMI (Table 2). Both meta-analyses von Hertzen H et al. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet, 1998; 352: von Hertzen H et al. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet, 2002; 360: Dada OA et al. A randomized, double-blind, noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria. Contraception 2010; 82: Creinin MD et al. Progesterone receptor modulator for emergency contraception: a randomized controlled trial. Obstet Gynecol 2006;108: Glasier A et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomized noninferiority trial and meta-analysis. Lancet 2010; 375:

22 excluded intake later than 72 hours after unprotected intercourse (i.e. off-label use of LNG) and women who had further acts of unprotected intercourse. Table 1: Meta-analysis on three WHO studies (Von Hertzen et al., 1998 and 2002; Dada et al., 2010) BMI (kg/m2) Underweight Normal Overweight Obese N total N pregnancies Pregnancy rate 1.83% 0.99% 0.57% 1.17% Confidence Interval Table 2: Meta-analysis on studies of Creinin et al., 2006 and Glasier et al., 2010 BMI (kg/m2) Underweight Normal Overweight Obese N total N pregnancies Pregnancy rate 1.56% 0.96% 2.36% 5.19% Confidence Interval The data are currently too limited and therefore insufficiently precise to draw definite conclusions whether efficacy is negatively influenced by increased body weight and BMI; for instance for the obese category (BMI 30) three pregnancies were reported in the first analysis, and eleven pregnancies in the second. It is unknown what the explanation is for the contradicting results in both meta-analyses. All together, the current data are considered not robust enough to support the current recommendation of decreased efficacy in women with body weight above 75 kg and inefficacy in women with body weight above 80 kg as is currently included in the product information of one LNG-containing emergency contraceptive medicinal product (Norlevo). A range of different factors have an impact on a woman s fertility and the ability of emergency contraceptives to prevent a pregnancy, e.g. timing of intake of emergency contraception in relation to intercourse, conception probability, further acts of unprotected intercourse, age, ethnicity, previous infections of the genital tract, male fertility, etc. This is reflected in the wide range of estimates of prevented fraction across different studies. Therefore, even if data from some studies suggest a lower ability of LNG-containing emergency contraceptives to prevent pregnancies in women of higher weight/bmi, this is only one factor influencing the effect and it is difficult to define a certain cut-off for weight/bmi at which no effect is present. Overall for of LNG-containing emergency contraceptives it is concluded that there is limited data on the effect of high body weight/high BMI on the contraceptive efficacy. The CHMP proposed that a warning in section 4.4 of the summary of product characteristics (SmPC) is an appropriate routine risk minimisation measure to reflect that limited and inconclusive data are present regarding a possible reduced efficacy in women with a high body weight/bmi. Further, the data of the two meta-analyses should be reflected in section 5.1 of the SmPC. This information should also be reflected in the package leaflet. Further, since the limited data available do not support with any certainty the conclusion that their contraceptive effect is reduced in women with high bodyweight, no adjustment of the dose is recommended at this stage, and any information that already is included in the section 4.2 of the SmPC making reference to effect and body weight should be removed. 22

23 Ulipristal acetate (UPA) Ulipristal acetate (UPA) (30 mg) (ellaone) is an orally synthetic progesterone receptor modulator, which acts via high affinity binding to the human progesterone receptor. The product is indicated for emergency contraception within 120 hours (5 days) of unprotected sexual intercourse or contraceptive failure. UPA has been approved in 73 countries worldwide and it is being marketed for five years. The data used in the analyses of effect of UPA in relation to weight/bmi are partly based on the same studies two abovementioned studies for LNG, and another randomised controlled study (HRA , HRA , HRA ) as well as an open label study (HRA ). Similar analyses were performed. A trend was observed in the UPA group for increasing number of pregnancies with increasing weight or BMI. However, the analyses are based on a limited number of women, especially in the highest body weight/bmi categories, which subsequently result in very wide and overlapping 95% confidence limits. While the analyses of data from the three randomised controlled trials in which 2,098 women received UPA indicate a weak effect of body weight or BMI on pregnancy rates, the open label study (n=1,241) indicated no such effect. From these data there is no clear indication of an effect of weight or BMI on efficacy in general, or specifically among overweight or obese women. The data are currently too limited and therefore insufficiently precise to draw definite conclusions whether efficacy is negatively influenced by increased body weight and BMI. Table 3: Meta-analysis on four clinical studies conducted with UPA BMI (kg/m 2 ) Underweight Normal Overweight Obese 30 - N total N pregnancies Pregnancy rate 0.00% 1.23% 1.29% 2.57% 95% Confidence Interval The CHMP concluded that a warning in section 4.4 of the SmPC is appropriate to indicate that limited and inconclusive data are present regarding a possible reduced efficacy in women with a high body weight/bmi and that in all women emergency contraception should be taken as soon as possible after unprotected intercourse, regardless of the woman s body weight or BMI. Further, the data of the metaanalysis should be presented in section 5.1 of the SmPC. The information in the SmPC should also be reflected in the package leaflet. In addition the CHMP is of the opinion that conducting a pharmacodynamic/pharmacokinetic (PD/PK) study may provide some information which may help to further characterise the risk of decreased efficacy in women with high body weight/bmi and ovulation inhibition. Considering the need to further characterise this risk, the MAHs are strongly recommended to investigate the pharmacodynamic effect (ovulation inhibition) of LNG in obese women in the future. 23

24 Overall conclusion For LNG-containing emergency contraceptives overall it is concluded that there is limited and inconsistent data on the effect of high body weight/high BMI on the contraceptive efficacy. In the three WHO studies (Von Hertzen et al., 1998 and 2002; Dada et al., 2010) no trend for a reduced efficacy with increasing body weight/bmi was observed, whereas in the two other studies (Creinin et al., 2006 and Glasier et al., 2010) a reduced contraceptive efficacy was observed with increasing body weight or BMI. Both meta-analyses excluded off-label use of LNG-containing of emergency contraceptives, i.e. intake later than 72 hours after unprotected intercourse and women who had further acts of unprotected intercourse. For UPA-containing emergency contraceptive products (ellaone) it is concluded that limited and inconclusive data suggest that there may be reduced efficacy of UPA with increased body weight in women. Further, in all women emergency contraception should be taken as soon as possible after unprotected intercourse. Benefit risk balance The Committee concluded that the benefit-risk balance of emergency contraceptive medicinal products containing LNG or UPA remains positive for all women regardless of body weight/bmi, subject to the warnings and changes to the product information agreed. Grounds for the variation to the terms of the marketing authorisation Whereas The Committee considered the procedure under Article 31 of Directive 2001/83/EC for the emergency contraceptive medicinal products containing LNG or UPA. The Committee reviewed all data from clinical studies, published literature, post-marketing experience, including responses submitted by the marketing authorisation holders (MAHs), on the efficacy of emergency contraceptive medicinal products containing LNG or UPA, in particular with regards to a possible effect of high weight/bmi of women. The CHMP concluded that the available data is limited and does not support a definite conclusion that increased bodyweight reduces efficacy of emergency contraceptives medicinal products containing LNG or UPA. Available data should be included in the product information, but no restrictions of use based on body weight/bmi are recommended at this stage. The Committee considered that in view of the currently available data, the benefit-risk balance of emergency contraceptive medicinal products containing LNG or UPA is favourable, subject to warnings and other changes to the product information. In particular, limited but inconclusive data suggest that there may be reduced efficacy of these medicinal products with increased body weight in women. The Committee, as a consequence, concluded that the benefit-risk balance of emergency contraceptive medicinal products containing LNG or UPA remains positive, subject to the warnings and changes to the product information agreed. 24

25 Annex III Amendments to relevant sections of the summary of product characteristics and package leaflet 25

26 [The existing product information shall be amended (insertion, replacement or deletion of the text as appropriate) to reflect the agreed wording as provided below] For Levonorgestrel-containing emergency contraceptive medicinal products A. Summary of product characteristics Section 4.2 Posology and method of [ ] [the phrase below should be deleted from this section] Special population: body weight 75 kg or more In clinical trials, contraceptive efficacy was reduced in women weighing 75 kg or more, and levonorgestrel was not effective in women who weighed more than 80 kg (see sections 4.4 and 5.1). [ ] Section 4.4 Special warnings and precautions for use [ ] Limited and inconclusive data suggest that there may be reduced efficacy of <invented name> with increasing body weight or body mass index (BMI) (see section 5.1). In all women, emergency contraception should be taken as soon as possible after unprotected intercourse, regardless of the woman s body weight or BMI. [ ] In clinical trials, contraceptive efficacy was reduced in women weighing 75 kg or more and levonorgestrel was not effective in women who weighed more than 80 kg (see sections 4.2 and 5.1). [ ] Section 5.1 Pharmacodynamic properties [.] [The information below should be deleted together with the table] In clinical trials, contraceptive efficacy was reduced in women weighing 75 kg or more and levonorgestrel was not effective in women who weighed more than 80 kg (see sections 4.2 and 4.4). 26

27 Pregnancy rate (95% CI) according to weight categories Weight (kg) <55 [55-65] [65-75] [75-85] 85 N total N pregnancies Pregnancy rate 0.9% 1.3% 1.4% 6.4% 5.7% Confidence Interval [ ] [ ] [ ] [ ] [ ] [The information below should be added in this section together with the two tables which follow] There is limited and inconclusive data on the effect of high body weight/high BMI on the contraceptive efficacy. In three WHO studies no trend for a reduced efficacy with increasing body weight/bmi was observed (Table 1), whereas in the two other studies (Creinin et al., 2006 and Glasier et al., 2010) a reduced contraceptive efficacy was observed with increasing body weight or BMI (Table 2). Both meta-analyses excluded intake later than 72 hours after unprotected intercourse (i.e. off-label use of levonorgestrel) and women who had further acts of unprotected intercourse. Table 1: Meta-analysis on three WHO studies (Von Hertzen et al., 1998 and 2002; Dada et al., 2010) BMI (kg/m2) Underweight Normal Overweight Obese 30 N total N pregnancies Pregnancy rate Confidence Interval % 0.99% 0.57% 1.17% Table 2: Meta-analysis on studies of Creinin et al., 2006 and Glasier et al., 2010 BMI (kg/m2) Underweight Normal Overweight Obese 30 N total N pregnancies Pregnancy rate Confidence Interval % 0.96% 2.36% 5.19% [.] 27

28 B. Package leaflet [ ] When should emergency contraception be used? [ ] Studies suggest that <invented name> is less effective in women weighing 75 kg or more and not effective in women weighing more than 80 kg. Ask your doctor or pharmacist for advice on alternative methods of emergency contraception. 2. BEFORE YOU USE <invented name> <strength> TABLET [ ] Take special care with <invented name> <strength> tablet - [ ] - if you weigh 75 kg or more (see What <invented name> <strength> tablet is and what it is used for for further details) [ ] In all women, emergency contraception should be taken as soon as possible after unprotected intercourse. There is some evidence that <invented name> may be less effective with increasing body weight or body mass index (BMI), but these data were limited and inconclusive. Therefore, <invented name> is still recommended for all women regardless of their weight or BMI. You are advised to speak to a healthcare professional if you are concerned about any problems related to taking emergency contraception. [ ] 28