ESTELLE-35ED TABLET

APEX PHARMA MARKETING PTE. LTD.

APEX PHARMA MARKETING PTE. LTD.

Therapeutic

Prescription Only

TABLET, FILM COATED

**4.2 Dosage and Method of Administration** _**Method of Administration**_ Oral use. _**Dosage Regimen**_ _How to take Estelle-35ED_ Estelle-35ED is to be taken regularly in order to achieve the therapeutic efficacy and the required contraceptive protection. Previously used hormonal contraception should be discontinued. The dose regimen of Estelle-35ED is similar to the usual regimen of most of the combined oral contraceptives. Thus, the same administration rules must be considered. Combined oral contraceptives, when taken correctly, have a failure rate of approximately 1% per year. The irregular intake of Estelle-35ED can lead to intermenstrual bleedings and could deteriorate the therapeutic and contraceptive reliability. Tablets must be taken in the order directed on the package every day at about the same time with some liquid as needed. One yellow tablet is to be taken daily for 21 consecutive days, followed by one white tablet for 7 days during which time a withdrawal bleed usually occurs. This usually starts on day 2–3 after the last yellow tablet and may not have finished before the next pack is started. _How to start Estelle-35ED_ - _No preceding hormonal contraceptive use (in the past month)_ The first yellow tablet has to be started on day 1 of the woman’s natural cycle (i.e. the first day of her menstrual bleeding). Starting on days 2–5 is allowed, but during the first cycle a barrier method is recommended in addition for the first 7 days of tablet-taking. - _Changing from a combined hormonal contraceptive (Combined oral contraceptive/COC), vaginal ring or transdermal patch_ The woman should start with Estelle-35ED preferably on the day after the last hormone-containing tablet of her previous COC, but at the latest on the day following the usual tablet-free or hormone-free tablet interval of her COC. In case a vaginal ring or transdermal patch has been used, the woman should start using Estelle-35ED preferably on the day of removal of the last ring or patch of a cycle pack, but at the latest when the next application would have been due. - _Changing from a progestogen-only-method (minipill, injection, implant) or from a progestogen-releasing intrauterine system (IUS)_ The woman may switch any day from the minipill (from an implant or the IUS on the day of its removal, from an injectable when the next injection would be due), but should in all of these cases be advised to additionally use a barrier method for the first 7 days of tablet-taking. - _Following first-trimester abortion_ The woman may start immediately. When doing so, she does not need additional contraceptive measures. - _Following delivery or second-trimester abortion_ For breastfeeding women see section, “Pregnancy and Lactation” – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. Women should be advised to start at day 21 to 28 after delivery or second-trimester abortion. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days of tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of Estelle-35ED use or the woman has to wait for her first menstrual period. _Management of missed tablets_ If the user is **less than 12 hours** late in taking any yellow tablet, contraceptive protection is not reduced. Missed doses of white inactive tablets contained in Estelle-35ED can be ignored. If she has missed taking a yellow tablet, the woman should take the tablet as soon as she remembers and should take further yellow tablets at the usual time. If she is **more than 12 hours** late in taking any yellow tablet, contraceptive protection may be reduced. The management of missed yellow tablets can be guided by the following two basic rules: 1. Yellow tablet-taking must never be discontinued for longer than 7 days 2. 7 days of uninterrupted yellow tablet-taking are required to attain adequate suppression of the hypothalamic-pituitary-ovarian-axis. _Accordingly the following advice can be given in daily practice:_ - _Week 1_ The user should take the last missed yellow tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. In addition, a barrier method such as a condom should be used for the next 7 days. If intercourse took place in the preceding 7 days, the possibility of a pregnancy should be considered. The more yellow tablets are missed and the closer they are to the regular white inactive tablet interval, the higher the risk of a pregnancy. - _Week 2_ The user should take the last missed yellow tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. Provided that the woman has taken her tablets correctly in the 7 days preceding the first missed yellow tablet, there is no need to use extra contraceptive precautions. However, if this is not the case, or if she missed more than 1 yellow tablet, the woman should be advised to use extra precautions for 7 days. - _Week 3_ The risk of reduced reliability is imminent because of the forthcoming white inactive tablet-taking interval. However, by adjusting the tablet-intake schedule, reduced contraceptive protection can still be prevented. By adhering to either of the following two options, there is therefore no need to use extra contraceptive precautions, provided that in the 7 days preceding the first missed yellow tablet the woman has taken all tablets correctly. If this is not the case, the woman should be advised to follow the first of these two options and to use extra precautions for the next 7 days as well. 1. The user should take the last missed yellow tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. The next pack must be started as soon as the current pack is finished, i.e., no gap should be left between packs. The user is unlikely to have a withdrawal bleed until the end of the second pack, but she may experience spotting or breakthrough bleeding on tablet-taking days. 2. The woman may also be advised to discontinue tablet-taking from the current pack. She should then have a tablet-free interval of up to 7 days, including the days she missed tablets, and subsequently continue with the next pack. If the woman missed taking yellow tablets and subsequently has no withdrawal bleed in the first normal white tablet-taking interval, the possibility of a pregnancy should be considered. _Advice in case of gastro-intestinal disturbances_ In case of severe gastro-intestinal disturbances, absorption may not be complete and additional contraceptive measures should be taken. If vomiting occurs within 3–4 hours after tablet-taking, the advice concerning missed tablets, as given in section, “Management of missed tablets”, is applicable. If the woman does not want to change her normal tablet-taking schedule, she has to take the extra tablet(s) needed from another pack. _Length of use_ The length of use depends on the severity of the symptoms of androgenization and their response to treatment. In general, treatment should be carried out over several months. Time to relief of symptoms is at least three months. Acne and seborrhea usually respond sooner than hirsutism. The need to continue treatment should be evaluated periodically by the treating physician. Should there be a recurrence of symptoms, weeks or months after discontinuation of tablet-taking, treatment with Estelle-35ED may be resumed. In case of a restart of Estelle-35ED (following a 4-week or greater pill free interval), the increased risk of VTE should be considered (see section, “Special warnings and precautions for use” – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _**Additional information on special populations**_ Children and adolescents Estelle-35ED is only indicated after menarche. Geriatric patients Not applicable. Estelle-35ED is not indicated after menopause. Patients with hepatic impairment Estelle-35ED is contraindicated in women with severe hepatic diseases as long as liver function values have not returned to normal. See also section, “Contraindications”. Patients with renal impairment Estelle-35ED has not been specifically studied in renally impaired patients. Available data do not suggest a change in treatment in this patient population.