Method of administration: Oral use.
Dosage regimen: How to take Cyproterone acetate + Ethinylestradiol (Diane-35): Cyproterone acetate + Ethinylestradiol (Diane-35) 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 Cyproterone acetate + Ethinylestradiol (Diane-35) 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 Cyproterone acetate + Ethinylestradiol (Diane-35) 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 tablet is to be taken daily for 21 consecutive days. Each subsequent pack is started after a 7-day tablet-free interval, during which time a withdrawal bleed usually occurs. This usually starts on day 2-3 after the last coated tablet and may not have finished before the next pack is started.
How to start Cyproterone acetate + Ethinylestradiol (Diane-35): No preceding hormonal contraceptive use (in the past month): Tablet-taking has to start 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 Cyproterone acetate + Ethinylestradiol (Diane-35) 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 previous COC. In case a vaginal ring or transdermal patch has been used, the woman should start using Cyproterone acetate + Ethinylestradiol (Diane-35) 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 Use in Pregnancy & Lactation.
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 Cyproterone acetate + Ethinylestradiol (Diane-35) 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 tablet, contraceptive protection is not reduced. The woman should take the tablet as soon as she remembers and should take further tablets at the usual time.
If she is more than 12 hours late in taking any tablet, contraceptive protection may be reduced. The management of missed tablets can be guided by the following two basic rules: 1. tablet-taking must never be discontinued for longer than 7 days.
2. 7 days of uninterrupted 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 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 tablets are missed and the closer they are to the regular tablet-free interval, the higher the risk of a pregnancy.
Week 2: The user should take the last missed 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 tablet, there is no need to use extra contraceptive precautions. However, if this is not the case, or if she missed more than 1 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 tablet-free 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 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 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 tablets and subsequently has no withdrawal bleed in the first normal tablet-free 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 Management of missed tablets as previously mentioned, 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 relieve 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 Cyproterone acetate + Ethinylestradiol (Diane-35) may be resumed. In case of a restart of Cyproterone acetate + Ethinylestradiol (Diane-35) (following a 4 week or greater pill free interval), the increased risk of VTE should be considered (see Precautions).
Additional information on special populations: Pediatric patients: Cyproterone acetate + Ethinylestradiol (Diane-35) is only indicated after menarche.
Geriatric patients: Not applicable. Cyproterone acetate + Ethinylestradiol (Diane-35) is not indicated after menopause.
Patients with hepatic impairment: Cyproterone acetate + Ethinylestradiol (Diane-35) is contraindicated in women with severe hepatic diseases as long as liver function values have not returned to normal. See also Contraindications.
Patients with renal impairment: Cyproterone acetate + Ethinylestradiol (Diane-35) has not been specifically studied in renally impaired patients. Available data do not suggest a change in treatment in this patient population.
