XANTHADU

Method of administration: oral use. 02 mg, film-coated tablets The tablets must be taken every day at about the same time, if necessary with a little liquid, in the order shown on blister strip. Tablet taking is continuous. One tablet is to be taken daily for 28 consecutive days.

Each subsequent strip is started the day after the last tablet of the previous strip. Withdrawal bleeding usually starts on day 2-3 after starting the placebo tablets (last row) and may not have finished before the next strip is started.

e. the first day of her menstrual bleeding). 02 mg, film-coated tablets preferably on the day after the last active tablet (the last tablet containing the active substances) of her previous COC, but at the latest on the day following the usual tablet-free or placebo tablet interval of her previous COC.

02 mg, film-coated tablets preferably on the day of removal, but at the latest when the next application would have been due. • Changing from a progestogen-only-method (progestogen-only pill, injection, implant) or from a progestogen-releasing intrauterine system (IUS) The woman may switch any day from the progestogen-only pill (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 need not take additional contraceptive measures. • Following delivery or second-trimester abortion 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. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of COC use or the woman has to wait for her first menstrual period.

6. Management of missed tablets Placebo tablets from the last (4th) row of the blister can be disregarded. However, they should be discarded to avoid unintentionally prolonging the placebo tablet phase.

The following advice only refers to missed active tablets:

If the user is less than 24 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 24 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. the recommended hormone-free tablet interval is 4 days, 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: • Day 1-7 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 placebo tablet phase, the higher the risk of a pregnancy.

• Day 8-14 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 she has missed more than 1 tablet, the woman should be advised to use extra precautions for 7 days. • Day 15-24 The risk of reduced reliability is imminent because of the forthcoming placebo tablet phase. 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 noneed 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, she should follow the first of these two options and 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 until the active tablets are used up. The 4 placebo tablets from the last row mustbe discarded.

The user is unlikely to have a withdrawal bleed until the end of the active tablets section of the second blister strip, but she may experience spotting or breakthrough bleeding on tablet-taking days. 2. The woman may also be advised to discontinue active tablet-taking from the current blister strip.

She should then take placebo tablets from the last row for up to 4 days, including the days she missed tablets, and subsequently continue with the next blister strip. If the woman missed tablets and subsequently has no withdrawal bleed in the placebo tablet phase, the possibility of a pregnancy should be considered.

Advice in case of gastro-intestinal disturbances In case of severe gastro-intestinal […]

4. 02 mg, film-coated tablets. The table below reports adverse reactions by MedDRA system organ classes (MedDRA SOCs). The frequencies are based on clinical trial data. The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions.

4. 4: • Venous thromboembolic disorders; • Arterial thromboembolic disorders; • Hypertension; • Liver tumours; • Occurrence or deterioration of conditions for which association with COC use is not conclusive: Crohn's disease, ulcerative colitis, epilepsy, uterine myoma, porphyria, systemic lupus erythematosus, herpes gestationis, Sydenham's chorea, haemolytic uremic syndrome, cholestatic jaundice; • Chloasma; • Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal.

The frequency of diagnosis of breast cancer is very slightly increased among OC users. As breast cancer is rare in women under 40 years of age the excess number is small in relation to the overall risk of breast cancer. Causation with COC use is unknown.

4. 5). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions the national reporting system listed in Appendix V.

02 mg, film-coated tablets should be discussed with the woman. 02 mg, film-coated tablets should be discontinued. In case of suspected or confirmed VTE or ATE, CHC use should be discontinued. In case anti-coagulant therapy is started, adequate alternative contraception should be initiated because of the teratogenicity of anticoagulant therapy (coumarins).

Circulatory Disorders Risk of venous thromboembolism (VTE) The use of any combined hormonal contraceptive (CHC) increases the risk of venous thromboembolism (VTE) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone are associated with the lowest risk of VTE.

02 mg, film-coated tablets may have up to twice this level of risk. 02 mg, film- coated tablets, how her current risk factors influence this risk, and that her VTE risk is highest in the first ever year of use. There is also some evidence that the risk is increased when a combined hormonal contraceptive is re-started after a break in use of 4 weeks or more.

In women who do not use a CHC and are not pregnant about 2 out of 10,000 will develop a VTE over the period of one year. However, in any individual woman the risk may be far higher, depending on her underlying risk factors (see below).

It is estimated1 that out of 10,000 women who use a CHC containing drospirenone, between 9 and 12 women will develop a VTE in one year; this compares with about 62 in women who use a levonorgestrel-containing CHC. In both cases, the number of VTEs per year is fewer than the number expected during pregnancy or in the postpartum period.

VTE may be fatal in 1-2% of the cases. g. hepatic, mesenteric, renal or retinal veins and arteries. Risk factors for VTE The risk for venous thromboembolic complications in CHC users may increase substantially in a woman with additional risk factors, particularly if there are multiple risk factors (see table).

3). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors – in this case her total risk of VTE should be considered. 3).

Table:

Risk factors for VTE Risk factor Comment Obesity (body mass index over 30 Risk increases substantially as BMI 1 These incidences were estimated from the totality of the epidemiological study data, using relative risks for the different products compared with levonorgestrel-containing CHCs.

6 kg/m²) rises. Particularly important to consider if other risk factors also present. Prolonged immobilisation, major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma Note: temporary immobilisation including air travel >4 hours can also be a risk factor for VTE, particularly in women with other risk factors In these situations it is advisable to discontinue use of the pill (in the case of elective surgery at least four weeks in advance) and not resume until two weeks after complete remobilisation.

Another method of contraception should be used to avoid unintentional pregnancy. 02 mg, film-coated tablets has not been discontinued in advance. g. before 50). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any combined hormonal contraceptive use Other medical conditions associated with VTE Cancer, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis) and sickle cell disease Increasing age Particularly above 35 years There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in the onset or progression of venous thrombosis.

6). Symptoms of VTE (deep vein thrombosis and pulmonary embolism) In the event of symptoms women should be advised to seek urgent medical attention and to inform the healthcare professional that she is taking a CHC. Symptoms of deep vein thrombosis (DVT) can include: - unilateral swelling of the leg and/or foot or along a vein in the leg; - pain or tenderness in the leg which may be felt only when standing or walking, - increased warmth in the affected leg; red or discoloured skin on the leg.

Symptoms of pulmonary embolism (PE) can include: - sudden onset of unexplained shortness of breath or rapid breathing; - sudden coughing which may be associated with haemoptysis; - sharp chest pain; - severe light headedness or dizziness; - rapid or irregular heartbeat.

g. “shortness of breath”, “coughing”) are […]

Combined hormonalcontraceptives (CHCs) should not be used in the presence of any of the conditions listed below. Should any of the conditions appear for the first time during CHC use, the product should be stopped immediately. g. g. g.

g. transient ischaemic attack, TIA) o Known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant). o History of migraine with focal neurological symptoms.

g. 5).