ILYSSA

Method of administration: oral use. Posology How to take Ilyssa The tablets must be taken every day at about the same time, if necessary with a little liquid, in the order shown on the blister pack. Tablet taking is continuous. One tablet is to be taken daily for 28 consecutive days.

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

e. the first day of her menstrual bleeding). • Changing from a combined hormonal contraceptive(combined oral contraceptive (COC), vaginal ring or transdermal patch) The woman should start with Ilyssa 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.

In case a vaginal ring or transdermal patch has been used the woman should start using Ilyssa 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 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, 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 must be discarded.

The next blister pack must be started right away. The user is unlikely to have a withdrawal bleed until the end of the active tablets section 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 active tablet-taking from the current blister pack. 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 pack.

If the woman missed tablets and subsequently has no withdrawal bleed in the placebo tablet phase, the possibility of a pregnancy should be considered. , vomiting or diarrhoea), absorption may not be complete and additional contraceptive measures should be taken.

If vomiting occurs within […]

4. The following adverse drug reactions have been reported during use of drospirenone and ethinylestradiol. 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. 1 ) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000) Not known (cannot be estimated from the available data) bolism (VTE) Arterial thromboem bolism (ATE) Phlebitis Vascular disorder Epistaxis Syncope Gastrointestin al disorders Nausea Abdominal pain Vomiting Dyspepsia Flatulence Gastritis Diarrhoea Abdomen enlarged Gastrointesti nal disorder Gastrointesti nal fullness Hiatus hernia Oral candidiasis Constipation Dry mouth Hepatobiliary disorders Biliary pain Cholecystitis Skin and subcutaneous tissue disorders Acne Pruritus Rash Chloasma Eczema Alopecia Dermatitis acneiform Dry skin Erythema nodosum Hypertrichos is Skin disorder Skin striae Contact dermatitis Photosensitiv e dermatitis Skin nodule Erythema multiforme.

4. 4: Special warning and precautions for use: - 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; - In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema; 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Warnings If any of the conditions or risk factors mentioned below is present, the suitability of Iyssa should be discussed with the woman. In the event of aggravation, or first appearance of any of these conditions or risk factors, the woman should be advised to contact her doctor to determine whether the use of Ilyssa 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.

Other products such as Ilyssa may have up to twice this level of risk. The decision to use any product other than one with the lowest VTE risk should be taken only after a discussion with the woman to ensure she understands the risk of VTE with Ilyssa, how her current risk factors influence this risk, and that her VTE risk is highest in the first year of use.

There is also some evidence that the risk is increased when a CHC 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. Number of VTE events per 10,000 women in one year 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.

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 kg/m²) Risk increases substantially as BMI 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 patch/pill/ring (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. Antithrombotic treatment should be considered if Ilyssa has not been discontinued in advance. g. before 50). 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. g. respiratory tract infections). Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discolouration of an extremity. If the occlusion occurs in the eye symptoms can range […]

Combined hormonal contraceptives (CHCs) should not be used in the following conditions . 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).

g. 1. 5).