SERISIMA

Method of administration Oral use. Posology How to take Serisima One tablet of Serisima daily for 21 consecutive days. Serisima must be taken both for the hormonal contraception and for the treatment of moderate acne in women according to the following instructions.

The tablets should be taken at approximately the same time of the day each day, if necessary with some liquid. g. “Mo” for Monday). The rest of the intake is done the in arrow direction, until the blister pack is consumed. After the first 21 tablets have been taken, a break is made for 7 days.

Two to four days after the last tablet, a withdrawal bleed typically begins. Whether or not a bleed has occurred, the new blister pack is initiated after the 7 treatment-free days. The contraceptive protection also occurs during the 7-day intake pauses.

Apparent improvement of acne usually takes at least three months and further improvement has been reported after six months of treatment. Women should be assessed 3-6 months after treatment initiation and periodically thereafter to review the need for continuation of treatment.

How to start of Serisima • No previous use of hormonal contraception in the past month: The first day of the cycle (first day of the menstruation) will begin with the intake. When taken correctly, contraception starts on the first day of dosing.

If the intake starts between days 2 and 5, during the first 7 days of the tablet-taking a non-hormonal method of contraception (barrier methods) should be additionally used. • Switching from another combination compound to hormonal contraception (combined oral contraceptive, vaginal ring, transdermal patch): Depending on the type of the previously combined oral contraceptive, the intake of Serisima should start either the day after the usual tablet-free interval, following the use of the last active tablet, or the day after the intake of the last placebo tablet of the previously completed combined oral contraceptive.

If a transdermal patch or a vaginal ring was used before, then, the intake of Serisima should start the day after the usual ring-free or patch-free interval. • Switching from a progestogen-only method (mini-pill, implants, injectable forms) or from an intrauterine device: If the mini-pill has been taken before, the switch can be made any day; the conversion from an implant or an intrauterine device has to happen on the day of the removal; and for an injection compound, at the moment when the next injection is due.

In any case, during the first 7 days of the intake of Serisima, it is necessary to use a non-hormonal protection method (barrier method). • After an abortion in the first trimester, the intake of Serisima can be started immediately.

In this case, no additional contraceptive measures are necessary. 6). Since in the period immediately following childbirth, the risk of thromboembolic events is increased, the intake of oral contraceptives should not be started until 21 to 28 days after childbirth for non-lactating mothers or after an abortion in the second trimester.

During the first 7 days of intake, a non-hormonal contraceptive method (barrier method) should be additionally used. If intercourse has already taken place, pregnancy should be excluded or it is necessary to wait until the first spontaneous menstruation before beginning to take the medication.

Management of missed doses The contraceptive effect of Serisima can be reduced if it is not taken regularly. If the intake is missed once, but resumed within 12 hours from the usual intake time, the contraceptive effect is not affected.

All following tablets should be taken again at the usual time. If the tablet is taken more than 12 hours after the usual intake time, the contraceptive effect can no longer be guaranteed. The probability of pregnancy becomes higher the closer the forgotten tablet is to the tablet-free interval.

If the usual withdrawal bleed does not occur following the forgotten dose, pregnancy should be excluded until a new blister pack is started. The two following rules apply in case of missing to take the tablet: 1. The intake of the tablet should not be interrupted for longer than 7 days.

2. A regular intake of the tablets for at least 7 days is necessary to effectively eliminate the hypothalamus-hypophyseal-ovary axis. In case of missed tablets, the management is as follows: • Week 1 The woman 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. However, during the next 7 days an additional barrier method such as a condom should be used. 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 tablet-free interval the higher the risk of a pregnancy. • Week 2 The woman 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 the 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 additional contraceptive precautions. If this is not the case or if she missed more than 1 tablet, the woman should be advised to use additional precautions for 7 days.

• Week 3 A full contraceptive protection cannot be ensured anymore because of the forthcoming 7-days 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 for additional contraceptive precautions, provided that in the 7 days […]

942) with Serisima as oral contraception and for the treatment of moderate acne after failure of suitable topical therapies or oral antibiotic treatment in women who elect to use an oral contraceptive are summarized in the following below.

The frequency of possible side effects listed below are defined as:

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) Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

0) Common Uncommon Rare Not Know Infections and infestations Vaginitis / vulvovaginitis, vaginal candidiasis or other fungal vulvo-vaginal infections Salpingo-oophoritis, urinary tract infections, cystitis, mastitis, cervicitis, fungal infections candidiasis, oral herpes, influenza, bronchitis, sinusitis, upper respiratory infections, viral infections Neoplasms benign, malignant and unspecified (including cysts and polyps) Uterine leiomyoma, lipoma of breast Blood and lymphatic system disorders Anemia Immune system disorders Hypersensitivity Exacerbation of symptoms of hereditary and acquired angioedema.

0) Common Uncommon Rare Not Know Gastrointestinal disorders Abdominal pain 2, nausea, vomiting, diarrhea Gastritis, Enteritis, Dyspepsia Skin and subcutaneous tissue disorders Akne, alopezie, rash3, pruritus4 Dermatitis allergic, dermatitis atopic / neurodermatitis, eczema, psoriasis, hyperhidrosis, chloasma, pigmentation disorder/ hyperpigmentation, seborrhea, dandruff, hirsutism, skin disorders, skin reactions, Peau d’orange , spider naevus Urticaria, erythema nodosum, erythema multiforme Musculoskeletal and connective tissue disorders Back pain, muskoskeletal discomfort, myalgia, pain in the extremity Reproductive system and breast disorders Breast pain5 Abnormal withdrawal bleeding6, intermenstrual bleeding7, breast enlargement8, breast oedema, dysmenorrhea, genital/vaginal discharge, ovarian cysts, pelvic pain Cervical dysplasia, cysts adnexa uteri pain of the adnexa uteri pain, breast cyst, fibrocystic breast disease, dyspareunia, galactorrhea, menstrual disorders Breast discharge Congenital, familial and genetic disorders Manifestation of asymptomatic accessory breast General disorders and administration site conditions Fatigue 9 Chest pain, oedema peripheral, influenz-like ilness, inflammation, pyrexia, irritability Fluid retention Investigations Weight increased10 Blood triglycerides increased, hypercholesterolemia, weight decreased, weight fluctuation 1 Including increased heart rate 2 Including te upper and lower adominal pain, abdominal discomfort/distension 3 Includes rash makulares 4 Including pruritus generalized 5 Including breast discomfort and breast tenderness 6 Including menorrhagia, hypomenorrhoe, oligomenorrhea and amenorrhea 7 Consists of vaginal hemorrhage and metrorrhagia 8 Including breast engorgement and breast swelling 9 Including asthenia and malaise The most appropriate MedDRA term to describe a certain adverse reaction is listed.

Synonyms or related conditions are not listed, but should be taken into account as well. 4 ‘Special warnings and precautions for use’. Tumors - 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. - Liver tumors (benign and malignant) - Cervical Cancer Other conditions - Women with hypertriglyceridemia (increased risk of pancreatitis when using COCs) - Hypertension - Occurrence or deterioration of conditions for which association with COC use is not conclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss - Liver function disturbances - Changes in glucose tolerance or effect on peripheral insulin resistance - Crohn’s disease, ulcerative colitis.

5). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorization 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 Serisima 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 Serisima 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 teratogenicity of anticoagulant therapy (coumarins).

Warnings If any of the conditions or risk factors mentioned below is present, the suitability of Serisima 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 Serisima 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 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.

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 Serisima, 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 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 estimated that out of 10,000 women who use a levonorgestrel-containing CHC about 61 will develop a VTE in one year.

• It is estimated2 that out of 10,000 women who use a CHC that containing dienogest and ethinylestradiol between 8 and 112 women will develop a VTE in one year. , Thes number of VTEs per year is fewer than the number expected in women during pregnancy or in the postpartum period.

VTE may be fatal in 1-2% of 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 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 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 trauma Note: temporary immobilisation including air travel >4 hours can also be a risk factor for VTE, particularly in women with other risk factors resume until two weeks after complete remobilisation.

Another method of contraception should be used to avoid unintentional pregnancy. Antithrombotic treatment should be considered if Serisima 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 CHC 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 […]

5). Combined hormonal contraceptives (CHCs) should not be used in the following conditions. Should any of the below listed conditions appear for the first time during the CHCs use, the product must 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. 4) or to the presence of one serious risk factor such as: • diabetes mellitus with vascular symptoms • severe hypertension • severe dyslipoproteinaemia - - Presence or history of pancreatitis, if it is associated with severe hypertriglyceridemia.

- - Presence or history of hepatic disease, as long as liver function values have not returned to normal (also Dubin-Johnson and Rotor Syndrome). - - Presence or history of liver tumors (bening or malignant) . g. in the breast or in the endometrium) - - Undiagnosed vaginal bleeding.

- - Hypersensitive to any of the active substances or to any of the excipients.