DIENOGEST/ETHINYLESTRADIOL

Posology How to take Dienogest/Ethinylestradiol 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. One tablet of Dienogest/Ethinylestradiol daily for 21 consecutive days.

g. “Mo” for Monday). The rest of the intake is done the in arrow direction, until the blister pack is consumed. Each subsequent pack is started after a 7-day tablet-free interval, during which time a withdrawal bleeding usually occurs.

This usually starts on day 2-3 after the last tablet and may not have finished before the next pack is started. Apparent improvement of acne usually takes at least three months and further improvement has been reported after six months of treatment.

e. the first day of her menstrual bleeding) will begin with the intake. 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.

• Changing from another combined oral contraceptive (COC): The woman should start with Dienogest/ Ethinylestradiol preferably on the day after the hormone-containing tablet of her previous COC, but, at the latest, on the day following the usual tablet-free or horomone-free tablet interval of her previous COC.

• Changing from a vaginal ring or transdermal patch: The woman should start using Dienogest/ Ethinylestradiol 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 (progestogen-only pill, injection, implant) or from an progestogen-releasing intrauterine system (IUS): The woman may switch any day from the progestogen-only pill (from an implant or an IUS on the day of its removal, from an injectable when the next injection would be due), but, in all of these cases, should be advised to additionally use a non-hormonal protection method (barrier method) for the first 7 days of the intake of Dienogest/Ethinylestradiol.

• Following a first trimester abortion: The woman may started immediately. When doing so, no additional contraceptive measures are necessary. • Following delivery or a second trimester abortion Since in the period immediately following childbirth, the risk of thromboembolic events is increased, women should be advised to start at day 21 to 28 days after delivery or after an abortion in the second trimester.

When starting later, the woman should be advised to additionally use a non-hormonal contraceptive method (barrier method). 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 The contraceptive effect of Dienogest/Ethinylestradiol can be reduced if it is not taken regularly. 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 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 day 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 she has 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 7-day 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, 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. , 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 […]

942) are summarised in the table below. Within each frequency grouping, adverse effects are presented in order of decreasing seriousness. Frequencies are defined as common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), and rare (≥1/10,000 to <1/1,000).

Additional ADRs identified only during postmarketing surveillance, and for which a frequency could not be estimated, are listed under “not known”. System organ class Common Uncommon Rare Unknown Infections and infestations Vaginitis / vulvovaginitis Vaginal candidiasis or other fungal vulvovaginal infections Salpingo-oophoritis Urinary tract infections Cystitis Mastitis Cervicitis Fungal infections Candidiasis Oral herpes Influenza Bronchitis Sinusitis Upper respiratory infections Viral infections Neoplasms(including cysts and polyps) Uterine leiomyoma Lipoma of breast Blood and lymphatic system disorders Anaemia Immune system disorders Hypersensitivity Endocrine disorders Virilism Metabolism and nutrition disorders Increased appetite Anorexia Psychiatric disorders Depressive mood Depression Mental disorders Insomnia Sleep disorder Aggression Mood altered Libido decreased Libido increased Nervous system disorders Headaches Migraines Dizziness Ischemic stroke Cerebrovascular disorder Dystonia Eye disorders Dry eye Eye irritation Oscillopsia Visual impairment Contact lens intolerance Ear and labyrinth disorders Sudden hearing loss Tinnitus Vertigo Hearing impairment Cardiac disorders Cardiovascular disorders Tachycardia3 Vascular disorders Hypotension Hypertension Venous thromboembolism (VTE) Arterial thromboembolism (ATE) Pulmonary embolism Thrombophlebitis Diastolic hypertension Orthostatic hypotension Orthostatic circulatory dysregulation Hot flush Varicose veins Vein disorder Veins pain Diseases of the respiratory tract, thoracic and mediastinal disorders Asthma Hyperventilation 3 Including increased heart rate.

Gastrointestinal disorders Abdominal pain4 Nausea Vomiting Diarrhea Gastritis Enteritis Dyspepsia Skin and subcutaneous tissue disorders Acne Alopecia Rash5 Pruritus6 Dermatitis allergic Dermatitis atopic / neurodermatitis Eczema Psoriasis Hyperhidrosis Chloasma Pigmentation disorder / hyperpigmentation Seborrhea Dandruff Hirsutism Skin disorders Skin reaction Peau d’orange Spider naevus Urticaria Erythema nodosum Erythema multiforme Exacerbation of symptoms of hereditary and acquired angioedema Musculoskeletal and connective tissue disorders Back pain Muskoskeletal discomfort Myalgia Pain in extremity 4 Including upper and lower abdominal pain, abdominal discomfort/distension.

5 Including rash macular. 6 Including pruritus generalised. Reproductive system and breast disorders Breast pain7 Abnormal withdrawal bleeding8 Intermestrual bleeding9 Breast enlargement10 Breast oedema Dysmenorrhoea Genital/vaginal discharge Ovarian cyst Pelvic pain Cervical dysplasia Adnexa uteri cyst Adnexa uteri pain Breast cyst Fibrocystic breast disease Dyspareunia Galactorrhea Menstrual disorders Breast gland secretion General disorders and administration site conditions Fatigue11 Chest pain Oedema peripheral Influenza-like illness Inflammation Pyrexia Irritability Fluid retention Investigations Weight increase Blood triglycerides increase Hypercholesterolemia Weight decrease Weight fluctuation Congenital, familial and genetic disorders Manifestation of asymptomatic accessory breast 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”. 7 Including breast discomfort and breast tenderness. 8 Including menorrhagia, hypomenorrhoea, oligomenorrhoea, and amenorrhoea.

9 Consisting of vaginal haemorrhage and metrorrhagia. 10 Including breast engorgement and breast swelling. 11 Including asthenia and malaise. Tumours • 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 tumours (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; haemolytic uremic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis- related hearing loss • Exogenous estrogens may induce or exacerbate symptoms of hereditary and acquired angioedema.

• Liver function disturbances • Changes in glucose tolerance or effect on peripheral insulin resistance • Crohn’s disease, ulcerative colitis • Chloasma Interactions Breakthrough bleeding and/or contraceptive failure may result from interactions of other drugs (enzyme inducers) with oral contraceptives (see section “Interaction with other medicinal products and other forms of interaction”).

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 Dienogest/Ethinylestradiol 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 Dienogest/Ethinylestradiol 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.

6 fold 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 Dienogest/Ethinylestradiol, 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). Epidemiological studies in women who use low dose (<50 μg ethinylestradiol) combined oral contraceptives have found that out of 10,000 women between about 6 and 12 will develop a VTE in one year.

It is estimated that out of 10,000 women who use a low dose CHC that contains levonorgestrel, about 61 will develop a VTE in one year. It is estimated2 that out of 10,000 women who use a CHC containing dienogest and ethinylestradiol between 8 and 11 women will develop a VTE in one year.

The 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 the cases. 6. 30). 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 Dienogest/Ethinylestradiol 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 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 non- specific and might be […]

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. deep venous thrombosis [DVT] or pulmonary embolism [PE]).

• Known hereditary or acquired predisposition for venous thromboembolism, such as APC-resistance, (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency. 4). 4). g. g. angina pectoris). g. transient ischaemic attack, TIA).

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

4) or to the presence of one serious risk factor such as: o diabetes mellitus with vascular symptoms. o severe hypertension. o severe dyslipoproteinaemia. • Pancreatitis or a history, thereof if associated with severe hypertriglyceridemia.

• Presence or history of severe hepatic disease, as long as liver function values have not returned to normal. • Presence or history of liver tumours (benign or malignant). g. of the genital organs or the breasts). • Undiagnosed vaginal bleeding.

1. 5).