LIZINNA

For oral administration. Adults How to take Lizinna One tablet is taken daily at the same time (preferably in the evening) without interruption for 21 days, followed by a break of 7 tablet-free days. Each subsequent pack is started after the 7 tablet-free days have elapsed.

Additional contraceptive precautions are not then required. During the tablet-free period, bleeding can be expected, usually beginning 2 to 4 days after the last tablet. Starting treatment It is preferable that tablet intake from the first pack is started up to and including day 5 of menstruation in which case no extra contraceptive precautions are necessary.

Lizinna can be started at any other time, if pregnancy can reasonably be excluded. In this case additional contraceptive precautions must be taken for the first 7 days of tablet taking Switching from another contraceptive Hormonal methods: Lizinna can be started immediately if the patient has been using the current hormonal method consistently and correctly, or if pregnancy can reasonably be excluded.

There is no need to wait for the next menstruation. Additional contraceptive precautions are not required.

Non-hormonal methods:

If Lizinna is started after the first 5 days of menstruation, additional contraceptive precautions are required for the next 7 days. Post-partum administration Following a vaginal delivery, oral contraceptive administration to non-breast- feeding mothers can be started 21 days post-partum provided the patient is fully ambulant and there are no puerperal complications.

No additional contraceptive precautions are required. If post-partum administration begins more than 21 days after delivery, additional contraceptive precautions are required for the first 7 days of pill-taking. If intercourse has taken place post-partum, oral contraceptive use should be delayed until the first day of the first menstrual period.

6. Use after Abortion or Miscarriage After an abortion or miscarriage that occurs prior to 24 weeks gestation, oral contraceptives can be started immediately. An additional method of contraception is not needed. After an induced or spontaneous abortion that occurs at or after 24 weeks gestation, hormonal contraceptives may be started either on Day 21 post- abortion or on the first day of the first spontaneous menstruation, whichever comes first.

Description of selected adverse reactions An increased risk of arterial and venous thrombotic and thromboembolic events, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary embolism has been observed in women using CHCs.

4. These adverse drug reactions (ADRs) require immediate medical attention and/or cessation of oral contraceptive use. The following ADRs may also require immediate medical attention and/or cessation of CHC use: retinal vein thrombosis, new onset of migraine -type headache, breast cancer, hepatic tumours, adenomas, high blood pressure, angioedema, urticaria and hypersensitivity.

Alternative non-hormonal methods of contraception should be used, while appropriate diagnostic and therapeutic measures are undertaken. 9%). 8%). 9%). The incidence of these ADRs was highest in cycle 1 and decreased over time with the exception dysmenorrhoea.

8%). The 5 clinical trials (2 randomised active-controlled trials and 3 uncontrolled open- label trials), which were used to evaluate the safety of , included 1,891 healthy women of child bearing potential. In 3 trials, subjects were followed for up to 24 cycles and in the other 2 trials for up to 12 cycles.

An additional uncontrolled study (n=8,331) reported ADRs by treatment cycle for up to 24 cycles. As the frequency of ADRs vary according to the cycle of treatment, the highest cycle incidence has been used to assign the ADR to a frequency category.

The table below displays all ADRs that have been reported with the use of Norgestimate / Ethinylestradiol in clinical trials or from post marketing experiences with norgestimate and ethinyl estradiol tablets.

The displayed frequency categories use the following convention:

Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from the available data). Infections and infestations Common Urinary tract infection, vaginal infection Neoplasms benign, malignant and unspecified (including cysts and polyps) Uncommon Cervical dysplasia Rare Breast cyst Frequency not known Hepatic adenomas , breast cancer, benign breast neoplasm, focal nodular hyperplasia, fibroadenoma of breast Immune system disorders Common Hypersensitivity Metabolism and nutrition disorders Common Fluid retention Uncommon Increase and decrease in appetite, weight fluctuation Rare Appetite disorder Frequency not known Dyslipidaemia Psychiatric disorders Common Mood altered, depression, nervousness, insomnia Uncommon Anxiety, libido disorder Nervous system disorders Very common Headache Common Migraine, dizziness Uncommon Syncope, paraesthesia Frequency not known Cerebrovascular accident, convulsion Eye disorders Uncommon Visual impairment, dry eye Frequency not known Intolerance to contact lenses, retinal vascular thrombosis* Ear and labyrinth disorders Rare Vertigo Cardiac disorders Uncommon Palpitations Rare Tachycardia Frequency not known Myocardial infarction Vascular disorders Uncommon Thrombosis, hypertension, hot flush Rare Venous thromboembolism, Arterial thromboembolism Frequency not known Deep venous thrombosis* Respiratory, thoracic and mediastinal disorders Uncommon Dyspnoea Frequency not known Pulmonary embolism* Gastrointestinal disorders Very common Gastrointestinal disorder, vomiting, diarrhoea, nausea Common Gastrointestinal pain, abdominal pain, abdominal distension, constipation, flatulence Rare Pancreatitis Hepato-biliary disorders Rare Hepatitis Frequency not known Transaminase increased Skin and subcutaneous tissue disorders Common Acne, rash Uncommon Alopecia, hirsutism, urticaria, pruritus, erythema, skin discolouration Rare Hyperhidrosis, photosensitivity reaction Frequency not known Angioedema, erythema nodosum, night sweats Musculoskeletal and connective tissue disorders Common Muscle spasms, pain in extremity, back pain Uncommon Myalgia Reproductive system and breast disorders Very common Dysmenorrhoea, metrorrhagia, abnormal withdrawal bleeding Common Amenorrhoea, genital discharge, breast pain Uncommon Breast discharge, breast enlargement, ovarian cyst, vulvovaginal dryness Rare Vaginal discharge Frequency not known Suppressed lactation General disorders and administration site conditions Common Chest pain, oedema, asthenic conditions Investigations Common Weight increased Uncommon Weight decreased * Not seen in clinical trials therefore frequency cannot be estimated.

Warnings If any of the conditions/risk factors mentioned below is present, the suitability of Lizinna 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 Lizinna should be discontinued.

Exclude likelihood of pregnancy before starting treatment. Undiagnosed vaginal bleeding should be investigated further. Serum folate levels may be depressed by oral contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives.

8). Depression can be serious and is a well-known risk factor for suicidal behaviour and suicide. Women should be advised to contact their physician in case of mood changes and depressive symptoms, including shortly after initiating the treatment.

Medical examination/consultation Prior to the initiation or reinstitution of Lizinna a complete medical history (including family history) should be taken and pregnancy must be ruled out. 4). It is important to draw a woman’s attention to the information on venous and arterial thrombosis, including the risk of Lizinna compared with other CHCs, the symptoms of VTE and ATE, the known risk factors and what to do in the event of a suspected thrombosis.

The woman should also be instructed to carefully read the user leaflet and to adhere to the advice given. The frequency and nature of examinations should be based upon established practice guidelines and should be adapted to the individual woman.

Women should be advised that oral contraceptives DO NOT protect against HIV infections (AIDS) or any other sexually transmitted disease. Conditions requiring supervision − The theoretical or proven risks usually outweigh the advantages of using Combined Oral Contraceptives (COCs) in the conditions listed below.

g. g. g. g. 4) or to the presence of one serious risk factor such as: − diabetes mellitus with vascular symptoms − severe hypertension − severe dyslipoproteinaemia • Acute or chronic liver disease, including hepatitis (viral or non-viral) or severe cirrhosis, or a history of these conditions until at least 3 months after abnormal liver function tests have returned to normal; hepatic adenomas or carcinomas.

• Known or suspected carcinoma of the breast. 1. Should any of these conditions occur for the first time during use of Lizinna, the tablets should be discontinued immediately. 5).