BIJUVE

Posology Bijuva is a combined HRT The capsule should be taken every day without interruption. Take one capsule daily with a meal. 4) should be used. Continuous combined treatment may be started with Bijuva depending on the time since menopause and severity of symptoms.

Women experiencing a natural menopause should commence treatment with Bijuva 12 months after their last natural menstrual bleed. For surgically induced menopause, treatment may start immediately Patients changing from a continuous sequential or cyclical preparation should complete the 28 day cycle and then change to Bijuva.

Patients changing from another continuous combined preparation may start therapy at any time. Missed dose If a dose has been forgotten, it should be taken as soon as possible. If more than 12 hours have elapsed, treatment should be continued with the next tablet without taking the forgotten capsule.

The likelihood of breakthrough bleeding or spotting may be increased. Paediatric population Bijuva is not indicated in children. Method of administration Oral

a. 4%). 7) Source: TXC12-05 CSR, Table 43 Abbreviations: E2 - 17β-estradiol; P – progesterone b. Tabulated list of adverse reaction Clinical trial data The safety of estradiol and progesterone capsules was assessed in a 1-year, Phase 3 trial that included 1,835 postmenopausal women (1684 were treated with estradiol and progesterone capsules once daily and 151 women received placebo.

Most women (~70%) in the active treatment groups were treated for ≥ 326 days. The table below details the adverse reactions when taking Bijuva 1 mg/100 mg. MedDRA System Organ Class Very common ≥ 1/10 Common ≥ 1/100, < 1/10 Uncommon ≥ 1/1,000, < 1/100 Rare ≥ 1/10,000, < 1/1,000 MedDRA System Organ Class Very common ≥ 1/10 Common ≥ 1/100, < 1/10 Uncommon ≥ 1/1,000, < 1/100 Rare ≥ 1/10,000, < 1/1,000 Blood and lymphatic system disorders Anaemia, Ear and labyrinth disorders Vertigo Endocrine disorders Hirsutism Eye disorders Visual impairment Gastrointestinal disorders Abdominal distension, Abdominal pain, Nausea Abdominal discomfort, abdominal tenderness, Constipation, diarrhea, Dyspepsia, Dry mouth, oral discomfort, Vomiting, Dysgeusia, Flatulence Pancreatitis acute General disorders and administration site conditions Fatigue Chills Immune system disorders Hypersensitivity Infections and infestations Gastroenteritis, Furuncle, Vaginal infection, Vulvovaginal candidiasis, Vulvovaginal mycotic infection, Otitis media acute Investigations Weight increased Weight decreased, Prothrombin time prolonged, Protein S increased, Liver function test abnormal, Blood pressure abnormal, blood fibrinogen MedDRA System Organ Class Very common ≥ 1/10 Common ≥ 1/100, < 1/10 Uncommon ≥ 1/1,000, < 1/100 Rare ≥ 1/10,000, < 1/1,000 increased, blood alkaline phosphatase increased, aspartate aminotransferase increased, alanine aminotransferase increased, activated partial thromboplastin time prolonged Metabolism and nutrition disorders Fluid retention, Hyperlipidemia, Hyperphagia Hyperuricemia Musculoskeletal and connective tissue disorders Back pain Musculoskeletal pain, Pain in extremity, arthralgia, muscle spasms Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer, adnexa uteri cyst Nervous system disorders Dizziness, Headache Disturbance in attention, Memory impairment, Migraine with aura, Paresthesia, Parosmia, Somnolence Psychiatric disorders Sleep disorder, Abnormal dreams, Agitation, Anxiety, Depression, Insomnia, Irritability, Mood swings, Libido increased Reproductive system Breast Breast pain, pelvic pain, Breast disorders (calcification, MedDRA System Organ Class Very common ≥ 1/10 Common ≥ 1/100, < 1/10 Uncommon ≥ 1/1,000, < 1/100 Rare ≥ 1/10,000, < 1/1,000 and breast disorders tenderness uterine pain/spasm, vaginal discharge, Vaginal haemorrhage discharge, discomfort, enlargement swelling, fibrocystic disease, nipple pain, benign breast neoplasm) Uterine/Cervical disorders (dysplasia, polyp, cyst, uterine haemorrhage, leiomyoma, uterine polyp, bleeding), Endometrial hypertrophy, abnormal biopsy, hot flush, metrorrhagia, post-menopausal haemorrhage, Vulvovaginal pruritus Skin and subcutaneous tissue disorders Acne, Alopecia Dry skin, Pruritus, Rash, Telangiectasia Vascular disorders Hypertension, Superficial thrombophlebitis Breast Cancer risk • An up to 2-fold increased risk of having breast cancer diagnosed is reported in women taking combined oestrogen-progestogen therapy for more than 5 years.

For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually, and HRT should only be continued as long as the benefit outweighs the risk.

Evidence regarding the risks associated with HRT in the treatment of premature menopause is limited. Due to the low level of absolute risk in younger women, however, the balance of benefits and risks for these women may be more favourable than in older women.

Medical examination/follow up Before initiating or reinstituting HRT, a complete personal and family medical history should be taken. Physical (including pelvic and breast) examination should be guided by this and by the contraindications and warnings for use.

During treatment, periodic check-ups are recommended of a frequency and nature adapted to the individual woman. Women should be advised what changes in their breasts should be reported to their doctor or nurse (see 'Breast cancer' below).

g. mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual. Conditions which need supervision If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, the patient should be closely supervised.

g. g. liver adenoma) - Diabetes mellitus with or without vascular involvement - Cholelithiasis - Migraine or (severe) headache - Systemic lupus erythematosus - A history of endometrial hyperplasia (see below) - Epilepsy - Asthma - Otosclerosis Reasons for immediate withdrawal of therapy: Therapy should be discontinued in cases where a contraindication is discovered and in the following situations: - Jaundice or deterioration in liver function - Significant increase in blood pressure - New onset of migraine-type headache - Pregnancy Endometrial hyperplasia and carcinoma In women with an intact uterus the risk of endometrial hyperplasia and carcinoma is increased when oestrogens are administered alone for prolonged periods.

g. g. g. angina, myocardial infarction); - Acute liver disease or a history of liver disease as long as liver function tests have failed to return to normal; - Porphyria; - Known hypersensitivity to the active substances or to any of the excipients.