common-spc P. 1 of 9 SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT <invented name> 100 mg, soft capsule <invented name> 200 mg, soft capsule 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 1 soft capsule contains: <invented name> 100 mg: Progesterone (micronised) 100 mg <invented name> 200 mg: Progesterone (micronised) 200 mg Excipient with known effect: Soybean lecithin For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Capsule, soft <invented name> 100 mg: Round, slightly yellow soft capsule, containing whitish oily suspension. <invented name> 200 mg: Ovoid, slightly yellow soft capsule, containing whitish oily suspension. Size of the capsule: 100 mg: round 5 200 mg: oval 10 4. CLINICAL PARTICULARS 4.1 Therapeutic indications <invented name> is indicated in adults. Cycle disorders due to progesterone insufficiency, particularly menstrual irregularities, - Adjunctive use in hormone replacement therapy (HRT) with an estrogen in postmenopausal women with an intact uterus. 4.2 Posology and method of administration Posology common-spc P. 2 of 9 The recommended dose is as follows, according to the indication: In luteal failure (irregular periods): The treatment should be taken for 10 days per cycle, usually from the 17th to 26th day inclusive. The average dosage is 200 to 300 mg of progesterone per day, taken as 1 or 2 divided doses, i.e. 200 mg in the evening at bedtime plus 100 mg in the morning if required. In the treatment of menopause: oestrogen-only therapy is not recommended on its own in menopausal women with an intact uterus. A single intake of 200 mg progesterone at bedtime has to be added at least 12 to 14 days per month, i.e. in the last 2 weeks of each treatment sequence, followed by approximately one week without any replacement therapy and during which withdrawal bleeding may occur. Paediatric population There is no relevant use of <invented name> in the paediatric population. Method of administration This product is intended for oral use only. The medicinal product should not be taken with food, preferably in the evening at bedtime. The second intake should be in the morning. 4.3 Contraindications This medicinal product must not be used in the following situations: Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Undiagnosed genital bleeding Severe liver dysfunction Liver tumours Suspected or confirmed breast or genital organ neoplasia Thromboembolic diseases, active or in the history Cerebral haemorrhage Porphyria In case of a contraindication related with estrogens when <invented name> is use for HRT in conjunction with an estrogen (see summaries of product characteristics of the particular estrogen-containing medicinal product). 4.4 Special warnings and precautions for use Under the recommended conditions for use, this treatment is NOT A CONTRACEPTIVE. If the treatment sequence is started too early in the month, particularly before the 15th day of the cycle, the cycle may be shortened or bleeding may occur. common-spc P. 3 of 9 Patients must be monitored closely if they have a history of venous thrombosis. If uterine bleeding is present, do not prescribe before establishing a cause, particularly with endometrial investigations. Because of the metabolic risks and risks of thromboembolism which cannot be entirely excluded, administration should be discontinued in the event of: . Occular disorders such as reduced vision, diplopia and retinal vascular lesions; . Venous thromboembolic or thrombotic events, regardless of location; . Severe headaches. If the patient develops amenorrhoea during treatment, ensure that she is not pregnant. 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. Investigations, including appropriate imaging tools, e.g. mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual. Endometrial hyperplasia In women with still intact endometrium, regular period-like withdrawal bleeding may occur early on in the treatment, which decreases or stops altogether with increasing atrophy of the endometrium in the course of long-term treatment. In the absence of this withdrawal bleeding, endometrial hyperplasia should be excluded by suitable measures. Breakthrough bleeding and spotting may occur during the first few months of the treatment. If break-through bleeding or spotting appears after some time on therapy, or continues after treatment has been discontinued, the reason should be investigated, which may include endometrial biopsy to exclude endometrial malignancy. The risks of combined use of estrogens and progestogens for postmenopausal hormone therapy are described in detail in the summaries of product characteristics of the particular estrogen- containing medicinal products. <invented name> contains soybean lecithin <invented name> contains soybean lecithin and may cause hypersensitivity reactions (urticaria and anaphylactic shock). If a patient is allergic to peanut or soya, the patient should not use this medicinal product (see section 4.3). 4.5 Interaction with other medicinal products and other forms of interaction Drugs known to induce the hepatic CYP450-3A4 such as barbiturates, anti-epileptic agents (phenytoin, carbamazepine), rifampicin, phenylbutazone, spironolactone, griseofulvin, some common-spc P. 4 of 9 antibiotics (ampicillin, tetracyclines) and also herbal products containing St. John’s wort (Hypericum perforatum) may increase the elimination of progesterone. Ketoconazole and other inhibitors of CYP450-3A4 may increase bioavailability of progesterone. Progesterone may affect the results of laboratory tests of hepatic and/or endocrine functions. Progestogens may decrease glucose tolerance and thus, may increase insulin resistance or resistance to any other antidiabetic agents used in patients with diabetes mellitus. 4.6 Fertility, pregnancy and lactation Pregnancy A large amount of data on pregnant women indicate no malformative nor feto/neonatal toxicity of progesterone. Breastfeeding There is insufficient information on the excretion of progesterone/metabolites in human milk. Secretion of progesterone into breast milk has not been studied in detail. <invented name> should not be used during breastfeeding. Fertility As this medicinal product is indicated to support luteal failure in subfertile or infertile women, there is not deleterious known effect on fertility. 4.7 Effects on ability to drive and use machines Drivers and machine operators in particular are alerted to the risks of drowsiness and/or dizziness associated with oral use of this medicinal product. These problems can be avoided by taking the capsules at bedtime. 4.8 Undesirable effects The following adverse reactions have been seen by oral route of administration: Rare System organ Common Uncommon Very rare 1/10000; class 1/100; <1/10 1/1000; ≤1/100 ≤1/10000 ≤1/1000 Menstruation Mastodynia Reproductive irregular system and Amenorrhoea breast disorders Metrorrhagia Headaches Drowsiness Depression Nervous system Fleeting dizzy disorders sensations common-spc P. 5 of 9 Vomiting Nausea Gastrointestinal Diarrhoea disorders Constipation Hepatobiliary Cholestatic disorders jaundice Immune system Anaphylactoid Urticaria disorders reactions Skin and Pruritus Chloasma subcutaneous Acne tissue disorders Drowsiness and/or fleeting dizzy sensations are seen particularly with concomitant hypoestrogenism. These effects disappear immediately without compromising the benefit of treatment when doses are reduced or estrogenism is increased. If the treatment sequence is started too early in the month, particularly before the 15th day of the cycle, the cycle may be shortened or intercurrent bleeding may occur. Changes in periods, amenorrhoea or intercurrent bleeding have been observed and associated with the use of progesterone in general. Other adverse reactions have been reported in association with estrogen/progestogen treatment used as hormone replacement therapy in postmenopausal women: - Estrogen-dependent benign or malignant tumour, e.g. endometrial carcinoma. - Venous thromboembolisms, i.e. thrombosis of the deep leg or pelvic veins as well as pulmonary embolism occur more often in users of hormone replacement therapy than in non- users. - Myocardial infarction and stroke. - Gall bladder disorders. - Skin and subcutaneous tissue disorders: chloasma, erythema multiforme, erythema nodosum, and vascular purpura. - Probable dementia. Detailed information on the side effects of combined use of oestrogens and gestagens for postmenopausal hormone therapy are described in the summaries of product characteristics for the particular estrogen-containing medicinal products. 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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V. common-spc P. 6 of 9