KLIOFEM

Kliofem is a continuous combined HRT product intended for use in women with an intact uterus. One tablet should be taken orally once a day without interruption, preferably at the same time every day. 4) should be used. In women with amenorrhoea and not taking HRT or women in transition from another continuous combined HRT product, treatment with Kliofem may be started on any convenient day.

In women in transition from a sequential HRT regimen, treatment should start right after their withdrawal bleeding has ended. If the patient has forgotten to take a tablet, the tablet should be taken as soon as possible within the next 12 hours.

If more than 12 hours have passed, the tablet should be discarded. Forgetting a dose may increase the likelihood of breakthrough bleeding and spotting.

Clinical experience The most frequently reported adverse events in the clinical trials with Kliofem were vaginal bleedings and breast pain/tenderness, reported in approximately 10% to 30% of patients. Vaginal bleedings usually occurred in the first months of treatment.

Breast pain usually disappeared after a few months of therapy. All adverse events observed in the randomised clinical trials with a higher frequency in patients treated with Kliofem or similar HRT products as compared to placebo, and which on an overall judgement are possibly related to treatment, are presented in the table below: 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 Infections and infestations Genital candidiasis or vaginitis, see also Reproductive system and breast disorders Immune system disorders Hypersensitivity, see also Skin and subcutaneous tissue disorders Metabolism and nutrition disorders Fluid retention, see also General disorders and administration site conditions Psychiatric disorders Depression or depression aggravated Nervousness Nervous system disorders Headache, migraine or migraine aggravated Vascular disorders Thrombophlebitis superficial Pulmonary embolism Thrombophlebitis deep Gastrointestinal disorders Nausea Abdominal pain, abdominal distension or abdominal discomfort Flatulence or bloating Skin and subcutaneous tissue disorders Alopecia, hirsutism or acne Pruritus or Urticaria Musculoskeletal, connective tissue and bone disorders Back pain Leg cramps Reproductive system and breast disorders Breast pain or breast tenderness Vaginal haemorrhage Breast oedema or breast enlargement Uterine fibroids aggravated or uterine fibroids recurrence or uterine fibroids General disorders and administration site conditions Oedema peripheral Drug ineffective Investigations Weight increased Post-marketing experience In addition to the above mentioned adverse drug reactions, those presented below have been spontaneously reported, and are by an overall judgement considered possibly related to Kliofem treatment.

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 and 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 case 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.

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 − Known hypersensitivity to the active substances or to any of the excipients − Porphyria.