ESTRIOL

5 mg of estriol) per day with an applicator. 5 mg estriol) should be used twice a week. 4) should be used. 4). 5 mg/g vaginal cream is not a contraceptive. 5 mg/g vaginal cream in the paediatric population. Missed dose In case of daily use during the first weeks of treatment If the missed dose is noticed on the following day, it should not be made up.

In that case, the usual dosing schedule should be resumed. In case of 2 applications per week The missed dose should be administered as soon as possible. Method of administration Vaginal use. 5 mg/g vaginal cream should ideally be applied in the evening before going to bed by inserting the applicator deep into the vagina.

Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: 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).

System organ class Uncommon Rare Very rare Reproductive system and breast disorders Mastodynia (during the first weeks of treatment), a feeling of heat or itching in the vagina (at the start of treatment) Uterine bleeding (even after discontinuation) General disorders and administration site conditions Weight gain due to fluid retention (Migraine-type) headaches Vascular disorders Increased blood pressure Gastrointestinal disorders Nausea or other gastrointestinal symptoms Musculoskeletal and connective tissue disorders Leg cramps or “heavy legs” Skin and subcutaneous tissue disorders Allergic skin reactions (with itching, redness, swelling) Class effects associated with systemic HRT The following risks have been associated with systemic HRT and apply to a lesser extent for oestrogen products for vaginal application of which the systemic exposure to oestrogen remains within the normal postmenopausal range.

4). 56). For women aged 50 to 54 years taking 5 years of HRT, this results in about 1 extra case per 2 000 users. In women aged 50 to 54 who are not taking HRT, about 2 women in 2 000 will be diagnosed with ovarian cancer over a 5-year period.

e. deep vein thrombosis or pulmonary embolism. 4). 5-fold increased relative risk of ischaemic stroke. The risk of haemorrhagic stroke is not increased during use of HRT. 4). 6) 3 (1 – 5) * No differentiation was made between ischaemic and haemorrhagic stroke.

4) 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.

• For the treatment of postmenopausal symptoms, hormone replacement therapy (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 section “Breast cancer” below).

g. mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual. 5 mg/g vaginal cream. 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 Endometrial hyperplasia and carcinoma • In women with an intact uterus the risk of endometrial hyperplasia and carcinoma is increased when systemic oestrogens are administered alone for prolonged periods.

• For oestrogen products for vaginal application of which the systemic exposure to oestrogen remains within the normal postmenopausal range, it is not recommended to add a progestogen. • Endometrial safety of long-term (more than one year) or repeated use of local vaginally administered oestrogen is uncertain.

Therefore, if repeated, treatment should be reviewed at least annually. • Unopposed oestrogen stimulation may lead to premalignant or malignant transformation in the residual foci of endometriosis. Therefore, caution is advised when using this product in women who have undergone hysterectomy because of endometriosis, especially if they are known to have residual endometriosis.

• If bleeding or spotting appears at any time during therapy, the reason should be investigated, which may include endometrial biopsy to exclude endometrial malignancy. 5 mg estriol) nor should this maximum dose be used for longer than several weeks (maximum 4 weeks).

One epidemiological study has shown that long-term treatment with low doses of oral estriol, but not vaginal estriol, may increase the risk for endometrial cancer. This risk increased with the duration of treatment and disappeared within one year after the treatment was terminated.

The increased risk mainly concerned less invasive and highly differentiated tumors. The following risks have been associated with systemic HRT and apply to a lesser extent for oestrogen products for vaginal application of which the systemic exposure to the oestrogen remains within the normal postmenopausal range.

However, they should be considered in case of long-term or repeated use of this medicinal product. Breast cancer Epidemiological evidence from a large meta-analysis suggests no increase in risk of breast cancer in women with no history of breast cancer using low-dose vaginally applied oestrogen.

It is unknown if low-dose vaginal oestrogens stimulate recurrence of breast cancer. HRT, especially oestrogen-progestagen combined treatment, increases the density of mammographic images, which may adversely affect the radiological detection of breast cancer.

Clinical studies reported that the likelihood of developing increased mammographic density was lower in subjects treated with estriol than in subjects treated with other oestrogens. It is unknown whether this medicine carries the same risk.

In several population-based control-studies, estriol was found not to be associated with an increased risk of breast cancer, in contrast to other oestrogens. However, the clinical implications of these findings are as yet unknown. Therefore, it is important that the risk of being diagnosed with breast cancer is discussed with the patient and weighed against the known benefits of HRT.

Ovarian cancer Ovarian cancer is much rarer than breast cancer. Epidemiological evidence from a large meta-analysis suggests a slightly increased risk in women using oestrogen-only systemic HRT, which becomes apparent within 5 years of use and diminishes over time after stopping.

e. […]

– Known, past or suspected breast cancer. g. endometrial cancer). – Undiagnosed genital bleeding. – Untreated endometrial hyperplasia. – Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism). g. 4). 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. 1.