GYNEST

Gynest Cream is an oestrogen-only product for intravaginal use. 4). Guidance on how to start therapy and maintenance Gynest Cream can be started any time after the manifestation of atrophic vaginitis or associated symptoms (eg dyspareunia, pruritus).

The recommended initial daily dose is one applicator full per day. A maintenance dose of one applicator full twice a week may be used after restoration of the vaginal mucosa has been achieved. 4) should be used. Attempts to discontinue medication should be made at three to six month intervals following physical examination.

Missed Dose:

When a dose is inadvertently forgotten, resume dosing when the omission is realized.

Administration:

Gynest Cream is to be applied into the vagina, using an applicator. 5mg estriol. The filled applicator should be inserted high into the vagina and emptied, preferably in the evening. Remove the cap from a new tube and use the top of the cap to pierce the metal seal on the tube.

One end of the applicator is fitted with a plunger. Ensure the plunger is fully inserted into the applicator. Screw the other end of the applicator onto the tube. Squeeze the tube, so that the barrel of the applicator fills with cream.

Unscrew the applicator and replace the cap on the tube. Lie down, with knees bent and spread apart. Gently insert the open end of the applicator well into the vagina. Push the plunger firmly but gently as far as it will go to empty the cream into the vagina.

Keeping the plunger pressed down firmly, grip the applicator by the barrel and remove it. There is no relevant indication for use of Gynest in children

No undesirable effects were reported in two open, uncontrolled clinical trials of short duration involving 47 women. However, in a double-blind, placebo controlled clinical trial of 30 women treated with Gynest, the following undesirable effects were reported in the estriol pessary treatment group more frequently than in the placebo group: Breast pain, micturition frequency increased, vaginal discharge, cystitis, leg pain, pre- menstrual tension, lower abdominal pain, palpitations and depression.

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.

Endometrial cancer risk Postmenopausal women with a uterus The endometrial cancer risk is about 5 in every 1000 women with a uterus not using HRT. 4). Depending on the duration of oestrogen-only use and oestrogen dose, the increase in risk of endometrial cancer in epidemiology studies varied from between 5 and 55 extra cases diagnosed in every 1000 women between the ages of 50 and 65.

Adding a progestogen to oestrogen-only therapy for at least 12 days per cycle can prevent this increased risk. 2)). Ovarian cancer Long-term use of oestrogen-only and combined oestrogen-progestogen HRT has been associated with a slightly increased risk of ovarian cancer.

In the Million Women Study 5 years of HRT resulted in 1 extra case per 2500 users. e. deep vein thrombosis or pulmonary embolism. 4). 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 Other adverse events which have been reported in association with oestrogen/progestogen treatment are: • Gall bladder disease. • Skin and subcutaneous tissue disorders: chloasma; erythema multiforme; erythema nodosum; vascular purpura.

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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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.

3). As there is a possible relationship between allergy to peanuts and allergy to soya, patients with soya allergy should also avoid Gynest Cream. 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 contra-indications 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). Investigations, including appropriate imaging tools eg 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. It should be taken into account that these conditions may recur or be aggravated during treatment with Gynest Cream, in particular: - Leiomyoma (uterine fibroids) or endometriosis - Risk factors for thromboembolic disorders (see below) - Risk factors for oestrogen dependent tumours, eg 1st degree heredity for breast cancer - Hypertension - Liver disorders (eg 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 contra-indication 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 of time.

8). After stopping treatment risk may remain elevated for at least 10 years. The addition of a progestogen cyclically for at least 12 days per month/28 day cycle or continuous combined oestrogen-progestogen therapy in non-hysterectomised women prevents the excess risk associated with oestrogen-only HRT.

The endometrial safety of long-term or repeated use of topical vaginal oestrogens is uncertain. Therefore, if repeated, treatment should be reviewed at least annually, with a special consideration given to any symptoms of endometrial hyperplasia or carcinoma.

Break-through bleeding and spotting may occur during the first months of 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.

Unopposed oestrogen stimulation may lead to premalignant or malignant transformation in the residual foci of endometriosis. Therefore, the addition of progestogens to oestrogen replacement therapy should be considered in women who have undergone hysterectomy because of endometriosis, if they are known to have residual endometriosis.

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 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 taking low dose vaginally applied oestrogens. It is unknown if low dose vaginal oestrogens stimulate recurrence of breast cancer.

8) Oestrogen-only therapy • The Women’s Health Initiative (WHI) trial found no increase in the risk of breast cancer in hysterectomised women using oestrogen-only HRT. 8). HRT, especially oestrogen-progestogen combined treatment, increases the density of mammographic images which may adversely affect the radiological detection of breast cancer.

Ovarian cancer Ovarian cancer is much rarer than breast cancer. Long-term (at least 5-10 years) use of oestrogen-only HRT products has been associated with a slightly increased risk of ovarian […]

3 Contra-indications • Known hypersensitivity to estriol or any of the excipients. 4) • Active or recent arterial thromboembolic disease (eg 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.