Prescribing Information

Prescribing Information
Oestrogel (estradiol) Pump-Pack

For full prescribing information, including side effects, precautions and contraindications, please consult the Summary of Product Characteristics(SPC).

Presentation: Transdermal gel containing 17β-estradiol 0.06% w/w. Each pump actuation is 1.25 g of Oestrogel, which contains 0.75mg of 17β-estradiol. Indication: 1: Hormone Replacement Therapy (HRT) for oestrogen deficiency symptoms in postmenopausal women. 2: Prevention of osteoporosis in postmenopausal women at high risk of future fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of osteoporosis. The experience treating women older than 65 years is limited. Dosage and Administration: Oestrogel is an oestrogen-only product to be administered daily on a continuous basis for women without a uterus. In women with an intact uterus, a progestogen should be added for at least 12 days each month. The pump pack will require priming before using a new pump pack for the first time. The first dose dispensed should be discarded. The gel should be applied to at least 750 cm² of clean, dry, intact areas of skin (e.g. arms, shoulders, inner thighs). It should not be applied on or near the breasts or on the vulval region. The patient should apply the gel herself and avoid skin contact with others, particularly a male partner, for at least 1 hour after application. Menopausal and postmenopausal symptoms: The usual starting dose is 2 pumps (2.5 g containing 1.5 mg 17β-estradiol) once daily. If effective relief is not obtained after one month’s treatment, this may be increased to a maximum of 4 measures (5 g containing 3.0 mg estradiol) daily. For initiation and continuation of treatment, the lowest effective dose for the shortest duration should be used. Prevention of postmenopausal osteoporosis: The minimum effective dose is 2.5 g Oestrogel once daily. For full details of usage please refer to the SPC. Contraindications: Hypersensitivity to estradiol or any of the excipients; known, past or suspected breast cancer; known or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer); undiagnosed genital bleeding; untreated endometrial hyperplasia; previous or current venous thromboembolism (deep vein thrombosis, pulmonary embolism), known thrombophilic disorders, active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction); acute liver disease or history of liver disease whilst liver function tests are abnormal; porphyria. Warnings and Precautions: HRT should only be initiated for symptoms that adversely affect quality of life. The risks and benefits should be reviewed annually and HRT only continued as long as the benefit outweighs the risk. A personal and family medical history should be taken before initiating or reinstituting HRT. Periodic check-ups are recommended during treatment. Physical examination and investigations including appropriate imaging tools should be carried out according to the clinical needs of the patient. Patients should be closely supervised if any of the following conditions are present, have occurred previously and/or have been aggravated during pregnancy or previous hormone treatment since they may recur or be aggravated during treatment with Oestrogel: leiomyoma (uterine fibroids) or endometriosis; risk factors for thromboembolic disorders; risk factors for oestrogen-dependent tumours; hypertension; liver disorders; diabetes mellitus with or without vascular involvement; cholelithiasis; migraine or severe headache; systemic lupus erythematosus; history of endometrial hyperplasia; epilepsy; asthma and otosclerosis. Oestrogel should be discontinued if a contraindication is discovered or the following occur: jaundice or deterioration in liver function; significant increase in blood pressure; new onset of migraine-type headache; pregnancy. In women with an intact uterus the risk of endometrial hyperplasia and carcinoma is increased when oestrogens are administered for prolonged periods of time. Break through bleeding and spotting may occur during the first months of treatment but if they occur after some time on therapy or continue after treatment has been discontinued the reason should be investigated. Unopposed oestrogen stimulation may lead to premalignant or malignant transformation in the residual foci of endometriosis. Evidence shows an increased risk of breast cancer in women taking combined oestrogen-progestogen or oestrogen-only HRT that is dependent on the duration of taking HRT. HRT increases the density of mammographic images which may adversely affect the radiological detection of breast cancer. Evidence suggests a slight increased risk of ovarian cancer in women taking oestrogen-only or combined oestrogen-progestogen HRT. 

HRT is associated with a 1.3 to 3-fold risk of developing venous thromboembolism (i.e. deep vein thrombosis or pulmonary embolism) especially in the first year of use. HRT should be stopped 4 to 6 weeks prior to elective surgery if prolonged immobilisation is to follow. The benefit-risk of HRT should be considered in women already on chronic anticoagulant treatment. If venous thromboembolism occurs during treatment, HRT should be discontinued. Patients should contact their doctors immediately if they have potential thromboembolic symptoms (painful swelling of a leg, sudden chest pain or dyspnoea). Combined oestrogen-progestogen and oestrogen-only therapy are associated with up to a 1.5-fold increase in risk of ischaemic stroke. The risk increases with age. Care should be taken with women with cardiac or renal dysfunction since oestrogens may cause fluid retention. Women with pre-existing hypertriglyceridaemia should be followed closely during oestrogen replacement or HRT since pancreatitis can result from rare cases of large increases in plasma triglycerides. Oestrogens increase binding proteins such as thyroid, corticoid and sex-hormone binding globulins leading to increased circulating hormones. There is some evidence of increased risk of probable dementia in women who start HRT after the age of 65. Interactions: Patients should avoid strong skin cleaners and detergents, skin products of high alcoholic content (e.g. astringents, sunscreens) and keratolytics which may alter the barrier structure or function of the skin. Also, any skin medication which alters skin production (e.g. cytotoxic drugs) should be avoided. The metabolism of oestrogens may be increased, (leading to a decreased effect and changes in the uterine bleeding profile) by enzyme-inducing products (e.g. phenobarbital, phenytoin, carbamazepine, rifampicin, rifabutin, nevirapine, efavirenz). Ritonavir, nelfinavir and St John’s wort may also induce the metabolism of oestrogens. As transdermal administration avoids the first pass effect in the liver, transdermally applied oestrogens may be less affected by enzyme inducers than oral hormones. Pregnancy and breastfeeding: Oestrogel is not indicated in pregnancy or during breastfeeding. If pregnancy occurs during medication with Oestrogel, the treatment should be withdrawn immediately. Undesirable effects: The following commonly (≥1/100; ≤1/10) occur with HRT: headache, nausea, abdominal pain, breast swelling/pain, breast enlargement, dysmenorrhoea, menorrhagia, metrorrhagia, leucorrhoea, endometrial hyperplasia, weight change (increase or decrease), water retention with peripheral oedema. The following uncommonly (≥1/1,000; <1/100) occur with HRT: depression, mood swings, vertigo, migraine, venous thromboembolic disease, flatulence, vomiting, pruritus, benign breast neoplasm, increased volume of uterine, leiomyoma, vaginitis/vaginal candidiasis, asthenia. The following risks apply in relation to systemic oestrogen/progestogen treatment: breast cancer; endometrial cancer; ovarian cancer; venous thromboembolism; coronary artery disease; ischaemic stroke. For further information on side effects and risk estimates, please consult the SPC. Overdose: Symptoms may include breast pain, excessive production of cervical mucous, nausea, and withdrawal bleeding. There are no specific antidotes and treatment should be symptomatic. 

NHS Price: 80g dispenser £4.80. Legal category: POM. Marketing Authorisation number: PL 28397/0002. Marketing Authorisation Holder: Besins Healthcare, Avenue Louise, 287, Brussels, Belgium. Date of preparation of Prescribing Information: September 2021 OES/2021/033 

Prescribing information
Utrogestan (micronised progesterone) 100mg

For full prescribing information, including side effects, precautions and contraindications, please consult the Summary of Product Characteristics (SPC).

Presentation: Soft white capsule containing 100 mg micronised progesterone. Indication: Adjunctive use with oestrogen in post-menopausal women with an intact uterus as HRT. Dosage and Administration: Oral capsules which should not be taken with food as this increases the bioavailability of the capsules. The recommended dose is 2 capsules daily at bedtime for twelve days in the last half of each therapeutic cycle (Day 15 to 26). Withdrawal bleeding may occur in the following week. Alternatively, 1 capsule can be given at bedtime from Day 1 to Day 25 of each therapeutic cycle, withdrawal bleeding being less with this treatment schedule. Dose for elderly is the same. Not indicated in children. For full details of usage see SPC. Contraindications: Known past or suspected breast cancer; hypersensitivity to progesterone , soybean lecithin, peanut or any of the excipients; undiagnosed genital bleeding; known or suspected estrogen-dependent malignant tumours (e.g. genital tract carcinoma); thrombophlebitis; thrombophilic disorders; acute liver disease or history of liver disease; previous or current thromboembolism disorders; cerebral haemorrhage; porphyria, breast-feeding. Warnings and Precautions: HRT should only be initiated for symptoms that adversely affect quality of life. 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. Women should be encouraged to be aware of their breasts and report any changes 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. Utrogestan 100mg is not a treatment for premature labour, in confirmed pregnancy or as a contraceptive. Conditions which may need supervision: The following may recur or be aggravated during treatment with Utrogestan 100 mg: leiomyoma or endometriosis; risk factors for thromboembolic disorders, risk factors for oestrogen dependent tumours (e.g. 1^st degree heredity for breast cancer), hypertension, liver disorders (e.g. liver adenoma); diabetes mellitus; cholelithiasis; migraine or severe headache; systemic lupus erythematosus; endometrial hyperplasia; epilepsy; asthma; otosclerosis; depression; photosensitivity. Therapy should be immediately discontinued if the following occur: jaundice or deterioration in liver function, significant increase in blood pressure, new onset of migraine, pregnancy, unexplained loss of vision, proptosis or diplopia, papilloedema, retinal vascular lesions. The use of HRT is associated with an increased risk of deep vein thrombosis (DVT) or pulmonary embolism. The overall evidence suggests an increased risk of breast cancer in women taking combined oestrogen-progestagen and possibly also oestrogen-only HRT, that is dependent on the duration of taking HRT. Combined oestrogen-progestagen are associated with an increased risk of ischaemic stroke.

Utrogestan 100 mg Capsules contain soybean lecithin and may cause hypersensitivity reactions (urticarial and anaphylactic shock in hypersensitive patients). As there is a possible relationship between allergy to soya and allergy to peanut, patients with peanut allergy should avoid using Utrogestan 100mg Capsules. FOR THE FULL LIST OF WARNINGS AND PRECAUTIONS PLEASE CONSULT SECTION 4.4 OF THE FULL SPC. Interactions: Drugs known to induce the hepatic CYP450-3A4 (e.g. barbiturates, anti-epileptic agents (phenytoin, carbamazepine), rifampicin, phenylbutazone, bromocriptine, spironolactone, griseofulvin, some antibiotics (ampicillins, tetracyclines) and herbal products containing St. John’s wort, may increase metabolism and the elimination of progesterone. Ketokonazole and other inhibitors of CYP450-3A4 such as ritonavir and nelfinavir may increase bioavailability of progesterone. Utrogestan 100mg may raise the plasma concentration of ciclosporin, diazepam, tizanidine. Aminoglytethimide reduces plasma concentrations of medroxyprogesterone acetate and megestrol. Progesterone may enhance or reduce the anticoagulant effect of coumarins. Progesterone antagonises the anticoagulant effect of phenindione. Use of ulipristal acetate reduces efficacy of progesterone. An adjustment in anti-diabetic dosage may be required. Breakthrough bleeding may occur when using terbinafine with Utrogestan 100mg. They may also affect the laboratory tests of hepatic and/or endocrine functions. Pregnancy and lactation: If pregnancy occurs during medication, Utrogestan 100mg should be withdrawn immediately. Prescription of progesterone beyond the first trimester may reveal gravidic cholestasis. Utrogestan 100mg is not indicated during breast-feeding. Progesterone is distributed into breast milk. Effects on ability to drive and use machines: Utrogestan 100mg may cause drowsiness and/or dizziness. Undesirable effects: Frequency not known, from post-marketing experience: Abdominal pain, nausea, fatigue, headache, somnolence, dizziness, vaginal haemorrhage, pruritus. The following risks apply in relation to systemic oestrogen/progestogen treatment: breast cancer; endometrial cancer; ovarian cancer; venous thromboembolism; coronary artery disease; ischaemic stroke. For further information on side effects and risk estimates please consult the SPC of both products. Overdose: Symptoms may include drowsiness, somnolence, dizziness, or fatigue. NHS Price: Utrogestan 100 mg capsules – £5.13 for 30 capsules. Legal category: POM. Marketing Authorisation Number: Utrogestan 100 mg capsules – PL 28397/0003. Marketing Authorisation Holder: Besins Healthcare, Avenue Louise, 287, Brussels, Belgium. Date of preparation of prescribing information: October 2020 BHUK/2020/098

Prescribing Information
Imvaggis (Estriol) 0.03 mg pessary

For full prescribing information, including side effects, precautions and contraindications, please consult the Summary of Product Characteristics(SPC).

Presentation: Pessaries containing 0.03 mg of estriol. Indication: Local treatment of vaginal symptoms of estrogen deficiency in postmenopausal women. Dosage and Administration: During the first 3 weeks of treatment, 1 pessary is administered daily. Thereafter, a maintenance dose of 1 pessary twice a week is recommended. The pessary should be introduced deeply into the vagina, preferably in the evening before going to bed. For initiation and continuation of treatment, the lowest effective dose for the shortest duration should be used. Contraindications: Hypersensitivity to estriol or any of the excipients; known, past or suspected breast cancer; known or suspected estrogen-dependent malignant tumours (e.g. endometrial cancer); undiagnosed genital bleeding; untreated endometrial hyperplasia; previous or current venous thromboembolism (deep vein thrombosis, pulmonary embolism), known thrombophilic disorders, active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction); acute liver disease or history of liver disease whilst liver function tests are abnormal; porphyria. Warnings and Precautions: Local estrogen therapy should only be initiated for symptoms that adversely affect quality of life. The risks and benefits should be reviewed annually, and therapy should only be continued as long as the benefit outweighs the risk. Estriol must not be combined with estrogen preparations for systemic treatment. Patients should be closely supervised if any of the following conditions are present, have occurred previously and/or have been aggravated during pregnancy or previous hormone treatment since they may recur or be aggravated during treatment with Estriol: leiomyoma (uterine fibroids) or endometriosis; risk factors for thromboembolic disorders; risk factors for estrogen-dependent tumours; hypertension; liver disorders; diabetes mellitus with or without vascular involvement; cholelithiasis; migraine or severe headache; systemic lupus erythematosus; history of endometrial hyperplasia; epilepsy; asthma and otosclerosis. Estriol should be discontinued if a contraindication is discovered or the following occur: jaundice or deterioration in liver function; significant increase in blood pressure; new onset of migraine-type headache; pregnancy. An increased risk of endometrial hyperplasia or uterine cancer has not been attributed to treatment with estriol by vaginal use. Endometrial safety of long-term (>1 year) or repeated use of local vaginally administered estrogen is uncertain. Therefore, if repeated, treatment should be reviewed at least annually.

If break through bleeding and spotting occurs during therapy or continues after treatment has been discontinued the reason should be investigated.Unopposed estrogen stimulation may lead to premalignant transformation in the residual foci of endometriosis The following risks have been associated with systemic HRT and apply to a lesser extent to estrogen products for vaginal application where systemic exposure is very low, however they should be considered in case of long term or repeated use: Breast cancer, ovarian cancer, venous thromboembolism, coronary artery disease, ischaemic stroke, and certain other conditions including fluid retention. Therefore, patients with cardiac or renal dysfunction should be carefully observed. Interactions: Due to minimal systemic absorption following vaginal administration of low-dose estriol pessaries, systemic drug interactions are unlikely. However, interactions with other locally applied vaginal treatments should be considered. If estriol pessaries are used simultaneously with condoms made of latex, it can decrease the tensile strength and thus impair the safety of condoms. Pregnancy and breastfeeding: Estriol pessaries are not indicated in pregnancy or during breastfeeding. If pregnancy occurs during treatment with Estriol pessaries, the treatment should be withdrawn immediately. Undesirable effects: At the beginning of treatment, when the vaginal epithelial layers are still atrophic, local irritation may occur as a sensation of heat, pain and/or itching. They are often transient and of mild intensity. The following commonly (>1/100; <1/10) occur: vulvovaginal burning, pruritus, pain and dysuria. The following are uncommon (≥1/1,000; <1/100): vaginal discharge, anorectal discomfort. Overdose: Toxicity for estriol is very low. Overdose of Estriol pessaries by vaginal application is unlikely. Symptoms that may occur in the case of a high dose accidentally ingested are nausea, vomiting and vaginal bleeding in females. NHS Price: 24 pessaries, £13.38. Legal category: POM. Marketing Authorisation number: PL 42714/0001. Marketing Authorisation Holder: Besins Healthcare (UK) Ltd, Lion Court, 25 Proctor Street, Holborn, London, WC1V 6NY, UK. Date of preparation of Prescribing Information: April 2020. BHUK/2020/033

BHUK/2021/121 August 2021