Vagifem諾舒芬

Vagifem

estradiol

Manufacturer:

Novo Nordisk

Distributor:

Firma Chun Cheong
/
DKSH
Full Prescribing Info
Contents
Estradiol.
Description
Each vaginal tablet contains estradiol hemihydrate equivalent to estradiol 10 mcg.
Excipients/Inactive Ingredients: Tablet Core: Hypromellose, lactose monohydrate, maize starch and magnesium stearate. Film-coating: Hypromellose and macrogol 6000.
Action
Pharmacotherapeutic Group: Natural and semisynthetic oestrogens, plain. ATC Code: G03CA03.
Pharmacology: Pharmacodynamics: The active ingredient, synthetic 17β-estradiol, is chemically and biologically identical to endogenous human estradiol.
Endogenous 17β-estradiol induces and maintains the primary and secondary female sexual characteristics. The biological effect of 17β-estradiol is carried out through a number of specific oestrogen receptors. The steroid receptor complex is bound to the cells DNA and induces synthesis of specific proteins.
Maturation of the vaginal epithelium is dependent upon oestrogens. Oestrogens increase the number of superficial and intermediate cells and decrease the number of basal cells in vaginal smear.
Oestrogens maintain vaginal pH around normal range (4.5) which enhances normal bacterial flora.
A 12-month double-blind, randomised, parallel-group, placebo-controlled, multicentre study was conducted to evaluate the efficacy and safety of Vagifem 10 mcg in the treatment of postmenopausal vaginal atrophy symptoms.
After 12 weeks of treatment with Vagifem 10 mcg the change from baseline in comparison with placebo treatment, demonstrated significant improvements in the 3 primary endpoints: Vaginal Maturation, Index and Value, normalisation of vaginal pH and relief of the moderate/severe urogenital symptoms considered bothersome by some subjects.
Endometrial safety of Vagifem 10 mcg was evaluated in the previously mentioned trial and a second, open-label, multicenter trial. In total, 386 women underwent endometrial biopsy at the beginning and at the end of 52 weeks treatment. Incidence rate of hyperplasia and/or carcinoma was 0.52% (95% Cl 0.06%, 1.86%), indicating no increased risk.
Pharmacokinetics: Absorption: Oestrogens are well absorbed through the skin, mucous membranes and the gastrointestinal tract. After vaginal administration, estradiol is absorbed circumventing first-pass metabolism.
A 12-weeks, single-center, randomised, open label, multiple dose and parallel-group trial was conducted to evaluate the extent of systemic absorption of estradiol from the Vagifem 10 mcg tablet. Subjects were randomised 1:1 to receive either 10 mcg or 25 mcg Vagifem. Plasma levels of estradiol (E2), oestrone (E1) and oestrone sulfate (E1S) were determined. The AUC(0-24) for plasma E2 levels increased almost proportionally after the administration of 10 mcg and 25 mcg Vagifem. The AUC(0-24) indicated higher systemic estradiol levels for the 10 mcg E2 tablet as compared to baseline on treatment days 1, 14 and 83, being statistically significant at days 1 and 14 (see corresponding table). However, average plasma E2 concentrations [Cave(0-24)] at all evaluated days remained within the normal postmenopausal range in all subjects. The data from days 82 and 83 as compared to baseline indicate that there is no cumulative effect during twice weekly maintenance therapy.

Click on icon to see table/diagram/image

The levels of oestrone and oestrone sulfate seen after 12 weeks of Vagifem 10 mcg administration did not exceed baseline levels, i.e. no accumulation of oestrone or oestrone sulfate was observed.
Distribution: The distribution of exogenous oestrogens is similar to that of endogenous oestrogens. Oestrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. Oestrogens circulate in the blood largely bound to sex hormone binding globulin (SHBG) and albumin.
Biotransformation: Exogenous oestrogens are metabolised in the same manner as endogenous oestrogens. The metabolic transformations take place mainly in the liver. Estradiol is converted reversibly to oestrone, and both can be converted to estriol, which is the major urinary metabolite. In postmenopausal women, a significant portion of the circulating oestrogens exist as sulfate conjugates, especially oestrone sulfate, which serves as a circulating reservoir for the formation of more active oestrogens.
Elimination: Estradiol, oestrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates.
Special Patient Groups: The extent of systemic absorption of estradiol during treatment with Vagifem 10 mcg has been evaluated in postmenopausal women aged 60-70 years (mean age 65.4 years) only.
Toxicology: Preclinical Safety Data: 17β-Estradiol is a well-known substance.
Nonclinical studies provided no additional data of relevance to clinical safety beyond those already included in other sections.
Indications/Uses
Treatment of vaginal atrophy due to oestrogen deficiency in postmenopausal women (see Pharmacology: Pharmacodynamics under Actions).
The experience of treating women older than 65 years is limited.
Dosage/Direction for Use
Vagifem is administered intravaginally as local oestrogen therapy by use of an applicator.
Initial Dose: One (1) vaginal tablet daily for 2 weeks.
Maintenance Dose: One (1) vaginal tablet twice a week.
Treatment may start on any convenient day.
If a dose is forgotten, it should be taken as soon as the patient remembers. A double dose should be avoided.
For initiation and continuation of treatment of postmenopausal symptoms, the lowest effective dose for the shortest duration (see Precautions) should be used.
Vagifem is a local vaginal therapy and in women with an intact uterus, progestagen treatment is not necessary (see Endometrial Hyperplasia and Carcinoma under Precautions).
Vagifem may be used in women with or without an intact uterus.
Vaginal infections should be treated before start of the Vagifem therapy.
Administration: 1. Open the blister pack at the plunger end.
2. Insert the applicator in the vagina until resistance is met (8-10 cm).
3. Release the tablet by pressing the plunger.
4. Withdraw the applicator and discard.
Overdosage
Vagifem is intended for intravaginal use and the dose of estradiol is very low. Overdose is therefore unlikely, but if it occurs, treatment is symptomatic.
Contraindications
Hypersensitivity to the active substances or to any of the excipients; known, past or suspected breast cancer; known, past or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer); undiagnosed genital bleeding; untreated endometrial hyperplasia; previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism); known thrombophilic disorders (e.g. protein C, protein S or antithrombin deficiency, see Precautions); active or previous arterial thromboembolic disease (e.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.
Special Precautions
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 hormone therapy, a complete personal and family medical history should be obtained. Physical (including pelvic and breast) examination should be guided by this and by 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 the 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.
The pharmacokinetic profile of Vagifem shows that there is very low systemic absorption of estradiol during treatment (see Pharmacology: Pharmacokinetics under Actions), however, being a HRT product, the following needs to be considered, especially for long-term or repeated use of this product.
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 oestrogen treatment, in particular: Leiomyoma (uterine fibroids) or endometriosis; risk factors for thromboembolic disorders (see as follows); risk factors for oestrogen-dependent tumours, e.g. 1st degree heredity for breast cancer; hypertension; liver disorders (e.g. liver adenoma); diabetes mellitus with or without vascular involvement; cholelithiasis; migraine or (severe) headache; systemic lupus erythematosus; a history of endometrial hyperplasia (see as follows); epilepsy; asthma; otosclerosis.
The pharmacokinetic profile of Vagifem shows that there is very low absorption of estradiol during treatment (see Pharmacology: Pharmacokinetics under Actions). Due to this, the recurrence or aggravation of the above mentioned conditions is less likely than with systemic oestrogen treatment.
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.
Vagifem is a locally acting low dose estradiol preparation and therefore the occurrence of the below mentioned conditions is less likely than with systemic oestrogen treatment.
Endometrial Hyperplasia and Carcinoma: Women with an intact uterus with abnormal bleeding of unknown aetiology or women with an intact uterus who have previously been treated with unopposed oestrogens should be examined with special care in order to exclude hyperstimulation/malignancy of the endometrium before initiation of treatment with Vagifem. In women with an intact uterus, the risk of endometrial hyperplasia and carcinoma is increased when oestrogens are administered alone for prolonged periods. The reported increase in endometrial cancer risk among systemic oestrogen-only users varies from 2- to 12-fold compared with non-users, depending on both duration of treatment and on oestrogen dose. After stopping treatment, risk remains elevated for at least 10 years.
During Vagifem treatment, a minor degree of systemic absorption may occur in some patients, especially during the first two weeks of once daily administration.
However, average plasma E2 concentrations [Cave(0-24)] at all evaluated days remained within the normal postmenopausal range in all subjects (see Pharmacology: Pharmacokinetics under Actions).
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, with special consideration given to any symptoms of endometrial hyperplasia or carcinoma.
As a general rule, oestrogen replacement therapy should not be prescribed for longer than one year without another physical, including gynaecological examination, being performed.
If bleeding or spotting appears at any time during therapy, the reason should be investigated, which may include endometrial biopsy to exclude endometrial malignancy.
The woman should be advised to contact her doctor in case bleeding or spotting occurs during treatment with Vagifem.
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.
Breast Cancer: 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.
The Women's Health Initiative (WHI) trial found no increase in risk of breast cancer in hysterectomised women using oestrogen-only HRT. Observational studies have mostly reported a small increase in risk of having breast cancer diagnosed that is substantially lower than found in users of oestrogen-progestagen combinations.
The excess risk becomes apparent within a few years of use but returns to baseline within a few (at most 5) years after stopping treatment.
A relationship between breast cancer risk and low-dose local vaginal oestrogen therapy is uncertain. HRT, especially oestrogen-progestagen 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 cancer. Some studies including the WHI trial suggest that the long-term use of combined HRT may confer a similar or slightly smaller risk (see Adverse Reactions).
A relationship between ovarian cancer risk and low dose local vaginal oestrogen therapy is uncertain.
Venous Thromboembolism: HRT is associated with a 1.3- to 3-fold risk of developing VTE, i.e. deep vein thrombosis or pulmonary embolism. The occurrence of such an event is more likely in the first year of HRT than later (see Adverse Reactions).
Patients with known thrombophilic states have an increased risk of VTE and HRT may add to this risk. HRT is therefore contraindicated in these patients (see Contraindications).
Generally recognised risk factors for VTE include use of oestrogens, older age, major surgery, prolonged immobilisation, obesity (BMI >30 kg/m2), pregnancy/postpartum period, systemic lupus erythematosus (SLE) and cancer. There is no consensus about the possible role of varicose veins in VTE.
A relationship between venous thromboembolism and low dose local vaginal oestrogen therapy is uncertain.
As in all postoperative patients, prophylactic measures need to be considered to prevent VTE following surgery. If prolonged immobilisation is to follow elective surgery, temporarily stopping HRT 4 to 6 weeks earlier is recommended. Treatment should not be restarted until the woman is completely mobilised.
In women with no personal history of VTE but with first degree relative with a history of thrombosis at young age, screening may be offered after careful counselling regarding its limitations (only a proportion of thrombophilic defects are identified by screening).
If a thrombophilic defect is identified which segregates with thrombosis in family members or if the defect is ‘severe’ (eg, antithrombin, protein S or protein C deficiencies or a combination of defects) HRT is contraindicated.
Women already on chronic anticoagulant treatment require careful consideration of the benefit-risk of use of HRT.
If VTE develops after initiating therapy, the drug should be discontinued. Patients should be told to contact their doctors immediately when they are aware of a potential thromboembolic symptom (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).
Coronary Artery Disease (CAD): There is no evidence from randomised controlled trials of protection against myocardial infarction in women with or without existing CAD who received combined oestrogen-progestagen or oestrogen-only HRT.
Randomised controlled data found no increased risk of CAD in hysterectomised women using oestrogen-only therapy.
Ischaemic Stroke: Combined oestrogen-progestagen and oestrogen-only therapy are associated with an up to 1.5-fold increase in risk of ischaemic stroke. The relative risk does not change with age or time since menopause. However, as the baseline risk of stroke is strongly age-dependent, the overall risk of stroke in women who use HRT increases with age (see Adverse Reactions).
A relationship between ischaemic stroke and low-dose local vaginal oestrogen therapy is uncertain.
Other Conditions: Oestrogens may cause fluid retention, and therefore patients with cardiac or renal dysfunction should be carefully observed.
Women with pre-existing hypertriglyceridaemia should be followed closely during oestrogen replacement or hormone replacement therapy, since rare cases of large increases of plasma triglycerides leading to pancreatitis have been reported with oestrogen therapy in this condition. The relationship between pre-existing hypertriglyceridaemia and low dose local vaginal oestrogen therapy is unknown.
Oestrogens increase thyroid binding globulin (TBG), leading to increased circulating total thyroid hormone [as measured by protein-bound iodine (PBI)], T4 levels (by column or by radio immunoassay) or T3 levels (by radioimmunoassay). T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Other binding proteins may be elevated in serum, i.e. corticoid binding globulin (CBG), sex-hormone-binding globulin (SHBG) leading to increased circulating corticosteroids and sex steroids, respectively. Free or biologically active hormone concentrations are unchanged. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).
The minimal systemic absorption of estradiol with local vaginal administration (see Pharmacology: Pharmacokinetics under Actions) is likely to result in less pronounced effects on plasma binding proteins than with systemic hormones.
Hormone replacement therapy does not improve cognitive function. There is some evidence from the WHI trial of increased risk of probable dementia in women who start using continuous combined or oestrogen-only HRT after the age of 65.
Intravaginal applicators may cause minor local trauma, especially in women with serious vaginal atrophy.
Effects on Ability to Drive and Use Machines: No effects known.
Use In Pregnancy & Lactation
Use in Pregnancy: Vagifem is not indicated during pregnancy. If pregnancy occurs during medication with Vagifem, treatment should be withdrawn immediately. The results of most epidemiology studies to date relevant to inadvertent foetal exposure to oestrogens indicate no teratogenic or foetotoxic effects.
Use in Lactation: Vagifem is not indicated during lactation.
Adverse Reactions
Adverse Events from Clinical Trials: More than 673 patients have been treated with Vagifem 10 mcg in clinical trials, including over 497 patients treated up to 52 weeks.
Oestrogen-related adverse events such as breast pain, peripheral oedema and postmenopausal bleedings have been reported at very low rates, similar to placebo, with Vagifem 10 mcg, but if they occur, they are most likely present only at the beginning of the treatment. The adverse events observed with a higher frequency in patients treated with Vagifem 10 mcg as compared to placebo and which are possibly related to treatment are presented as follows.
Common (≥1/100 to <1/10): Nervous System Disorders: Headache.
Gastrointestinal Disorders: Abdominal pain.
Reproductive System and Breast Disorders: Vaginal haemorrhage, vaginal discharge or vaginal discomfort.
Uncommon (≥1/1000 to <1/100): Infections and Infestations: Vulvovaginal mycotic infection.
Gastrointestinal Disorders: Nausea.
Skin and Subcutaneous Tissue Disorders: Rash.
Investigations: Increased weight.
Vascular Disorders: Hot flush, hypertension.
Post-Marketing Experience: In addition to the previously mentioned adverse drug reactions, those presented below have been spontaneously reported for patients being treated with Vagifem 25 mcg and are considered possibly related to treatment. The reporting rate of these spontaneous adverse reactions is very rare (<1/10,000 patient years).
Neoplasms Benign and Malignant (Including Cysts and Polyps): Breast cancer, endometrial cancer.
Immune System Disorders: Generalized hypersensitivity reactions (e.g. anaphylactic reaction/shock).
Metabolism and Nutrition Disorders: Fluid retention.
Psychiatric Disorders: Insomnia, depression.
Nervous System Disorders: Aggravated migraine.
Vascular Disorders: Deep venous thrombosis.
Gastrointestinal Disorders: Diarrhoea.
Skin and Subcutaneous Tissue Disorders: Urticaria, rash erythematous, rash pruritic, genital pruritus.
Reproductive System and Breast Disorders: Endometrial hyperplasia, vaginal irritation, vaginal pain, vaginismus, vaginal ulceration.
General Disorders and Administration Site Conditions: Drug ineffective.
Investigations: Weight increased, blood oestrogen increased.
Other adverse reactions have been reported in association with oestrogen treatment.
Risk estimates have been drawn from systemic exposure and it is not known how these apply to local treatments: Myocardial infarction; congestive heart disease; stroke; gallbladder disease; skin and subcutaneous disorders (chloasma, erythema multiforme, erythema nodosum, vascular purpura); increase in size of fibroids; epilepsy; libido disorder; deterioration of asthma; probable dementia over the age of 65 years (see Precautions).
Breast Cancer Risk: Risk estimates have been drawn from systemic exposure and it is not known how these apply to local treatments.
An up to 2-fold increased risk of having breast cancer diagnosed is reported in women taking combined oestrogen-progestagen therapy for more than 5 years.
Any increased risk in users of oestrogen-only therapy is substantially lower than that seen in users of oestrogen-progestagen combinations.
The level of risk is dependent on the duration of use (see Precautions).
Results of the largest randomised placebo-controlled trial (WHI study) and largest epidemiological study [Million Women Study (MWS)] are presented.
Million Women Study - Estimated Additional Risk of Breast Cancer After 5-Years Use: Oestrogen-Only HRT: Age range: 50-65 years.
Incidence per 1,000 never-users of HRT over a 5-year period*: 9-12.
Risk ratio and 95% CI**: 1.2.
Additional cases per 1,000 HRT users over 5 years (95% CI): 1-2 (0-3).
Combined Oestrogen-Progestagen: Age range: 50-65 yrs.
Incidence per 1,000 never-users of HRT over a 5-year period*: 9-12.
Risk ratio and 95% CI**: 1.7.
Additional cases per 1,000 HRT users over 5 years (95% CI): 6 (5-7).
*Taken from baseline incidence rates in developed countries.
**Overall risk ratio. The risk ratio is not constant but will increase with increasing duration on use.
Note: Since the background incidence of breast cancer differs by EU country, the number of additional cases of breast cancer will also change proportionately.
US WHI Studies - Additional Risk of Breast Cancer After 5-Years Use: Conjugated Equine Estrogen (CEE) Oestrogen-Only: Age range: 50-79 years.
Incidence per 1,000 women in placebo arm over 5 years: 21.
Risk ratio and 95% CI: 0.8 (0.7-1.0).
Additional cases per 1,000 HRT users over 5 years (95% CI): -4 (-6-0)*.
CEE + Medroxyprogesterone Acetate (MPA) Oestrogen-Progestagen**: Age range: 50-79 years.
Incidence per 1,000 women in placebo arm over 5 years: 17.
Risk ratio and 95% CI: 1.2 (1.0-1.5).
Additional cases per 1,000 HRT users over 5 years (95% CI): 4 (0-9).
*WHI study in women with no uterus, which did not show an increase in risk of breast cancer.
**When the analysis was restricted to women who had not used HRT prior to the study there was no increased risk apparent during the first 5 years of treatment: after 5 years the risk was higher than in non-users.
Endometrial Cancer Risk: Postmenopausal women with a uterus: The endometrial cancer risk is about 5 in every 1,000 women with a uterus not using HRT. In women with a uterus, use of systemic oestrogen-only HRT is not recommended because it increases the risk of endometrial cancer (see Precautions).
Depending on the duration of systemic 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 1,000 women between the ages of 50 and 65.
Adding a progestagen to systemic oestrogen-only therapy for at least 12 days per cycle can prevent this increased risk. In the Million Women Study the use of five years of combined (sequential or continuous) HRT did not increase risk of endometrial cancer (RR of 1.0 (0.8-1.2)). (See Precautions.)
Ovarian Cancer: Risk estimates have been drawn from systemic exposure and it is not known how these apply to local treatments.
Long-term use of oestrogen-only and combined oestrogen-progestagen 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 2,500 users.
Risk of Venous Thromboembolism: Risk estimates have been drawn from systemic exposure and it is not known how these apply to local treatments.
HRT is associated with a 1.3- to 3-fold increased relative risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. The occurrence of such an event is more likely in the first year of using HRT (see Precautions).
Results of the WHI studies are presented.
WHI Studies - Additional Risk of VTE Over 5-Years Use: Oral Oestrogen-Only*: Age range: 50-59 years.
Incidence per 1,000 women in placebo arm over 5 years: 7.
Risk ratio and 95% CI: 1.2 (0.6-2.4).
Additional cases per 1,000 HRT users: 1 (-3-10).
Oral Combined Oestrogen-Progestagen: Age range: 50-59 years.
Incidence per 1,000 women in placebo arm over 5 years: 4.
Risk ratio and 95% CI: 2.3 (1.2-4.3).
Additional cases per 1,000 HRT users: 5 (1-13).
*Study in women with no uterus.
Risk of Coronary Artery Disease: Risk estimates have been drawn from systemic exposure and it is not known how these apply to local treatments.
The risk of coronary artery disease is slightly increased in users of combined oestrogen-progestagen HRT over the age of 60 (see Precautions).
Risk of Ischaemic Stroke: Risk estimates have been drawn from systemic exposure and it is not known how these apply to local treatments.
The use of oestrogen-only and oestrogen-progestagen therapy is associated with an up to 1.5-fold increased relative risk of ischaemic stroke. The risk of haemorrhagic stroke is not increased during use of HRT.
This relative risk is not dependent on age or on duration of use, but as the baseline risk is strongly age-dependent, the overall risk of stroke in women who use HRT will increase with age, see Precautions.
WHI Studies Combined - Additional Risk of Ischaemic Stroke* Over 5-Years Use: Age range: 50-59 years.
Incidence per 1,000 women in placebo arm over 5 years: 8.
Risk ratio and 95% CI: 1.3 (1.1-1.6).
Additional cases per 1,000 HRT users over 5 years: 3 (1-5).
*No differentiation was made between ischaemic and haemorrhagic stroke.
Drug Interactions
As the oestrogen in Vagifem is administered within the vagina and due to the low levels of estradiol release, it is unlikely that any clinically relevant drug interactions will occur with Vagifem. However, the metabolism of oestrogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes, such as anticonvulsants (e.g. phenobarbital, phenytoin, carbamazepine) and anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz).
Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones. Herbal preparations containing St. John’s wort (Hypericum perforatum) may induce the metabolism of oestrogens.
Caution For Usage
Instructions for Use/Handling and Disposal: How to Use Vagifem: Tear off one single blister pack. Open the end.
Insert the applicator carefully into the vagina. Stop when resistance is felt (8-10 cm).
To release the tablet, gently press the push button until a click is felt. The tablet will stick to the wall of the vagina straight away. It will not fall out if the patient stands up or walk.
Take out the applicator and throw it away.
Incompatibilities: Not applicable.
Special Precautions for Disposal and Other Handling: Any unused product or waste material should be disposed of in accordance with local requirements.
Storage
Store below 30°C. Do not refrigerate.
MIMS Class
Oestrogens, Progesterones & Related Synthetic Drugs
ATC Classification
G03CA03 - estradiol ; Belongs to the class of natural and semisynthetic estrogens used in estrogenic hormone preparations.
Presentation/Packing
Vag tab 10 mcg (film-coated, white, biconvex tablet engraved with "NOVO 278" on one side with a diameter of 6 mm) x 18's (w/ applicator).
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