Vagifem 10 μg Vaginal tablets

Vagifem u00ae 10 u03bcg is indicated for the treatment of atrophic vaginitis due to oestrogen deficiency. The experience of treating women older than 65 years is limited.

Vagifem u00ae 10 u03bcg is administered intravaginally using the applicator. Initial dose: One vaginal tablet daily for two weeks. Maintenance dose: One vaginal tablet twice a week.
Treatment may be started on any convenient day. If a dose is forgotten, it should be used 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 should be used. Vagifem u00ae 10 u03bcg may be used in women with or without an intact uterus. During treatment, especially during the first 2 weeks, absorption may be seen but as plasma estradiol levels usually do not exceed normal postmenopausal levels the addition of a progestogen is not recommended.
Administration
1. Open the blister pack at the plunger end.
2. Insert the applicator in the vagina until resistance is met (8 u2013 10 cm).
3. Release the tablet by pressing the plunger.
4. Withdraw the applicator and discard. The used applicator may be disposed together with household waste.

• Personal and family history of breast cancer;
• Known or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer);
• Undiagnosed genital bleeding;
• Untreated endometrial hyperplasia;
• Previous proven deep vein thrombosis (DVT);
• Previous pulmonary embolism;
• Inherited thrombophilia or known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency);
• Active or recent arterial thromboembolic disease (e.g. coronary artery disease, angina pectoris, myocardial infarction, stroke);
• Active liver disease. 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 of Vagifem u00ae (see section 6.1);
• Porphyria;
• Patients known with inherited genetic mutations: BRCA1 and BRCA2 genes;
• Early menstrual periods (before the age of 12 years);
• History of non-cancerous breast diseases (atypical hyperplasia or lobular carcinoma in situ);
• Previous treatment using radiation therapy to the chest or breast;
• Previous exposure to diethylstilbestrol (DES);
• Not for use during pregnancy.

A careful assessment of the risks and benefits should be undertaken at least annually and Vagifem u00ae 10 u03bcg should only be continued as long as there are no contraindications to treatment after 5 years of usage and the benefit outweighs the risk.
Medical examination/follow-up
Before initiating or reinstituting Vagifem u00ae 10 u03bcg therapy, a complete personal and family medical history should be obtained. Physical examination (including pelvic and breast) should be guided by this and by the contraindications and warnings for use.
During treatment, periodic check-ups are recommended at 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.
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;
• A history of, or risk factors for, thromboembolic disorders (see u2018Venous thromboembolismu2019 below);
• 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 u2018Endometrial hyperplasiau2019 below);
• Epilepsy;
• Asthma;
• Otosclerosis.

• Jaundice or deterioration in liver function;
• Significant increase in blood pressure;
• New onset of migraine-type headache;
• Pregnancy.

Due to a local administration of Vagifem u00ae 10 u03bcg, interactions of clinical relevance are not expected. However, interactions with other locally applied vaginal treatments should be considered. The metabolism of oestrogens may be increased by concomitant use of substances known to induce medicine-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 Johnu2019s wort (Hypericum perforatum) may induce the metabolism of oestrogens.

Pregnancy
Vagifem u00ae 10 u03bcg is contraindicated during pregnancy. If pregnancy occurs during medication with Vagifem u00ae 10 u03bcg, treatment should be withdrawn immediately.
Lactation
Vagifem u00ae 10 u03bcg is contraindicated during lactation.

No effects known.

The most commonly reported adverse reactions are: vulvovaginal mycotic infection and vulvovaginal pruritus. Oestrogenu2013related adverse events such as breast pain, peripheral oedema and postmenopausal bleedings have been reported. Those adverse events observed with a higher frequency in patients treated with Vagifem u00ae 10 u03bcg as compared to placebo and which are possibly related to treatment are presented below.
System Organ Class
Common (u2265 1/100 to < 1/10)
Uncommon (u2265 1/1 000 to < 1/100)
Rare (u2265 1/10 000 to < 1/1 000)
Infections and infestations:
Genital candidiasis or vaginitis, see also u2018Reproductive system and breast disordersu2019
Vulvovaginal mycotic infection
Nervous system disorders:
Headache
Vascular disorders:
Hot flush, hypertension
Gastrointestinal disorders:
Nausea, abdominal pain, abdominal distension or abdominal discomfort, dyspepsia, vomiting, flatulence
Skin and subcutaneous issue disorders:
Rash
System Organ Class
Common (u2265 1/100 to < 1/10)
Uncommon (u2265 1/1 000 to < 1/100)
Rare (u2265 1/10 000 to < 1/1 000)
Reproductive system and breast disorders:
Vaginal haemorrhage, vaginal discharge or vaginal discomfort, breast oedema, breast enlargement, breast pain or breast tenderness
General disorders and administration site conditions:
Peripheral oedema
Investigations:
Increased body mass
Post-marketing experience:
In addition to the above mentioned adverse reactions, those presented below have been spontaneously reported for patients being treated with Vagifem u00ae, and are considered possibly related to treatment. The frequencies for the below mentioned adverse reactions cannot be interpreted because these reactions are reported voluntarily from a population of uncertain size:
u2022 Neoplasms benign and malignant (including cysts and polyps): Breast cancer;
u2022 Immune system disorders: Generalised hypersensitivity reactions (e.g. anaphylactic reaction/shock);
u2022 Metabolism and nutrition disorders: Fluid retention;
u2022 Psychiatric disorders: Insomnia;
u2022 Nervous system disorders: Migraine aggravated;
u2022 Vascular disorders: Deep venous thrombosis;
u2022 Gastrointestinal disorders: Diarrhoea;
u2022 Skin and subcutaneous tissue disorders: Urticaria, rash, pruritus;
u2022 Reproductive system and breast disorders: Vulvovaginal pain, pruritus genital;
u2022 General disorders and administration site conditions: Application site reaction, medicine ineffective, injury associated with device.
1 Including vulvovaginal burning sensation.
2 Local allergic reactions including vulvovaginal erythema, genital erythema, vulvovaginal rash, genital rash.
3 Minor local trauma caused by intravaginal applicator.
The following adverse reactions have been reported in association with systemic oestrogen treatment:
u2022 Myocardial infarction, congestive heart disease;
u2022 Stroke;
u2022 Gall bladder disease;
u2022 Skin and subcutaneous disorders: chloasma, erythema multiforme, erythema nodosum, vascular purpura, pruritus;
u2022 Risk of developing endometrial cancer, endometrial hyperplasia or increase in size of uterine fibroids;
u2022 Insomnia;
u2022 Epilepsy;
u2022 Libido disorder NOS (not otherwise specified);
u2022 Deterioration of asthma;
u2022 Probable dementia.

Vagifem u00ae 10 u03bcg is intended for intravaginal use and the dose of estradiol is very low. Overdose is therefore unlikely, but if it occurs, treatment should be symptomatic.