Ovestin

Package leaflet: Information for the user

Warning! Keep the leaflet, information on the immediate packaging in a foreign language!
Ovestin
1 mg/g, vaginal cream
Estriol
Please read the entire leaflet carefully before using this medicine, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet:

1. What Ovestin is and what it is used for
2. Important information before using Ovestin
3. How to use Ovestin
4. Possible side effects
5. How to store Ovestin
6. Contents of the pack and other information

1. What Ovestin is and what it is used for

Ovestin belongs to a group of medicines called local estrogen replacement therapy (ERT) for vaginal use.
The medicine contains the female sex hormone estriol (an estrogen). Ovestin is used in postmenopausal women, at least 12 months after the natural cessation of menstruation.
Ovestin is used to relieve menopausal symptoms affecting the vagina, such as dryness or irritation.
In medical terms, this condition is known as "atrophic vaginitis". It is caused by decreased estrogen levels in the body and occurs naturally after menopause.
If the ovaries have been surgically removed before menopause (a procedure called oophorectomy), estrogen production drops rapidly.
Estrogen deficiency may cause vaginal dryness and increased sensitivity of the vaginal walls, leading to painful sexual intercourse, inflammation, and intense vaginal itching. Estrogen deficiency may also cause urinary incontinence and recurrent urinary bladder infections. These symptoms often improve with estrogen-containing medicines. Noticeable improvement usually occurs within a few days or weeks after starting treatment.
Ovestin works by replacing the estrogen normally produced by a woman's ovaries. The medicine is administered vaginally, so the hormone is released exactly where it is needed. This may help relieve vaginal discomfort.
Improvement may take several days or even weeks to become noticeable.
In addition to the indications described above, Ovestin may also be used:

• to accelerate healing of wounds after vaginal surgery
• to improve the assessment of cervical smears in postmenopausal women.

2. Important information before using Ovestin

Medical history and regular check-ups
Hormone replacement therapy (HRT) involves risks that should be considered when deciding whether to start or continue HRT.
Experience with treating women who have premature menopause (due to ovarian failure or surgical removal of ovaries) is limited. In women with premature menopause, the risks associated with HRT may differ. Always consult your doctor.
Before starting (or resuming) HRT, your doctor will take a detailed medical history, including family medical conditions. Your doctor may also decide to perform a physical examination, including, if necessary, a breast examination and/or a gynecological examination via the vagina.
After starting Ovestin, you should have regular check-ups with your doctor (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing Ovestin treatment.
You should have regular breast examinations as recommended by your doctor.

When not to use Ovestin:
Do not use Ovestin if any of the following apply to you. If in doubt, consult your doctor before using Ovestin.

When not to use Ovestin:

• if you are allergic to estriol or any of the other ingredients of this medicine (listed in section 6 "Contents of the pack and other information").
• if you currently have or have had in the past breast cancer, or if breast cancer is suspected.
• if you currently have an oestrogen-dependent tumour, for example cancer of the lining of the womb (endometrial cancer), or if such a tumour is suspected.
• if you have vaginal bleeding of unknown cause.
• if you have untreated excessive thickening of the lining of the womb (endometrial hyperplasia).
• if you currently have or have ever had blood clots in the blood vessels (venous thromboembolism), for example in the blood vessels of the legs (deep vein thrombosis) or in the lungs (pulmonary embolism).
• if you have blood clotting disorders (such as: protein C deficiency, protein S deficiency, or antithrombin deficiency).
• if you currently have or recently had arterial blood clot-related diseases, such as: heart attack, stroke or angina pectoris.
• if you currently have or have ever had liver disease, and liver function test results have not returned to normal.
• if you have a rare inherited blood disorder called "porphyria".

If any of the above conditions occurs for the first time while using Ovestin, stop using the medicine immediately and contact your doctor without delay.

Warnings and precautions
Before starting treatment, inform your doctor if any of the following conditions are currently present or have occurred previously, as these symptoms may recur or worsen during treatment with Ovestin. If so, you should have more frequent check-ups:

• uterine fibroids (leiomyoma)
• growth of endometrial tissue outside the uterus (endometriosis) or previous excessive growth of the lining of the uterus (endometrial hyperplasia)
• increased risk of blood clots [see section "Blood clots in the veins (venous thromboembolism)"]
• increased risk of developing oestrogen-dependent cancer (e.g. breast cancer in mother, sister or grandmother)
• high blood pressure
• liver disorders, such as benign liver tumour
• diabetes with or without vascular complications
• gallstones
• migraine or severe headache
• autoimmune disease affecting multiple internal organs (systemic lupus erythematosus - SLE; chronic connective tissue disease with skin lesions throughout the body)
• epilepsy
• asthma
• a disease affecting the inner ear and causing hearing loss (otosclerosis)
• fluid retention associated with heart or kidney disease
• hereditary or acquired angioedema.

Inform your doctor if you have hepatitis C and are being treated with medicines such as: ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin. Taking these medicines together with certain oestrogen-containing medicines may increase liver function test results (elevated liver enzyme ALT); the risk of this occurring with Ovestin is currently unknown.
Tell your doctor if you notice any changes in your condition while using Ovestin.

Stop using Ovestin and contact your doctor immediately if any of the following symptoms occur during HRT:

• any of the conditions listed under "When not to use Ovestin"
• yellowing of the skin or whites of the eyes (jaundice), which may indicate liver disease
• swelling of the face, tongue and/or throat and/or difficulty swallowing or hives, together with breathing difficulties, suggesting angioedema
• significant increase in blood pressure (possible symptoms: headache, fatigue, dizziness)
• first occurrence of migraine-type headaches
• pregnancy
• symptoms indicating blood clots, such as:
  • painful swelling and redness in the legs
  • sudden chest pain
  • difficulty breathing. More information is provided in the section "Blood clots in the veins (venous thromboembolism)".

Note: Ovestin is not a contraceptive. If less than 12 months have passed since your last menstrual period or if you are under 50 years of age, you may need to use an additional method of contraception. Consult your doctor.

HRT and cancer

Excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial cancer)
Long-term use of oestrogen-only HRT in tablet form may increase the risk of developing cancer of the lining of the womb (endometrium).
It is not certain whether a similar risk exists with repeated or long-term use (longer than one year) of Ovestin. However, Ovestin has been shown to be absorbed into the bloodstream only to a very small extent, and therefore adding a progestogen is not necessary.
Bleeding or spotting is usually not a cause for concern, but you should consult your doctor. It may be a sign of endometrial thickening.
To avoid stimulating the endometrium, do not exceed the maximum dose or use it for longer than a few weeks (maximum 4 weeks).

The risks described below apply to HRT medicines that enter the bloodstream. However, Ovestin is applied locally in the vagina and is absorbed into the bloodstream only in very small amounts. It is less likely that the conditions listed below will worsen or recur during Ovestin use, but if you have any doubts, consult your doctor.

Breast cancer
Data indicate that using Ovestin does not increase the risk of breast cancer in women who have never had it before. It is not known whether Ovestin can be safely used in women who have had breast cancer.
You should regularly examine your breasts and consult your doctor if you notice any changes, such as:

• skin dimpling
• changes in the nipple
• any visible or palpable lumps.

Additionally, screening mammograms are recommended as advised by your doctor.

Ovarian cancer
Ovarian cancer is rare – much rarer than breast cancer. Oestrogen-only HRT is associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer increases with age. For example, among women aged 50 to 54 who do not use HRT, ovarian cancer will be diagnosed in about 2 out of 2000 women over a 5-year period. Among women who use HRT for 5 years, ovarian cancer will be diagnosed in about 3 out of 2000 women (i.e. about 1 additional case).

Effect of HRT on the heart or circulation

Blood clots in the veins (venous thromboembolism)
The risk of developing blood clots in the veins is about 1.3 to 3 times higher in women using HRT than in those who do not, especially during the first year of treatment.
Blood clots can have serious consequences, and if a clot travels to the lungs, it may cause chest pain, shortness of breath, fainting, or even death.
The likelihood of developing venous blood clots increases with age and in the following situations. If any of the following apply to you, inform your doctor:

• prolonged immobility due to major surgery, injury, or illness (see also section 3 "Need for surgery")
• significant overweight (body mass index above 30 kg/m²)
• blood clotting disorders requiring long-term anticoagulant treatment
• history of blood clots in the legs, lungs, or other organs in a close relative
• systemic lupus erythematosus (SLE; chronic connective tissue disease with skin lesions throughout the body)
• cancer.

Symptoms of thrombosis are listed in the section "When to stop using Ovestin and contact your doctor immediately".

Comparison
Among women over 50 who do not use HRT, about 4 to 7 out of 1000 women can be expected to develop venous thrombosis over a 5-year period.
Among women over 50 who have used oestrogen-only HRT for more than 5 years, the number of cases will be 5 to 8 per 1000 women (i.e. 1 additional case).

Heart disease (heart attack)
In women using oestrogen-only HRT, the risk of developing heart disease is not increased.

Stroke
The risk of stroke is about 1.5 times higher in women using HRT than in those who do not. The number of additional stroke cases associated with HRT use increases with age.

Comparison
Among women over 50 not using HRT, about 8 out of 1000 women can be expected to have a stroke over 5 years, while among women of the same age using HRT, the figure is 11 per 1000 women over 5 years (i.e. 3 additional cases).

Other conditions
HRT does not prevent memory loss. Some evidence suggests a higher risk of memory loss in women who start HRT after age 65. Consult your doctor about this.

Ovestin and other medicines
Tell your doctor or pharmacist about any other medicines you are currently taking, have recently taken, or plan to take, including over-the-counter medicines, herbal remedies, or other natural products.
Some medicines may affect the action of Ovestin, leading to irregular bleeding. These include:

• antiepileptic medicines (such as: phenobarbital, phenytoin, and carbamazepine)
• medicines used to treat tuberculosis (such as: rifampicin, rifabutin)
• medicines used in HIV infection (such as: nevirapine, efavirenz, ritonavir, and nelfinavir)
• herbal products containing St. John's wort (Hypericum perforatum)

Laboratory tests
If you need to have blood tests, inform your doctor or laboratory staff that you are using Ovestin, as it may affect the results of certain tests.

Ovestin with food and drink
Food and drink do not affect the action of Ovestin.

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, you should consult your doctor or pharmacist before using this medicine.
Ovestin is intended for use only in postmenopausal women.
If you become pregnant, stop using Ovestin and consult your doctor.
Breastfeeding women should consult their doctor before using Ovestin.

Driving and using machines
Using Ovestin should not affect your ability to drive or operate machinery. However, individual responses to the medicine may vary.

Ovestin contains cetyl alcohol and stearyl alcohol.
The medicine may cause local skin reactions (e.g. contact dermatitis).

3. How to use Ovestin

This medicine should always be used exactly as directed by your doctor or pharmacist. If in doubt,
please consult your doctor or pharmacist.
For atrophic changes in the lower urinary and genital tract, the recommended dose is
1 application daily for the first few weeks (up to a maximum of 4 weeks), after which the dose should be
gradually reduced to 1 application twice a week.
To improve wound healing in postmenopausal women who have undergone vaginal procedures,
the recommended dose is 1 application daily for 2 weeks prior to the procedure and 1 application twice
a week for 2 weeks following the procedure.
To facilitate interpretation of cervical smear results in postmenopausal women, the recommended
dose is 1 application every other day during the week preceding the smear test.
Ovestin cream should be administered intravaginally using the applicator, preferably before going to
bed at night.
1 application (applicator filled to the circular mark) contains 0.5 g of cream, equivalent to
0.5 mg of estriol.

1. Remove the cap from the tube, turn it over, and open the tube with the sharp end.
2. Screw the applicator onto the tube. Ensure that the plunger is fully inserted into the applicator.

3. Slowly squeeze the cream into the applicator until resistance is felt from the plunger (the plunger will stop at the position marked by the red ring indicated by arrows in the illustration below).

4. Unscrew the applicator from the tube and replace the cap on the tube.
5. In a lying position, insert the tip of the applicator containing the cream deeply into the vagina.
6. Slowly push the entire cream content into the vagina using the plunger.

7. After use, remove the plunger from the applicator by overcoming the resistance point, and wash both parts thoroughly with warm water and soap. Do not use detergents. After washing, rinse both parts well. DO NOT PLACE THE APPLICATOR IN HOT OR BOILING WATER.
8. The device can be reassembled by inserting the plunger back into the applicator, overcoming the resistance point.

After the tube is empty, the applicator should be discarded.
Your doctor will aim to prescribe the lowest possible dose, to be used for the shortest duration necessary
to relieve your symptoms.
If you feel that the effect of Ovestin is too strong or too weak, please consult your doctor.
Use of a higher than recommended dose of Ovestin
If more than the recommended dose has been used, consult your doctor or pharmacist immediately.
Ingestion of the cream does not pose a health or life hazard. However, you should inform your doctor.
Symptoms of overdose most commonly include nausea and vomiting. In women, vaginal bleeding may also
occur after a few days.
Missed dose of Ovestin
Do not use a double dose to make up for a missed dose.
If a dose is missed, take it as soon as possible, unless the next scheduled dose is due the following day.
If the missed dose is noticed on the day of the next scheduled application, skip the missed dose and continue
with the next dose according to the previously established schedule.
Need for surgery
Patients scheduled for surgery should inform the surgeon that they are using Ovestin. It may be necessary to
discontinue the medicine approximately 4 to 6 weeks before surgery to reduce the risk of blood clots (see section 2, “Venous thrombosis”). Please ask your doctor when you may resume using Ovestin.
If you have any further questions about the use of this medicine, please consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
The following conditions are reported more frequently in women using systemic hormone therapy (HT) – i.e. therapy in which hormones enter the bloodstream – than in women not using HT. These risks are less relevant for locally administered medicines such as Ovestin:

• ovarian cancer
• blood clots in the veins of the legs or lungs (venous thromboembolism)
• stroke
• possible memory loss if HT is initiated after the age of 65. For more information on these adverse effects, see section 2.

Depending on the dose used and individual patient sensitivity, the following adverse effects may occur:

• breast swelling and tenderness
• slight vaginal bleeding
• increased vaginal discharge
• nausea
• fluid retention, usually noticeable as swelling of the ankles or feet
• local irritation or itching
• flu-like symptoms.

In most patients, these symptoms resolve after the first few weeks of treatment.
The following adverse effects have been reported during the use of other HT medicines:

• inflammation of the gallbladder
• various skin disorders
  • skin discolouration, especially on the face or neck, known as "chloasma" (melasma)
  • painful red nodules on the skin (erythema nodosum)
  • rash with target-shaped redness or ulceration (erythema multiforme).

Reporting of adverse effects
If any adverse effects occur, including those not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can also be reported directly to the Department for Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel: +48 22 49-21-301, Fax: +48 22 49-21-309, website: https://smz.ezdrowie.gov.pl
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Ovestin

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Store below 25°C. Do not freeze.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Ovestin contains

• The active substance in Ovestin vaginal cream is estriol, 1 milligram per 1 gram of cream.
• The other ingredients are: octyldodecanol, cetyl palmitate, glycerol, cetyl alcohol, stearyl alcohol, polysorbate 60, sorbitan stearate, lactic acid, chlorhexidine dihydrochloride, sodium hydroxide, purified water.

What the medicine looks like and contents of the pack
Ovestin is a white to almost white, homogeneous, smooth cream with a mild, characteristic odour.
It is supplied in an aluminium tube with a plastic cap, together with an applicator, in a cardboard box.
Pack size: 15 g of cream in a tube.
For more detailed information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Portugal, country of export:
Aspen Pharma Trading Limited
3016 Lake Drive
Citywest Business Campus
Dublin 24
Ireland
Manufacturer:
Aspen Bad Oldesloe GmbH
Industriestrasse 32-36
D-23843 Bad Oldesloe
Germany
Parallel importer:
Medezin Sp. z o.o.
Zbąszyńska 3
91-342 Łódź
Repackaged in:
Medezin Sp. z o.o.
Zbąszyńska 3
91-342 Łódź
Marketing authorisation number in Portugal, country of export: 8566307
Parallel import authorisation number: 122/21