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 this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents:

1. What Ovestin is and what it is used for
2. What you need to know 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 known as 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 last natural menstrual period.

Ovestin is used to relieve menopausal symptoms in the vagina, such as dryness or irritation. In medical terminology, 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 decreases rapidly.

Estrogen deficiency may cause dryness and increased sensitivity of the vaginal walls, leading to painful sexual intercourse, inflammation, and intense itching of the vagina. 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 postoperative wounds in women who have undergone 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) carries certain risks that should be considered when deciding whether to start or continue HRT.
Experience with treating women who experience 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 full medical and family history. Your doctor may also decide to perform a physical examination, including, if necessary, a breast examination and/or a vaginal gynecological examination.
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 you are unsure, consult your doctor before using Ovestin.

Do not 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 breast cancer or if breast cancer is suspected.
• if you currently have an estrogen-dependent tumour, for example cancer of the endometrium (lining of the womb), 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 blood vessels (venous thromboembolism), for example in the deep veins 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 have recently had arterial diseases caused by blood clots, such as myocardial infarction (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 occur for the first time while using Ovestin, stop treatment 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 they may recur or worsen during treatment with Ovestin. If this happens, you should have more frequent check-ups:

• uterine fibroids (leiomyoma)
• endometriosis (growth of endometrial cells outside the uterus) or previous excessive growth of the endometrium (endometrial hyperplasia)
• increased risk of blood clots [see section “Blood clots in veins (venous thromboembolism)”]
• increased risk of developing estrogen-dependent tumours (e.g. breast cancer in mother, sister, or grandmother)
• hypertension (high blood pressure)
• liver disorders, such as benign liver tumour
• diabetes with or without vascular complications
• gallstones
• migraine or severe headache
• systemic autoimmune disease affecting multiple organs (systemic lupus erythematosus – SLE; chronic connective tissue disease with skin lesions throughout the body)
• epilepsy
• asthma
• otosclerosis (a disease affecting the ear bones and causing hearing loss)
• 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 medications such as ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin. Concurrent use of these drugs with certain estrogen-containing medicines may increase liver function test results (elevated liver enzyme ALT activity); 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, combined with breathing difficulties, suggesting angioedema
• significant increase in blood pressure (possible symptoms: headache, fatigue, dizziness)
• new onset of migraine-type headaches
• pregnancy
• symptoms suggesting 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 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 Womb Lining (Endometrial Hyperplasia) and Cancer of the Womb Lining (Endometrial Cancer)
Long-term use of oral estrogen-only HRT may increase the risk of developing cancer of the endometrium (lining of the womb).
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, as it may be a sign of endometrial thickening.
To prevent endometrial stimulation, do not exceed the maximum dose or use it for longer than a few weeks (maximum 4 weeks).

The risks described below apply to systemic HRT medicines that enter the bloodstream. Ovestin, however, is applied locally in the vagina and is absorbed into the blood 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 breast cancer before. It is not known whether Ovestin can be safely used in women who have had breast cancer.

You should have regular breast examinations 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 – significantly rarer than breast cancer. Estrogen-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 50–54 not using HRT, about 2 in 2,000 women will be diagnosed with ovarian cancer within 5 years. Among women using HRT for 5 years, about 3 in 2,000 women will be diagnosed (i.e. about 1 additional case).

Effects of HRT on the Heart or Circulatory System

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

• prolonged immobilization due to major surgery, injury, or illness (see also section 3 “Need for surgery”)
• significant obesity (body mass index over 30 kg/m²)
• blood clotting disorders requiring long-term anticoagulant therapy
• history of venous thrombosis in the legs, lungs, or another organ 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 not using HRT, about 4 to 7 in 1,000 women can be expected to develop venous thrombosis within 5 years.
Among women over 50 using estrogen-only HRT for more than 5 years, the number increases to 5 to 8 in 1,000 women (i.e. 1 additional case).

Heart Disease (Heart Attack)
In women using estrogen-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 not using it. The number of additional stroke cases associated with HRT increases with age.

Comparison
Among women over 50 not using HRT, about 8 in 1,000 women can be expected to have a stroke within 5 years. Among women of the same age using HRT, the rate is 11 in 1,000 women within 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 all medicines you are currently taking or have recently taken, including those you plan to take, even if they are available without a prescription, herbal remedies, or other natural products.
Some medicines may affect the action of Ovestin, leading to irregular bleeding. These include:

• antiepileptic drugs (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 Breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, 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 contact your doctor.
Breast-feeding women should consult their doctor before using Ovestin.

Driving and Using Machines
Ovestin is not expected to 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 you are unsure,
you should consult your doctor or pharmacist.
For atrophic changes in the lower urogenital tract, the recommended dose is 1 application per day for the first 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 per day for 2 weeks before the procedure and 1 application twice a week for 2 weeks after 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 collection.
Ovestin cream should be administered intravaginally using the applicator, preferably before going to bed at night.
1 application (applicator filled to the mark indicated by a circular line) contains 0.5 g of cream, corresponding 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 a red ring, as indicated by the 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 applicator tip 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 into the applicator, overcoming the resistance point.

After emptying the tube, 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 symptoms.
If you feel that the effect of Ovestin is too strong or too weak, you should consult your doctor.
Use of a higher than recommended dose of Ovestin
If more than the recommended dose has been used, contact 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, the medicine should be used as soon as possible, unless the missed dose is noticed on the day of the next scheduled application. If the missed dose is noticed on the day of the next application, the missed dose should be skipped and the next dose administered 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 Ovestin approximately 4 to 6 weeks before surgery to reduce the risk of blood clots (see section 2, "Blood clots in veins"). Ask your doctor when you may resume using Ovestin.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
The following diseases are reported more frequently in women using systemic HRT (hormone replacement therapy) administered via the bloodstream than in women not using HRT. These risks are less relevant to locally administered treatments such as Ovestin:

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

Depending on the dosage used and individual patient sensitivity, the following adverse reactions may occur:

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

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

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

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

5. How to store the medicine Ovestin

Keep the medicine out of the sight and reach of children.
Do not store above 25°C. Do not freeze.
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.
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 is estriol. One gram of cream contains 1 mg of estriol.
  Other ingredients are: cetyl alcohol, stearyl alcohol, octyldodecanol, cetyl palmitate, glycerol, polysorbate 60, sorbitan stearate, lactic acid, chlorhexidine dihydrochloride, sodium hydroxide, purified water.

What Ovestin 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 polyethylene cap and an applicator made of styrene-acrylonitrile copolymer with a polyethylene plunger, packed 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 Austria, 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:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź, Poland
Repackaged in:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź, Poland
Austrian MA number, country of export: 17453
Parallel import licence number: 38/25