Oekolp

Patient Information Leaflet

OEKOLP, 1 mg/g, vaginal cream
Estriol
Please read all of this leaflet carefully before using this medicine, as it contains
important information for you.

• Keep this leaflet, as 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 someone else even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Table of Contents

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

1. What Oekolp is and what it is used for

Oekolp belongs to a group of medicines called local estrogen replacement therapy for vaginal use. The medicine contains the female sex hormone estriol (an estrogen). Oekolp is used in postmenopausal women, at least 12 months after the natural cessation of menstruation.

Oekolp is used to relieve menopausal symptoms affecting 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 lead to vaginal dryness and increased sensitivity of the vaginal walls, resulting in painful sexual intercourse, inflammation, and intense itching of the vagina. Estrogen deficiency may also cause urinary incontinence and recurrent urinary tract infections. These symptoms often improve with estrogen-containing medicines. Noticeable improvement usually occurs within a few days or weeks after starting treatment.

Oekolp 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 become noticeable only after a few days or even weeks.

In addition to the above indications, Oekolp cream 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 Oekolp

Medical history and regular check-ups
Hormone replacement therapy (HRT) carries risks that should be considered when deciding whether to start or continue treatment.
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 vaginal examination.
After starting Oekolp, 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 treatment with Oekolp.
You should have regular breast examinations as recommended by your doctor.

When not to use Oekolp
Do not use Oekolp if any of the following apply to you. If you are unsure, consult your doctor before using Oekolp.

Do not use Oekolp:

• If you are allergic to estriol or any of the other ingredients of this medicine (listed in section 6).
• If you currently have or have ever had breast cancer, or if breast cancer is suspected.
• If you have an estrogen-dependent tumour, for example endometrial cancer (cancer of the 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 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 have recently had arterial diseases caused by blood clots, 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 health conditions occur for the first time while using Oekolp, stop treatment immediately and contact your doctor without delay.

Warnings and precautions
Before starting treatment, inform your doctor if any of the following conditions currently exist or have occurred previously, as they may recur or worsen during treatment with Oekolp. If this occurs, you should have more frequent check-ups:

• Uterine fibroids (leiomyoma)
• Endometriosis (growth of endometrial cells outside the uterus) or a history of excessive growth of the lining of the uterus (endometrial hyperplasia)
• Increased risk of blood clots (see section "Blood clots in veins (venous thromboembolism)")
• Increased risk of developing estrogen-dependent cancer (e.g. breast cancer in mother, sister, or grandmother)
• Hypertension
• Liver disorders, such as benign liver tumour
• Diabetes mellitus, with or without vascular complications
• Gallstones
• Migraine or severe headache
• Systemic autoimmune disease affecting multiple internal organs (systemic lupus erythematosus – SLE; chronic connective tissue disease with skin lesions throughout the body)
• Epilepsy
• Asthma
• Otosclerosis (a disease affecting the ear ossicles and causing hearing loss)
• Fluid retention associated with heart or kidney disease
• Hereditary or acquired angioedema.

Inform your doctor if you have hepatitis C (HCV) and are being treated with medications such as: ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin, glecaprevir/pibrentasvir, or the combination sofosbuvir/velpatasvir/voxilaprevir. More information can be found in section "Oekolp and other medicines".
Tell your doctor if you notice any changes in your condition while using Oekolp.

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

• Any of the conditions listed in the section "When not to use Oekolp"
• 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, accompanied by breathing difficulties, suggesting angioedema
• A significant increase in blood pressure (which may present as headache, fatigue, dizziness)
• New onset of migraine-type headaches
• Pregnancy
• Symptoms indicating blood clot formation, such as:
  • Painful swelling and redness in the legs
  • Sudden chest pain
  • Breathing difficulties. More information is provided in the section "Blood clots in veins (venous thromboembolism)".

Note: Oekolp 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 should use contraception to prevent pregnancy. Consult your doctor.
When using latex condoms during treatment with Oekolp cream, their strength may be reduced, thereby decreasing their protective effectiveness.

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 systemic estrogen-only HRT in tablet form may increase the risk of developing cancer of the uterine lining (endometrium).
It is not certain whether a similar risk exists with repeated or long-term (longer than one year) use of Oekolp. However, Oekolp has been shown to be absorbed into the bloodstream only to a very small extent, and therefore the addition of a progestogen is not necessary.
Bleeding or spotting is usually not a cause for concern, but you should contact 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 several weeks (maximum 4 weeks).

The risks described below apply to HRT medicines that circulate systemically in the blood. Oekolp, however, is intended for local vaginal use and is absorbed into the blood only to a very small extent. Worsening or recurrence of the conditions mentioned below during treatment with Oekolp is less likely, but if you have any concerns, consult your doctor.

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

• Dimpling or retraction of the skin
• Changes in the nipple
• Any visible or palpable lumps or thickening.

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 to 54 who do not use HRT, about 2 out of 2,000 women will be diagnosed with ovarian cancer over a 5-year period. Among women using HRT for 5 years, about 3 out of 2,000 women will be diagnosed (i.e. about 1 additional case).

Effect of HRT on the heart or circulatory system

Blood clots in veins (venous thromboembolism)
The risk of blood clots in veins is approximately 1.3 to 3 times higher in women using HRT than in those who do not, especially during the first year of treatment.
Venous thromboembolism can be serious. 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 these 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 therapy
• History of blood clots in the legs, lungs, or another organ in a close relative
• Systemic lupus erythematosus
• Cancer.

Symptoms of venous thromboembolism are listed in the section "Stop using Oekolp and contact your doctor immediately".

Comparison
Among women over 50 years of age not using HRT, approximately 4 to 7 out of 1,000 women can be expected to develop venous thrombosis over a 5-year period.
Among women over 50 using estrogen-only HRT for more than 5 years, the number increases to 5 to 8 per 1,000 women (i.e. 1 additional case).

Heart disease (myocardial infarction)
In women using estrogen-only HRT, the risk of 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 increases with age.

Comparison
It is estimated that among women over 50 not using HRT, about 8 out of 1,000 women will experience a stroke over 5 years. Among women of the same age using HRT, the rate is 11 per 1,000 women over 5 years (i.e. 3 additional cases).

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

Oekolp and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription, herbal medicines, or other natural products. Also inform any other healthcare professionals prescribing or dispensing medicines that you are using Oekolp.
Some medicines may affect the effectiveness of Oekolp, and Oekolp may interfere with the action of other medicines, potentially causing 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)

HRT may affect the way some other medicines work:

• Antiviral treatments for hepatitis C (HCV) (such as combination regimens with ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin; glecaprevir/pibrentasvir; or sofosbuvir/velpatasvir/voxilaprevir) may cause increased liver function parameters in blood tests (elevated liver enzyme AlAT activity) in women using combined hormonal contraceptives containing ethinylestradiol. Oekolp contains estriol instead of ethinylestradiol. It is not known whether elevated AlAT activity may occur when Oekolp is used concurrently with such combination HCV treatments.

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

Oekolp with food and drink
Food and drink do not affect the effectiveness of Oekolp treatment.

Pregnancy and breastfeeding
Oekolp is intended for use only in postmenopausal women.

Pregnancy
If you become pregnant, stop using Oekolp and contact your doctor.

Breastfeeding
Women who are breastfeeding should consult their doctor before using Oekolp.

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

Oekolp contains propylene glycol
This medicine may cause skin irritation.

3. How to use Oekolp

This medicine should always be used as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.

For atrophic conditions of the lower urogenital tract, the usual dose is 0.5 g
of cream (½ the volume of the applicator) once daily for the first weeks (maximum 4 weeks), after which
the dose should be gradually reduced to 0.5 g of cream (½ the volume of the applicator) twice weekly.
If necessary, the dose may exceptionally be increased to a maximum of 1 g per day (full applicator volume,
corresponding to 1 mg of estriol). This dose (1 g of cream per day) must not be exceeded.

The cream is administered intravaginally using the supplied reusable applicator, in a lying position.
Alternatively, when applying to external genital organs, a thin layer of cream should be applied to the affected
areas and gently rubbed in with the fingers.

To improve wound healing in postmenopausal women undergoing vaginal procedures, the usual regimen is
0.5 g of cream daily (½ the volume of the applicator) for 2 weeks prior to the procedure, followed by
0.5 g of cream (½ the volume of the applicator) twice weekly for 2 weeks after the procedure.

To facilitate interpretation of cervical smear results in postmenopausal women, the usual regimen is
0.5 g of cream (½ the volume of the applicator) every other day during the week preceding the smear test.

Oekolp is best administered deeply into the vagina in the evening before bedtime, using the applicator (Fig.
1–3).

The applicator consists of a green plunger and a barrel with a narrow chamber for the cream.
There are ridges at various points on the plunger that cause it to stop at these points and can only be moved
further by overcoming slight resistance. The first ridge is located near the handle of the applicator and
does not yet indicate a dose.

To administer 0.5 g of cream (½ the applicator's capacity), the green plunger
should be pulled out approximately halfway until slight resistance is felt. The plunger will then
protrude from the applicator by about 6 cm. To administer 1 g of cream (full applicator), the plunger
should be pulled out completely, i.e., until it stops. The plunger will then protrude from the applicator
by about 10 cm. Next, open the tube and place the applicator, with its wide end, onto the tube (1).
Squeezing the tube fills the applicator with cream (2).
Then remove the applicator from the tube and gently insert it as deeply as possible into the vagina,
while lying down with legs slightly apart. By gently pressing the green plunger, the cream is released
into the vagina (3). The plunger should be inserted into the body only up to the last ridge. It will then
protrude by approximately 2 cm.

After use, the applicator should be washed in warm water for about 30 seconds. The green plunger
may be removed during cleaning. To do this, press the rounded end of the plunger into the applicator
(overcoming slight resistance) and pull it completely out from the opposite side (the wide end of the applicator).

After cleaning and drying, reinsert the green plunger with its rounded end into the wider end of the applicator
and push it completely into the applicator until it can be pulled out again from the narrower side.
In this case, slight resistance must again be overcome (4). The applicator is now ready for reuse.

When applying to external genital organs, apply a thin layer of the appropriate amount (½ the applicator's capacity) of cream.

Before each reuse, inspect the applicator for visible damage. An applicator with visible damage must not be reused.
It should be discarded with household waste.

The treating physician 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 Oekolp is too strong or too weak, consult your doctor.

Use of more than the recommended dose of Oekolp
If more than the recommended dose is used, consult a doctor or pharmacist immediately.
Accidental ingestion of the cream does not pose a health or life hazard. Nevertheless, inform the doctor.
Symptoms of overdose are most commonly nausea and vomiting; in women, vaginal bleeding may also occur after a few days.

Missed dose of Oekolp
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 previously established dosing schedule.

Stopping treatment with Oekolp
If treatment is interrupted, consult your doctor on how to resume the medication.

Need for surgery
Patients scheduled for surgery should inform the surgeon that they are using Oekolp.
It may be necessary to discontinue the medication approximately 4 to 6 weeks before surgery to reduce the risk
of blood clots (see section 2 "Venous thromboembolism (venous thrombosis)"). Ask your doctor when you may
resume using Oekolp.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them.
The following conditions are more frequently reported in women using hormone replacement therapy (HRT) medicines that circulate in the bloodstream, compared to women who do not use HRT. This risk is lower with medicines administered vaginally, such as Oekolp:

• ovarian cancer
• presence of blood clots in the veins of the legs or lungs (venous thromboembolic disease)
• stroke
• possible memory loss when starting HRT after the age of 65.

For more information on adverse effects, see section 2.
Depending on the doses used and the patient's sensitivity, the following adverse effects may occur:

• swelling and increased tenderness of the breasts
• slight vaginal bleeding
• increased vaginal discharge
• nausea
• fluid retention in tissues, usually manifesting 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 medicines in hormone replacement therapy:

• inflammation of the gallbladder
• various skin disorders:
  • skin pigmentation changes, especially on the face or neck (chloasma)
  • painful red nodules on the skin (erythema nodosum)
  • rash with target-shaped red lesions or erosions (erythema multiforme).

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist.
Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the 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.
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store the medicine Oekolp

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the tube and carton after: "Expiry date". The expiry date refers to the last day of the stated month.
Store the medicine below 25°C.
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 package and other information

What Oekolp contains

• The active substance is estriol at a concentration of 1 milligram per gram.
• The other ingredients are: dequalinium chloride, sodium docosanoyl lactylate, propylene glycol, dimethicon 350, self-emulsifying glyceryl monostearate, medium-chain saturated triglycerides, Softisan 601 consisting of 80–90% mono-, di-, and triglyceride esters of saturated fatty acids (C–C) and 10–20% macrogol cetostearyl ether, purified water.

What Oekolp looks like and contents of the pack
A homogeneous, white cream. Supplied in an aluminum tube with a plastic applicator, packed in a cardboard box.
The pack contains 25 g of cream.

Marketing Authorisation Holder and Manufacturer
DR. KADE Pharmazeutische Fabrik GmbH
Rigistrasse 2
12277 Berlin
Germany

For further information, contact the representative of the Marketing Authorisation Holder:
Kadefarm Sp. z o.o.
Sierosław, ul. Gipsowa 18
62-080 Tarnowo Podgórne, Poland
Tel.: +48 61 862 99 43
e-mail: [email protected]