Gynoflor

Patient Information Leaflet

Gynoflor
50 mg + 0.03 mg, vaginal tablets
(Lactobacillus acidophilus + Estriolum)
Please read 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 questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents

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

1. What Gynoflor is and what it is used for

Gynoflor contains active substances identical to those naturally present in
the healthy female vagina. A healthy vagina maintains biological balance and has natural
defensive mechanisms protecting it against infections. The main component of these defense mechanisms
is live bacteria Lactobacillus acidophilus, which produce lactic acid and other substances with
antimicrobial activity. The production of lactic acid creates an acidic environment favorable for
the growth of lactobacilli and inhibiting the growth of pathogenic microorganisms.

Disruption or destruction of the vaginal flora containing lactobacilli may occur due to
treatment with certain medications (e.g. antibiotics), local infections, systemic illness, or
poor hygiene (vaginal douching and showering). Gynoflor contains live
lactic acid bacteria in a high dose, which helps restore the natural flora of the vagina.

In addition to natural vaginal flora, a healthy vaginal epithelium is also important for the
natural protective mechanisms of the vagina. The vaginal epithelium may become damaged
due to hormonal fluctuations or hormone deficiency (particularly in the perimenopausal and postmenopausal period) and vaginal infections.

As a second active substance, Gynoflor contains estriol, a natural female sex hormone.
Estriol, even in the very low dose contained in Gynoflor, promotes regeneration of the vaginal epithelium, ensures adequate blood supply, proper thickness, elasticity, and moisture. This also supports the growth of lactic acid bacteria in the vagina.

Lactobacillus acidophilus and estriol exert their action locally within the vagina.

Lactose, used in the manufacture of vaginal tablets, may also be rapidly fermented into lactic acid by lactic acid bacteria. Multiplication of lactobacilli and re-colonization of the vagina with these bacteria begins already after the first application of the medicine.

Gynoflor belongs to a group of medicines known as Hormone Replacement Therapy (HRT) for vaginal administration.

Gynoflor is used:

• to restore Lactobacillus acidophilus flora after local or systemic treatment with antimicrobial or chemotherapeutic agents.
• 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 naturally occurs after menopause. Gynoflor acts by replacing 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 alleviate vaginal discomfort.
• for the treatment of vaginal discharge of unknown origin (leucorrhea), and for the treatment of mild to moderate cases of vaginal infection when there is no absolute necessity for antimicrobial chemotherapy.

2. Important information before using Gynoflor

Medical history and regular check-ups
Hormone replacement therapy (HRT) carries risks that should be considered when a woman decides whether to start or continue HRT.
Experience in treating women in early menopause (due to ovarian failure or surgical intervention) is limited. If a woman experiences early menopause, the risks associated with HRT may differ. Please consult your doctor.
Before starting (or resuming) HRT, your doctor should take a full medical and family history. Your doctor may decide to perform examinations such as breast examination and/or gynecological examination, if necessary.
If you start treatment with Gynoflor, you should consult your doctor at least once a year. During follow-up visits, you should discuss with your doctor the benefits and risks of continuing Gynoflor treatment.
Women should undergo regular breast screening examinations as recommended by their doctor.

When to exercise particular caution when using Gynoflor
Before starting treatment, inform your doctor if you currently have or have previously had any of the following conditions, as they may recur or worsen during Gynoflor treatment. In such cases, your doctor may recommend more frequent monitoring:

• uterine fibroids;
• endometriosis (endometrial tissue outside the uterine cavity) or past history of excessive endometrial proliferation (endometrial hyperplasia);
• increased risk of blood clots (see "Venous blood clots (venous thromboembolism)");
• increased risk of estrogen-dependent tumors (e.g. breast cancer in mother, sister, or grandmother);
• high blood pressure;
• liver disease, e.g. benign liver tumor;
• diabetes;
• gallstones;
• migraine or severe headaches;
• systemic autoimmune disease affecting multiple organs – systemic lupus erythematosus;
• epilepsy;
• asthma;
• disease affecting the eardrum and hearing (otosclerosis);
• very high levels of fats (triglycerides) in the blood;
• fluid retention due to impaired heart or kidney function;
• hereditary or acquired angioedema.

When not to use Gynoflor
Do not use Gynoflor if any of the following conditions apply. If you are unsure whether any of the following points apply to you, you should consult your doctor before starting Gynoflor.

• if breast cancer has been diagnosed, occurred previously, or is suspected;
• if an estrogen-dependent tumor has been diagnosed or is suspected, e.g. endometrial cancer (cancer of the endometrium);
• if unexplained vaginal bleeding has occurred;
• if excessive thickening of the endometrium (endometrial hyperplasia) has been diagnosed and has not been treated;
• if venous blood clots (thrombosis) have been diagnosed or occurred previously, e.g. in the legs (deep vein thrombosis) or lungs (pulmonary embolism);
• if a blood clotting disorder is present (e.g. protein C, protein S or antithrombin deficiency);
• if a disease caused by arterial blood clots is present or has recently occurred, e.g. myocardial infarction, stroke, or angina pectoris;
• if phlebitis is present or has occurred previously;
• if problems occurred during previous use of estrogen-containing medications;
• if liver disease has been diagnosed or occurred previously and liver function tests have not returned to normal;
• if jaundice is present or occurred during pregnancy;
• if a rare inherited blood disorder – porphyria – has been diagnosed;
• if liver diseases known as Rotor syndrome or Dubin-Johnson syndrome have been diagnosed (both are inherited syndromes in which the liver cannot properly excrete bilirubin);
• if cerebrovascular disease or coronary artery disease has been diagnosed;
• if congenital deafness known as otosclerosis is present;
• if endometriosis (endometrial tissue outside the uterus) is present or suspected;
• if the patient has not reached sexual maturity;
• if hypersensitivity (allergy) to estriol, Lactobacillus acidophilus, or any of the other ingredients of this medicine (listed in section 6) has been diagnosed.

If any of the above conditions occurs for the first time during treatment with Gynoflor, stop using the medicine immediately and contact your doctor as soon as possible.

Warnings and precautions
Before using Gynoflor, discuss this with your doctor or pharmacist.
Breast tenderness or increased vaginal discharge may indicate that the estrogen dose is too high.
In elderly patients, Gynoflor should be used with particular care, especially if the following conditions are present:
heart failure, kidney or liver dysfunction, hypertension, epilepsy, migraine, history of thromboembolic disorders, endometriosis, fibrocystic breast disease, or diabetes.

Stop using Gynoflor and contact your doctor immediately
if any of the following conditions occur during treatment with Gynoflor:

• occurrence of any of the conditions listed under "When not to use Gynoflor" above;
• yellowing of the skin or eyes (jaundice). These may be symptoms of liver disease;
• swelling of the face, tongue and/or throat and/or difficulty swallowing, or hives including breathing difficulties, suggesting angioedema;
• significant increase in blood pressure (symptoms include headache, fatigue, and dizziness);
• a new onset of migraine headache;
• pregnancy;
• if symptoms of blood clots occur, such as:
  • painful swelling and redness in the legs,
  • sudden chest pain,
  • difficulty breathing. For more information, see "Venous blood clots (venous thromboembolism)".

Note: Gynoflor is not a contraceptive. If less than 12 months have passed since the last menstrual period or if the patient is under 50 years of age, additional contraception may be necessary. Please consult your doctor.

HRT and cancer
Endometrial hyperplasia and endometrial cancer
Long-term use of oral HRT containing only estrogen may increase the risk of developing endometrial cancer.
It is not known whether a similar risk exists with repeated or prolonged (longer than one year) use of Gynoflor. However, Gynoflor is minimally absorbed into the bloodstream and therefore the addition of 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.
The risks described above apply to systemic HRT medicines that enter the bloodstream. Gynoflor is administered locally via the vaginal route and is very poorly absorbed into the blood. It is less likely that the conditions listed below will worsen or recur during treatment with Gynoflor, but if in doubt, consult your doctor.

Breast cancer
Data indicate that using Gynoflor does not increase the risk of breast cancer in women who have never previously had the disease. It is not known whether Gynoflor can be safely used in women who have had breast cancer.

Regularly examine your breasts. Contact your doctor if you notice any of the following changes:

• skin indentation,
• changes in the nipple,
• presence of lumps that are visible or palpable.

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 depends on age. For example, among women aged 50 to 54 years 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 have used HRT for 5 years, it occurs in about 3 out of 2000 women (i.e. about 1 additional case).

Effect of HRT on the heart and circulation
Venous blood clots (venous thromboembolism)
The risk of venous blood clots is 1.3 to 3 times higher in women using HRT compared to non-users, especially during the first year of use.
Venous blood clots can have serious consequences and, if they travel to the lungs, may cause chest pain, shortness of breath, loss of consciousness, or even death.
The risk of venous blood clots is higher if the patient is older or if any of the following situations apply. Inform your doctor if any of the following apply to you:

• inability to walk for prolonged periods due to major surgery, injury, or illness (see also section 3, "If surgery is planned");
• significant obesity (BMI > 30 kg/m²);
• thromboembolic disorders requiring long-term anticoagulant therapy;
• history of blood clots in the legs, lungs, or other organs in the patient or a close family member;
• systemic lupus erythematosus;
• cancer diagnosis.

If symptoms of blood clots occur, see "Stop using Gynoflor and contact your doctor immediately".

Comparison
Among women aged 50 to 59 years who do not use HRT, the estimated number of venous blood clots over 5 years is 4 to 7 per 1000 women.
Among women aged 50 to 59 years using estrogen-only HRT for more than 5 years, the number is 5 to 8 per 1000 (i.e. 1 additional case).

Heart disease (myocardial infarction)
There is no increased risk of heart disease in women using estrogen-only HRT.

Stroke
The risk of stroke is approximately 1.5 times higher in women using HRT compared to non-users. The number of additional stroke cases due to HRT use increases with age.

Comparison
Among women aged 50 to 59 years who do not use HRT, the average number of strokes over 5 years is estimated at 8 per 1000 women. Among women aged 50 to 59 years using HRT, the number is 11 per 1000 over 5 years (i.e. 3 additional cases).

Other conditions
HRT does not prevent memory loss. The risk of possible memory loss may be somewhat higher in women who start HRT after age 65. Consult your doctor.

Gynoflor and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, including over-the-counter medicines, herbal remedies, or other natural products.
Concurrent use of antimicrobial agents (e.g. locally or systemically acting antibiotics) may reduce the effectiveness of Gynoflor.

Specific interactions with other medicines
The likelihood of interactions with other medicines is low because Gynoflor is administered locally via the vaginal route.
Gynoflor may affect other locally administered vaginal treatments, but the probability of interactions with other medicines is low.
Do not use vaginal douches or irrigations during treatment with Gynoflor.

Gynoflor with food and drink
Food and drink do not affect the use of Gynoflor.

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy
Do not use Gynoflor if you are pregnant.
If you become pregnant, stop using Gynoflor immediately and contact your doctor.
Based on limited experience with the components of Gynoflor during pregnancy, there is no evidence of adverse effects on pregnancy or the fetus/newborn. Both active substances, Lactobacillus acidophilus and estriol, occur naturally in the human body, and after administration of Gynoflor, their concentrations are not higher than those found in healthy postmenopausal women.

Breastfeeding
Do not use Gynoflor during breastfeeding.

Driving and operating machinery
The effect of Gynoflor on driving or operating machinery is unknown.

3. How to use Gynoflor

Use Gynoflor exactly as directed by your doctor. If in doubt, consult your doctor.
Your doctor will select the lowest effective dose for the shortest possible duration necessary to treat your symptoms.
If you feel that the effect of Gynoflor is too strong or too weak, consult your doctor or pharmacist.

For restoring the normal vaginal environment and in cases of vaginal discharge (leucorrhoea):
1–2 vaginal tablets per day for 6 to 12 days.

For atrophic vaginitis:
1 vaginal tablet per day for 6 to 12 days, followed by 1 tablet 1–2 times per week as maintenance therapy.

Instructions for use
Insert the vaginal tablets deeply into the vagina in the evening, before going to bed. It is best to lie down with knees slightly bent.
During menstruation, treatment should be interrupted and resumed after menstrual bleeding has stopped.

Gynoflor contains ingredients that do not dissolve completely. Therefore, remnants of the tablet may occasionally be noticed on underwear. This does not affect the efficacy of Gynoflor.
In rare cases of severe vaginal dryness, the vaginal tablet may not dissolve at all and may be expelled from the vagina in an unchanged form. In such cases, treatment is not optimal. However, this is not harmful to the vagina. To avoid this situation, the tablet may be moistened with a small amount of water before insertion into a very dry vagina.

During treatment with Gynoflor, use sanitary pads.

If Gynoflor is accidentally taken orally
If Gynoflor is accidentally taken by mouth, no adverse effects are expected.

If surgery is required
If you are scheduled for surgery, inform the surgeon that you are using Gynoflor. It may be necessary to stop using Gynoflor approximately 4 to 6 weeks before surgery to reduce the risk of venous thrombosis (see section 2, "Blood clots in veins"). Ask your doctor when you can resume using Gynoflor.

Use of more than the recommended dose of Gynoflor
If too many vaginal tablets are used, no adverse effects are expected, but you should inform your doctor.

Missed dose of Gynoflor
Do not use a double dose to make up for a missed dose.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although they do not occur in everyone.
Shortly after application of Gynoflor, a slight burning or stinging sensation may be felt (in 1% of patients).
There is no need to discontinue treatment in such cases. However, if discomfort persists, medical advice should be sought as soon as possible.
In rare cases, intolerance reactions such as redness and itching have been reported.
One case of allergy to the Lactobacillus lyophilisate contained in Gynoflor has been reported.
In such cases, medical advice should be sought as soon as possible.
The following diseases are reported more frequently in women taking systemic HTZ circulating in the bloodstream compared to women not using HTZ. This risk is lower with vaginal products such as Gynoflor:

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

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist, or nurse.
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: +48 22 49 21 301
Fax: +48 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 Gynoflor

Keep this medicine out of sight and reach of children.
Store between 2°C and 8°C.
Vaginal tablets may be stored at room temperature during the recommended treatment period, for a period of 6 to 12 days.
Do not use this medicine after the expiry date stated on the carton and blister pack following EXP. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the package and other information

What Gynoflor contains
The active substances are: 50 milligrams of lyophilized lactic acid bacteria (Lactobacillus acidophilus) and 30 micrograms of estriol (Estriolum).
The other ingredients are: lactose monohydrate, microcrystalline cellulose, anhydrous disodium phosphate, magnesium stearate (E470b), sodium carboxymethyl starch (type A).

What Gynoflor looks like and contents of the pack
White to beige spotted oval, biconvex vaginal tablets.
6 tablets in a blister.
1 or 2 blisters in a cardboard box.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
GEDEON RICHTER POLSKA Sp. z o.o.
ul. Ks. J. Poniatowskiego 5
05-825 Grodzisk Mazowiecki
Poland

Manufacturer
Haupt Pharma Amareg GmbH
Donaustaufer Str. 378
93-055 Regensburg
Germany

For further information about this medicine, please contact:
GEDEON RICHTER POLSKA Sp. z o.o.
Medical Department
ul. Ks. J. Poniatowskiego 5
05-825 Grodzisk Mazowiecki
Poland
Tel. +48 (22)755 96 48
[email protected]