Donaflore

Package leaflet: Information for the patient

DONAFLOR 50 mg + 30 micrograms vaginal tablets

Lactobacillus acidophilus and estriol
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Donaflor is and what it is used for

DONAFLOR belongs to a group of medicines called vaginal Hormone Replacement Therapy (HRT). It is used to relieve menopausal symptoms in the vagina, such as dryness or irritation, which in medical terms is described as “vaginal atrophy” and is caused by a decrease in estrogen levels in your body. This occurs naturally after menopause. DONAFLOR works by replacing the estrogens normally produced by a woman's ovaries. It is inserted into the vagina, so that the hormone is released exactly where needed. This can reduce vaginal discomfort.
Donaflor contains the active substances Lactobacillus acidophilus (which has a protective function with respect to the vagina) and estriol (a sex hormone).
Donaflor is used for:

• vaginal discharge of unknown origin (vaginal secretion) or mild to moderate cases of bacterial infection of the vagina (vaginosis), when the use of antibiotic medicines is not entirely necessary.
• restoration of the vaginal bacterial flora (lactobacilli) after local and/or systemic treatment with antibiotic or chemotherapeutic medicines.
• inflammation of the vaginal mucosa due to deficiency of the sex hormone estrogen during menopause and post-menopause (atrophic vaginitis), or as concomitant treatment during systemic hormone replacement therapy. Donaflor may also be used as a preventive treatment to reduce the recurrence of candida infections (a fungus).

2. What you should know before using Donaflor

Personal medical history and routine medical check-ups
Hormone Replacement Therapy (HRT) carries risks that must be considered when deciding whether to start or continue treatment.
Experience in treating women with premature menopause (caused by ovarian failure or surgical intervention) is limited. If you have premature menopause, the risks of HRT may differ. Please discuss this with your doctor.
Before starting (or restarting) HRT, your doctor will ask about your personal and family medical history. Your doctor may decide to perform a clinical examination, which could include a breast examination and/or, if necessary, an internal examination.
Once you have started treatment with DONAFLOR, you should see your doctor for regular check-ups (at least once a year). During these visits, discuss with your doctor the benefits and risks of continuing DONAFLOR.
Have regular medical check-ups for your breasts, as recommended by your doctor.

Do not use Donaflor
If any of the following conditions apply to you. If you are unsure about any of the points listed below, speak with your doctor before taking Donaflor.
Do not take Donaflor:

• If you have or have ever had breast cancer, or if you suspect you may have it;
• If you have a tumour sensitive to oestrogens, such as cancer of the lining of the womb (endometrium), or if you suspect you may have it;
• If you have unexplained vaginal bleeding;
• If you have untreated excessive thickening of the lining of the womb (endometrial hyperplasia);
• If you have or have ever had a blood clot in a vein (thrombosis), for example in the legs (deep vein thrombosis) or lungs (pulmonary embolism);
• If you have a blood clotting disorder (such as deficiency of protein C, protein S or antithrombin);
• If you have or have recently had a disease caused by blood clots in the arteries, such as a heart attack (myocardial infarction), stroke or angina;
• If you have or have ever had liver disease and liver function tests have not returned to normal;
• If you have a rare inherited blood disorder called "porphyria";
• If you are allergic (hypersensitive) to oestriol or any of the other ingredients of DONAFLOR (listed in section 6);
• If you have severe purulent vaginal inflammation;
• If you are a young woman before sexual maturity.

If any of the above conditions occurs for the first time while using Donaflor, stop using it immediately and consult your doctor without delay.

When to be particularly cautious with Donaflor
Inform your doctor if you have ever had any of the following conditions before starting treatment, as they may recur or worsen during therapy with Donaflor. In such cases, you should have more frequent medical check-ups:

• Fibroids in the uterus;
• Growth of the uterine lining outside the uterus (endometriosis) or a history of excessive growth of the uterine lining (endometrial hyperplasia);
• Increased risk of developing blood clots (see "Blood clots in a vein (thrombosis)");
• Increased risk of developing an oestrogen-sensitive cancer (e.g. if your mother, sister or grandmother had breast cancer);
• High blood pressure;
• Liver disease, such as benign liver tumour;
• Diabetes;
• Gallstones (biliary);
• Migraine or severe headache;
• An autoimmune disease affecting multiple organs (systemic lupus erythematosus, SLE);
• Epilepsy;
• Asthma;
• A disease affecting the eardrum and hearing (otosclerosis);
• Very high levels of fat in the blood (triglycerides);
• Fluid retention due to heart or kidney problems;
• Hereditary or acquired angioedema.

Stop treatment with Donaflor and consult a doctor immediately
If you experience any of the following conditions during Hormone Replacement Therapy (HRT) with Donaflor:

• Any of the conditions listed under "Do not use Donaflor";
• 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 associated with breathing difficulties, indicative of angioedema;
• A marked increase in blood pressure (symptoms may include headache, fatigue, dizziness);
• A new-onset migraine-type headache;
• If you become pregnant;
• If you notice signs of a blood clot, such as:
  • Painful swelling and redness in the legs;
  • Sudden chest pain;
  • Difficulty breathing. For further information, see "Blood clots in a vein (thrombosis)".

Note: Donaflor 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 still use additional contraception to prevent pregnancy. Speak with your doctor for advice.

Hormone Replacement Therapy (HRT) and cancer

Excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the lining of the womb (endometrial carcinoma)
Long-term use of oestrogen-only HRT tablets may increase the risk of developing cancer of the lining of the womb (endometrium).
It is not certain whether a similar risk exists with Donaflor when used repeatedly or for long-term treatment (more than one year). However, Donaflor has shown very low systemic absorption into the bloodstream, so the addition of a progestogen is not required.

If you experience bleeding or spotting, it is usually not a cause for concern, but you should make an appointment to see your doctor. It could be a sign that your uterine lining (endometrium) has become thicker.

The following risks apply to systemic HRT medicines that circulate in the bloodstream. However, Donaflor is intended for local vaginal treatment and has very low systemic absorption. It is less likely that the conditions listed below will worsen or recur during treatment with Donaflor, but you should consult your doctor if you are concerned.

Breast cancer
Evidence suggests that the use of Donaflor does not increase the risk of breast cancer in women who have never had breast cancer. It is not known whether Donaflor can be used safely in women who have previously had breast cancer.
Check your breasts regularly. Consult your doctor if you notice any changes such as:

• Skin dimpling;
• Changes in the nipple;
• Any lumps that you can see or feel. In addition, you are advised to participate in mammographic screening programmes when offered.

Ovarian cancer
Ovarian cancer is rare, much rarer than breast cancer. The use of oestrogen-only Hormone Replacement Therapy (HRT) has been associated with a slight increase in the risk of ovarian cancer.
The risk of ovarian cancer varies with age. For example, among women aged 50 to 54 who do not take HRT, about 2 in 2000 will be diagnosed with ovarian cancer over a 5-year period. Among women who have taken HRT for 5 years, there will be about 3 cases per 2000 users (i.e. about 1 additional case).

Effect of Hormone Replacement Therapy (HRT) on the heart and circulation

Blood clots in a vein (thrombosis)
The risk of venous blood clots is approximately 1.3 to 3 times higher in users of HRT compared to non-users, especially during the first year of use.
Venous blood clots can be serious; if one travels to the lungs, it can cause chest pain, shortness of breath, fainting or even death.
The likelihood of developing a venous blood clot increases with age and if any of the following conditions apply to you. Inform your doctor if any of these situations apply to you:

• You are unable to walk for prolonged periods due to surgery, injury or serious illness (see also section 3, "If you need surgery");
• You are severely overweight (BMI >30 kg/m²);
• You have a blood clotting disorder requiring long-term treatment with anticoagulant medication;
• A close relative has ever had a blood clot in the leg, lung or another organ;
• You have systemic lupus erythematosus (SLE);
• You have cancer.

For symptoms of a blood clot, see "Stop using Donaflor and consult a doctor immediately".

Comparison
Among women in their fifties who do not use HRT, on average, 4 to 7 out of 1000 are expected to develop a venous blood clot over a 5-year period.
Among women in their fifties taking oestrogen-only HRT for more than 5 years, there will be 5 to 8 cases per 1000 users (i.e. 1 additional case).

Heart disease (heart attack)
For women taking oestrogen-only therapy, there is no increased risk of developing heart disease.

Stroke
The risk of stroke is approximately 1.5 times higher in users of Hormone Replacement Therapy (HRT) compared to non-users. The number of additional stroke cases due to HRT use increases with age.

Comparison
Among women in their fifties who do not use HRT, on average, 8 out of 1000 are expected to have a stroke over a 5-year period. Among women in their fifties taking HRT, there will be 11 cases per 1000 users over 5 years (i.e. 3 additional cases).

Other conditions

• Hormone Replacement Therapy does not prevent memory loss. There is some evidence of an increased risk of memory loss in women who start HRT after age 65. Speak with your doctor for advice.

Other medicines and Donaflor
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including over-the-counter medicines, herbal remedies or other natural products, and if you are using other locally applied vaginal treatments.
Do not use vaginal washes or douches during treatment with Donaflor.
Concomitant treatment with anti-infectives (e.g. local or systemic antibiotics) may reduce the effectiveness of Donaflor.

Donaflor with food, drinks and alcohol
Due to the topical use and local action of Donaflor, interactions with food, drinks or alcohol are not expected.

Pregnancy, breastfeeding and fertility
If you become pregnant, stop taking Donaflor and contact your doctor. Donaflor is contraindicated during pregnancy and breastfeeding (see section: Stop treatment with Donaflor and consult a doctor immediately).
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Driving and using machines
Donaflor has no or negligible effect on the ability to drive or operate machinery.

3. How to use Donaflor

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. Your doctor will aim to prescribe the lowest effective dose necessary to treat your symptoms and for the shortest possible duration. Speak with your doctor if you think the dose is too strong or not strong enough.

Vaginal discharge, vaginal infections, treatment to restore vaginal bacterial flora:
The recommended dose is:

• 1-2 vaginal tablets daily for 6-12 days.

Interrupt treatment during menstruation and resume treatment immediately afterwards.

Atrophic vaginitis (inflammation of the vaginal mucosa), postmenopausal vaginal discharge:
The recommended dose is:

• 1 vaginal tablet daily during the first week, followed by a maintenance dose of 1 vaginal tablet once or twice a week.

Use in children and adolescents
Donaflor must not be used in young women who have not yet reached sexual maturity.

Method of administration
For vaginal use.

The vaginal tablets should be inserted deeply into the vagina at bedtime. It is best to insert the tablet while lying down, with knees bent slightly.

If the vagina is very dry, the vaginal tablets may be moistened with a small amount of water before insertion to aid disintegration.

Undissolved tablet residues:
Donaflor contains components that do not dissolve completely; undissolved remnants of the tablet may occasionally be found in underwear. This does not affect the medicine's effectiveness.

If you use more Donaflor than you should
If you accidentally use an excessive dose of Donaflor, contact your doctor immediately or go to the nearest hospital.

If you are scheduled for surgery
If you are scheduled for surgery, inform your surgeon that you are using Donaflor. It may be necessary to stop using Donaflor approximately 4-6 weeks before surgery to reduce the risk of blood clots (see section 2, Blood clots in a vein). Ask your doctor when you can start using Donaflor again.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
The following side effects, listed by frequency, have been observed with Donaflor:
Uncommon side effects (may affect up to 1 in 100 people):

• Sensation of mild stinging or burning (immediately after administration)

Rare side effects (may affect up to 1 in 1,000 people):

• Vulvovaginal itching
• Allergic reaction with redness and itching

An allergy to the lactobacillus lyophilisate contained in Donaflor has been reported in one case.
With incorrect use of the medicine, isolated cases of adverse events have been reported following oral ingestion, such as vomiting (1), diarrhoea (1), increased menstruation (1), and stomach burning (1).
The following conditions are reported more frequently in women using systemic hormone replacement therapy (HRT) medicines than in women not using HRT.
These risks are less common with treatments administered vaginally, such as Donaflor:

• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• stroke;
• possible memory loss if hormone replacement therapy is started after the age of 65. For further information on these side effects, see section 2.

The following side effects have been reported with other HRTs:

• gallbladder disease
• various skin disorders:
  • skin discolouration, particularly on the face or neck, known as “pregnancy spots” (chloasma);
  • painful red skin nodules (erythema nodosum);
  • skin rash with redness or sores in a target-like pattern (erythema multiforme).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Donaflor

Keep this medicine out of the 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 that month.
Store in a refrigerator (2°C – 8°C) in the original packaging to protect the medicine from light and
moisture.
Storage of Donaflor at room temperature during the treatment period (1-2 weeks) does not
affect the product's efficacy.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Donaflor contains

• The active substances are Lactobacillus acidophilus ATCC 4356: 50.0 mg of lyophilisate containing at least 100 million live bacteria, and estriol 30 micrograms.
• The other components are lactose, microcrystalline cellulose, magnesium stearate, sodium starch glycolate, disodium phosphate.

Description of the appearance of Donaflor and package contents
Vaginal tablets. Pack sizes: 6 and 12 vaginal tablets.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Exeltis Italia s.r.l. – Via Lombardia, 2/a – 20068 Peschiera Borromeo (MI) - Italy
Manufacturer:
Haupt Pharma Amareg GmbH – Donaustaufer Strasse 378; DE-93055 Regensburg, Germany