PACKAGE LEAFLET: INFORMATION FOR THE USER

DUFASTON 10 mg film-coated tablets

dydrogesterone
PLEASE READ THIS LEAFLET CAREFULLY BEFORE USING THIS MEDICINE

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. Never give it to other people, even if their symptoms are the same as yours, because it could be harmful.
If any of the side effects worsens, or if you notice any side effect not listed in this leaflet, inform your doctor or pharmacist.

The full name of the medicine is Dufaston 10 mg film-coated tablets. In this leaflet, the abbreviated name "Dufaston" is used.
Contents of this leaflet:

What DUFASTON is and what it is used for
What you need to know before taking DUFASTON
How to use DUFASTON
Possible side effects
How to store DUFASTON
Contents of the pack and other information.

1. WHAT IS DUFASTON AND WHAT IS IT USED FOR

What is Dufaston
DUFASTON contains a medicine called dydrogesterone.

Dydrogesterone is a synthetic hormone.
It is very similar to the natural hormone progesterone produced by the body.
Medicines like Dufaston are called progestogens.

What Dufaston is used for
Dufaston may be taken alone or together with estrogens. Whether you also need to take an estrogen depends on the reason why you are taking Dufaston.
Dufaston is used:

To treat symptoms of menopause (this treatment is known as hormone replacement therapy or HRT)
- These symptoms vary from woman to woman.
- They may include hot flushes, night sweats, sleep disturbances, vaginal dryness, and urinary symptoms.
For conditions caused by insufficient production of progesterone in the body:
- Threatened miscarriage and recurrent miscarriage
- Infertility due to low progesterone levels
- Dysmenorrhoea (painful menstruation)
- Endometriosis (when tissue similar to the lining of the uterus grows outside the uterus)
- Irregular menstrual cycles
- Secondary amenorrhoea (absence of menstruation before menopause)
- Functional menometrorrhagia (excessive bleeding during menstruation or bleeding between periods).

How Dufaston works
The body normally balances the levels of the natural hormone progesterone with estrogen (the other main female hormone). If the body does not produce enough progesterone, Dufaston replaces it and restores the balance.
Your doctor may ask you to take estrogens together with Dufaston. This depends on the reason why you are taking Dufaston.
In some women receiving HRT, taking estrogens alone may cause abnormal thickening of the lining of the uterus (endometrium). This risk may also be present even if you do not have a uterus but have a history of endometriosis.
Taking dydrogesterone for part of the menstrual cycle helps prevent thickening of the endometrium.

2. WHAT YOU SHOULD KNOW BEFORE USING DUFASTON

Do not use DUFASTON:
if you are hypersensitive to the active substance or to any of the excipients in Dufaston (listed in
section 6)
if you have experienced vaginal bleeding of unknown cause
if you have or suspect you may have a progesterone-dependent tumour (whose growth is sensitive
to progestogens), such as the brain tumour called meningioma
if you have or have had breast cancer or suspect you may have it
if you have excessive thickening of the uterine wall (endometrial hyperplasia) that is untreated
if you have or have ever had a blood clot in a vein (thrombosis) in your legs (deep vein thrombosis) or in your lungs (pulmonary embolism)
if you suffer from a blood clotting disorder (such as protein C deficiency, protein S deficiency, or antithrombin deficiency)
if you have or have recently had an illness caused by blood clots in the arteries, such as a heart attack, stroke, or angina
if you have or have had liver disease and liver function tests have not returned to normal
if you have a rare inherited blood disorder called "porphyria"
Do not take Dufaston if you are in any of the above conditions. If you are unsure, consult your doctor or pharmacist before taking Dufaston. If any of the conditions listed above occur for the first time during treatment with Dufaston, stop taking it immediately and consult your doctor without delay.
If you are taking Dufaston together with an oestrogen, for example as part of HRT, please read the “Do not use” section in the leaflet of the oestrogen you are taking.

Warnings and precautions
Inform your doctor if you have or have ever had any of the following conditions before starting treatment, as they may recur or worsen during treatment with Dufaston. If this occurs, you should consult your doctor more frequently for check-ups:

fibroids within the uterus
growth of uterine tissue 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 tumour (due to having a mother, sister, or grandmother with breast cancer)
high blood pressure
liver disorder, such as benign liver tumour
diabetes
gallstones
migraine or severe headaches
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

Stop taking Dufaston and see a doctor immediately
if, during HRT, you notice any of the following:

any of the conditions listed in the section "Do not use Dufaston"
yellowing of the skin or whites of the eyes (jaundice). These may be signs of liver disease
a marked increase in blood pressure (symptoms may include headache, fatigue, dizziness)
first occurrence of a headache resembling migraine
pregnancy
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)".

Children and adolescents
Dufaston is not indicated for use in girls before their first menstruation. The efficacy and tolerability of Dufaston in adolescents aged between 12 and 18 years is unknown.

Exercise particular caution with Dufaston:
If you need to take Dufaston for abnormal bleeding, your doctor should investigate the cause of the bleeding before starting treatment with this medicine.

If unexpected bleeding or spotting occurs, it is usually not a cause for concern. This is more likely to occur during the first few months of treatment with Dufaston.
However, schedule an appointment with your doctor promptly if the bleeding or spotting:

continues beyond the first few months
starts after you have been on treatment for some time
continues after stopping treatment. This could indicate that the uterine lining is becoming thicker. Your doctor should investigate the cause of the bleeding or spotting and may perform a test to rule out cancer of the uterine lining.

Before taking Dufaston, discuss with your doctor or pharmacist if you have any of the following conditions:

depression
liver problems
a rare inherited blood disorder called “porphyria”. If you have any of these conditions (or are unsure), talk to your doctor or pharmacist before taking Dufaston. It is particularly important to report whether the conditions listed have worsened during pregnancy or previous hormone therapies. Your doctor may decide to monitor you more closely during treatment. If you notice worsening or recurrence of any of the listed conditions while taking Dufaston, your doctor may discontinue treatment.

Dufaston and HRT
Alongside its benefits, HRT carries certain risks that you and your doctor should consider when deciding whether to take this treatment. If you are taking Dufaston with an oestrogen as part of HRT, the following information is important. Also read the information in the patient leaflet of the oestrogen you are taking.

Premature menopause
Evidence on the risks of HRT used to treat premature menopause is limited. In younger women, the risk level is low. This means that the benefit-risk balance for younger women receiving HRT for premature menopause may be more favourable than for older women.

Medical check-ups
Before starting or restarting HRT, your doctor will ask about your personal and family medical history and may decide to examine your breasts or pelvis (lower abdomen).
Before and during treatment, your doctor may carry out screening tests such as mammography (a breast X-ray). They will advise you how often these tests should be done. Once you start taking Dufaston, you should see your doctor for regular check-ups (at least once a year).

Endometrial cancer and endometrial hyperplasia
Women who have a uterus and take oestrogen-only HRT over a long period have an increased risk of:

endometrial cancer (cancer of the uterine lining)
endometrial hyperplasia (abnormal thickening of the uterine lining). Taking Dufaston together with oestrogen (for at least 12 days in a 28-day cycle) or as continuous combined oestrogen-progestogen therapy can prevent this additional risk.

Breast cancer
Women taking combined oestrogen-progestogen HRT or oestrogen-only HRT have an increased risk of breast cancer. The risk depends on how long HRT is taken. The additional risk of breast cancer becomes evident after about 3 (1–4) years. After stopping HRT, the additional risk will decrease over time, but this risk may persist for 10 years or more if HRT has been used for over 5 years.
Make sure to:

have regular breast examinations (your doctor will tell you how often)
regularly check your breasts for changes such as:
- skin dimpling
- changes in the nipple
- any visible or palpable hardening. If you notice any changes, see your doctor immediately.

Ovarian cancer
Ovarian cancer is rare – much rarer than breast cancer. The use of oestrogen-only therapy or oestrogen-progestogen therapy 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 years not taking HRT, about 2 out of 2,000 will be diagnosed with ovarian cancer within 5 years. Among women taking HRT for 5 years, there will be about 3 cases per 2,000 women treated (i.e., about 1 additional case).

Blood clots in a vein (thrombosis)
HRT increases the risk of venous thrombosis. The risk may be up to three times higher compared to women not taking HRT. The risk is greatest during the first year of treatment.
You are more likely to develop thrombosis if:

you are older
you have cancer
you are very overweight
you are taking an oestrogen
you are pregnant or have recently given birth
you (or your close relatives) have previously had thrombosis affecting the legs or lungs
you are immobile for a long time due to surgery, trauma, or illness (see also Surgery)
you have a condition called “systemic lupus erythematosus” (SLE) – a disease causing joint pain, skin rashes, and fever. If you are in any of the above conditions (or are unsure), ask your doctor whether you can take HRT.

If you experience swelling with pain in your legs, sudden chest pain, or difficulty breathing:

seek medical attention immediately
do not take HRT again until your doctor authorises you to continue. These may be symptoms of venous thrombosis.

Additionally, inform your doctor or pharmacist if you are taking medications to prevent thrombosis (anticoagulants) such as warfarin. Your doctor should carefully evaluate the benefits and risks of taking HRT.

Surgery
If you are scheduled for surgery, inform your doctor before the procedure that you are taking HRT. Do so well in advance. You may need to stop HRT several weeks before surgery. In some cases, you may require additional treatments before and after surgery. Your doctor will tell you when to restart HRT.

Heart disease
HRT does not help prevent heart disease. Women taking oestrogen-progestogen HRT have a slightly increased risk of heart disease compared to those not taking it. The risk of heart disease also increases with age. The number of additional cases of heart disease due to oestrogen-progestogen HRT is very low in healthy women recently entering menopause. The number of additional cases increases with advancing age.
If you experience chest pain spreading to the arm or neck:

seek medical attention immediately
do not take HRT again until your doctor authorises you to continue. The pain could be a symptom of a heart attack.

Stroke
Taking oestrogen-progestogen HRT or oestrogen-only HRT increases the risk of stroke. The risk may be up to 1.5 times higher compared to women not taking HRT. The relative risk between users and non-users does not change with age or time since menopause. The risk of stroke increases with age. This means that the overall risk of stroke in women taking HRT increases with age.
If you experience a sudden, unexplained, severe headache or migraine (with or without vision problems):

seek medical attention immediately
do not take HRT again until your doctor authorises you to continue. This could be an early sign of stroke.

Other conditions
HRT does not prevent memory loss. There is some evidence of an increased risk of memory loss in women who start HRT after age 65. Talk to your doctor for advice.

Other medicines and Dufaston
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription and herbal preparations.
In particular, inform your doctor or pharmacist if you are taking the following medicines.
These medicines may reduce the effect of Dufaston and cause bleeding or spotting:

herbal preparations containing St. John’s wort, sage, or Ginkgo biloba
antiepileptic drugs such as phenobarbital, phenytoin, carbamazepine
drugs for infections such as rifampicin, rifabutin, nevirapine, efavirenz
drugs for HIV/AIDS such as ritonavir, nelfinavir. If you are taking any of these medicines (or are unsure), talk to your doctor or pharmacist before taking Dufaston.

Dufaston with food and water
DUFASTON may be taken regardless of food intake.

Pregnancy, breastfeeding and fertility
Pregnancy
There may be an increased risk of hypospadias (a congenital defect of the penis involving the urinary opening) in children whose mothers took certain progestogens. However, this increased risk is not yet certain. To date, there is no evidence that taking dydrogesterone during pregnancy is harmful. More than 10 million pregnant women have taken Dufaston.

Talk to your doctor before taking Dufaston if you are pregnant.
If you become pregnant or think you might be, consult your doctor. They will discuss with you the benefits and risks of taking Dufaston during pregnancy.

Breastfeeding
If you are breastfeeding, do not take Dufaston. It is not known whether Dufaston passes into breast milk or affects the infant. Studies with other progestogens show that a small amount passes into breast milk.

Fertility
There is no evidence that dydrogesterone reduces fertility when taken as recommended by your doctor.

Driving and using machines
You may experience drowsiness or dizziness after taking Dufaston. This is more common in the first few hours after taking the medicine. If this occurs, do not drive or operate machinery. Wait to see how Dufaston affects you before driving or using machines.

Important information about some excipients in Dufaston
Dufaston contains lactose (milk sugar). If you know you cannot tolerate or digest certain sugars (i.e., have sugar intolerance), discuss this with your doctor before taking this medicine. This may concern rare inherited disorders affecting how the body uses lactose, such as “total lactase deficiency” or “glucose-galactose malabsorption”.

3. HOW TO TAKE DUFASTON

Dufaston should always be taken exactly as prescribed by your doctor. If you are unsure, check with your doctor or pharmacist. Your doctor will adjust the dose according to what is appropriate for you.

Taking the medicine

Swallow each tablet with water.
You may take the tablets with or without food.
If you need to take more than one tablet, divide the doses throughout the day. For example, take one tablet in the morning and one in the evening.
Try to take the tablets at the same time each day. This ensures a constant level of medicine in your body and will also help you remember to take the tablets.
The break line on the tablets is only intended to facilitate breaking the tablet for easier swallowing. It must not be used to take half a tablet.

How many tablets to take
The number of tablets to take and the duration of treatment depend on the reason for your treatment.
If you still have natural menstrual cycles, the first day of your cycle is when bleeding starts. If you no longer have natural cycles, your doctor will determine when the first day of your cycle is and when you should start taking the tablets.

For treating menopausal symptoms

If you are on 'sequential' HRT (you take an oestrogen tablet or use an oestrogen patch every day of the 28-day cycle):
- Take 1 tablet daily.
- Take the tablet during the last 14 days of the 28-day cycle.
If you are on 'cyclic' HRT (you take an oestrogen tablet or use an oestrogen patch for 21 days, followed by a 7-day treatment-free interval):
- Take 1 tablet daily.
- Take the tablet during the last 12–14 days of the oestrogen therapy.
If necessary, your doctor may increase the dose to 2 tablets daily.

Threatened miscarriage:

If you have not previously had a miscarriage:
- Take an initial dose of up to 4 tablets.
- Then take 2 or 3 tablets daily until symptoms have disappeared.

Recurrent miscarriage:

If you have had previous miscarriages:
- Take 2 tablets daily.
- Continue taking the medicine until the 12th week of pregnancy.

Infertility due to low progesterone levels:

Take 1 or 2 tablets daily.
Take them from the second half of the cycle until the first day of the next cycle.
The starting day of treatment and the number of days you take the tablets depend on the length of your cycle.
Continue treatment for at least 3 consecutive cycles.

Dysmenorrhoea (painful menstruation):

Take 1 or 2 tablets daily.
Take them only from day 5 to day 25 of the cycle.

Endometriosis:

Take 1 to 3 tablets daily.
You may need to take the tablets:
- Every day of the cycle.
- Only from day 5 to day 25 of the cycle.

Irregular menstrual cycles:

Take 1 or 2 tablets daily.
Take them from the second half of the cycle until the first day of the next cycle.
The starting day of treatment and the number of days you take the tablets depend on the length of your cycle.

Secondary amenorrhoea (absence of menstruation before menopause):

Take 1 or 2 tablets daily.
Continue for 14 days during the second half of the theoretical cycle.

Functional menometrorrhagia (excessive blood loss during menstruation or bleeding between periods):

If treatment is intended to stop bleeding:
- Take 2 or 3 tablets daily.
- Continue for at least 10 days.
For continuous treatment:
- Take 1 or 2 tablets daily.
- Continue during the second half of the cycle.
The starting day of treatment and the number of days you take the tablets depend on the length of your cycle.

If you take more DUFASTON than you should
If you (or anyone else) have taken an excessive dose of DUFASTON, it is unlikely to cause harm. No treatment is necessary. If you are concerned, contact your doctor.

If you forget to take Dufaston

Take the missed tablet as soon as you remember. However, if more than 12 hours have passed since you were supposed to take it, skip the missed dose and take the next tablet at the usual time.
Do not take a double dose to make up for a forgotten tablet.
You may experience bleeding or slight spotting if you miss a dose.

If you stop taking Dufaston
Do not stop treatment with Dufaston without consulting your doctor.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, Dufaston can cause adverse reactions, although not everybody experiences them.
The following adverse reactions may occur with this medicine:

Adverse reactions when Dufaston is taken alone
Stop taking Dufaston and contact your doctor immediately if you experience any of the following adverse reactions:

Liver problems – signs may include yellowing of the skin and whites of the eyes (jaundice), feeling tired, general malaise, or stomach pain (affects fewer than 1 in 100 treated patients)
Allergic reactions – signs may include difficulty breathing or systemic reactions such as feeling unwell, nausea, diarrhoea, or low blood pressure (affects fewer than 1 in 1,000 treated patients)
Swelling of the skin of the face and neck which may cause breathing difficulties (affects fewer than 1 in 1,000 treated patients). Stop taking Dufaston and contact your doctor immediately if you notice any of the above adverse reactions.

Other adverse reactions with Dufaston taken alone:
Common (affects fewer than 1 in 10 treated patients)

Headache, migraine
Nausea
Breast tenderness or pain
Irregular, heavy, or painful menstrual cycles
Absence of menstruation or less frequent menstruation than normal

Uncommon (affects fewer than 1 in 100 treated patients)

Weight gain
Dizziness
Depressed mood
Vomiting
Allergic reactions such as skin rash, severe itching, or urticaria
Abnormal liver function, such as jaundice, malaise, abdominal pain

Rare (affects fewer than 1 in 1,000 treated patients)

Drowsiness
Breast swelling
A type of anaemia caused by destruction of red blood cells
Fluid retention-related swelling, often in the lower legs or ankles
Increase in size of progestin-sensitive tumours (such as meningioma)

Adverse reactions in younger patients are expected to be similar to those observed in the adult population.

Adverse reactions when Dufaston is taken with an oestrogen (combined oestrogen-progestogen therapy)
If you are taking Dufaston together with an oestrogen, please also read the package leaflet accompanying the oestrogen-containing medicine. See also section "Before using Dufaston" for further information on the adverse reactions listed below.

Stop taking Dufaston and contact your doctor immediately if you experience any of the following adverse reactions:

Swelling with pain in the legs, sudden chest pain, or difficulty breathing. These may be signs of thrombosis.
Chest pain spreading to the arm and neck. This could be a sign of myocardial infarction.
Severe and unexplained headache or migraine (with or without visual disturbances). These could be signs of stroke. Stop taking the medicine and contact your doctor immediately if you experience any of the adverse events listed above.

Arrange a doctor’s appointment promptly if you notice:

Dimpling of the breast skin, nipple changes, or any visible or palpable hardening. These could be signs of breast cancer.

Other adverse reactions associated with taking Dufaston together with an oestrogen include abnormal thickening or cancer of the endometrium, or ovarian cancer.

If any of the adverse reactions worsen, or if you notice any adverse reaction not listed in this leaflet, inform your doctor or pharmacist.

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

5. HOW TO STORE DUFASTON

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after Exp. The expiry date refers to the last day of that month.
Do not use this medicine if you notice any visible signs of deterioration.
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. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What Dufaston contains
The active substance is dydrogesterone.

Each film-coated tablet contains 10 mg of dydrogesterone.
The excipients in the core are: lactose, hypromellose, maize starch, colloidal anhydrous silica, magnesium stearate.
The coating excipient is: Opadry White Y-1-7000 [hypromellose, Macrogol 400, titanium dioxide (E171)].

Description of the appearance of Dufaston and contents of the pack
The tablets are round, biconvex, white, with a diameter of 7 mm, and have a break line. The code '155' is imprinted on both sides of the break line.

The tablets are packaged in blisters made of an aluminum foil and a PVC film.
The pack contains 14 or 42 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder
Theramex Ireland Limited
3rd Floor, Kilmore House,
Park Lane,
Spencer Dock
Dublin 1,
D01 YE64
Ireland

Manufacturer
Abbott Biologicals B.V., Olst - The Netherlands.