Duphaston

PACKAGE LEAFLET: INFORMATION FOR THE USER

Warning! Keep the leaflet. The information on the immediate packaging is in a foreign language!
Duphaston
10 mg, film-coated tablets
Dydrogesterone
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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 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 side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Duphaston is and what it is used for

What Duphaston is
Duphaston contains an active substance called "dydrogesterone".

• Dydrogesterone is a synthetic hormone.
• It is very similar in structure and action to the hormone "progesterone", naturally produced in the body.
• Medicines such as Duphaston are known as progestogens.

What Duphaston is used for
Duphaston may be used alone or in combination with oestrogen. The concomitant use of oestrogen depends on the indication.
Duphaston is used in the treatment of:

• Disorders caused by insufficient production of progesterone in the body, such as:
• painful menstruation
• endometriosis – a condition in which endometrial tissue occurs outside the uterine cavity
• absence of menstruation in the premenopausal period
• irregular menstruation
• menstrual bleeding that is excessively heavy or occurs at irregular times (intermenstrual bleeding)
• premenstrual syndrome
• infertility due to low progesterone levels, and
• to reduce the risk of miscarriage
• Symptoms of menopause – this treatment is known as Hormone Replacement Therapy (HRT).
• These symptoms vary among women.
• They may include hot flushes, night sweats, sleep disturbances, vaginal dryness, and urinary tract disorders.

How Duphaston works
Normally, the body produces appropriate amounts of natural progesterone and natural oestrogen (another important female hormone) in balanced proportions. When the body does not produce enough progesterone, Duphaston supplements this deficiency and restores hormonal balance.
Your doctor may prescribe concomitant oestrogen therapy with Duphaston, depending on the indication.
In some women receiving HRT, taking oestrogen alone may cause endometrial hyperplasia (thickening of the lining of the uterus). This may also occur in women who have had a hysterectomy or who have a history of endometriosis. Taking dydrogesterone for part of the cycle prevents endometrial hyperplasia in these patients.

2. Important information before taking Duphaston

When not to take Duphaston

• if the patient is allergic to dydrogesterone or any of the other ingredients of Duphaston (listed in section 6).
• if there is or there is a justified suspicion of a tumour dependent on progesterone for its growth – such as a brain tumour called "meningioma".
• if there are vaginal bleedings of unknown cause.

Do not take Duphaston if any of the above apply to the patient. In case of doubt, consult a doctor or pharmacist before taking Duphaston.

If taking Duphaston together with oestrogen, e.g. as HRT, please also read section 2 of the patient leaflet included with the oestrogen-containing medicine.

Warnings and precautions

If Duphaston is taken due to abnormal bleeding, the doctor will determine the cause of the bleeding before starting treatment.

Usually, unexpected vaginal bleeding or spotting is not a cause for concern. This may occur especially during the first few months of taking Duphaston. However, contact your doctor immediately if bleeding or spotting:

• lasts longer than a few months
• occurs after a period of time since starting treatment
• continues even after stopping treatment.

These may be symptoms of endometrial hyperplasia. The doctor will investigate the cause of the bleeding or spotting and may recommend tests to rule out endometrial cancer.

Consult your doctor or pharmacist before starting to take Duphaston if any of the following conditions apply:

• depression
• liver disease
• a rare inherited blood disorder called "porphyria".

If any of the above warnings apply to the patient (or if in doubt), consult a doctor or pharmacist before starting Duphaston. It is especially important to inform the doctor if any of the above conditions worsened during pregnancy or previous hormone therapy. If symptoms worsen or recur during treatment with Duphaston, the doctor may advise stopping treatment.

Duphaston and HRT

HRT carries certain risks in addition to its benefits, which the patient and doctor must consider before starting treatment. When taking Duphaston together with oestrogen as HRT, the following information is important. Also refer to the patient leaflet included with the oestrogen-containing medicine.

Early menopause

Limited data are available on the risks of using HRT at the onset of early menopausal symptoms. The risk is lower in younger women. This means that the benefit-risk ratio of HRT is more favourable in younger women than in older women.

Medical examinations

Before starting or restarting HRT, the doctor will take a full patient and family history. The doctor may also recommend breast and pelvic examinations.

Before and during treatment, the doctor may recommend screening tests such as mammography (X-ray of the breast). The doctor will advise how often these tests should be performed. After starting treatment with Duphaston, regular check-ups with the doctor should be scheduled (at least once a year).

Endometrial cancer and endometrial hyperplasia

Women with an intact uterus who take oestrogen-only HRT for a prolonged period have an increased risk of:

• endometrial cancer
• endometrial hyperplasia

Taking Duphaston together with oestrogen (for at least 12 days per month in a 28-day cycle) or as continuous combined therapy can prevent this additional risk.

Breast cancer

Evidence confirms that taking combined oestrogen-progestagen HRT, or oestrogen-only HRT, increases the risk of breast cancer. The additional risk depends on how long the patient takes HRT. This increased risk becomes apparent after about 3 years (1-4) of HRT use. After stopping HRT, the additional risk gradually decreases, but may persist for 10 years or longer if HRT was taken for more than 5 years.

You should:

• have regular check-ups – your doctor will advise how often
• regularly examine your breasts yourself for the following changes:
  • skin dimpling
  • changes in the nipple
  • visible or palpable lumps.

If any changes are noticed, contact your doctor immediately.

Ovarian cancer

Ovarian cancer is rare – significantly rarer than breast cancer. HRT containing oestrogen alone or combined oestrogen-progestagen therapy 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 who do not use HRT, ovarian cancer will be diagnosed in about 2 out of 2000 women over 5 years. Among women who have used HRT for 5 years, it will occur in about 3 out of 2000 women (i.e. about 1 additional case).

Blood clots

HRT increases the risk of venous blood clots. This risk is about 3 times higher than in women not using HRT. The risk is highest during the first year of HRT use.

The likelihood of blood clots is greater if:

• the patient is older
• the patient has cancer
• the patient is overweight
• the patient is taking oestrogens
• the patient is pregnant or has recently given birth
• the patient (or a close family member) has a history of blood clots in the legs or lungs
• the patient is immobile due to surgery, injury, or illness (see information in the section "Surgery" below)
• the patient has systemic lupus erythematosus – a disease causing joint pain, rash, and fever.

If any of the above risk factors apply to the patient (or if in doubt), consult a doctor to ensure it is safe to start HRT.

If there is painful swelling of the legs, sudden chest pain, or difficulty breathing, you should:

• contact your doctor immediately
• stop taking HRT until the doctor decides whether to resume treatment.

These may be symptoms of blood clots.

Also inform your doctor or pharmacist if you are taking anticoagulant medicines (blood thinners) such as warfarin. The doctor will pay special attention to the benefits and risks of HRT.

Surgery

If surgery is planned, inform the doctor that you are taking HRT. It may be necessary to stop HRT a few weeks before surgery. In some cases, alternative treatment may be needed before and after surgery. The doctor will advise when you can restart HRT.

Heart disease

HRT does not prevent heart disease. The likelihood of heart disease is slightly higher in women taking oestrogen and progestagen as HRT than in women not using HRT. The risk of heart disease increases with age. The number of additional cases of heart disease due to oestrogen-progestagen HRT is very small in healthy women with early menopausal symptoms but before menopause. The number of additional cases increases with age.

If chest pain radiating to the arm or neck occurs, you should:

• contact your doctor immediately
• stop taking HRT until the doctor resumes treatment.

This pain may be a sign of myocardial infarction.

Stroke

Taking HRT as oestrogen-progestagen therapy or oestrogen-only therapy increases the risk of stroke. This risk is up to 1.5 times higher than in women not using HRT. The increase in risk for HRT users compared to non-users does not change with age or time since menopause. However, because the risk of stroke is strongly age-dependent, the overall risk of stroke in women using HRT increases with age.

If a severe, unexplained headache or migraine (with or without visual disturbances) occurs, you should:

• contact your doctor immediately
• stop taking HRT until the doctor resumes treatment.

This may be an early sign of stroke.

Children and adolescents

Duphaston is not indicated for use in children before their first menstruation. It is not known whether Duphaston is safe and effective in adolescents aged 12-18 years.

Duphaston and other medicines

Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines you plan to take, including over-the-counter medicines and herbal remedies.

In particular, inform your doctor or pharmacist if you are taking:

• herbal remedies containing St John's wort (Hypericum perforatum), sage, or rue;
• anticonvulsants (e.g. used to treat epilepsy) – such as phenobarbital, carbamazepine, phenytoin;
• antibacterial medicines (used to treat infections) – such as rifampicin, rifabutin, nevirapine, efavirenz;
• antiviral medicines (used to treat HIV infection - AIDS) – such as ritonavir, nelfinavir.

The above medicines may reduce the effectiveness of Duphaston and lead to bleeding and spotting. If you are taking any of these medicines (or if in doubt), consult your doctor or pharmacist before starting HRT.

Duphaston with food and drink

Duphaston can be taken with or without food.

Pregnancy, breastfeeding and fertility

If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning a pregnancy, consult your doctor before taking this medicine.

Pregnancy

There may be an increased risk of hypospadias (a congenital malformation of the penis where the urethral opening is in an abnormal position) in children whose mothers took certain progestagens. However, this increased risk has not been definitively confirmed. There is currently no evidence that using dydrogesterone during pregnancy is harmful. More than 10 million pregnant women have taken Duphaston.

• If you are pregnant, consult your doctor before taking Duphaston.
• If you become pregnant or suspect you are pregnant, contact your doctor. The doctor will discuss the benefits and risks of taking Duphaston during pregnancy.

Breastfeeding

Do not take Duphaston while breastfeeding. It is not known whether Duphaston passes into breast milk or affects the infant. Studies with other progestagens have shown that small amounts of the drug pass into breast milk.

Fertility

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

Driving and using machines

After taking Duphaston, mild drowsiness or dizziness may occur. This is more likely during the first few hours after taking the medicine. If these symptoms occur, do not drive or operate tools or machinery. The patient should wait and observe how the medicine affects her before deciding to drive or operate tools or machinery.

Duphaston contains lactose monohydrate

If you have been told by your doctor that you have an intolerance or difficulty digesting certain sugars, consult your doctor before taking this medicine. This applies to rare inherited disorders affecting the body's ability to use lactose, such as "lactase deficiency" or "glucose-galactose malabsorption syndrome".

3. How to take Duphaston

Duphaston should always be taken exactly as directed by your doctor. If you are unsure, consult your doctor or pharmacist. Your doctor will adjust the dose according to your individual needs.

Taking the medicine

• Swallow the tablet with water.
• The tablet may be taken with or without food.
• If you are taking more than one tablet per day, doses should be evenly spaced throughout the day; for example, one tablet in the morning and one in the evening.
• Try to take the tablets at the same time each day. This helps maintain a constant level of the medicine in your body and also helps you remember to take it.
• The break line on the tablet is intended only to facilitate swallowing and should not be used to divide the dose in half.

How much to take
The number of tablets and the days on which they are taken depend on the condition being treated. If you still have menstrual periods, day 1 of the cycle is the first day of bleeding. If you no longer have natural periods, your doctor will determine the first day of the cycle and when to start taking the tablets.

Treatment of painful menstruation (dysmenorrhoea)

• Take 1 or 2 tablets per day.
• Use only from day 5 to day 25 of the cycle.

Treatment of endometriosis

• Take 1 to 3 tablets per day.
• Your doctor will decide whether to take the tablets:
  • Every day of the cycle, or
  • Only from day 5 to day 25 of the cycle.

Treatment of amenorrhoea before menopause

• Take 1 or 2 tablets per day.
• Use for 14 days during the second half of the expected cycle.

Treatment of irregular menstruation

• Take 1 or 2 tablets per day.
• Use from the second half of the cycle until the first day of the next cycle.
• The day treatment starts and the number of days the medicine is taken depend on the length of the cycle.

Treatment of abnormal uterine bleeding

• For treatment aimed at stopping bleeding:
  • Take 2 or 3 tablets per day.
  • Use for up to 10 days.
• For continuous treatment:
  • Take 1 or 2 tablets per day.
  • Use during the second half of the cycle.
  • The day treatment starts and the number of days the medicine is taken depend on the length of the cycle.

Treatment of premenstrual syndrome (PMS)

• Take 2 tablets per day.
• Use from the second half of the cycle until the first day of the next cycle.
• The day treatment starts and the number of days the medicine is taken depend on the length of the cycle.

Use to reduce the risk of miscarriage

• In women with no history of previous miscarriage:
  • Take an initial dose of up to 4 tablets.
  • Then take 2 or 3 tablets per day until symptoms subside.
• In women with a history of previous miscarriage:
  • Take 2 tablets per day.
  • Continue until the 12th week of pregnancy.

Treatment of infertility due to low progesterone levels

• Take 1 or 2 tablets per day.
• Use from the second half of the cycle until the first day of the next cycle.
• The day treatment starts and the number of days the medicine is taken depend on the length of the cycle.
• Treatment should be continued for at least 3 consecutive cycles.

Treatment of menopausal symptoms – Hormone Replacement Therapy (HRT)

• In women using sequential HRT (taking an oestrogen tablet or using an oestrogen patch throughout a 28-day cycle):
  • Take 1 tablet of Duphaston once daily.
  • Use during the last 14 days of each 28-day cycle.
• In women using cyclic HRT (taking an oestrogen tablet or using an oestrogen patch for 21 days followed by a 7-day oestrogen-free interval):
  • Take 1 tablet of Duphaston per day.
  • Use during the last 12 to 14 days of oestrogen therapy.
• If necessary, your doctor may increase the dose to 2 tablets per day.

Taking more Duphaston than recommended
It is unlikely that taking too many Duphaston tablets (by you or someone else) would be harmful. Specific treatment is not required. However, if you are concerned or experience any worrying symptoms, contact your doctor.

If you forget to take Duphaston

• If you miss a dose, take it as soon as possible. However, if more than 12 hours have passed since the scheduled time, do not take the missed tablet; instead, take the next tablet at your usual time.
• Do not take a double dose to make up for a missed dose.
• Missing a dose may result in bleeding or spotting.

Stopping Duphaston
Do not stop taking Duphaston without consulting your doctor.

4. Possible adverse reactions

Like any medicine, Duphaston may cause adverse reactions, although not everyone experiences them. The following adverse reactions may occur during treatment with Duphaston:

Adverse reactions during treatment with Duphaston alone
If any of the following adverse reactions occur, stop taking Duphaston immediately and contact your doctor:

• Liver disorders – symptoms may include yellowing of the skin or whites of the eyes (jaundice), weakness, general malaise or stomach pain (affects less than 1 in 100 patients)
• Allergic reactions – symptoms may include difficulty breathing or systemic symptoms such as nausea, vomiting, diarrhoea or low blood pressure (affects less than 1 in 1,000 patients)
• Swelling of the skin around the face and throat, which may cause difficulty breathing (affects less than 1 in 1,000 patients). If any of the above adverse symptoms occur, stop taking Duphaston immediately and contact your doctor.

Other adverse reactions during treatment with Duphaston alone
Common (affects less than 1 in 10 patients)

• Migraine, headache
• Nausea
• Tenderness or pain in the breasts
• Irregular, heavy or painful menstrual bleeding
• Absence of menstruation or menstrual bleeding occurring less frequently than normal.

Uncommon (affects less than 1 in 100 patients)

• Weight gain
• Dizziness
• Depression
• Vomiting
• Skin allergic reactions – such as rash, severe itching or urticaria.

Rare (affects less than 1 in 1,000 patients)

• Somnolence
• Breast swelling
• A type of anaemia occurring due to breakdown of red blood cells
• Fluid retention causing oedema, commonly affecting the lower legs or ankles
• Increase in size of tumours under the influence of progestagens (such as meningioma).

In younger patients, similar adverse reactions as those observed in adults may be expected.

Adverse reactions during treatment with Duphaston combined with oestrogen (HRT – oestrogen with progestagen)
If Duphaston is taken together with oestrogen, please also read the patient leaflet provided with the oestrogen-containing medicine. For further information regarding the adverse reactions listed below, see section "Important information before taking Duphaston".

If any of the following adverse reactions occur, stop taking Duphaston immediately and contact your doctor:

• Painful swelling of the legs, sudden chest pain or difficulty breathing. These may be symptoms of blood clots.
• Chest pain radiating to the arm or neck. These may be symptoms of myocardial infarction.
• Severe, unexplained headache or migraine (with or without visual disturbances). These may be symptoms of stroke. If any of the above adverse symptoms occur, stop taking Duphaston immediately and contact your doctor.

Contact your doctor immediately if you notice:

• Dimpling of the skin on the breast, changes in the nipple, or visible or palpable lumps. These may be symptoms of breast cancer.

Other adverse reactions occurring during treatment with Duphaston combined with oestrogen include:

• Excessive growth of the endometrium
• Endometrial cancer
• Ovarian cancer.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301; Fax: +48 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 Duphaston

Keep this medicine out of sight and reach of children.
No special storage conditions are required.
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 should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the package and other information

What Duphaston contains

• The active substance is dydrogesterone.
• Each coated tablet contains 10 mg of dydrogesterone.
• Other ingredients are: monohydrate lactose, hypromellose, corn starch, colloidal anhydrous silica, magnesium stearate. Coating: Opadry Y-1-7000 (hypromellose, polyethylene glycol 400, titanium dioxide (E 171)).

What Duphaston looks like and contents of the pack
White, round, biconvex, scored coated tablets with the imprint “155” on both sides of the break line on one side of the tablet.
20 coated tablets in PVC/Al blisters packed in a cardboard box.
For further information, please contact the Marketing Authorisation Holder or the Parallel Importer.
Marketing Authorisation Holder in Romania, the country of export:
VIATRIS HEALTHCARE LIMITED
Damastown Industrial Park, Mulhuddart
Dublin 15, Dublin
Ireland
Manufacturer:
Abbott Biologicals B.V.
Veerweg 12
8121 AA Olst
The Netherlands
Parallel Importer:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Repackaged in:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Marketing Authorisation Numbers in Romania, the country of export: 2078/2009/02
2078/2009/01
Parallel Import Licence Number: 151/20