Patient Information Leaflet: Information for the User

Didrogesterone Adalvo 10 mg film-coated tablets

Didrogesterone
Generic medicine
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 questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as 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

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

1. What is Didrogesterone Adalvo and what is it used for?

This medicinal product contains the active substance didrogesterone.
Didrogesterone is a synthetic progestogenic hormone. Progestogenic hormones have approximately the same effect as natural progesterone. Together with estrogens, they regulate the menstrual cycle.

Didrogesterone Adalvo is used:

For conditions occurring when the body does not produce sufficient progesterone:
to regulate the menstrual cycle;
in the presence of endometrial tissue outside the uterus (endometriosis);
painful menstruation;
absence of menstruation;
menstruation with excessive blood loss and/or irregular cycles;
infertility due to low progesterone levels;
luteal phase support during assisted reproductive technology (ART) treatment;
reduction of the risk of threatened miscarriage;
in cases of recurrent spontaneous abortions (repeated miscarriages).
In hormone replacement therapy (HRT): Together with estrogen, didrogesterone tablets are used to:
prevent abnormalities of the [uterine] endometrial mucosa during treatment of postmenopausal symptoms.

The body normally maintains a balance between the levels of the two natural female hormones, progesterone and estrogen. If the body does not produce enough progesterone, this medicine supplements it and restores the hormonal balance.
Your doctor may prescribe you estrogen to be taken together with this medicine. This depends on the reason for which you are taking didrogesterone tablets.
For some women receiving Hormone Replacement Therapy (HRT), taking estrogen alone may cause abnormal thickening of the uterine mucosa. This may also occur even if you do not have a uterus but have a history of endometriosis (presence of endometrial tissue outside the uterus). Taking this medicine during part of the menstrual cycle can help prevent excessive thickening of the uterine mucosa.

2. What you should know before taking Didrogesterone Adalvo

Do not take Didrogesterone Adalvo

if you are allergic to dydrogesterone or to any of the other ingredients of this medicine (listed in section 6);
if you have or have had hormone-sensitive tumours, or if there is suspicion that you may have hormone-sensitive tumours;
if you have vaginal bleeding of unknown cause;
if you are using this medicine to support the luteal phase as part of assisted reproductive technology treatment, and your doctor diagnoses miscarriage or spontaneous abortion, treatment with dydrogesterone must be stopped;
if you currently have or have previously had severe liver disease and liver function tests have not returned to normal;
if you have a meningioma or have been previously diagnosed with a meningioma (a usually benign tumour of the tissue layer between the brain and the skull).

Do not take this medicine if any of the above conditions apply to you. If you are unsure, consult your
doctor or pharmacist before taking this medicine.
If dydrogesterone is administered in combination with another hormone (estrogen) (e.g. as
hormone replacement therapy in connection with menopausal symptoms), you must carefully
consider the contraindications of estrogen, listed in the package leaflet of that product.
Warnings and precautions
If you are taking this medicine for menstrual cycles with abnormal bleeding, your doctor must
first determine the cause of such bleeding before this medicine is administered to you.
If unexpected vaginal bleeding or withdrawal bleeding occurs, this is generally not concerning. It is
common, especially during the first few months of using this medicine.
However, make an appointment with your doctor immediately if the bleeding or withdrawal
bleeding:

lasts for more than a few months,
starts after several months of treatment,
persists even after you have stopped treatment.

This may be a sign of thickening of the uterine lining. Your doctor will need to investigate the cause
of the bleeding or withdrawal bleeding and may perform a test to determine whether you have
endometrial cancer.
Contact your doctor in the following situations:

If you develop a migraine-type headache while using dydrogesterone that you have never had before.
If you experience severe headaches or more frequent migraines than usual.
If your blood pressure increases significantly and suddenly.
If you have a stroke.
If you have thrombosis.
If you have abnormal vaginal bleeding.
If you are using dydrogesterone due to risk of miscarriage, your condition and that of the fetus must be monitored during treatment.
If you experience low mood.
If you have rare conditions known to be influenced by sex hormones, such as: severe itching, cholestasis-related jaundice, pregnancy-related herpes, a specific metabolic disorder (porphyria), and otosclerosis (a condition involving hardening of the middle ear, leading to hearing loss).
Meningioma: The use of this medicine has been linked to the development of a usually benign tumour of the tissue layer between the brain and the skull (meningioma). If you are diagnosed with meningioma, your doctor will discontinue treatment (see section "Do not take..."). If you notice any symptoms such as vision changes (e.g. double or blurred vision), hearing loss or ringing in the ears, loss of smell, headache worsening over time, memory loss, seizures, or weakness in the arms or legs, inform your doctor immediately.

If any of the above points apply to you, or if you are unsure, contact your doctor or pharmacist. It is
particularly important to inform them if any of the above conditions have ever worsened during
pregnancy or previous hormone therapy. Your doctor may wish to monitor your condition more
closely during treatment. If problems worsen or recur while you are using this medicine, your doctor
may consider it necessary to discontinue treatment.
Didrogesterone Adalvo and Hormone Replacement Therapy (HRT)
In addition to benefits, HRT carries certain risks that you and your doctor should consider when deciding whether to use these medicines. If you are taking dydrogesterone tablets in combination with an estrogen as part of HRT, the following information is important. Also read the package leaflet of the estrogen.
Premature menopause
There is limited evidence on the risks of HRT used to treat premature menopause. In younger women, the risk level is low. This means that the benefit-risk ratio for younger women using HRT for premature menopause may be more favourable than for older women.
Medical examinations
Before starting (or restarting) HRT, your doctor must be fully informed about your personal and close family medical history. You will need a complete medical and gynecological examination. Regular check-ups, including breast examination, will be performed during treatment.
Periodic, careful assessment of the benefits and risks of HRT—at least once a year—is necessary to determine whether treatment should continue. During use, you may need regular check-ups by your doctor.
Cancer of the uterine lining (endometrial cancer)
Long-term use of estrogens without the addition of progestogens increases the risk of cancer and abnormal growth of the uterine lining in women who have a uterus. To reduce this risk, estrogens must be used together with progestogen tablets for at least 12 days per month.
HRT and breast cancer
Studies have shown that the use of Hormone Replacement Therapy (HRT), either as a combination of estrogen-progestogen or estrogen alone, increases the risk of breast cancer. The additional risk depends on how long you take HRT. The additional risk appears after 3 years of use. After stopping HRT, the additional risk gradually decreases, but may persist for 10 years or more if HRT has been used for over 5 years.
Your doctor will inform you about which breast changes require medical consultation.
HRT and ovarian cancer
Ovarian cancer is rare, much rarer than breast cancer.
A slight increase in the risk of ovarian cancer has been reported with the use of estrogen-only or estrogen-progestogen combination HRT.
The risk of ovarian cancer depends on age. Among women aged 50 to 54 who have not used HRT, about 2 out of 2,000 will be diagnosed with ovarian cancer within 5 years. Among women who have used HRT for 5 years, there will be about 3 cases per 2,000 users (i.e. about 1 additional case).
HRT and thrombosis
Studies have shown that women using HRT have approximately 1.3 to 3 times higher likelihood of developing venous thrombosis (formation of a blood clot in a vein in the legs, lungs, or other parts of the body) compared to women not using HRT. This additional risk is highest during the first year of HRT use.
A blood clot can be serious and, if it reaches the lungs, may cause chest pain, shortness of breath, fainting, and even death.
The risk of venous thrombosis is higher if:

you are elderly
you have cancer
you are very overweight
you are taking an estrogen
you are pregnant or have recently given birth
you have previously had venous thrombosis, coagulation disorders, or a family history (close relatives) of venous thrombosis
you have been immobilized for a prolonged period due to surgery, trauma, or illness (see also information in the "Surgery" section)
you have systemic lupus erythematosus (an autoimmune disease)

If any of the above conditions apply to you, or if you are unsure, ask your doctor whether you can take
HRT.
If you develop venous thrombosis or pulmonary embolism while using HRT, you must stop taking
HRT immediately. Inform your doctor immediately of any symptoms that may indicate venous
thrombosis or pulmonary embolism, such as swelling with pain in one leg, sudden chest pain, or
shortness of breath.
If you are already taking a blood thinner, e.g. warfarin, inform your doctor. In such cases, the benefits and risks of HRT must be carefully evaluated.
Surgery
If you are scheduled for surgery, inform your doctor well in advance that you are taking HRT. In such cases, it may be necessary to discontinue HRT several weeks before the planned surgery. In some cases, you may need additional treatments before and after surgery. Your doctor will advise you when to restart HRT.
HRT and coronary heart disease
Two major studies with a specific type of HRT (conjugated estrogens combined with medroxyprogesterone acetate) have shown that the risk of cardiovascular disease may increase during the first year of HRT use. It is not yet clear whether this applies to other types of HRT medicines.
If you experience chest pain spreading to the arm or neck, you must:

seek immediate medical attention
stop taking HRT until your doctor authorizes you to resume. The pain may be a symptom of heart attack.

HRT and stroke
The risk of stroke increases by approximately 1.5 times in women taking HRT compared to women not taking HRT. The number of additional stroke cases due to HRT use increases with age.
Comparison
Among women in their fifties not using HRT, an average of 8 out of 1,000 will have a stroke within 5 years. Among women in their fifties using HRT, there are 11 stroke cases per 1,000 users within 5 years (i.e. 3 additional cases per 1,000).
If you experience unexplained and severe headache or migraine (with or without vision problems), you must:

seek immediate medical attention
stop taking HRT until your doctor authorizes you to resume. This may be a sign of stroke.

Children and adolescents up to 18 years of age
This medicine must not be used in girls before their first menstruation. Safety and efficacy are not known in young people aged between 12 and 18 years.
Other medicines and Didrogesterone Adalvo
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without prescription.
Inform your doctor if you are taking or have taken any of the following medicines. These medicines may reduce treatment effectiveness and may also cause irregular bleeding.

herbal remedies containing St John’s wort (Hypericum perforatum),
medicines for epilepsy (such as phenobarbital, phenytoin, carbamazepine, primidone),
medicines for infections (such as rifampicin),
medicines for HIV (AIDS) (such as ritonavir, nevirapine, efavirenz),
medicines for hepatitis C virus

If any of the above points apply to you, or if you are unsure, contact your doctor or pharmacist
before taking dydrogesterone tablets.
Didrogesterone Adalvo with food and drinks
This medicine can be taken with or without food.
Pregnancy, breastfeeding and fertility
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.
Pregnancy
There may be an increased risk of a birth defect affecting the urethra of the penis (hypospadias) in children whose mothers have taken certain progestogens. However, this increased risk is not yet certain. More than 9 million pregnant women have taken dydrogesterone tablets. To date, there is no evidence that taking dydrogesterone during pregnancy is harmful.
Breastfeeding
Do not take this medicine if you are breastfeeding. It is not known whether it is excreted in breast milk or has effects on the infant. Studies with other progestogens show that a small amount passes into breast milk.
Fertility
To the best of current knowledge, this medicine does not impair fertility when taken as recommended by your doctor.
Driving and using machines
You may experience mild drowsiness when taking dydrogesterone tablets. This is more likely within the first few hours after taking the medicine. If this occurs, do not drive or operate machinery. Wait to see how the medicine affects you before driving or operating machinery.
Didrogesterone Adalvo contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking this medicine.

3. How to take Didrogesterone Adalvo

Take this medicine exactly as instructed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
How to take Didrogesterone Adalvo

Take each tablet with water.
You may take the tablets with or without food.
If you are taking more than 1 tablet per day, divide the doses as evenly as possible throughout the day. For example, take one tablet in the morning and one tablet in the evening.
Try to take the tablets at the same time each day. This will ensure a constant level of the medicine in your body. It will also help you remember to take the tablets.
The tablets have a score line, which is intended to facilitate breaking the tablet to aid swallowing. The score line is not intended for dividing the tablet into equal parts.

How much Didrogesterone Adalvo should I take?
The number of tablets to take and the days on which to take them depend on the reason for your treatment. If
you still have menstrual periods, the first day of the cycle is the day on which bleeding starts. If you
no longer have menstrual periods, your doctor will determine the first day of the cycle and when you should start
taking the tablets.
For menstrual cycle regulation:

Take 1 tablet per day.
From day 11 to day 25 of the menstrual cycle.
With this dosing schedule, it is possible to achieve a menstrual cycle of 28 days.

For endometriosis (presence of uterine mucosal tissue outside the uterus):

Take 1 to 3 tablets per day.
You must take the tablets as follows: either throughout the entire menstrual cycle, or from day 5 to day 25 of the menstrual cycle.

For painful menstruation:

Take 1 or 2 tablets per day.
From day 5 to day 25 of the menstrual cycle.

For menstruation with excessive blood loss or irregular periods:

To stop menstruation: o Take 2 tablets per day. o For 5–7 days. Subsequently, you will experience a heavy withdrawal bleed.
For continuous treatment: o Take 1 tablet per day. o During the second half of the menstrual cycle. The start date and number of days for taking the tablets depend on the length of your menstrual cycle. Withdrawal bleeding generally occurs a few days after the last

tablet of didrogesterone.
For infertility due to low progesterone levels:

Take 1 tablet per day.
From day 14 to day 25 of the menstrual cycle.
Continue treatment for at least 3 consecutive cycles.

For luteal phase support in assisted reproductive technology treatment:

Take 3 tablets per day, starting from the day of oocyte retrieval. Administration of this medicine should continue for 12 weeks if pregnancy is confirmed.

For reducing the risk of threatened miscarriage:

Start with 4 tablets. Then take 1 tablet every 8 hours. If symptoms do not disappear or recur, take 2 tablets every 8 hours.
Treatment should continue for one week after symptoms have disappeared. Afterwards, the dose may be gradually reduced.

If you have had recurrent miscarriages:

1 tablet twice daily until week 20 of pregnancy. Afterwards, the dose may be gradually reduced. Treatment should preferably be started before conception.

For absent menstruation before menopause:

Take 1 or 2 tablets per day.
From day 11 to day 25 of the menstrual cycle.

For prevention of endometrial abnormalities during treatment of postmenopausal symptoms:

Based on a 28-day estrogen treatment cycle: 1 or 2 tablets per day for 14 days of the cycle. Withdrawal bleeding generally occurs a few days after the last tablet.

If you take more Didrogesterone Adalvo than you should
If you (or someone else) have taken an excessive amount of this medicine, this is generally not
harmful. No treatment is necessary. If you are concerned, contact your doctor.
If you forget to take Didrogesterone Adalvo

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

If you forget to take Didrogesterone Adalvo when it is used for luteal phase support
in assisted reproductive technology treatment

Take the missed tablet as soon as you remember and inform your doctor.

If you stop taking Didrogesterone Adalvo
Do not stop taking this medicine without first consulting your doctor.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Side effects when Didrogesterone Adalvo is used alone:
Stop taking Didrogesterone Adalvo and contact your doctor immediately if you experience any of the following side effects:

Liver problems – signs may include yellowing of the skin and whites of the eyes (jaundice), weakness, general feeling of malaise, or stomach pain (occurs in fewer than 1 in 100 people).
Allergic reactions – signs may include difficulty breathing or systemic reactions such as nausea, vomiting, diarrhoea, or low blood pressure (occurs in fewer than 1 in 1,000 people).
Swelling of the skin of the face and neck which may cause difficulty breathing (may affect up to 1 in 1,000 people). Immediately stop taking this medicine if you experience any of the above-mentioned side effects.

Other side effects when Didrogesterone Adalvo is used alone:
Very common (may affect more than 1 in 10 people):

Vaginal bleeding

Common (may affect up to 1 in 10 people):

Migraine, headache
Nausea, vomiting, abdominal pain
Irregular, heavy, or painful menstruation
Absence of menstruation or periods less frequent than normal
Breast tenderness or pain

Uncommon (may affect up to 1 in 100 people):

Depressed mood
Dizziness
Vomiting
Liver problems (yellowing of the skin and whites of the eyes, feeling of weakness, general malaise, or stomach pain)
Allergic skin reactions such as rashes, severe itching, or hives
Weight gain

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

Increase in size of progestin-sensitive tumours (e.g. meningioma)
Anaemia due to excessive breakdown of blood cells (haemolytic anaemia)
Hypersensitivity
Somnolence
Sudden fluid accumulation in the skin and mucous membranes (e.g. throat or tongue), difficulty breathing and/or itching and skin rash, often as an allergic reaction (angioneurotic oedema)
Breast swelling
Swelling due to fluid retention, often in the lower legs or ankles.

Side effects when Didrogesterone Adalvo is taken with an oestrogen (combined oestrogen-progestogen therapy)
If you are taking this medicine together with an oestrogen, also read the patient information leaflet of the oestrogen. See section 2 “What you need to know before taking Didrogesterone Adalvo” for further information on the side effects listed above.
Stop taking Didrogesterone Adalvo and contact your doctor immediately if you experience any of the following side effects:

Swelling with pain in the legs, sudden chest pain, or difficulty breathing. These may be signs of a blood clot.
Chest pain spreading to the arm and neck. This may be a sign of a heart attack.
Severe and unexplained headache or migraine (with or without vision problems). These may be signs of a stroke. Immediately stop taking this medicine if you experience any of the above-mentioned side effects.

Arrange a doctor’s visit promptly if you notice the following:

Dimpling of the breast skin, changes in the nipple, or if you see or feel lumps. These may be signs of breast cancer.

Other side effects when dydrogesterone is used with an oestrogen include abnormal thickening or cancer of the uterine lining or ovarian cancer.

Reporting of side effects
If you experience any side effects, 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 available at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Didrogesterone Adalvo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and blister after
Exp. The expiry date refers to the last day of that month.
Do not store above 25°C.
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 Didrogesterone Adalvo contains

The active substance is dydrogesterone. Each film-coated tablet contains 10 mg of dydrogesterone.
The other components in the tablet core are: monohydrate lactose, pregelatinized maize starch, hypromellose 2910 E464, anhydrous colloidal silica and magnesium stearate E572.
The other components in the tablet coating are: monohydrate lactose, hypromellose E464, titanium dioxide E171, triacetin E1518.

Description of the appearance of Didrogesterone Adalvo and package contents

The tablets are white to off-white, round, biconvex, film-coated tablets (approximately 7.1 mm in diameter), marked with '711' on one side and smooth on the other (see also section 3 of this leaflet).
The tablets are packed in PVC/PVDC-Al blisters. Available in boxes containing 10, 14, 20, 30 or 42 tablets per box. Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Adalvo Limited
Malta Life Sciences Park, Building 1, Level 4,
Sir Temi Zammit Buildings,
San Ġwann SĠN 3000 Malta
Manufacturer
Haupt Pharma Münster GmbH
Schleebrüggenkamp 15 48159 Münster Germany
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park, Paola PLA 3000 Malta
QUALIMETRIX S.A.
579 MESOGEION AVENUE
AGIA PARASKEVI 15343 ATHENS Greece
Adalvo Limited
Malta Life Sciences Park, Building 1, Level 4,
Sir Temi Zammit Buildings, San Ġwann SĠN 3000 Malta

Dydrogesterone Adalvo