PAUDIEN

Package leaflet: Information for the user

Paudien 1 mg/2 mg tablets

estradiol valerate / dienogest
Equivalent medicine
Please read all of this leaflet carefully before you start 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 pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4. Contents of this leaflet:
  1. What Paudien is and what it is used for
  2. What you need to know before taking Paudien
  3. How to take Paudien
  4. Possible side effects
  5. How to store Paudien
  6. Contents of the pack and other information

1. What Paudien is and what it is used for

Paudien is indicated as Hormone Replacement Therapy (HRT).
It contains two types of female hormones: an oestrogen and a progestogen.
Paudien is used in postmenopausal women who are at least 1 year past their last menstrual period.
Paudien is used for:
Relieving symptoms that occur after menopause
During menopause, the amount of oestrogen produced by a woman's body decreases.
This can cause symptoms such as sudden warmth in the face, neck and chest ("hot flushes"). Paudien relieves these
symptoms after menopause. Paudien will be prescribed to you only if your symptoms are seriously affecting your daily life.

2. What you should know before taking Paudien

Medical history and regular check-ups
The use of HRT carries risks that must be considered when deciding whether to start or continue taking it.
Experience in treating women with premature menopause (due to ovarian failure or surgery) is limited.
If you have premature menopause, the risks of using 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 physical examination. This may include a breast examination and/or a pelvic examination, if necessary.
Once you have started Paudien, 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 Paudien.
Have regular breast examinations as recommended by your doctor.

Do not take Paudien
If any of the following conditions apply to you. If you have any doubts about any of the points listed below, consult your doctor before taking Paudien.
Do not take Paudien if:

• you have or have ever had breast cancer, or suspect you may have it;
• you have an estrogen-sensitive cancer, such as cancer of the lining of the womb (endometrium), or suspect you may have it;
• you have unexplained vaginal bleeding;
• you have excessive thickening of the lining of the womb (endometrial hyperplasia) that has not been treated;
• you have or have ever had a blood clot in a vein (thrombosis), such as in the legs (deep vein thrombosis) or in the lungs (pulmonary embolism);
• you have a blood clotting disorder (such as protein C, protein S or antithrombin deficiency);
• you have or have recently had an arterial disease caused by blood clots, such as heart attack, stroke, or angina;
• you have or have had liver disease and liver function tests have not returned to normal;
• you suffer from a rare inherited blood disorder called "porphyria";
• you are allergic to estradiol valerate, dienogest, or any of the other ingredients of this medicine (listed in section 6).

If any of the above conditions occurs for the first time while you are taking Paudien, stop taking it immediately and consult your doctor without delay.

Warnings and precautions
Inform your doctor if you have ever had any of the following conditions before starting treatment, as they may recur or worsen during treatment with Paudien. In such cases, you should have more frequent medical check-ups:

• fibroids in the womb;
• growth of tissue outside the womb (endometriosis) or history of abnormal growth of the womb lining (endometrial hyperplasia);
• increased risk of developing blood clots (see section 2 "Blood clots in veins (thrombosis)");
• increased risk of developing an estrogen-sensitive cancer (such as 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 immune system disorder affecting multiple organs (systemic lupus erythematosus, SLE);
• epilepsy;
• asthma;
• a disorder affecting the eardrum and hearing (otosclerosis);
• very high levels of fats in the blood (triglycerides);
• fluid retention due to kidney or heart problems;
• hereditary or acquired angioedema.

Stop taking Paudien and consult your doctor immediately
If you notice any of the following illnesses or conditions while taking HRT:

• any of the conditions listed in section 2 "Do not take Paudien";
• yellowing of the skin or whites of the eyes (jaundice). These may be signs of liver disease;
• swelling of the face, tongue and/or throat and/or difficulty swallowing or hives, together with breathing difficulties, which are indicative of angioedema;
• a marked increase in blood pressure (symptoms may include headache, fatigue, dizziness);
• headaches resembling migraines that occur for the first time;
• 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 section 2 "Blood clots in veins (thrombosis)".

Note: Paudien is not a contraceptive. If less than 12 months have passed since your last menstrual period or you are under 50 years of age, you may still need to use an additional contraceptive method to prevent pregnancy. Discuss this with your doctor.

HRT and cancer

Excessive thickening of the womb lining (endometrial hyperplasia) and cancer of the womb lining (endometrial cancer)
Taking estrogen-only HRT increases the risk of excessive thickening of the womb lining (endometrial hyperplasia) and of cancer of the womb lining (endometrial cancer).
The progestogen in Paudien protects against this additional risk.

Irregular bleeding
You may experience irregular bleeding or spotting during the first 3–6 months of taking Paudien.
However, if irregular bleeding:

• continues beyond the first 6 months,
• starts after you have been taking Paudien for more than 6 months,
• continues after stopping Paudien, consult your doctor as soon as possible.

Breast cancer
Evidence shows that taking combined estrogen-progestogen hormone replacement therapy (HRT) or estrogen-only HRT increases the risk of breast cancer. The additional risk depends on how long HRT is used. This additional risk appears within 3 years of use. After stopping HRT, the additional risk decreases over time, but may persist for 10 years or more if HRT has been used for more than 5 years.

Comparison:
Among women aged 50–54 years not taking HRT, breast cancer will be diagnosed in an average of about 13–17 women per 1000 over a 5-year period.
Among women aged 50 who start taking estrogen-only HRT for 5 years, there will be 16–17 cases per 1000 users (i.e. 0–3 additional cases).
Among women aged 50 who start taking combined estrogen-progestogen HRT for 5 years, there will be 21 cases per 1000 users (i.e. 4–8 additional cases).
Among women aged 50–59 years not taking HRT, breast cancer will be diagnosed in an average of 27 women per 1000 over a 10-year period.
Among women aged 50 who start taking estrogen-only HRT for 10 years, there will be 34 cases per 1000 users (i.e. 7 additional cases).
Among women aged 50 who start taking combined estrogen-progestogen HRT for 10 years, there will be 48 cases per 1000 users (i.e. 21 additional cases).

• Check your breasts regularly. Consult your doctor if you notice any changes such as:
  • skin dimpling;
  • changes in the nipple;
  • lumps that can be seen or felt.

In addition, you are advised to participate in mammographic screening programmes when offered. For mammographic screening, it is important to inform the nurse/healthcare professional performing the X-ray that you are using HRT, as this medicine can increase breast density, which may affect the mammogram result. When breast density is increased, a mammogram may not detect all lumps.

Ovarian cancer
Ovarian cancer is rare – much rarer than breast cancer. The use of estrogen-only or combined estrogen-progestogen 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 50–54 years not taking HRT, about 2 women in 2000 will be diagnosed with ovarian cancer over a 5-year period. For women taking HRT for 5 years, there will be about 3 cases in 2000 treated women (i.e. about 1 additional case).

Effect of HRT on heart and circulation

Blood clots in veins (thrombosis)
The risk of blood clots in veins is 1.3 to 3 times higher in women taking HRT than in those not taking it, especially during the first year of use.
Blood clots can be serious, and if one travels to the lungs, it can cause chest pain, difficulty breathing, fainting, or even death.
Your risk of developing a blood clot in a vein increases with age and if any of the following apply to you. Inform your doctor if any of these situations apply to you:

• you are unable to walk for long periods due to surgery, injury, or 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 a medicine used to prevent blood clots;
• 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 signs of a blood clot, see "Stop taking Paudien and consult your doctor immediately".

Comparison:
Considering women around 50 years of age not taking HRT, on average, 4 to 7 out of 1000 may develop a blood clot in a vein over a 5-year period.
For women around 50 years of age who have taken combined estrogen-progestogen HRT for more than 5 years, there will be 9 to 12 cases per 1000 users (i.e. 5 additional cases).

Heart disease (heart attack)
There is no evidence that HRT prevents heart attacks.
Women over 60 years of age who use combined estrogen-progestogen HRT have a slightly higher chance of developing heart disease compared to those not using HRT.

Stroke
The risk of stroke is about 1.5 times higher in women taking HRT than in those not taking it. The number of additional stroke cases due to HRT use increases with age.

Comparison:
Considering women around 50 years of age not taking HRT, on average, 8 out of 1000 are expected to have a stroke over a 5-year period. For women around 50 years of age taking HRT, there will be 11 cases per 1000 users over 5 years (i.e. 3 additional cases).

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

Other medicines and Paudien
Some medicines may interfere with the effect of Paudien. This could lead to irregular bleeding. This applies to the following medicines:

• Medicines for epilepsy (such as barbiturates, phenytoin, primidone, carbamazepine, and possibly oxcarbazepine, topiramate, and felbamate).
• Medicines for tuberculosis (such as rifampicin, rifabutin).
• Medicines for HIV and Hepatitis C infection (so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as nevirapine, efavirenz, ritonavir, and nelfinavir).
• Herbal remedies containing St John's wort (Hypericum perforatum).
• Medicines for the treatment of fungal infections (such as griseofulvine, itraconazole, ketoconazole, voriconazole, and fluconazole).
• Medicines for the treatment of bacterial infections (such as clarithromycin and erythromycin).
• Medicines for the treatment of certain heart conditions, or for high blood pressure (such as verapamil and diltiazem).
• Grapefruit juice.

HRT may affect how some other medicines work:

• an epilepsy medicine (lamotrigine), as it could increase the frequency of seizures.
• Combination regimens for hepatitis C virus (HCV) based on ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir may cause an increase in liver function blood test results (increase in liver enzyme ALT) in women using COCs containing ethinylestradiol. Paudien contains estradiol valerate instead of ethinylestradiol. It is not known whether an increase in liver enzyme ALT can occur when Paudien is used with this HCV combination regimen. Your doctor will advise you. Inform your doctor or pharmacist if you are taking or have recently taken or might take any other medicines, including those without a prescription, herbal medicines, or other natural products. Your doctor will advise you.

Laboratory tests
If you need to have blood tests, inform your doctor or laboratory staff that you are taking Paudien, as this medicine may affect the results of certain tests.

Pregnancy and breastfeeding
Paudien is used only for postmenopausal women. If you become pregnant, stop taking Paudien and contact your doctor.

Driving and using machines
No effects on the ability to drive or operate machinery have been observed.

Paudien contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Paudien

Always take this medicine exactly as your doctor has told you. Consult your doctor or pharmacist if you have any doubts.
Your doctor will prescribe the lowest effective dose to treat your symptoms for the shortest possible duration. Consult your doctor if you think this dose is too strong or not strong enough.

• Take 1 tablet every day, preferably at the same time each day.
• Swallow the tablet whole with a glass of water.
• You may take Paudien with or without food.
• Start the next calendar pack the day after finishing the current calendar pack.
• Do not take a break between packs.

If you are currently taking other HRT preparations
Continue until you have finished your current pack and taken all tablets for that month.
Take the first tablet of Paudien the following day. Do not take a break between the previous HRT tablets and Paudien tablets.
If you are using an HRT treatment with a one-week break
Start Paudien the day after the treatment-free period.
If this is your first HRT treatment
You may start taking Paudien tablets at any time.
If you take more Paudien than you should
If you accidentally take too many Paudien tablets, you may feel unwell, experience vomiting or have bleeding similar to menstruation. No specific treatment is required, but if you are concerned, consult your doctor or pharmacist.
If you forget to take Paudien
If you forget to take your tablet at the usual time and are less than 24 hours late, take a tablet as soon as possible. Then take the next tablet at your usual time.
If you are more than 24 hours late, leave the missed tablet in the pack. Continue taking the remaining tablets at your usual time each day. Do not take a double dose to make up for the missed tablet. If you forget to take the tablet for several days, you may experience bleeding.
If you stop taking Paudien
You may start experiencing again the usual symptoms of menopause, which may include hot flushes, sleep disturbances, nervousness, dizziness or vaginal dryness. Consult your doctor or pharmacist if you wish to stop taking Paudien.
If you need surgery
If you are scheduled for surgery, inform your surgeon that you are taking Paudien. You may need to stop taking Paudien approximately 4 to 6 weeks before the operation to reduce the risk of blood clots (see section 2 "Blood clots in veins (venous thrombosis)"). Ask your doctor when you can start taking Paudien again.
If you have any further 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 everyone gets them.
The following diseases are reported more frequently in women using HRT than in women who do not
use HRT:

• breast cancer;
• abnormal growth or cancer of the lining of the uterus (endometrial hyperplasia or cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• heart disease;
• stroke;
• possible memory loss if HRT is started after the age of 65. For further information on these adverse effects, see section 2. The following adverse reactions may occur during treatment with Paudien.

Unexpected menstrual-like bleeding is common during the first months of treatment with Paudien.
It is usually temporary and normally resolves with continued treatment. If not, contact your
doctor.
Common (may affect up to 1 in 10 people)

• headache
• malaise
• breast pain, hot flushes, vaginal bleeding

Uncommon (may affect up to 1 in 100 people)

• weight gain
• fatigue, loss of appetite leading to weight loss, aggressive reaction, difficulty sleeping, drowsiness, nervousness, inability to achieve orgasm, decreased sexual activity
• migraine, dizziness, tingling, hyperactivity
• venous blood clots (leg pain) (see also section 2 "Blood clots in veins [thrombosis]"), inflammation of veins, high blood pressure, nosebleeds
• abdominal pain, diarrhoea, general malaise, constipation, flatulence, dry mouth
• liver pain
• dry skin with scaly red patches known as psoriasis, acne, itching, increased sweating, dry skin
• muscle pain, leg cramps
• problems with the lining of the uterus, vaginal candidiasis, painful menstruation, genital itching
• fatigue, generalized fluid retention in tissues, facial swelling

The following adverse reactions have been reported with other HRTs:

• gallbladder disease;
• various skin disorders:
  • skin discoloration, especially on the face or neck, known as "pregnancy mask" (chloasma),
  • red, painful skin nodules (erythema nodosum),
  • skin rash with red patches or lesions (erythema multiforme).

Reporting of side effects
If you experience any adverse reaction, including those not listed in this leaflet, contact your
doctor or pharmacist. You can also report adverse reactions directly via the system
http://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 Paudien

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date 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 medicines 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 Paudien contains

• The active substances are 1 mg of estradiol valerate and 2 mg of dienogest.
• The other components are iron oxide, monohydrate lactose, magnesium stearate, maize starch, povidone, anhydrous colloidal silicon dioxide. Description of the appearance of Paudien and pack contents: Paudien tablets are pinkish, round, with a diameter of 6 mm. They are supplied in calendar packs containing 28, 3 x 28 or 6 x 28 tablets. Not all pack sizes may be marketed.

Marketing Authorization Holder
Farmitalia S.r.l.
Via Pinciana 25
00198 Rome, Italy
Manufacturer
Dr. Kade Pharmazeutische Fabrik GmbH
Rigistraße 2
12277 Berlin (Germany)
This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Germany: Ladivella 1 mg/2 mg Tabletten
Netherlands: LaFleur 1 mg/2 mg tabletten
Belgium: Laclimella 1 mg/2 mg comprimés
Luxembourg: Laclimella 1 mg/2 mg comprimés
Italy: Paudien 1 mg/2 mg compresse