Probella

Patient Information Leaflet

Probella, 2 mg tablets
Dienogest
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet as 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 adverse effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Leaflet Contents

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

1. What Probella is and what it is used for

Probella is used in the treatment of endometriosis (painful symptoms caused by abnormally located endometrial tissue). Probella contains a hormone, a progestogen called dienogest.

2. Important information before using Probella

When NOT to take Probella

• If you currently have a blood clot (venous thromboembolic disease) in your blood vessels. This may occur, for example, in the blood vessels of the legs (deep vein thrombosis) or lungs (pulmonary embolism). See also "Probella and venous blood clots" below.
• If you currently have or have previously had a severe arterial disease, including cardiovascular disease such as myocardial infarction, stroke, or heart disease causing reduced blood flow (angina pectoris). See also "Probella and arterial blood clots" below.
• If you have diabetes with blood vessel damage.
• If you currently have or have previously had severe liver disease (and liver function parameters have not returned to normal). Symptoms of liver disease may include yellowing of the skin and/or itching of the whole body.
• If you currently have or have previously had a benign or malignant liver tumour.
• If you currently have, have previously had, or are suspected of having a malignant tumour dependent on sex hormones, such as breast cancer or a genital organ tumour.
• If you have unexplained vaginal bleeding.
• If you are allergic (hypersensitive) to dienogest or any of the other ingredients of this medicine (listed in section 6 and at the end of section 2).

If any of these conditions occurs for the first time while taking Probella, you must
immediately stop taking the medicine and consult your doctor.
Warnings and precautions

While taking Probella, you must not use hormonal contraceptives
in any form (tablet, patch, vaginal ring).
Probella is NOT a contraceptive. To prevent pregnancy, you should use
condoms or other non-hormonal contraceptive methods.
In certain situations, special caution is required when using Probella.
Regular medical examinations may be necessary. You should inform your doctor if any of the following
conditions apply to you.
If:

• You have previously had a blood clot (venous thromboembolic disease), or a close family member had a blood clot at a relatively young age;
• A close relative has breast cancer;
• You have ever had depression;
• You have high blood pressure or develop high blood pressure while taking Probella;
• You develop liver disease while taking Probella. Symptoms may include: yellowing of the skin, eyes, or itching of the whole body. Inform your doctor if such symptoms occurred during a previous pregnancy;
• You have diabetes or had gestational diabetes during a previous pregnancy;
• You have ever had chloasma (brownish patches on the skin, especially on the face). In such a case, avoid excessive exposure to sunlight or ultraviolet radiation;
• You experience lower abdominal pain while taking Probella.

While taking Probella, the chance of becoming pregnant is reduced because Probella may
affect ovulation.
If pregnancy occurs while taking Probella, there is a slightly increased risk
of ectopic pregnancy (the embryo develops outside the uterus). Before starting Probella,
you should inform your doctor if you have previously had an ectopic pregnancy or have
tubal disorders.

Probella and severe uterine bleeding

Uterine bleeding, for example in women with a condition where the uterine lining (endometrium)
grows into the muscular layer of the uterus, known as adenomyosis, or benign uterine tumours,
sometimes called uterine fibroids, may worsen during treatment with Probella. If
bleeding is heavy and persists for a long time, this may lead to a decrease in
red blood cells (anaemia), which may be severe in some cases. In case of
anaemia, discuss with your doctor whether discontinuation of Probella is necessary.

Probella and changes in bleeding pattern

Most women treated with Probella experience changes in menstrual bleeding patterns
(see section 4. "Possible side effects").

Probella and venous blood clots

Some studies suggest a slight, statistically non-significant increased risk
of blood clots in the legs (venous thromboembolic disease) associated with the use of medicines
containing progestogens, such as Probella. Very rarely, blood clots may cause
severe, permanent disability or even death.

The risk of venous blood clots increases:

• With age;
• If you are overweight;
• If you or a close relative had a blood clot in the leg (thrombosis), lungs (pulmonary embolism), or another organ at a young age;
• If surgery is planned, a serious accident has occurred, or prolonged immobilisation is expected. It is important to inform your doctor in advance about taking Probella, as treatment may need to be discontinued. Your doctor will advise when to restart Probella. Usually, this is two weeks after recovery.

Probella and arterial blood clots

There is limited evidence of an association between the use of medicines containing progestogens, such
as Probella, and an increased risk of arterial blood clots, for example in the blood vessels
of the heart (myocardial infarction) or brain (stroke). In women with hypertension, the risk
of stroke may be slightly increased with the use of medicines such as Probella.

The risk of arterial blood clots increases:

• In women who smoke – quitting smoking is recommended when taking Probella, especially in women over 35 years of age;
• If you are overweight;
• If a close relative had a myocardial infarction or stroke at a young age;
• If you have high blood pressure.

You should consult your doctor before taking Probella.
You must stop taking Probella and contact your doctor immediately
if you notice possible symptoms of a blood clot, such as:

• Severe pain and/or swelling in one leg;
• Sudden severe chest pain, which may radiate to the left arm;
• Sudden shortness of breath;
• Sudden cough without an obvious cause;
• Any unusual, severe, or prolonged headache or worsening of migraine;
• Partial or complete blindness or double vision;
• Difficulty speaking or inability to speak;
• Dizziness or fainting;
• Weakness, strange sensation, or numbness in any part of the body.

Probella and cancer

Current data do not clearly indicate whether Probella increases the risk of breast cancer or not.
Breast cancer has been observed slightly more frequently in women taking hormones compared
to women not taking hormones, but it is unknown whether this is caused by the treatment.
For example, it may be due to the fact that more tumours are detected and detected
earlier in women taking hormones because they are examined more frequently by a doctor. The incidence
of breast cancer gradually decreases after stopping hormonal treatment.
It is important to examine your breasts regularly and contact your doctor if you detect
any lump.
In rare cases, benign liver tumours have been reported in women using hormones, and in even
rarer cases, malignant liver tumours. Contact your doctor if you experience severe
abdominal pain.

Probella and osteoporosis

Changes in bone mineral density (BMD)

The use of Probella may affect bone strength in adolescents (12 to less than 18 years).
Therefore, if the patient is under 18 years of age, the doctor will individually assess the benefits and risks of using Probella, taking into account possible risk factors for bone loss (osteoporosis).
If you are taking Probella, for bone health you should ensure adequate intake of calcium
and vitamin D through diet or supplements.
If you are at increased risk of developing osteoporosis (weakening of bones due to
loss of bone minerals), your doctor will carefully evaluate the benefits and risks of
treatment with Probella, as Probella has a moderate suppressive effect on
the body's production of estrogen (another type of female hormone).

Probella and other medicines

You should always inform your doctor about any medicines or herbal products you are currently taking.
You should also inform any other doctor or dentist prescribing a new medicine (or a pharmacist)
that you are taking Probella.
Some medicines may affect the blood concentration of Probella and reduce its effectiveness or
cause adverse effects.
These include:

• Medicines used for the following conditions:
  o Epilepsy (e.g. phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate);
  o Tuberculosis (e.g. rifampicin);
  o HIV and hepatitis C virus infections (protease inhibitors and non-nucleoside reverse transcriptase inhibitors, such as ritonavir, nevirapine, efavirenz);
  o Fungal infections (griseofulvin, ketoconazole);
• St. John's wort ( Hypericum perforatum ).

Before taking any medicine, consult your doctor or pharmacist.
Probella with food and drink

While taking Probella, you should avoid drinking grapefruit juice, as it may
increase the blood concentration of Probella. This may increase the risk of
adverse effects.
Laboratory tests

If a blood test is required, inform your doctor or laboratory staff
that you are taking Probella, as Probella may affect the results of certain tests.
Pregnancy and breastfeeding

Probella must not be used during pregnancy or breastfeeding.
Driving and operating machinery

No effect on the ability to drive or operate machinery has been observed in individuals taking Probella.
Probella contains lactose

If you have previously been diagnosed with an intolerance to certain sugars, you should contact
your doctor before taking this medicine.
Children and adolescents

Probella must not be used in girls before their first menstrual period.
The use of Probella may affect bone strength in adolescents (12 to less than 18 years).
Therefore, if the patient is under 18 years of age, the doctor will individually assess the benefits and risks of using
Probella, taking into account possible risk factors for bone loss (osteoporosis).

3. How to use Probella

Probella must always be taken exactly as directed by the physician. In case of doubt, the patient should contact the doctor or pharmacist again. The usual dose for adults is 1 tablet per day.
The following information applies to Probella unless otherwise instructed by the physician. The patient should follow these instructions carefully; otherwise, she may not obtain the full benefit of Probella treatment.
Treatment with Probella may be started on any day of the natural cycle.
Adults: One tablet should be taken daily, preferably at the same time each day, and if necessary, with a small amount of liquid. After finishing one pack, the next pack should be started immediately without a break. Tablets should be continued to be taken also during menstrual bleeding days.

Overdose of Probella
There have been no reports of serious harmful effects following a single intake of an excessive number of Probella tablets. However, if in doubt, the patient should contact the doctor.

Missed dose or occurrence of vomiting or diarrhoea
The effectiveness of Probella will be reduced if a tablet is missed.
If one or more tablets are missed, only one tablet should be taken as soon as possible, and the patient should continue taking one tablet daily at the usual time.
If vomiting occurs within 3–4 hours after taking Probella, or if severe diarrhoea develops, there is a risk that the active substance of the tablet may not be absorbed by the body. This situation is almost equivalent to missing tablets. In case of vomiting or diarrhoea occurring within 3–4 hours after taking Probella, another tablet should be taken as soon as possible.
A double dose must not be taken to make up for a missed tablet.

Discontinuation of Probella
If the patient stops taking Probella, previous symptoms of endometriosis may recur.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although they do not occur in everyone.
These effects are more common during the first few months after starting Probella
and usually subside with continued use. Bleeding pattern changes may also occur,
such as spotting, irregular bleeding, or absence of menstruation.

Common (occur in 1 to 10 out of 100 patients)

• weight gain
• low mood, sleep problems, nervousness, loss of interest in sex, or mood changes
• headache or migraine
• nausea, abdominal pain, bloating, distended abdomen, or vomiting
• acne or hair loss
• back pain
• breast discomfort, ovarian cyst, or hot flushes
• uterine and (or) vaginal bleeding, including spotting
• weakness or irritability

Uncommon (occur in 1 to 10 out of 1,000 patients)

• anaemia
• weight loss or increased appetite
• anxiety, depression, or sudden mood changes
• autonomic nervous system imbalance (controls subconscious body functions, e.g. sweating) or attention disorders
• dry eyes
• tinnitus
• circulatory disturbances or palpitations
• low blood pressure
• shortness of breath
• diarrhoea, constipation, abdominal discomfort, gastritis, gingivitis
• dry skin, excessive sweating, generalized severe itching, hirsutism (male-pattern hair growth), brittle nails, pityriasis, dermatitis, abnormal hair growth, photosensitivity reaction, or pigmentation disorders
• bone pain, muscle cramps, pain and (or) heaviness in arms and hands or legs and feet
• urinary tract infection
• vaginal candidiasis, genital dryness, discharge, pelvic pain, atrophic genital inflammation with discharge (atrophic vulvovaginitis), or breast lump(s)
• fluid retention with swelling

Additional adverse effects in adolescents (12 to less than 18 years): loss of bone density.

Reporting of adverse effects
If any adverse effects occur, including those not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warszawa
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Probella

Keep in the original packaging to protect from light.
The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the stated month. The marking on the packaging after the abbreviation EXP indicates the expiry date, and after the abbreviation Lot indicates the batch number.
Medicines must 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 pack and other information

What Probella contains

• The active substance is dienogest. Each tablet contains 2 mg of dienogest.
• The other ingredients are: monohydrate lactose, corn starch, povidone (K30), magnesium stearate (vegetable origin).

What Probella looks like and contents of the pack
Probella tablets are round, white tablets with a diameter of 5 mm.
The tablets are supplied in a blister pack containing 28 tablets.
Boxes contain one, three or six blisters with 28 tablets each (calendar packs).
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel.: + 48 22 364 61 01
Manufacturer
Laboratorios León Farma, S.A.
C/ La Vallina s/n, Poligono Industrial Navatejera
24193-León
Spain