Zafrilla

Patient Information Leaflet

Zafrilla, 2 mg, tablets
Dienogest
Please read this leaflet carefully before taking this medicine, as 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 you personally. Do not share it with others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Zafrilla is and what it is used for

Zafrilla is used in the treatment of endometriosis (painful symptoms caused by
abnormal growth of the uterine lining outside the uterus). Zafrilla contains a hormone called a progestagen,
named dienogest.

2. Important information before taking Zafrilla

When not to take Zafrilla

Do not take Zafrilla if:

• you have a blood clot (venous thromboembolic disease) in your veins. This may occur, for example, in blood vessels in your legs (deep vein thrombosis) or lungs (pulmonary embolism). See also “Zafrilla and venous blood clots” below;
• you have or have had in the past severe arterial disease, including cardiovascular disease such as heart attack, stroke, or heart disease causing reduced blood flow (angina pectoris). See also “Zafrilla and arterial blood clots” below;
• you have diabetes with blood vessel damage;
• you have or have had in the past severe liver disease (and liver function tests have not returned to normal). Symptoms of liver disease may include yellowing of the skin and/or itching of the whole body;
• you have or have had in the past, or there is suspicion of, a benign or malignant tumour dependent on sex hormones, such as breast cancer or genital organ tumour;
• you have unexplained vaginal bleeding;
• you are allergic (hypersensitive) to dienogest or any of the other ingredients of this medicine (listed in section 6).

If any of these conditions occur for the first time while taking Zafrilla, you must
stop taking it immediately and contact your doctor.

Warnings and precautions

Before starting Zafrilla, discuss this with your doctor or pharmacist.
While taking Zafrilla, you must not use hormonal contraceptives
in any form (tablet, patch, vaginal ring).
Zafrilla is not a contraceptive. To prevent pregnancy, you should use
condoms or other non-hormonal contraceptive methods.

In certain situations, extra caution is required when taking Zafrilla. Regular medical check-ups may be necessary. Inform your doctor if any of the following apply to you:

• you have ever 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 Zafrilla;
• you develop liver disease while taking Zafrilla. Symptoms may include yellowing of the skin, eyes, or itching all over the body. Inform your doctor if you experienced such symptoms during a previous pregnancy;
• you have diabetes or had gestational diabetes during a previous pregnancy;
• you have ever had chloasma (brownish-yellow patches on the skin, especially on the face). In this case, avoid prolonged exposure to sunlight or ultraviolet radiation;
• you experience lower abdominal pain while taking Zafrilla.

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

Zafrilla and severe uterine bleeding

While taking Zafrilla, uterine bleeding may worsen, 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 referred to as uterine fibroids. If bleeding is heavy and persists for a long time, it may lead to a reduction in red blood cells (anaemia), which may be severe in some cases. If anaemia occurs, discuss with your doctor whether treatment with Zafrilla should be discontinued.

Zafrilla and changes in bleeding pattern

Most women treated with Zafrilla experience changes in their menstrual bleeding pattern (see section 4).

Zafrilla 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 progestagens, such as Zafrilla. Very rarely, blood clots may cause serious, permanent disability or even death.

The risk of venous blood clots increases:

• with age;
• if you are overweight;
• if you or a close family member has had a blood clot in the leg (thrombosis), lungs (pulmonary embolism), or another organ at a young age;
• if you are scheduled for surgery, have had a serious accident, or will be immobile for a prolonged period. It is important to inform your treating doctor that you are taking Zafrilla, as treatment may need to be interrupted. Your doctor will advise when you can restart Zafrilla. Usually, this is about two weeks after you are able to walk again.

Zafrilla and arterial blood clots

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

The risk of arterial blood clots increases:

• in women who smoke – it is strongly recommended that you stop smoking if you are taking Zafrilla, especially if you are over 35 years old;
• if you are overweight;
• if a close relative has had a heart attack or stroke at a young age;
• if you have high blood pressure.

Please consult your doctor before taking Zafrilla.

You must stop taking Zafrilla and contact your doctor immediately if you notice any possible symptoms of a blood clot, such as:

• severe pain and/or swelling in one leg;
• sudden severe chest pain, possibly radiating to the left arm;
• sudden shortness of breath;
• sudden cough without an obvious cause;
• any unusual, severe, or persistent headache or worsening of migraine;
• partial or complete blindness or double vision;
• difficulty speaking or inability to speak;
• dizziness or fainting;
• weakness, unusual sensation, or numbness in any part of the body.

Zafrilla and cancer

Current data do not clearly indicate whether Zafrilla 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 not known whether this is caused by the treatment. It may, for example, be due to the fact that more tumours are detected and detected earlier in women taking hormones because they are examined more frequently by doctors. The incidence of breast cancer gradually decreases after stopping hormonal treatment. Regular breast examinations are important, and you should contact your doctor if you detect a lump.

In rare cases, benign liver tumours have been reported in women taking hormones, and even more rarely, malignant liver tumours. Contact your doctor if you experience extremely severe abdominal pain.

Zafrilla and osteoporosis

Changes in bone mineral density (BMD)

Taking Zafrilla may affect bone strength in adolescents (12 to below 18 years).
If you are under 18 years of age, your doctor will individually assess the benefits and risks of using Zafrilla, taking into account possible risk factors for bone loss (osteoporosis).
If you are taking Zafrilla, 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 consider the benefits and risks of treatment with Zafrilla, as Zafrilla has a moderate effect in suppressing the body's production of oestrogen (another type of female hormone).

Children and adolescents

Zafrilla must not be used in girls before their first menstrual period.
Taking Zafrilla may affect bone strength in adolescents (12 to below 18 years).
Therefore, if you are under 18 years of age, your doctor will individually assess the benefits and risks of using Zafrilla, taking into account possible risk factors for bone loss (osteoporosis).

Zafrilla and other medicines

Inform your doctor or pharmacist about any medicines you are currently taking, have recently taken, or plan to take.
You should also inform any other doctor or dentist prescribing a new medicine (or pharmacist) that you are taking Zafrilla.
Some medicines may affect the blood concentration of Zafrilla and reduce its effectiveness or cause side effects.
These include:

• medicines used for the following conditions:
• epilepsy (e.g. phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate);
• tuberculosis (e.g. rifampicin);
• HIV infection and hepatitis C (protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as ritonavir, nevirapine, efavirenz);
• fungal infections (griseofulvin, ketoconazole);
• the herbal remedy St John’s wort (Hypericum perforatum).

Before taking any medicine, consult your doctor or pharmacist.

Zafrilla with food and drink

While taking Zafrilla, you should avoid drinking grapefruit juice, as it may increase the blood concentration of Zafrilla. This may increase the risk of side effects.

Laboratory tests

If you need to have a blood test, inform your doctor or laboratory staff that you are taking Zafrilla, as it may affect the results of certain tests.

Pregnancy, breastfeeding and fertility

Do not take Zafrilla during pregnancy or while breastfeeding.

Driving and using machines

No effects on the ability to drive or operate machinery have been observed in people taking Zafrilla.

Zafrilla contains lactose.
Patients previously diagnosed with intolerance to certain sugars should consult their doctor before taking this medicine.

3. How to take Zafrilla

This medicine should always be taken as directed by the physician. If in doubt, consult
your doctor or pharmacist.
The usual dose for adults is 1 tablet per day.
The following information applies to the use of Zafrilla unless otherwise instructed by the doctor.
It is important to follow these instructions, as failure to do so may result in the patient not obtaining
the full benefits of treatment with Zafrilla.
Treatment with Zafrilla may be started on any day of the natural cycle.
Adults: Take one tablet daily, preferably at the same time each day, with a small amount of liquid if necessary.
After finishing a pack, start the next one without a break. Continue taking tablets also during menstrual bleeding days.
Taking more Zafrilla than recommended
There have been no reports of serious harmful effects following a single intake of an excessive number of Zafrilla tablets. However, if in doubt, contact your doctor.
Missing a dose of Zafrilla, or experiencing vomiting or diarrhoea
The effectiveness of Zafrilla may be reduced if a tablet is missed. If one or more tablets are missed, take one tablet as soon as possible and continue taking one tablet at the usual time the next day.
If vomiting occurs within 3–4 hours after taking Zafrilla, or if severe diarrhoea develops, there is a risk that the active substance may not be fully absorbed into the body.
These situations are similar to missing a tablet. After vomiting or severe diarrhoea occurring within 3–4 hours of taking Zafrilla, take another tablet as soon as possible.
Do not take a double dose to make up for a missed tablet.
Stopping treatment with Zafrilla
If the patient stops taking Zafrilla, previous symptoms of endometriosis may return.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like any medicine, this medicine may cause adverse effects, although not everyone will experience them.
These effects are more common during the first months after starting treatment with Zafrilla
and usually subside with continued use. Changes in bleeding pattern may also occur, such as spotting, irregular bleeding, or absence of menstruation.

Common (occurring in up to 1 in 10 women)

• weight gain;
• low mood, sleep disturbances, nervousness, loss of interest in sex, or mood changes;
• headache or migraine;
• nausea, abdominal pain, flatulence, bloating, 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 (occurring in up to 1 in 100 women)

• anaemia;
• weight loss or increased appetite;
• anxiety, depression, or sudden mood changes;
• autonomic nervous system imbalance (which controls unconscious bodily functions, e.g. sweating), or attention disturbances;
• dry eyes;
• tinnitus;
• non-specific circulatory disorders or palpitations;
• low blood pressure;
• shortness of breath;
• diarrhoea, constipation, abdominal discomfort, gastritis, gingivitis;
• dry skin, excessive sweating, severe generalized itching, hirsutism (excessive hair growth in a male pattern), brittle nails, dandruff, skin inflammation, abnormal hair growth, photosensitivity, 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, vaginal discharge, pelvic pain, atrophic vaginitis with discharge (atrophic vulvovaginitis), or breast lump(s);
• fluid retention leading to oedema.

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

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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. Adverse effects can also be reported to the marketing authorisation holder. Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Zafrilla

Keep this medicine out of the sight and reach of children.
Store in the original packaging to protect from light.
No special temperature storage conditions apply to this medicine.
Do not use this medicine after the expiry date stated on the packaging following "EXP".
The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Zafrilla contains
The active substance is dienogest. Each tablet contains 2 mg of dienogest.
Other ingredients are: monohydrate lactose, pregelatinized corn starch, microcrystalline cellulose,
povidone K-25, crospovidone (type A), talc, magnesium stearate.

What Zafrilla looks like and contents of the pack
Zafrilla 2 mg are white or almost white, round, biconvex tablets with bevelled edges, embossed with the code "G93" on one side and "RG" on the other side. The tablet diameter is 7 mm.
Green PVC/aluminum blisters marked with days of the week, packed in cardboard boxes containing 28, 84 or 168 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
GEDEON RICHTER POLSKA Sp. z o.o.
ul. Ks. J. Poniatowskiego 5
05-825 Grodzisk Mazowiecki
Poland

Manufacturer:
Gedeon Richter Plc.
Gyömrői út 19-21
1103 Budapest
Hungary

For further information about the medicinal product and its names in other European Economic Area (EEA) countries, please contact:
GEDEON RICHTER POLSKA Sp. z o.o.
Medical Department
ul. Ks. J. Poniatowskiego 5
05-825 Grodzisk Mazowiecki
Poland
Tel. +48 (22) 755 96 48
[email protected]
Fax: +48 (22) 755 96 24
((logo of the marketing authorisation holder))