ZAFRIL 2 mg TABLETS

2. What you need to know before you take Zafril

Do not take Zafril:

• if you have a blood clot(thromboembolic disorder) in your veins. This can occur, for example, in the blood vessels of your legs (deep vein thrombosis) or lungs (pulmonary embolism). See also “Zafril and blood clots in the veins”below;
• if you have or have ever had a severe arterial disease, including cardiovascular disease, such as a heart attack, stroke, or heart diseasethat causes a reduction in blood flow (angina pectoris). See also “Zafril and blood clots in the arteries”below;
• if you have diabeteswith blood vessel damage;
• if you have or have ever had a severe liver disease(and liver function values have not returned to normal). Symptoms of liver disease can be yellowing of the skin and/or itching all over the body;
• if you have or have ever had a benign or malignant liver tumor;
• if you have or have ever had, or are suspected to have, a malignant tumorthat is dependent on sex hormones, such as breast cancer or genital organ cancer;
• if you have vaginal bleedingof unknown cause;
• if you are allergicto dienogest or any of the other ingredients of this medicine (listed in section 6).

If any of these disorders occur for the first time while taking Zafril, stop taking it immediately and consult your doctor.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Zafril.

You must not use hormonal contraceptives of any kind (pills, patches, intrauterine system) while taking Zafril.

Zafril is nota contraceptive. If you want to avoid pregnancy, you will need to use condoms or other non-hormonal contraceptive methods.

In some cases, you will need to take special care while taking Zafril, and it may be necessary for your doctor to examine you from time to time. Tell your doctor if you are in any of the following situations:

• if you have ever had a blood clot(venous thromboembolism) or a close relative has had a blood clot at a relatively early age;
• if you have a close relative who has had breast cancer;
• if you have ever had depression;
• if you have high blood pressureor develop high blood pressure while taking Zafril;
• if you develop liver diseasewhile taking Zafril. Symptoms can include yellowing of the skin or eyes or itching all over the body. Also, inform your doctor if you have had any of these symptoms in a previous pregnancy;
• if you have diabetesor have had diabetes temporarily in a previous pregnancy;
• if you have ever had chloasma(brown patches on the skin, especially on the face); if so, avoid excessive exposure to the sun or ultraviolet radiation;
• if you experience lower abdominal painwhile taking Zafril.

While taking Zafril, the likelihood of becoming pregnant is reduced because this medicine can affect ovulation.

If you become pregnant while taking Zafril, you have a slightly higher riskof having an ectopic pregnancy (the embryo develops outside the uterus). Inform your doctor before starting to take Zafril if you have had an ectopic pregnancy or have a condition that affects the function of the fallopian tubes.

Zafril and severe uterine bleeding

Uterine bleeding may worsen with the use of Zafril, for example, in women who have a condition where the uterine lining (endometrium) grows into the muscular layer of the uterus, known as adenomyosis or benign uterine tumors, sometimes called fibroids or uterine myomas (leiomyomas). If the bleeding is heavy and prolonged, it can lead to low red blood cell counts (anemia), which can be severe in some cases. If you have anemia, you should consult your doctor to determine if you should stop taking Zafril.

Zafril and changes in bleeding pattern

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

Zafril and blood clots in the veins

Some studies indicate that there may be a slight, non-statistically significant increase in the risk of blood clots in the legs (venous thromboembolism)associated with the use of progestogen-containing medications like Zafril. In very rare cases, blood clots can cause permanent disability and can be life-threatening.

The risk of blood clots in the veinsincreases:

• with age;
• if you are overweight;
• if you or a close relative have had a blood clot in the leg (thrombosis), lungs (pulmonary embolism), or other organ at a young age;
• if you need to undergo surgery, have had a serious accident, or have been immobilized for a prolonged period. It is essential that you inform your doctor in advance that you are taking Zafril, as you may need to stop treatment. Your doctor will tell you when to start taking Zafril again. This usually occurs about two weeks after regaining mobility.

Zafril and blood clots in the arteries

There is limited evidence of a link between progestogen-only preparations like Zafril and an increased risk of having a blood clot, for example, in the blood vessels of the heart (heart attack) or brain (stroke). In women with high blood pressure, these preparations may slightly increase the risk of stroke.

The risk of having a blood clot in the arteriesincreases:

• if you smoke. It is strongly recommended that you stop smoking while taking Zafril, 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.

Zafril and cancer

With the currently available data, it is not known for certain whether Zafril increases or does not increase the risk of breast cancer. It has been observed that breast cancer is slightly more common in women taking hormones compared to those not taking them, but it is not known if this is due to the treatment. For example, it is possible that more tumors are detected and detected earlier in women taking hormones because the doctor examines them more frequently. The occurrence of breast tumors decreases gradually after stopping hormonal treatment. It is essential that you regularly check your breastsand consult your doctor if you detect any lump.

In rare cases, in women taking hormones, benign liver tumors have been reported, and in fewer cases, malignant liver tumors. Contact your doctor if you experience unusually severe stomach pain.

Zafril and osteoporosis

Changes in bone mineral density (BMD)

Taking Zafril may affect bone strength in adolescents (12 to less than 18 years old). Therefore, if you are under 18 years old, your doctor will carefully weigh the benefits and risks of taking Zafril for you as an individual patient, considering possible risk factors for bone loss (osteoporosis).

If you take Zafril, it will be helpful for your bones to receive adequate calcium and vitamin D, either through your diet or with dietary supplements.

If you are at higher risk of osteoporosis (weakening of bones due to mineral loss), your doctor will carefully evaluate the risks and benefits of treatment with Zafril because Zafril causes moderate suppression of estrogen production (another type of female hormone) in your body.

Children and adolescents

Zafril is not indicated in girls before menarche (first menstruation).

Taking Zafril may affect bone strength in adolescents (12 to less than 18 years old). Therefore, if you are under 18 years old, your doctor will carefully weigh the benefits and risks of taking Zafril for you as an individual patient, considering possible risk factors for bone loss (osteoporosis).

Taking Zafril with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Also, inform any other doctor or dentist prescribing you another medicine (or pharmacist) that you are taking Zafril.

Some medicines may affect the levels of Zafril in your blood and make it less effective or cause side effects.

These include:

• medicines used to treat:

• epilepsy(e.g., phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate);
• tuberculosis(e.g., rifampicin);
• HIV and hepatitis C infections(protease inhibitors and non-nucleoside reverse transcriptase inhibitors, such as ritonavir, nevirapine, efavirenz);
• fungal infections(griseofulvin, ketoconazole).

• preparations containing St. John's Wort.

Consult your doctor or pharmacist before using any medicine.

Taking Zafril with food and drinks

During treatment with Zafril, you should avoid drinking grapefruit juice, as it can increase the levels of the medicine in your blood. This can increase the risk of having side effects.

Lab tests

If you need a blood test, inform your doctor or laboratory staff that you are taking Zafril, as Zafril may affect the results of some tests.

Pregnancy, breastfeeding, and fertility

Do not take Zafril if you are pregnant or breastfeeding.

Driving and using machines

No effects on the ability to drive and use machines have been observed in users of Zafril.

Zafril contains lactose

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Zafril

Follow the instructions for taking this medicine exactly as prescribed by your doctor. If you are unsure, consult your doctor or pharmacist again.

The recommended dose for adults is one tablet per day.

The following statements apply to Zafril unless your doctor tells you otherwise. Follow these instructions; otherwise, you will not benefit fully from treatment with Zafril.

You can start treatment with Zafril on any day of your natural cycle.

Adults: take one tablet every day, preferably at the same time, with a little liquid if necessary. When you finish one pack, start the next one without interruption. Continue taking the tablets even during the days of menstrual bleeding.

If you take more Zafril than you should

No serious harmful effects have been reported from taking too many Zafril tablets at once. However, if you are concerned, contact your doctor.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Zafril or have vomiting or diarrhea

Zafril will be less effective if you forget to take a tablet. If you forget one or more tablets, take a single tablet as soon as you remember, and then continue the next day, taking the tablet at the usual time.

If you have vomiting within 3-4 hours after taking a Zafril tablet or have severe diarrhea, there is a risk that your body will not absorb the active ingredient of the tablet. This is similar to what happens when you forget to take a tablet. After vomiting or diarrhea within 3-4 hours after taking Zafril, you should take another tablet as soon as possible.

Do not take a double dose to make up for forgotten doses.

If you stop taking Zafril

If you stop taking Zafril, the original symptoms of endometriosis may return.

If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. These effects are more common during the first few months after starting to take Zafril and usually disappear with continued use. You may also experience changes in your bleeding pattern, such as spotting, irregular bleeding, or complete cessation of menstruation.

Common(affect up to 1 in 10 people)

• weight gain;
• depressed mood, sleep disorders, nervousness, loss of interest in sex, or mood changes;
• headache or migraine;
• nausea, abdominal pain, flatulence, abdominal swelling, or vomiting;
• acne or hair loss;
• back pain;
• breast tenderness, ovarian cysts, or hot flashes;
• uterine/vaginal bleeding, including spotting;
• weakness or irritability.

Uncommon(affect up to 1 in 100 people)

• low red blood cell count (anemia);
• weight loss or increased appetite;
• anxiety, depression, or mood changes;
• autonomic nervous system imbalance (which controls unconscious body functions, e.g., sweating) or attention disorders;
• dry eye;
• ringing or buzzing in the ears (tinnitus);
• non-specific circulatory problems or palpitations;
• low blood pressure;
• breathing difficulties;
• diarrhea, constipation, abdominal discomfort, gastrointestinal inflammation, gingivitis;
• dry skin, excessive sweating, intense itching all over the body, male-pattern hair growth (hirsutism), fragile nails, dandruff, dermatitis, abnormal hair growth, hypersensitivity to light, or skin pigmentation problems;
• bone pain, muscle spasms, pain and/or heaviness in the arms and hands, or in the legs and feet;
• urinary tract infection;
• vaginal candidiasis, genital dryness, vaginal discharge, pelvic pain, atrophic vulvovaginitis, or one or more breast lumps;
• swelling due to fluid retention.

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

Reporting side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the National Pharmacovigilance System for Human Use Medicines: www.notificaraRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Zafril

Keep this medicine out of the sight and reach of children.

Store in the original packaging to protect from light.

This medicine does not require any special storage temperature.

Do not use this medicine after the expiry date stated on the packaging and blister after “EXP”. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Return the packaging and any unused medicine to the pharmacy's SIGRE Point. If you are unsure, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Zafril Composition

The active ingredient is dienogest. Each tablet contains 2 mg of dienogest.

The other components are lactose monohydrate, pregelatinized corn starch, microcrystalline cellulose, povidone K-25, crospovidone (type A), talc, and magnesium stearate.

Appearance of Zafril and Package Contents

Zafril 2 mg tablets are white or almost white, round, with flat faces and beveled edges, with "G 93" engraved on one face and "RG" on the other. The diameter of the tablets is 7 mm.

Zafril 2 mg tablets EFG are available in packages of 28, 84, and 168 tablets packaged in a green PVC//Al hard calendar blister pack in cardboard boxes.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Gedeon Richter Plc.

Gyömroi út 19-21

1103 Budapest

Hungary

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Gedeon Richter Ibérica S.A.

Sabino Arana, 28 – 4º 2ª

08028 Barcelona, Spain

This medication has been authorized in the EEA member states under the following names:

Date of the last revision of this prospectus:April 2021

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es)