Zafril 2 mg tablets EFG

Package leaflet: Information for the patient

Introduction

Package leaflet: information for the patient

Zafril 2 mg tablets EFG

dienogest

Read the entire leaflet carefully before you start 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 questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if these effects are not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Zafril is and what it is used for

Zafril is a medication for the treatment of endometriosis (painful symptoms caused by atypical localization of uterine lining tissue). Zafril contains a hormone, the progestogen dienogest.

2. What you need to know before starting to take Zafril

Do not take Zafril:

• if you have a blood clot (thromboembolic disorder) in the veins. This may occur, for example, in blood vessels of the legs (deep vein thrombosis) or the lungs (pulmonary embolism). See also “Zafril and blood clots in the veins” below;
• if you currently have or have ever had a serious arterial disease, including cardiovascular disease, such as a heart attack, stroke, or heart disease causing reduced blood flow (angina pectoris). See also “Zafril and blood clots in the arteries” below;
• if you have diabetes with blood vessel damage;
• if you currently have or have ever had a serious liver disease (and liver function values have not returned to normal). Symptoms of liver disease may include yellowing of the skin and/or itching all over the body;
• if you currently have or have ever had a benign or malignant liver tumor;
• if you currently have, have ever had, or are suspected of having a malignant hormone-dependent tumor, such as breast cancer or cancer of the genital organs;
• if you have vaginal bleeding of unknown cause;
• if you are allergic to dienogest or to any of the other ingredients of this medicine (listed in section 6).

If any of these conditions occurs for the first time while you are taking Zafril, stop taking it immediately and consult your doctor.

Warnings and precautions

Talk to your doctor or pharmacist before starting to take Zafril.

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

Zafril is not a contraceptive. If you wish to avoid pregnancy, you must use condoms or other non-hormonal contraceptive methods.

In some cases, you should take special care while taking Zafril, and your doctor may need to examine you periodically. Inform your doctor if you are in any of the following situations:

• if you have ever had a blood clot (venous thromboembolism), or if a close family member has had a blood clot at a relatively young age;
• if a close family member has had breast cancer;
• if you have ever had depression;
• if you have high blood pressure (hypertension) or develop hypertension while taking Zafril;
• if you develop liver disease while taking Zafril. Symptoms may include yellowing of the skin or eyes, or itching all over the body. Also inform your doctor if you experienced any of these symptoms in a previous pregnancy;
• if you have diabetes or had gestational diabetes in a previous pregnancy;
• if you have ever had chloasma (light brown patches on the skin, especially on the face); if so, avoid excessive exposure to sunlight or ultraviolet radiation;
• if you experience lower abdominal pain while taking Zafril.

While taking Zafril, your chance of becoming pregnant is reduced because this medicine may affect ovulation.

If you become pregnant while taking Zafril, you have a slightly higher risk of an ectopic pregnancy (the embryo develops outside the uterus). Inform your doctor before starting Zafril if you have previously had an ectopic pregnancy or if you have any fallopian tube dysfunction.

Zafril and severe uterine bleeding

Uterine bleeding may worsen with the use of Zafril, for example, in women who have a condition in which 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 (uterine leiomyomas). If bleeding is heavy and prolonged, it may lead to low red blood cell levels (anemia), which in some cases can be severe. If you have anemia, consult your doctor about whether 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 suggest there may be a slight, although not statistically significant, increased risk of blood clots in the legs (venous thromboembolism) associated with the use of medicines containing progestogens such as Zafril. Very rarely, blood clots can cause serious and permanent disabilities or may even be fatal.

The risk of blood clots in the veins 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 need to undergo surgery, have had a serious accident, or have been immobilized for a prolonged period. It is important to inform your doctor in advance that you are taking Zafril, as you may need to stop treatment temporarily. Your doctor will tell you when to restart taking Zafril. 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-containing preparations such as Zafril and an increased risk of blood clots, for example, in blood vessels of the heart (heart attack) or brain (stroke). In women with hypertension, these preparations may slightly increase the risk of stroke.

The risk of blood clots in the arteries increases:

• if you smoke. You are strongly advised to stop smoking while taking Zafril, especially if you are over 35 years old.
• if you are overweight;
• if one of your closest relatives has had a heart attack or stroke at a young age;
• if you have high blood pressure.

Zafril and cancer

Based on currently available data, it is not definitively known whether Zafril increases the risk of breast cancer or not. Breast cancer has been observed to be slightly more frequent in women taking hormones compared to those who do not, but it is unclear whether this is due to the treatment. For example, more tumors may be detected and at an earlier stage in women taking hormones because they are examined more frequently by their doctor. The incidence of breast tumors gradually decreases after stopping hormonal treatment. It is important that you regularly examine your breasts and consult your doctor if you detect any lump.

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

Zafril and osteoporosis

Changes in bone mineral density (BMD)

The use of Zafril may affect bone strength in adolescents (from 12 to less than 18 years of age). Therefore, if you are under 18 years of age, your doctor will carefully evaluate the benefits and risks of taking Zafril for you as an individual patient, taking into account possible risk factors for bone loss (osteoporosis).

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

If you are at increased risk of developing osteoporosis (weakening of bones due to loss of bone minerals), your doctor will carefully assess the risks and benefits of treatment with Zafril, as 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 menstrual period).

The use of Zafril may affect bone strength in adolescents (from 12 to less than 18 years of age). Therefore, if you are under 18 years of age, your doctor will carefully evaluate the benefits and risks of taking Zafril for you as an individual patient, taking into account possible risk factors for bone loss (osteoporosis).

Taking Zafril with other medicines

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

Likewise, inform any other doctor or dentist who prescribes you another medicine (or the pharmacist) that you are taking Zafril.

Some medicines may affect the blood levels of Zafril and make it less effective or cause adverse 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 virus infections (so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors such as ritonavir, nevirapine, efavirenz);

• fungal infections (griseofulvin, ketoconazole).

• herbal preparations containing St. John's wort.

Consult your doctor or pharmacist before using any medicine.

Taking Zafril with food and drink

During treatment with Zafril, you should avoid drinking grapefruit juice, as it may increase the levels of the medicine in the blood. This could increase the risk of adverse effects.

Laboratory tests

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

Pregnancy, breastfeeding, and fertility

Do not take Zafril if you are pregnant or during breastfeeding.

Driving and using machines

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

Zafril contains lactose

If your doctor has informed you that you have an intolerance to certain sugars, consult with him before taking this medicine.

3. How to take Zafril

Follow exactly the instructions for using this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

The recommended dose for adults is 1 tablet per day.

The following statements apply to Zafril unless your doctor has instructed you otherwise. Follow these instructions, otherwise you may not fully benefit from treatment with Zafril.

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

Adults: take one tablet every day, preferably at the same time each day, with some liquid if necessary. When you finish a pack, start the next one without interruption. Continue taking the tablets even during 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 at: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Zafril or experience vomiting or diarrhea

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

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

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

If you stop taking Zafril

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

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. These effects are more common during the first few months after starting 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.

Frequent (may affect up to 1 in 10 people)

• weight gain;
• depressive mood, sleep disorders, 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 cysts, or hot flushes;
• uterine/vaginal bleeding, including spotting;
• weakness or irritability.

Uncommon (may affect up to 1 in 100 people)

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

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

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is an effect not listed in this leaflet. You can also report them directly via the Spanish National Pharmacovigilance System for Human Medicines: www.notificaraRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 on the blister after “EXP”. The expiry date refers to the last day of the month indicated.

Medicines must not be disposed of via wastewater or household waste. Dispose of containers and unused medicines at the SIGRE collection point in your pharmacy. If in doubt, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Zafril

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

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

Appearance of Zafril and contents of the pack

Zafril 2 mg tablets are white or almost white, round, flat-faced with bevelled edges, marked with "G 93" on one side and "RG" on the other. The diameter of the tablets is 7 mm.

Zafril 2 mg tablets EFG are available in packs of 28, 84 and 168 tablets, presented in calendar blisters made of rigid PVC//Al in cardboard boxes.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Gedeon Richter Plc.

Gyömroi út 19-21

1103 Budapest

Hungary

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Gedeon Richter Ibérica S.A.

Sabino Arana, 28 – 4th floor, 2nd door

08028 Barcelona, Spain

This medicinal product has been authorized in the Member States of the EEA under the following names:

Date of the last review of this leaflet: April 2021

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