Atywia

PACKAGE LEAFLET: INFORMATION FOR THE USER

Warning! Keep this leaflet, information on the immediate packaging in a foreign language
Atywia (Velafee)
0.03 mg + 2 mg, coated tablets
Ethinylestradiolum + Dienogestum
Atywia and Velafee are different brand names for the same medicinal product.
Important information regarding combined hormonal contraceptives

• When used correctly, they are one of the most reliable reversible methods of contraception
• They slightly increase the risk of venous and arterial blood clots, especially during the first year of use or after restarting following a break of 4 weeks or more
• Be vigilant and consult a doctor if the user suspects symptoms of blood clot formation (see section 2 "Blood clots")

Please read this leaflet carefully before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

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

1. What Atywia is and what it is used for

Atywia is a combined oral contraceptive.
Each tablet contains two different hormones: dienogest (a progestogen) and ethinylestradiol (an estrogen).
When Atywia is taken according to the recommendations in this leaflet, the likelihood of becoming pregnant is very low.
Indications
Contraception.
Treatment of moderate acne in women who have decided to use oral contraceptives and in whom adequate topical treatment or oral antibiotic therapy has failed.

2. Important information before using Atywia

General notes
Before starting treatment with Atywia, you should read the information about blood clots in section 2. It is particularly important to become familiar with the symptoms of blood clots (see section 2 "Blood clots").
Improvement in acne symptoms usually occurs after three to six months of treatment, but skin condition may continue to improve even after six months of treatment. The patient should discuss with her doctor the need to continue treatment after three to six months, and then at regular intervals.

When not to use Atywia
Do not use Atywia if any of the conditions listed below apply to you. If any of these conditions apply, inform your doctor. Your doctor will discuss with you which alternative method of contraception may be more suitable.

• If you are allergic to ethinylestradiol or dienogest, or to any of the other ingredients of this medicine (listed in section 6).
• If you currently have (or have ever had) a blood clot in the veins of the legs (deep vein thrombosis), in the lungs (pulmonary embolism), or in other organs.
• If you know you have blood clotting disorders—for example, protein C deficiency, protein S deficiency, antithrombin III deficiency, factor V Leiden mutation, or antiphospholipid antibodies.
• If you are undergoing surgery or will be immobile for a prolonged period (see section 2 "Blood clots").
• If you have had a heart attack or stroke.
• If you have (or have had in the past) angina pectoris (a condition causing severe chest pain and may be the first sign of a heart attack) or transient ischaemic attack (temporary stroke-like symptoms).
• If you have any of the following conditions, which may increase the risk of arterial blood clots:
  • severe diabetes with blood vessel damage
  • very high blood pressure
  • very high levels of fats in the blood (cholesterol or triglycerides)
  • a condition called hyperhomocysteinemia
• If you currently have (or have ever had) a type of migraine called "migraine with aura"
• If you have had or currently have severe liver disease (until liver function tests return to normal)
• If you have had or currently have benign or malignant liver tumours
• If you have had or currently have a hormone-dependent cancer (e.g. breast or genital organ cancer)
• If you have vaginal bleeding of unknown cause
• If pregnancy has been confirmed or is suspected.

If any of the conditions listed above occur for the first time while taking Atywia, stop taking the medicine immediately and consult your doctor. During this time, use non-hormonal methods of contraception.
Do not use Atywia if you have hepatitis C and are taking antiviral medicines containing ombitasvir with paritaprevir and ritonavir, dasabuvir, glecaprevir with pibrentasvir, or sofosbuvir with velpatasvir and voxilaprevir (see also section "Atywia and other medicines").

Warnings and precautions
Before starting Atywia, discuss this with your doctor or pharmacist.

When to contact your doctor
Seek immediate medical advice if:

• You notice possible symptoms of a blood clot, which may indicate that you have a blood clot in the leg (deep vein thrombosis), in the lungs (pulmonary embolism), a heart attack, or a stroke (see section 2 below "Blood clots").

For a description of the symptoms of these serious adverse events, see "How to recognize a blood clot".

Special and regular medical monitoring is required if you are taking oral contraceptives and any of the conditions listed below apply.

Tell your doctor if you have any of the following conditions.
If any of these conditions appear or worsen during treatment with Atywia, you should also inform your doctor.

• If you smoke,
• If you have diabetes,
• If you are obese,
• If you have high blood pressure,
• If you have heart valve disorders or heart rhythm problems,
• If you have inflammation of the veins under the skin (superficial thrombophlebitis),
• If you have varicose veins,
• If there have been cases of thrombosis, heart attack, or stroke in close relatives,
• If you have migraines,
• If you have epilepsy,
• If you have high levels of fats in the blood (hypertriglyceridaemia) or a family history of this condition. Hypertriglyceridaemia is associated with an increased risk of pancreatitis,
• If you have a personal or family history of breast cancer,
• If you have liver or gallbladder disease,
• If you have Crohn's disease or ulcerative colitis (chronic inflammatory bowel diseases),
• If you have systemic lupus erythematosus (a disease affecting the body's natural defence system),
• If you have haemolytic uraemic syndrome (a blood clotting disorder leading to kidney failure),
• If you have sickle cell anaemia (an inherited disorder of red blood cells),
• If you require surgery or will be immobile for a prolonged period (see section 2 "Blood clots"),
• If you have recently given birth, as you are at increased risk of blood clots. Consult your doctor for advice on how soon after delivery you can start taking Atywia,
• If you have a condition that first appeared or worsened during pregnancy or previous use of steroid hormones (e.g. hearing loss, porphyria, herpes gestationis, Sydenham's chorea),
• If you have or have ever had skin discolouration (yellow-brown pigmentation changes, so-called chloasma); in such cases, avoid excessive exposure to sunlight or ultraviolet radiation,
• If you experience symptoms of angioedema, such as swelling of the face, tongue and/or throat and/or difficulty swallowing, or a skin rash with possible breathing difficulties, seek immediate medical attention. Medicines containing oestrogens may cause or worsen symptoms of hereditary or acquired angioedema.

If any of the symptoms listed above appear for the first time, recur, or worsen during treatment with Atywia, contact your doctor.

BLOOD CLOTS
Using combined hormonal contraceptives such as Atywia increases the risk of blood clots compared to not using such treatment. In rare cases, a blood clot may block a blood vessel and cause serious complications.

Blood clots may occur:

• in veins (hereinafter referred to as "venous thrombosis" or "venous thromboembolic disease")
• in arteries (hereinafter referred to as "arterial thrombosis" or "arterial thromboembolic events").

Recovery from a blood clot is not always complete. In rare cases, the consequences of a blood clot may be permanent or, very rarely, fatal.

Remember that the overall risk of harmful blood clots associated with the use of Atywia is low.

HOW TO RECOGNIZE A BLOOD CLOT
Seek immediate medical advice if you experience any of the following symptoms.

Is the patient experiencing any of these symptoms?	What is the patient most likely suffering from?
swelling of the leg or swelling along a vein in the leg or foot, particularly if accompanied by: pain or tenderness in the leg, which may occur only while standing or walking increased temperature in the affected leg change in skin color of the leg, such as pallor, redness, or cyanosis	Deep vein thrombosis
sudden onset of unexplained shortness of breath or rapid breathing sudden coughing without apparent cause, possibly associated with coughing up blood sharp chest pain, which may worsen with deep breathing severe dizziness or lightheadedness rapid or irregular heartbeat severe abdominal pain If the patient is unsure, she should consult a doctor, as some of these symptoms, such as cough or shortness of breath, may be mistaken for milder conditions such as respiratory tract infections (e.g. a cold).	Pulmonary embolism
Symptoms most commonly occur in one eye: sudden loss of vision or painless visual disturbances, which may progress to vision loss	Retinal vein thrombosis (blood clot in the eye)
chest pain, discomfort, pressure, heaviness feeling of tightness or fullness in the chest, arm, or below the breastbone feeling of fullness, indigestion, or choking discomfort in the lower body, radiating to the back, jaw, throat, arm, or stomach sweating, nausea, vomiting, or dizziness extreme weakness, anxiety, or shortness of breath rapid or irregular heartbeat	Myocardial infarction (heart attack)
sudden weakness or numbness of the face, arms, or legs, especially on one side of the body sudden confusion, speech disturbances, or difficulty understanding sudden visual disturbances in one or both eyes sudden difficulty walking, dizziness, loss of balance or coordination sudden, severe, or prolonged headache without known cause loss of consciousness or fainting with or without seizures	Stroke
A doctor should be consulted immediately, as the patient may be at risk of a subsequent stroke, even if symptoms are transient with nearly immediate and complete recovery.
swelling and slightly bluish discoloration of the skin of the arms or legs severe abdominal pain (acute abdomen)	Blood clots blocking other blood vessels

BLOOD CLOTS IN VEINS
What can happen if blood clots form in veins?

• The use of combined hormonal contraceptives is associated with an increased risk of blood clots in veins (venous thrombosis). Although these adverse events are rare, they most commonly occur during the first year of using combined hormonal contraceptives.
• If blood clots form in the veins of the leg or foot, this may lead to the development of deep vein thrombosis.
• If a blood clot travels from the leg and lodges in the lungs, it may cause pulmonary embolism.
• In very rare cases, a clot may form in another organ, such as the eye (retinal vein thrombosis).

When is the risk of blood clots in veins the highest?
The risk of developing blood clots in veins is greatest during the first year of taking combined hormonal contraceptives for the first time. The risk may also be higher when restarting combined hormonal contraceptives (the same or another product) after a break of 4 weeks or more.
After the first year, the risk decreases, although it remains higher than in women who do not use combined hormonal contraceptives.
If a woman stops taking Atywia, the risk of blood clots returns to normal within a few weeks.

What does the risk of blood clots depend on?
The risk depends on the individual's natural risk of venous thromboembolic disease and the type of combined hormonal contraceptive used.

• In a year, about 2 out of 10,000 women who do not use combined hormonal contraceptives and are not pregnant will develop blood clots.
• In a year, about 5–7 out of 10,000 women who use combined hormonal contraceptives containing levonorgestrel, norethisterone, or norgestimate will develop blood clots.
• In a year, about 8–11 out of 10,000 women who use combined hormonal contraceptives containing dienogest and ethinylestradiol, such as Atywia, will develop blood clots.
• The risk of developing blood clots depends on the individual's medical history (see "Factors that increase the risk of blood clots" below).

	Chance of developing blood clots within one year
Women who do not use combined hormonal contraceptive pills, patches, vaginal systems and who are not pregnant	About 2 in 10,000 women
Women using combined oral contraceptive pills containing levonorgestrel, norethisterone or norgestimate	About 5-7 in 10,000 women
Women using the medicine Atywia	About 8-11 in 10,000 women

Factors increasing the risk of venous blood clots
The risk of developing blood clots associated with the use of Atywia is small, but certain factors may increase this risk. The risk is higher:

• if the patient has significant overweight (body mass index (BMI) above 30 kg/m²)
• if a close relative of the patient has been diagnosed with blood clots in the legs, lungs, or other organs at a young age (e.g. under 50 years). In this case, the patient may have inherited clotting disorders
• if the patient requires surgery, will be immobilized for a prolonged period due to injury or illness, or has a leg in a cast. It may be necessary to discontinue Atywia several weeks before surgery or immobilization. If the patient must stop taking Atywia, consult the doctor about when it is safe to resume treatment.
• with increasing age (especially over 35 years)
• if the patient has given birth within the last few weeks.

The risk of developing blood clots increases with the number of risk factors present in the patient.
Air travel (>4 hours) may temporarily increase the risk of venous blood clots, particularly if the patient has another risk factor.
It is important to inform the doctor if any of the listed risk factors apply to the patient, even if uncertain. The doctor may decide to discontinue Atywia.
Inform the doctor if any of the above conditions change during treatment with Atywia, for example, if a close relative is diagnosed with unexplained thrombosis or if the patient gains significant weight.

ARTERIAL BLOOD CLOTS
What can happen if blood clots form in arteries?
As with venous blood clots, arterial clots can lead to serious consequences, such as myocardial infarction (heart attack) or stroke.

Factors increasing the risk of arterial blood clots
It is important to emphasize that the risk of myocardial infarction or stroke associated with Atywia use is very low, but may increase:

• with age (over 35 years);

• if the patient smokes. While using hormonal contraceptives such as Atywia, smoking should be discontinued. If the patient is unable to stop smoking and is over 35 years old, the doctor may recommend using another type of contraception;

• if the patient is overweight;

• if the patient has high blood pressure;

• if a close relative has had a myocardial infarction or stroke at a young age (under 50 years). In this case, the patient may also be at increased risk of myocardial infarction or stroke;

• if the patient or a close relative has high blood lipid levels (cholesterol or triglycerides);

• if the patient suffers from migraines, especially migraines with aura;

• if the patient has heart disease (valvular heart disease, cardiac arrhythmia such as atrial fibrillation);

• if the patient has diabetes.

If the patient has more than one of the above conditions or if any of them are particularly severe, the risk of arterial blood clots may be further increased. Inform the doctor if any of the above conditions change during treatment with Atywia, for example, if the patient starts smoking, a close relative is diagnosed with unexplained thrombosis, or if the patient gains significant weight.

If symptoms suggesting thrombosis occur, stop taking the tablets and consult a doctor immediately (see also "When to contact the doctor").

Oral contraception and cancer
Women taking oral contraceptives have a slightly higher incidence of breast cancer compared to women of the same age who do not use them. It is not known whether this difference is solely due to the use of hormonal contraceptives. It may also be due to the fact that women using hormonal contraception undergo more frequent examinations, leading to earlier detection of breast cancer. The difference in breast cancer incidence gradually decreases and disappears within 10 years after stopping oral contraceptives.

Rare cases of benign and, even more rarely, malignant liver tumours have been reported in women using combined oral contraceptives. These tumours may lead to life-threatening intra-abdominal bleeding. If severe upper abdominal pain occurs, the doctor should be informed immediately.

Malignant tumours may be life-threatening or lead to death.

There are reports of increased incidence of cervical cancer in women who have used oral contraceptives for a long time. However, this association may not be related to taking the tablets, but rather to sexual behaviour or other factors.

Psychiatric disorders
Some women using hormonal contraceptives, including Atywia, have reported depression or low mood. Depression can be severe and sometimes lead to suicidal thoughts. If mood changes or symptoms of depression occur, contact the doctor as soon as possible for further medical advice.

Atywia and other medicines
Inform the doctor or pharmacist about all medicines currently or recently taken, as well as any medicines the patient plans to take, including those available without a prescription.

Some medicines may affect the blood concentration of Atywia, reduce contraceptive effectiveness, and cause unexpected bleeding.

These include:

• medicines used to treat:
  • epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate, felbamate)
  • tuberculosis (e.g. rifampicin)
  • HIV and HCV infections (protease inhibitors and non-nucleoside reverse transcriptase inhibitors)
  • fungal infections (griseofulvin, azole antifungals such as itraconazole, voriconazole, fluconazole)
  • bacterial infections (macrolide antibiotics such as clarithromycin, erythromycin)
  • certain heart diseases, hypertension (calcium channel blockers, e.g. verapamil, diltiazem)
  • arthritis, degenerative joint disease (etoricoxib)
• St John's wort (Hypericum perforatum)
• grapefruit juice.

Oral contraceptives may affect the metabolism of other medicines such as lamotrigine, cyclosporine, melatonin, midazolam, theophylline, and tizanidine.

Do not use Atywia if the patient has hepatitis C and is taking antiviral medicines containing ombitasvir with paritaprevir and ritonavir, dasabuvir, glecaprevir with pibrentasvir, or sofosbuvir with velpatasvir and voxilaprevir, as they may cause abnormal liver function test results (increased liver enzyme AlAT activity). Before starting these medicines, the doctor will prescribe another type of contraception.

Atywia may be restarted approximately 2 weeks after completing the above-mentioned antiviral treatment. See section "When not to use Atywia".

When to contact the doctor
Contact the doctor immediately if:

• any concerning changes in health occur, particularly any of the symptoms listed in this leaflet (see also: "Warnings and precautions" and "How to use Atywia");
• there is a history of thrombosis, heart attack, or stroke in close relatives;
• a breast lump is detected;
• other medicines are to be used (see also "Atywia and other medicines");
• immobilization is expected or surgery is planned (inform the doctor at least 4 weeks in advance);
• heavy vaginal bleeding occurs;
• tablets are missed in the first week of the cycle (each first week of subsequent months of Atywia use), and intercourse occurred in the previous 7 days;
• acute diarrhoea occurs;
• withdrawal bleeding does not occur in two consecutive months or pregnancy is suspected (do not start the next pack without consulting the doctor).

Stop taking Atywia and contact the doctor immediately if any symptoms suggesting possible thrombosis, heart attack, or stroke occur:

• cough without apparent cause,
• severe chest pain, possibly radiating to the left arm,
• shortness of breath,
• headache of unusual severity or a migraine attack,
• partial or complete loss of vision or double vision,
• slurred speech or loss of speech,
• sudden sensory disturbances (hearing, smell, or touch),
• dizziness or fainting,
• numbness or weakness of part of the body,
• severe abdominal pain,
• severe pain or swelling in the legs.

The situations and symptoms listed above are described in more detail in other sections of this leaflet.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult a doctor or pharmacist before using this medicine.

Do not take Atywia during pregnancy or if pregnancy is suspected. If pregnancy is suspected, consult a doctor immediately.

Atywia is not recommended during breastfeeding.

Driving and operating machinery
No effect of Atywia on the ability to drive or operate machinery has been observed.

Atywia contains lactose monohydrate
Atywia contains lactose monohydrate. If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult the doctor before taking this medicine.

3. How to take Atywia

This medicine should always be taken exactly as directed by your doctor or pharmacist. If you are unsure,
you should consult your doctor or pharmacist.
This leaflet describes many situations in which you should stop taking Atywia or in which
its effectiveness may be reduced. It also outlines circumstances when sexual intercourse should be avoided or additional contraceptive methods should be used, e.g. condoms
or other mechanical methods. The calendar method and temperature-based methods should not be
used, as Atywia affects temperature changes and cervical mucus characteristics
associated with the menstrual cycle.
Atywia, like other oral contraceptives, does not protect against infection
with the HIV virus (AIDS) or sexually transmitted diseases.

How to take Atywia

• When and how should the tablets be taken?

The blister pack contains 21 coated tablets. Each tablet is marked on the packaging with the day of the week on which it should be taken. The tablets should be taken in the order indicated on the packaging, every day at approximately the same time, with a small amount of liquid if needed. One tablet should be taken daily for 21 consecutive days.
Each subsequent pack should be started after a 7-day break, during which no tablets are taken and withdrawal bleeding usually occurs. Bleeding usually begins 2–3 days after the last tablet and may continue into the next pack. This means that each new pack should always be started on the same day of the week, and withdrawal bleeding will generally occur on approximately the same days each month.

• Starting Atywia for the first time

If no oral contraceptives have been used in the past month
Tablet-taking should begin on Day 1 of the natural menstrual cycle (i.e. the first day of menstrual bleeding). Tablets may also be started between Day 2 and Day 5 of the cycle; in this case, during the first cycle, additional mechanical contraception is recommended for the first 7 days of tablet-taking.
If previously using another combined oral contraceptive
It is recommended to start taking Atywia on Day 1 after taking the last active tablet of the previous combined oral contraceptive, but no later than Day 1 after the usual tablet-free or placebo interval of the previous combined oral contraceptive.
If previously using a progestogen-only pill (mini-pill)
You may stop taking the mini-pill on any day and start taking Atywia at the same time instead. If sexual intercourse occurs during the first 7 days of taking Atywia, additional contraceptive methods (mechanical methods) should be used simultaneously.
If previously using injectable contraception, an implant, or a transdermal system releasing progestogen
Start taking Atywia on the day the next injection was due, or on the day of removal of the implant or system. If sexual intercourse occurs during the first 7 days of taking tablets, additional contraceptive methods (mechanical methods) should be used simultaneously.
After childbirth, miscarriage, or abortion

• After first-trimester abortion

Atywia may be started immediately. In this case, additional contraceptive methods are not necessary.

• After childbirth or second-trimester abortion

Breastfeeding women, see section 2. "Breastfeeding".
Your doctor should advise you to start taking tablets between 21 and 28 days after childbirth or second-trimester abortion. If tablet-taking is started later, your doctor should advise you to use additional mechanical contraception for the first 7 days of tablet-taking. If intercourse occurred before starting the combined oral contraceptive, pregnancy should be ruled out, or you should wait until the first menstrual bleeding occurs.

Taking more Atywia than recommended
Nausea, vomiting, or vaginal bleeding may occur. Such bleeding may even occur in girls who have not yet started menstruating but have accidentally taken this medicine.
There are no reports of severe adverse effects after taking multiple Atywia tablets at once. If you take more than the recommended dose or someone else takes it, inform your doctor.

Stopping Atywia
You may discontinue the medicine at any time. Your doctor will then suggest alternative contraceptive methods. If you stop taking the medicine because you wish to become pregnant, wait until the next natural menstrual period occurs. This will help determine the expected date of delivery.

Missed dose of Atywia
If less than 12 hours have passed since missing a tablet, the contraceptive effectiveness of Atywia is maintained. Take the missed tablet as soon as possible and take the next tablet at the usual time.
If more than 12 hours have passed since missing a tablet, the contraceptive effectiveness of Atywia may be reduced. The more consecutive tablets missed, the greater the risk of reduced contraceptive effect. The risk of pregnancy is particularly high if tablets are missed at the beginning or end of a pack. In such cases, follow the instructions below (see also the diagram below).
More than 1 tablet missed from the pack
Consult your doctor.
One tablet missed in the first week of the current pack
Take the missed tablet as soon as possible (even if this means taking two tablets at the same time), and continue taking the next tablets at the usual time. Use additional contraceptive methods (mechanical methods) for the next 7 days.
If sexual intercourse occurred in the week before the missed tablet, pregnancy may be possible. Inform your doctor immediately. Also refer to the "Missed tablet management chart".
One tablet missed in the second week of the current pack
Take the missed tablet as soon as possible (even if this means taking two tablets at the same time), and continue taking the next tablets at the usual time. The contraceptive effectiveness of Atywia is maintained, and additional pregnancy prevention methods are not necessary.
However, if previous dosing errors occurred or more than one tablet was missed, use an additional (mechanical) contraceptive method for 7 days.
One tablet missed in the third week of the current pack
You may choose one of the following options without needing additional contraceptive methods, provided correct dosing was maintained during the 7 days prior to the missed dose. Otherwise, apply the first of the two options below and use an additional contraceptive method for the next 7 days.

1. Take the missed tablet as soon as possible (even if this means taking two tablets at the same time), and continue taking the next tablets at the usual time. Start the next pack immediately after finishing the current one, i.e. without a 7-day break. Withdrawal bleeding will occur after finishing the second pack, but spotting or bleeding may occur during tablet-taking days.
2. Alternatively, stop taking tablets from the current pack, take a 7-day or shorter break (including the day the tablet was missed), then continue taking tablets from the next pack.

If you forget to take tablets and no withdrawal bleeding occurs during the first tablet-free interval, pregnancy may be possible. Contact your doctor before starting the next pack.

Missed tablet management chart

Missed more than

Consult your doctor

tablet from the current

pack

Sexual intercourse occurred
in the week
preceding missed
tablet
Yes
No

Take the missed tablet

Use additional
contraceptive method for

days

Finish taking
tablets from the pack
Only 1 tablet
missed

Take the missed tablet
( delay longer than

Finish taking
Week 2.
hours but less than
tablets from the pack
hours)

Take the missed tablet

Finish the pack

• • day break

Do not take a 7

• Continue taking

tablets from the next

pack
or
Week 3.

• Discard remaining tablets

from the pack

Take a break (no more

than 7 days, including the day
of missed tablet)

• Continue
  tablet-taking
  from the next
  pack

Managing the following situations:

• Gastrointestinal disturbances (vomiting)

If vomiting occurs, the active ingredients of Atywia may not be fully absorbed. If vomiting occurs within 3 to 4 hours after taking a tablet, follow the missed tablet instructions. If you have severe gastrointestinal disturbances, use additional contraceptive methods.

• Intention to delay withdrawal bleeding

To delay withdrawal bleeding, start the next pack immediately after finishing the current one, without a 7-day break. You may continue taking tablets until the pack is finished. If you wish bleeding to occur, simply stop taking tablets. During tablet-taking from the next pack, slight bleeding or spotting may occur. Begin the following pack after a 7-day break.

• Intention to change the day of withdrawal bleeding to another day of the week

If tablets are taken as directed, bleeding occurs approximately on the same day every 4 weeks. To shift the bleeding day to another day of the week, shorten the next tablet-free interval by the number of days you wish to shift the bleeding. For example, if bleeding usually starts on Fridays and you wish it to start on Tuesdays (3 days earlier), start the new pack 3 days earlier than usual. If the tablet-free interval is very short (e.g. 3 days or less), withdrawal bleeding may not occur during the break. Slight bleeding or spotting may occur during the next pack.

• Unexpected bleeding

During the first few months of taking Atywia, irregular vaginal bleeding (spotting or intermenstrual bleeding) may occur. Despite this, continue taking the tablets. Irregular vaginal bleeding usually resolves after 3 cycles of Atywia. If bleeding persists, becomes heavy, or recurs, inform your doctor.

• Absence of withdrawal bleeding

If all tablets were taken on time, there were no vomiting or severe diarrhoea, and no other medicines were taken concurrently, the likelihood of pregnancy is very low. Continue taking Atywia.
If withdrawal bleeding does not occur for two consecutive months, pregnancy is possible. Inform your doctor immediately. Do not start the next pack of Atywia until your doctor has ruled out pregnancy.

Additional information for specific patient groups
Children and adolescents
Atywia is indicated only after the onset of menstruation.
Elderly patients
Not applicable. Atywia is not indicated for postmenopausal women.
Patients with hepatic impairment
Atywia is contraindicated in women with severe liver disease. See also section 2 "When not to use Atywia".
Patients with renal impairment
Specific studies with Atywia have not been conducted in patients with renal impairment. Available data do not indicate a need to modify treatment in this patient group.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
If any adverse effects occur, especially severe and persistent ones, or changes in health status which the patient considers to be related to the use of Atywia, medical advice should be sought from a physician.
All women using combined hormonal contraceptives have an increased risk of venous blood clots (venous thromboembolic disease) or arterial blood clots (arterial thromboembolic disorders). For detailed information on various risk factors associated with the use of combined hormonal contraceptives, please refer to section 2, "Important information before using Atywia".

Serious adverse effects
Serious adverse effects associated with taking Atywia and their accompanying symptoms are described in the following sections of this leaflet: "Oral contraception and thrombosis" and "Oral contraception and cancer". Please read these sections for additional information and consult your doctor immediately if necessary.

Other possible adverse effects
The symptoms listed below have been reported by women taking Atywia, although they may not necessarily have been caused by the medicine.

Common (may affect fewer than 1 in 10 people):

• headache,
• breast pain, including breast discomfort and tenderness.

Uncommon (may affect fewer than 1 in 100 people):

• vaginal inflammation and (or) vulvovaginitis (inflammatory conditions of the genital organs),
• vaginal candidiasis (yeast infection) or other fungal infections of the vagina,
• increased appetite,
• depressed mood,
• dizziness,
• migraine,
• high or low blood pressure,
• abdominal pain, including upper and lower abdominal pain, discomfort and (or) bloating,
• nausea, vomiting or diarrhoea,
• acne,
• alopecia (hair loss),
• rash (including maculopapular rash), itching (sometimes of the whole body),
• changes in menstrual bleeding such as heavy, light, infrequent or absent periods,
• intermenstrual vaginal bleeding, uterine haemorrhage (irregular bleeding between periods),
• breast enlargement, including breast congestion and swelling,
• breast swelling,
• painful menstruation (painful periods),
• vaginal discharge,
• ovarian cysts,
• pelvic pain,
• fatigue, including asthenia (weakness) and malaise,
• changes in body weight (including weight gain, weight loss and weight fluctuations).

Rare (may affect fewer than 1 in 1,000 people):

• salpingo-oophoritis (inflammation of the ovaries and fallopian tubes),
• urinary tract infections,
• cystitis (bladder inflammation),
• mastitis (breast inflammation),
• cervicitis (inflammatory condition of the cervix),
• fungal infections,
• oral herpes,
• influenza,
• bronchitis,
• sinusitis,
• upper respiratory tract infections,
• viral infection,
• uterine leiomyoma,
• fibroadenoma of the breast,
• anaemia,
• hypersensitivity (allergic reaction),
• virilization (development of male secondary sexual characteristics in women),
• anorexia (severe loss of appetite),
• depression,
• psychiatric disorders,
• insomnia,
• sleep disorders,
• aggression,
• stroke (reduced or interrupted blood supply to part of the brain),
• cerebral circulation disorders (disorders of blood flow to part of the brain),
• dystonia (sustained muscle contractions causing twisting or abnormal postures),
• dry or irritated eyes,
• oscillopsia (subjective sensation of oscillating vision) or other visual disturbances,
• sudden hearing loss,
• tinnitus,
• dizziness,
• hearing disorders,
• cardiovascular disorders (disorders of blood supply to the heart),
• tachycardia (rapid heartbeat),
• venous and arterial thromboembolic events*
• pulmonary embolism (a blood clot travelling to the lungs),
• thrombophlebitis (vein inflammation, including blood clots),
• elevated diastolic blood pressure (the lowest level to which blood pressure drops between heartbeats),
• orthostatic hypotension (dizziness or fainting when rising from sitting or lying down),
• hot flushes,
• varicose veins,
• venous dysfunction or vein pain,
• asthma,
• hyperventilation,
• gastritis (inflammation of the stomach lining),
• enteritis (inflammation of the intestine),
• dyspepsia,
• skin reactions,
• skin disorders, including allergic dermatitis, neurodermitis and (or) atopic dermatitis, eczema, psoriasis,
• excessive sweating,
• chloasma (pigmented facial patch),
• pigmentary disorders and (or) discoloration,
• seborrhoea,
• pityriasis,
• hirsutism (excessive hair growth),
• skin disorders, skin reactions, "orange peel" skin appearance,
• spider angioma,
• back pain,
• musculoskeletal complaints,
• muscle pain,
• pain in arms and legs,
• cervical dysplasia (abnormal cell growth on the surface of the cervix),
• pain or cysts of the uterine appendages (ovaries and fallopian tubes),
• breast cysts,
• fibrocystic breast changes,
• painful sexual intercourse,
• galactorrhea (milk secretion),
• menstrual disorders,
• chest pain,
• swelling of legs and arms,
• influenza-like illnesses,
• inflammation,
• fever,
• irritability,
• hypercholesterolaemia,
• increased blood triglyceride levels,
• presence of supernumerary breast.

* Estimated frequency from epidemiological studies covering combined oral contraceptives. The term "venous and arterial thromboembolic events" includes: any obstruction and blood clot in peripheral deep veins, clots travelling through the circulatory system (e.g. to the lungs, known as pulmonary embolism or pulmonary infarction), myocardial infarction caused by blood clots, stroke caused by obstruction of blood vessels to or in the brain.

Frequency not known (cannot be estimated from available data):

• mood changes,
• decreased or increased libido (sexual drive),
• intolerance to contact lenses,
• skin changes (urticaria, nodular erythema, erythema multiforme),
• breast discharge,
• fluid retention.

The likelihood of developing blood clots may be higher if the patient has any other risk factors increasing this risk (see section 2, "For further information on risk factors for blood clots and symptoms of blood clots").

Seek immediate medical advice if the patient experiences symptoms of angioedema, such as swelling of the face, tongue and (or) throat and (or) difficulty swallowing, or skin rash with possible breathing difficulties (see also section "Warnings and precautions").

Description of selected adverse effects
Adverse effects with low frequency or delayed onset, considered to be associated with the group of combined oral contraceptives, are listed below (see also sections "When not to use Atywia" and "Warnings and precautions"):

Neoplasms

• The number of diagnosed cases of breast cancer among women using combined oral contraceptives is slightly increased. However, since breast cancer is rare in women under 40 years of age, the number of diagnoses is small in relation to the overall risk of breast cancer. A causal relationship between breast cancer and combined oral contraceptives is not known.
• Liver tumours (benign and malignant).

Other

• Women with hypertriglyceridaemia (increased blood fat levels, increasing the risk of pancreatitis during use of combined oral contraceptives)
• High blood pressure
• Occurrence or worsening of symptoms, the relationship of which to COC use is not established: jaundice and (or) pruritus associated with cholestasis (blocked bile flow); gallstones; metabolic disorders such as porphyria; systemic lupus erythematosus (chronic autoimmune disease); haemolytic-uraemic syndrome (a blood clotting disorder); neurological disorders known as Sydenham's chorea; herpes gestationis (a type of skin disease occurring during pregnancy); otosclerosis associated with hearing loss.
• Liver function disorders
• Changes in glucose tolerance or effects on peripheral insulin resistance
• Crohn's disease, ulcerative colitis
• Chloasma

Interactions
Intermenstrual bleeding and (or) reduced contraceptive effectiveness may be caused by interactions of other medicines with oral contraceptives (e.g. St John's wort (Hypericum perforatum), or medicines for epilepsy, tuberculosis, HIV infection and other infections). See section "Atywia with other medicines".

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 of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, telephone: +48 22 492 13 01, fax: +48 22 492 13 09; Website: https://smz.ezdrowie.gov.pl.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Atywia

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and the blister.
The expiry date refers to the last day of the stated month.
Translation of some information on the immediate packaging:
Ch.-D. und verw. bis: siehe Prägung – batch number and expiry date: see embossing.
Do not store above 30°C. Keep blisters in the outer packaging to protect from light.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the package and other information

What Atywia contains

• The active substances in this medicinal product are ethinylestradiol and dienogest.
• Other components of the medicinal product are:
  Tablet core: monohydrate lactose, magnesium stearate, corn starch, povidone K 30.
  Tablet coating: hypromellose, macrogol 400, titanium dioxide (E 171).

1 blister contains 21 film-coated tablets.
1 film-coated tablet contains 0.03 mg ethinylestradiol and 2 mg dienogest.

What Atywia looks like and contents of the pack
White, round, film-coated tablets.
Atywia is available in cardboard packaging containing 21, 63 or 126 film-coated tablets.
Each package includes a cardboard pouch intended for storing the blister.
For more detailed information, please contact the marketing authorization holder or the parallel importer.

Marketing Authorization Holder in Germany, the country of export:
Exeltis Germany GmbH
Adalperostrasse 84
85737 Ismaning
Germany

Manufacturer:
Laboratorios León Farma SA
La Vallina s/n, Pol. Ind. Navatejera
Navatejera-24008 León
Spain

Parallel Importer:
Medezin Sp. z o.o.
Zbąszyńska Street 3
91-342 Łódź
Poland

Repackaged by:
Medezin Sp. z o.o.
Zbąszyńska Street 3
91-342 Łódź
02-234 Warsaw
Poland

Marketing Authorization Number in Germany, the country of export: 87088.00.00
Parallel Import Authorization Number: 248/24