Atywia

Patient Information Leaflet

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

• When used correctly, they represent 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 patient suspects symptoms of blood clot formation (see section 2 "BLOOD CLOTS").

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

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm another person, even if their symptoms appear identical.
• If the patient experiences any adverse effects, including those not listed in this leaflet, inform a doctor or pharmacist. See section 4.

Table of contents:

1. What Atywia is and what it is used for
2. Important information 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 oestrogen).
When used according to the recommendations provided in this leaflet, the likelihood of becoming pregnant is very low.
Indications
Pregnancy prevention.
Treatment of women with moderate acne who have decided to use oral contraceptive tablets 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 be aware of 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. You should discuss with your 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 you have any of the conditions listed below. If you have any of these conditions, inform your doctor. Your doctor will discuss with you which alternative method of contraception would 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 deep veins of the legs (deep vein thrombosis), in the lungs (pulmonary embolism), or in other organs.
• If you know you have a blood clotting disorder—for example, protein C deficiency, protein S deficiency, antithrombin III deficiency, factor V Leiden mutation, or presence of 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 that 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 had in the past) 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 above conditions 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, paritaprevir, ritonavir, and dasabuvir or glecaprevir/pibrentasvir (see also section "Atywia with 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 below "BLOOD CLOTS").

For a description of the symptoms of these serious adverse effects, see "How to recognize the occurrence of blood clots".

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

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 family members,
• If you have migraines,
• If you have epilepsy,
• If you have high levels of fats in the blood (hypertriglyceridemia) or a family history of this condition. Hypertriglyceridemia is associated with an increased risk of developing pancreatitis,
• If you have a 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 defense system),
• If you have hemolytic uremic syndrome (a blood clotting disorder leading to kidney failure),
• If you have sickle cell anemia (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 to find out 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 currently have or have ever had skin discoloration (yellow-brown pigmentation, so-called chloasma); in such cases, avoid excessive exposure to sunlight or ultraviolet radiation,
• If you have hepatitis C and are taking medicines containing ombitasvir/paritaprevir/ritonavir and dasabuvir or glecaprevir/pibrentasvir (see section 2 "Atywia with other medicines"),
• If you experience symptoms of angioedema, such as swelling of the face, tongue and/or throat and/or difficulty swallowing, or a rash with possible breathing difficulties, seek immediate medical attention. Medicines containing estrogens may cause or worsen symptoms of hereditary or acquired angioedema.

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

BLOOD CLOTS
Using combined hormonal contraceptives such as Atywia is associated with an increased risk of blood clots compared to not using such medicines. In rare cases, a blood clot may block a blood vessel and cause serious complications.

Blood clots may occur:

• in veins (referred to as "venous thrombosis" or "venous thromboembolic disease")
• in arteries (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 caused by using Atywia is low.

HOW TO RECOGNIZE THE OCCURRENCE OF BLOOD CLOTS
Seek immediate medical advice if you experience any of the following symptoms.

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 venous blood clots (venous thromboembolism). 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 venous blood clots the highest?
The risk of developing venous blood clots is greatest during the first year of using combined hormonal contraceptives for the first time. The risk may also be higher when restarting combined hormonal contraceptives (the same or a different product) after a break of 4 weeks or more.
After the first year, the risk decreases, although it remains higher compared to not using combined hormonal contraceptives.
If a patient stops taking Atywia, the risk of blood clots returns to normal within a few weeks.

What factors influence the risk of venous blood clots?
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 are not using combined hormonal contraceptives and are not pregnant will develop blood clots.
• In a year, about 5–7 out of 10,000 women who are using combined hormonal contraceptives containing levonorgestrel, norethisterone, or norgestimate will develop blood clots.
• In a year, about 8–11 out of 10,000 women who are using 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 increasing the risk of venous blood clots" below).

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

• if the patient is overweight (body mass index (BMI) above 30 kg/m²);
• if a close relative of the patient has had 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 an inherited clotting disorder;
• if the patient requires surgery, is 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 during immobilization. If the patient must stop taking Atywia, she should consult her doctor about when it is safe to restart;
• with increasing age (especially over 35 years);
• if the patient has recently given birth (within the past 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 blood clots,
particularly if the patient has another risk factor listed above.
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, e.g. 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?
Similar to 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 heart attack or stroke associated with the use of Atywia is very small, but may increase:

• with age (over approximately 35 years);
• if the patient smokes. While using a hormonal contraceptive 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 heart attack or stroke at a young age (under 50 years). In this case, the patient may also be at increased risk of heart attack or stroke;
• if the patient or a close relative has high levels of lipids in the blood (cholesterol or triglycerides);
• if the patient suffers from migraines, particularly 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 blood clots may be further increased.
Inform the doctor if any of the above conditions change during treatment with Atywia, e.g. 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 immediately and consult a doctor without delay (see also "When to contact a doctor").

Oral contraception and cancer
Breast cancer occurs slightly more frequently in women who take oral contraceptives than in women of the same age who do not. 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 medical 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, which in some cases led to life-threatening intra-abdominal bleeding. If severe upper abdominal pain occurs, the doctor should be informed as soon as possible.
Malignant tumours may be life-threatening or fatal.

There have been reports of an increased incidence of cervical cancer in women who have used oral contraceptives for a long time. However, this association may not be directly related to the use of 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 may sometimes lead to suicidal thoughts. If mood changes or symptoms of depression occur, contact a doctor as soon as possible for further medical advice.

Atywia and other medicines
Inform the doctor or pharmacist about all medicines currently used, recently used, or planned for use, including over-the-counter medicines.

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 infection (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 conditions, 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, paritaprevir, ritonavir, and dasabuvir or glecaprevir/pibrentasvir, as this may lead to elevated liver function tests (increased liver enzyme ALT levels). The doctor will recommend another form of contraception before starting these antiviral medicines. Atywia may be restarted approximately 2 weeks after stopping antiviral treatment. See section "When not to use Atywia".

When to contact a doctor
Contact the doctor immediately if:

• any concerning changes in health occur, especially 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 or planned surgery is expected (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 consecutive 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 a doctor).

Stop taking Atywia and contact a doctor as soon as possible if any symptoms suggesting 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 any 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 become pregnant, 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 as soon as possible.
Atywia is not recommended during breastfeeding.

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

Atywia contains lactose, glucose, and soya lecithin
Atywia contains lactose and glucose. If the patient has previously been diagnosed with intolerance to certain sugars, she should consult her doctor before taking this medicine.
Atywia contains soya lecithin. Do not use if hypersensitivity to peanuts or soya has been diagnosed.

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
the effectiveness of the medicine may be reduced. It also specifies circumstances under which sexual
intercourse should be avoided or additional contraceptive methods used, such as
condoms or other mechanical methods. The calendar method and the temperature method must not
be used, because Atywia affects temperature changes and cervical mucus properties
characteristic of 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 on the pack is marked with the symbol of the day of the week on which it should be taken
(see "Translation of symbols for days of the week located next to each tablet on the primary packaging"
at the end of this leaflet). The tablets should be taken in the order indicated on the pack,
every day at approximately the same time, swallowing 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 taking the last tablet and
may continue into the start of the next pack. This means that each new pack should always be started
on the same day of the week, and bleeding will occur approximately on the same days
each month.

• Starting Atywia for the first time

If no oral contraceptives have been taken in the past month
Tablet-taking should begin on Day 1 of the natural menstrual cycle (i.e., the first day of
menstrual bleeding). Tablet-taking may also begin between Day 2 and Day 5 of the menstrual 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 regimen.

If previously using a progestogen-only pill (mini-pill)
You may stop taking the mini-pill on any day and instead take Atywia at the same time.
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, implant, or intrauterine hormonal system releasing progestogen
Atywia should be started on the day the next injection was due or on the day of implant or system removal.
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 induced abortion

• After first-trimester miscarriage

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

• After childbirth or second-trimester miscarriage

Breastfeeding women: see section 2. "Pregnancy and breastfeeding".
Your doctor should advise you to start taking tablets between 21 and 28 days after childbirth or
second-trimester miscarriage. 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 sexual intercourse occurred
before starting the combined oral contraceptive, ensure that you are not pregnant or wait until the
first natural menstrual period occurs.

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

Stopping Atywia
The medicine may be discontinued 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 the missed 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 the missed 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 rules below (see also the chart 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 once), 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 is possible. Inform your doctor immediately. Also refer to the "Missed tablet management chart" below.

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 once), 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 additional (mechanical) contraception 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 that correct dosing was maintained during the 7 days preceding the missed dose. Otherwise, follow the first of the two options below and use additional contraception for the next 7 days.

1. Take the missed tablet as soon as possible (even if this means taking two tablets at once), and continue taking the next tablets at the usual time. Start the next pack immediately after finishing the current pack, 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), and then continue taking tablets from the next pack.

If you forget to take tablets and no expected 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
Seek medical advice
1 tablet from the current
pack
Sexual intercourse occurred
in the week before
Week 1.
missed tablet
Did not occur

• Take the missed tablet
• Use additional contraception for 7 days
• Finish the tablets in the pack

Only 1 tablet missed
(more than 12 hours but less than 24 hours late)
Week 2.

• Take the missed tablet
• Finish the pack
• Do not take a 7-day break
• Continue with the next pack

or
Week 3.

• Discontinue remaining tablets in the pack
• Take a break (no more than 7 days, including the day the tablet was missed)
• Continue with the next pack

What to do in the following situations:

• Gastrointestinal disturbances (vomiting)

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

• Intention to delay withdrawal bleeding

To delay the onset of withdrawal bleeding, start the next pack immediately after finishing the current
pack, without a 7-day break. You may take tablets continuously until the pack is finished. If you wish
bleeding to occur, simply stop taking tablets. During use of the next pack, slight bleeding or spotting may occur. The following pack should be started 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 every 4 weeks on the same day.
To change the day of bleeding 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 genital bleeding (spotting or intermenstrual bleeding) may occur. Despite this, continue taking the tablets as directed. Irregular genital 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 episodes of vomiting or severe diarrhoea, and no other medicines were taken concurrently, the likelihood of pregnancy is very low. Continue taking Atywia as directed.
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
No specific studies have been conducted with Atywia in patients with renal impairment.
Available data do not indicate the need for dose adjustment in this patient group.

4. Possible adverse effects

Like any medicine, 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 that the patient considers related to the use of Atywia, consult a doctor.
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, 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: "BLOOD CLOTS" and "ORAL CONTRACEPTION AND CANCER". Please read these sections for additional information and consult a 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 occur in less than 1 in 10 people):

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

Uncommon (may occur in less 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),
• skin rash (including macular rash), itching (sometimes affecting the whole body),
• changes in bleeding patterns such as heavy, scanty, infrequent menstruation or complete absence of periods,
• intermenstrual vaginal bleeding, uterine haemorrhage (irregular bleeding between periods),
• breast enlargement, including breast engorgement 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 occur in less than 1 in 1,000 people):

• 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,
• breast fibroadenoma,
• 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 flow to part of the brain),
• cerebral circulation disorders (disorders of blood flow to part of the brain),
• dystonia (sustained muscle contractions causing, for example, 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 flow to the heart),
• tachycardia (rapid heartbeat),
• venous and arterial thromboembolic events*
• pulmonary embolism (blood clot travelling to the lungs),
• thrombophlebitis (vein inflammation, including blood clots),
• elevated diastolic pressure (the lowest level to which blood pressure drops between heartbeats),
• orthostatic hypotension (dizziness or fainting when rising from a sitting or lying position),
• hot flushes,
• varicose veins,
• venous dysfunction or vein pain,
• asthma,
• hyperventilation,
• gastritis (inflammation of the stomach lining),
• enteritis (inflammation of the intestine),
• indigestion,
• skin reactions,
• skin disorders, including allergic dermatitis, neurodermatitis and (or) atopic dermatitis,
• rash, psoriasis,
• excessive sweating,
• chloasma (pigmented facial patch),
• pigmentary disorders and (or) discoloration,
• seborrhoea,
• dandruff,
• hirsutism (excessive hair growth),
• skin disorders, skin reactions, "orange peel" skin appearance,
• spider angioma,
• back pain,
• bone and muscle 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 adnexa (ovaries and fallopian tubes),
• breast cysts,
• fibrocystic breast disease,
• painful sexual intercourse,
• galactorrhea (milk secretion),
• menstrual disorders,
• chest pain,
• swelling of arms and legs,
• flu-like illnesses,
• inflammation,
• fever,
• irritability,
• hypercholesterolaemia,
• increased blood triglyceride levels,
• presence of accessory breast tissue.

* Estimated frequency from epidemiological studies covering the group of combined oral contraceptives. The term "venous and arterial thromboembolic events" includes: any obstruction and clot in peripheral deep veins, clots travelling through the circulatory system (e.g. to the lungs, called 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),
• nipple discharge,
• fluid retention.

The likelihood of developing blood clots may be higher if the patient has any other risk factors (see section 2, "HOW TO RECOGNIZE THE OCCURRENCE OF BLOOD CLOTS").
Contact a doctor immediately 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 problems (see also section "Warnings and precautions").
Description of selected adverse effects
Adverse effects of low frequency or delayed onset, considered related to the group of combined oral contraceptives, are listed below (see also sections "When not to use Atywia" and "Warnings and precautions"):
Cancers

• The number of diagnosed cases of breast cancer among women using combined oral contraceptives is slightly increased. Since breast cancer is rare in women under 40 years of age, the number of diagnoses is small relative 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 with 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 the interaction of other medicines with oral contraceptives (e.g. St John's wort (Hypericum perforatum), or drugs 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 a doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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.
Reporting adverse effects helps provide more information on the safety of this 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 packaging. The expiry date refers to the last day of the stated month.
Do not store above 25°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Atywia contains

• The active substances are ethinylestradiol and dienogest. One coated tablet contains 0.03 mg ethinylestradiol and 2 mg dienogest.
• Other ingredients are:
  Core of the tablet: monohydrate lactose, magnesium stearate, corn starch, povidone K 30, talc.
  Coating of the tablet Opaglos 2 clear: sodium croscarmellose, monohydrate glucose, maltodextrin, sodium citrate, soybean lecithin.

What Atywia looks like and contents of the pack
Atywia is available in packs of: 1x21, 3x21, 6x21 coated tablets.
One blister contains 21 coated tablets.
A cardboard sachet is included in the package, in which the blister should be placed.
For more detailed information, please contact the responsible entity or parallel importer.
Responsible entity in Portugal, country of export:
Laboratórios EFFIK, Sociedade Unipessoal, Lda.
Rua Dom António Ribeiro, n 9
1495-049 Algés
Portugal
Manufacturer:
Laboratorios León Farma S.A.
La Vallina s/n, Polígono Industrial Navatejera
Villaquilambre 24008
León, Spain
Parallel importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Marketing Authorization number in Portugal, country of export: 5279161
Marketing Authorization number for parallel import: 39/17
Translation of the weekday symbols printed next to each tablet on the immediate packaging:
Seg - Monday
Ter - Tuesday
Qua - Wednesday
Qui - Thursday
Sex - Friday
Sab - Saturday
Dom - Sunday.