Qlairista (Estradiol) 28 Tablets

BRIEF PRODUCT INFORMATION

1. NAME OF HUMAN MEDICINAL PRODUCT QLAIRISTA® film coated tablet

2. QUALITATIVE AND QUANTITATIVE COMPOSITION Active ingredient (s): 26 hormones containing hormones and 2 non-hormone-coated tablets containing the hormone are in the following order; 2 dark yellow tablets, each containing 3 mg of estradiol valerate, 5 red colored tablets each containing 2 mg of estradiol valerate and 2 mg dienogest. 2 dark red colored tablets containing 1 mg of estradiol valerate. 2 pieces of white film coated tablets (without hormones).

Excipients: The tablets of the 5 different formulations in the QLAIRISTA package each contain different amounts of lactose monohydrate; Each of the dark yellow tablets contained 48.360 mg, each of which contained 47.360 mg of red tablets, 46.360 mg of light yellow tablets, 50.360 mg each of the dark red tablets, and 52.1455 mg lactose monohydrate each of the placebo tablets.

For excipients see 6.1.

3. PHARMACEUTICAL FORM Film-coated tablets Hormone-containing tablets are dark yellow, red, light yellow and dark red, biconvex, round tablets, and one side faces an equilateral hexagon in 'DD', 'DJ', 'DH' or 'DN'. prints. Hormone-free tablets are white, biconvex, round tablets, and one side has an 'DT' print in an equilateral hexagon.

4. CLINICAL PARTICULARS 4.1 Therapeutic indications Oral contraception.

4.2 Posology and method of administration Posology / frequency and duration of administration: Tablets should be taken with sufficient water every day in the order indicated on the box. The tablets will be taken continuously. One tablet per day will be taken every day for 28 consecutive days. The next day after the last tablet received in the previous box, the next box starts. Withdrawal bleeding usually begins when the last tablets in the box are removed and may be unfinished before starting the next box. In some women, bleeding begins after the first tablets of a new box are taken.

Method of administration: Failure rate when combined oral contraceptives are taken is approximately 1% per year. Failure rate increases if the pills are forgotten or not used properly.

1/17 If no

hormonal contraceptives were used in the previous month:

The intake of tablets should be started on the first day of the natural cycle (menstrual bleeding).

Transition from combined hormonal contraceptive (COC), vaginal ring or transdermal patch:should

QLAIRISTAbe started the day after the last tablet containing the previous COC. If a vaginal ring or a transdermal patch has been used before, the day on which QLAIRISTA is removed should be started.

Transition from the progestogen method (minipil, injection, implant), or from the progestogen-release intrauterine system (IUS)

. from the implant or from the US on the day of their removal, and from the injectable product on the day of the next injection. In all these cases, however, during the first 9 days after taking the tablet, additionally a barrier method should be used.

After abortion in the first trimester: tablets can be taken immediately. In this case additional contraceptive measures are not required.

After the birth or after the second trimester abortion: For those who are breastfeeding, see ab 4.6 Pregnancy and lactation Doğum.

21-28 after birth or second trimester abortion. should be started on days. If it is started, it should be asked to use an additional barrier method for the first 9 days after taking the tablet. However, if sexual intercourse has occurred, pregnancy should be excluded before beginning to use POPs, or until the first menstrual period.

What to do when tablets are forgotten:

White tablets that do not contain hormones that are forgotten may not be considered. However, to avoid unintentional extension of the hormone-free tablet period, these forgotten tablets should be discarded.

Recommendations in case of gastrointestinal disorders:case of

In thesevere gastrointestinal disorders, absorption may not be complete and additional contraceptive measures may be required.

If vomiting occurs within 3-4 hours of taking the hormone-containing tablet, the recommendations for forgotten tablets will be valid (see section 4.2 Posology and method of administration). If the usual tablet delivery program is not desired to be changed, the extra tablet required must be swallowed from another package.

The following recommendations are only for tablets with forgotten hormones:

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If the time taken to remove tablets is less than 12 hours, contraceptive protection is not reduced. It should be remembered that tablets should be taken, and subsequent tablets should be taken in usual times.

If the forgotten time for taking the tablet is longer than 12 hours, contraceptive protection may be reduced. Even if two tablets are meant to be taken at the same time, the tablet should be taken without being remembered. Subsequent tablets should be continued in their usual time. Depending on the days of forgetting the cycle of taking the tablet (see table below for details), reserve contraceptive measures should be taken according to the principles given below (eg a barrier method such as a condom).

DAY Color

Estradiol valerat (EV) / dienogest (DNG) The

principles that should be followed when a tablet is forgotten for more than 12 hours:

1 - 2 Dark yellow tablets

(3.0 mg EV) 3 - 7 Red tablets

(2.0 mg EV + 2.0 mg DNG) 8 - 17 Light yellow tablets

(2.0 mg EV + 3.0 mg DNG)

- The forgotten tablet is taken immediately, and the next tablet is

taken at regular time (even if this means taking two tablets on the same day) - The tablets continue to be taken as usual - for the next 9 days additional contraception is

applied

18 - 24 Light yellow tablets

(2.0 mg EV + 3.0 mg DNG)

- The used package is discarded and thea new package

first tablet is started by starting- The tablets continue to be taken as usual - Additional contraception isfor the next 9 days

applied25 - 26 Dark red tablets (1.0 mg EV)

- The forgotten tablet is taken immediately, and the next tablet is

taken at regular time (even if this means taking two tablets on the same day) - Additional contraception not required 27 - 28 White tablets

(Placebo)

- The forgotten tablet is discarded and the tabletsbeas usual

continue totaken- No additional contraception is required

Any day more than two tablets should not be taken. If it is forgotten to start a new package, or if it is forgotten to take the tablets on the 3rd - 9th day of the package, it can be conceived (in case of having sexual intercourse within 7 days of forgetting). The higher the number of tablets forgotten (from those with two combined hormones 3 to 24 days) and the closer the forgotten tablets to the non-hormone phase, the higher the risk of pregnancy.

The possibility of pregnancy should be taken into account if the tablet has been forgotten and there is no withdrawal bleed at the end of the package / at the beginning of the new package.

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Additional information on special populations: Kidney Failure: QLAIRISTA has not been specifically studied in patients with renal failure. The data available did not provide data on treatment change in this patient population. Liver Failure: QLAIRISTA is contraindicated in women with severe liver disease (see section 4.3 Contraindications). Pediatric population: QLAIRISTA is indicated only after menarche. Geriatric population: There is no use in the geriatric population. QLAIRISTA has no indication after menopause.

4.3 Contraindications Combined oral contraceptives (POPs) should not be used in the presence of any of the following tables. If any of these tables occur for the first time during POPs use, the drug should be discontinued immediately.

• Presence of venous or arterial thrombotic / thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, myocardial infarction) or cerebrovascular event in its current or past history;

• Presence of a pre-thrombosis (or transient ischemic attack, angina pectoris);

• a severe risk factor for venous or arterial thrombosis that may produce contraindications, or multiple risk factors (see section 4.4 Special warnings and precautions for use);

• A history of migraine with focal neurological symptoms;

• diabetes mellitus with vascular involvement;

• Severe liver disease and liver function tests have not yet returned to normal;

• Presence or presence of liver tumor (benign or malignant);

• the presence of malignancies (eg, genital organs or breasts) affected by sex steroids or suspected of malignancy;

• Undiagnosed vaginal bleeding;

• Presence or suspicion of pregnancy;

• Hypersensitivity to active substances or auxiliaries.

4.4 Special warnings and precautions for use Warnings If any of the following tables / risk factors are present, the benefits of using POPs should be weighed against the potential risks of each woman and discussed with the woman prior to the decision to use the drug. In case of aggravation, exacerbation or first occurrence of any of these conditions or risk factors, consult a female doctor. The doctor should then decide whether to use POPs or not.

There is no epidemiological study on the effects of POPs containing estradiol / estradiol valerate. All following cautions and precautions are from clinical and epidemiological data on POPs containing ethynylestradiol. It is not known whether these warnings and precautions apply to QLAIRISTA.

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Circulatory disorders: The

risk of VTE in the use of QLAIRISTA is currently unknown.

Epidemiological studies have shown the presence of a relationship between increased risk of arterial and venous thrombotic and thromboembolic diseases, such as myocardial infarction, deep vein thrombosis, pulmonary embolism, and cerebrovascular accident, with the use of COC containing ethinyl estradiol. These events are rare.

The risk of venous thromboembolism is highest in the first year of use. This risk increase is initially present during the initiation of a COC, initiation of re-treatment with the same POPs or a different POP (at least 4 weeks after the interval). A large-scale, prospective and 3-handed study data suggests that this risk increase is mainly present in the first 3 months.

The risk of total venous thromboembolism (VTE) in POPs containing low-dose estrogen (<50 μg ethinylestradiol) increased 2-3-fold compared to non-pregnant and non-POPs; The risk associated with pregnancy and childbirth is lower.

VTE can be life threatening or fatal outcome (1-2% of cases).

Venous thromboembolism (VTE), which occurs as deep vein thrombosis and / or pulmonary embolism, may occur during the use of all POPs.

It is extremely rare for POP users to use other blood vessels, e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries have been reported to occur thrombosis. There is no consensus on whether these events are related to the use of POPs.

Deep vein thrombosis (DVT) symptoms: swelling across the vein in the unilateral leg or leg; pain or tenderness that can only be felt when standing or walking, temperature increase in the affected leg; leg redness or discoloration.

Pulmonary embolism (PE) symptoms: sudden onset unexplained breathlessness or rapid breathing; sudden cough that can be bloody; deep chest pain that can increase with deep breathing; sense of anxiety; severe dizziness and dizziness; fast or irregular heartbeat. Some of these symptoms (eg örn shortness of breath olan, ayıp cough olm) are not unique symptoms, but may be interpreted as more common and less serious events (eg, respiratory tract infection).

The arterial thromboembolic event includes cerebrovascular event, vascular occlusion or myocardial infarction (MI). Symptoms of cerebrovascular accident: sudden sensory loss or weakness in the face, arm or leg, particularly on one side of the body; difficulty in sudden confusion, speech or understanding; sudden visual impairment in one or both eyes; sudden walking disorder, dizziness, loss of balance or coordination; sudden, severe or long-lasting headaches; unconsciousness or fainting with or without seizure. Other symptoms of vascular occlusion include sudden pain, swelling, and light blue color in one limb; acute abdomen.

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MI symptoms include pain, discomfort, pressure, weight, tightness or fullness behind the chest, arm and chest bone; discomfort in the back, jaw, throat, arm and stomach; toughness, indigestion or feeling of gas; sweating, nausea, vomiting or dizziness; fast and irregular heartbeat.

Arterial thromboembolic events can be life-threatening or fatal.

The risk of venous or arterial thrombotic / thromboembolic events or cerebrovascular event increases with the following factors:

- Increased age, - Obesity (body mass index over 30 kg / m2), - Positive family history (a relatively early age in the sibling or parents. age, venous or arterial thromboembolism). If a hereditary predisposition is suspected, the woman should be referred to a specialist before the decision to use POPs, - prolonged immobilization, major surgery, any surgical intervention in the legs, or major trauma. In such cases, it is recommended that POPs should be discontinued (at least four weeks prior to elective surgery) and should not be restarted until two weeks after complete remobilization. - Cigarette smoking (non-smoking women over 35 years of age who want to use COC

advice should be given to) - Dislipoproteinemia, - Hypertension, - Migraine - Valvular heart disease, - Atrial fibrillation,

There is no consensus on the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.

Consider the increased risk of thromboembolism in puerperium (see izm 4.6 Pregnancy and lactation P).

Other medical statements associated with adverse events in the circulatory system include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.

An increase in the frequency or severity of migraine during POPs use (may be a prodrome of a cerebrovascular event) may be a reason for immediate discontinuation of POPs.

Biochemical factors that may be indicative of hereditary or acquired predisposition to venous or arterial thrombosis include activated protein C (APC) resistance, hyperhomocysteinemia, antithrombin-III deficiency, protein C deficiency, protein S deficiency, and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

When deciding on the risk / benefit ratio, the physician must take into account that the appropriate treatment given in a given table may reduce the risk of associated thrombosis and that the risk associated with pregnancy is higher than the risk associated with low-dose POP (<0.05 mg etinylestradiol).

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Tumors: The most important risk factor for cervical cancer is persistent HPV infection. It has been pointed out that prolonged use of POPs in some epidemiological studies may increase this increased risk further; however, the extent to which this finding depends on the factors that make it difficult to achieve some other results (eg, sexual behavior, including the use of cervical screening and barrier contraceptives) remains controversial.

In a meta-analysis conducted on fifty-four epidemiological studies, it was reported that there was a slight increase in the relative risk of breast cancer diagnosis (RR = 1.24) in women currently using POPs. This risk excess is gradually disappeared within 10 years after discontinuation of POPs. Since breast cancer is rare in women under the age of 40, the number of breast cancer diagnoses in women who are currently using or using POPs is small compared to the overall risk of breast cancer. These studies do not provide data for causality. The pattern of increased risk may be due to earlier diagnosis of breast cancer in POP users, biological effects of POPs, or a combination of both. Breast cancer diagnosed in POPs users at any time in their lives tends to be clinically less advanced than those diagnosed in women who have never used them.

Benign liver tumors and rare malignant liver tumors have been reported in patients with POPs. In isolated cases, these tumors have led to life-threatening intraabdominal bleeding. If women with POPs develop severe upper abdominal pain, liver enlargement or intraabdominal bleeding, liver tumors should be considered in the differential diagnosis.

Malignant tumors can be life-threatening or fatal.

Other tables: In women with hypertriglyceridemia or family background, the risk of pancreatitis may increase when using POPs.

Although small increases in blood pressure have been reported in a large number of women receiving POPs, clinically significant increases are rare. However, if clinically significant and persistent hypertension develops during the use of POPs, the appropriate approach for the physician is the treatment of hypertension by cutting POPs. If normotensive values ​​are obtained with antihypertensive treatment, POPs may be re-initiated if appropriate.

The following tables have been reported to occur or deteriorate during both pregnancy and POPs use, but the data for the association with POPs are not definite; jaundice and / or pruritus due to cholestasis; gallstone formation; porphyria, systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham chorea; herpes gestationis; hearing loss due to otosclerosis.

In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.

Acute or chronic hepatic dysfunctions may require the use of POPs to be stopped until signs of liver function return to normal. Thefirsta pregnancy

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relapse of cholestatic jaundice which occurred during theor earlier sex steroid use duringrequires the discontinuation of COC.

Although POPs may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence that the therapeutic regimen needs to be altered in low-dose diabetic patients (containing <0.05 mg ethinylestradiol). However, diabetic women should be observed carefully during COC use.

Crohn's disease and ulcerative colitis were associated with COC use.

Especially in women who have chloasma gravidarum, chloasma may occasionally occur. Women with a tendency to chloasma should avoid sun exposure or ultraviolet radiation when using POPs.

Lactose: The tablets in 5 different formulations in QLAIRISTA packaging contain different amounts of lactose monohydrate; Each of the dark yellow tablets contained 48.360 mg, each of which contained 47.360 mg of red tablets, 46.360 mg of light yellow tablets, 50.360 mg each of the dark red tablets, and 52.1455 mg lactose monohydrate each of the placebo tablets.

Patients with galactose intolerance, such as galactosemia, are rare. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose galactose malabsorption should not use this drug.

Medical examination / consultation: A complete medical history should be obtained and a physical examination should be performed before the introduction of POPs or after a given interval. Contraindications to these procedures (see kontr 4.3 Contraindications er) and warnings (see dır 4.4 Special warnings and precautions for use rehberlik) should be guided and periodically repeated, periodical medical assessments are also important, because contraindications (eg transient ischemic attack) or risk factors (eg family history of venous or arterial thrombosis) may occur during POPs use for the first time. The frequency and nature of these assessments should be based on established practice guidelines, and should be adapted to the particular situation of the female individual; however, pelvic organ examinations including blood pressure, breasts, abdomen and cervical cytology should be included.

It should be explained to women that oral contraceptives do not provide protection against HIV infection (AIDS) and other sexually transmitted diseases.

Decrease in effectiveness: POPs activity may be reduced by the following events; tablets containing hormone which is forgotten (see section ”4.2 Posology and mode of administration / what to do when tablets are forgotten ğı), gastro-intestinal disorders when taking hormone-containing tablets (see 4.2 Posology and mode of administration / recommendations in case of gastrointestinal disturbances () or other concurrently taken drugs (see etkileşim 4.5 Interactions with other medicinal products and other forms of interaction ().

Cycle control:

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Irregular hemorrhages (stains-like bleedings or intermittent hemorrhages) may occur with all POPs, especially during the first months of use, so the evaluation to be performed for any irregular bleeding is significant only after an adaptation period of around three cycles. there will be.

If bleeding irregularities permanent or if the previously occurs after the cycle is normal, in this case non-hormonal causes should be considered and malignancy or indicated to make the necessary diagnostic procedures to exclude pregnancy. these actions may include abortion.

Some women free withdrawal bleeding hormones white If COC is taken as described in amas 4.2 Posology and mode of administration kadın, the woman is unlikely to become pregnant, but if the POPs were not taken in accordance with these instructions before the first withdrawal bleed. or, if withdrawal bleeding has not occurred twice, the pregnancy should be eliminated before continuing with the use of POPs.

4.5 Interactions with other medicinal products and other forms of interaction Note: For the identification of potential interactions, refer to the product information of the concurrent drugs.

Interaction studies were performed only in adults.

Interactions of other medicinal products with QLAIRISTA: Interactions of oral contraceptives with other drugs (enzyme inducers, some antibiotics) may result in intermediate bleeding and / or contraceptive failure. Women who are being treated with microsomal enzyme-inducing drugs or antibiotics should use a barrier method or select another contraceptive method, as well as POP. The barrier method should be maintained for as long as the drugs are administered together and for 28 days after the application is finished.

Generally, maximal enzyme stimulation is not observed for 2tedir3 weeks but can continue for at least 4 weeks following discontinuation of drug therapy.

Substances that reduce POPs (enzyme-inducing drugs and antibiotics)

Enzyme induction (increased hepatic metabolism): Drugs that induce microsomal enzymes (eg phenytoin, barbiturates, pyrimidone, carbamazepine, rifampicin, and possibly oxcarbazepine, topiramate, felbamate, griseofulvin and St. John's plant The products may interact with and may result in increased clearance of sex hormones.

Women receiving short-term treatment with any of the aforementioned medicinal product classes or with individual active substances other than rifampicin (up to one week) should use a barrier method in addition to POP for 14 days after and simultaneously with simultaneous drug use.

The effect of CYP 3A4 inducer rifampicin was investigated in healthy postmenopausal women. Co-administration of rifampicin with estradiol