Claira, 2 mg+2 mg, 3 mg+2 mg and 1 mg, 3 mg 84 pcs

Pharmacotherapeutic group
Combination contraceptive (estrogen + gestagen)
ATX code
G03AB
Pharmacological properties
The contraceptive effect of combined oral contraceptives (OCs) is based on the interaction of various factors, the most important of which are ovulation suppression and changes in the properties of cervical mucus. Besides prevention of unwanted pregnancy, OCs have a number of positive characteristics that, when taken together with their negative characteristics (see “Special considerations,” “Side effects”), may help in choosing the most appropriate method of contraception. In women taking OCs the painfulness and intensity of menstrual bleeding decreases, thus reducing the risk of iron deficiency anemia. Besides, there is data on reduction of risk of endometrial and ovarian cancer development.
The estrogen in Klyra preparation is estradiol valerate, a precursor of natural human 17β-estradiol (1 mg of estradiol valerate corresponds to 0,76 mg of 17β-estradiol) The estrogen component used in this OC, thus, differs from estrogens usually used in OCs which are synthetic estrogens ethinyl estradiol or its precursor mestranol, both containing an ethynyl group in position 17α. This group causes higher metabolic stability, but also more expressed action on the liver.
Administration of Claira leads to a less pronounced effect on the liver compared to triphasic OCs containing ethinylestradiol and levonorgestrel. It was shown that the effect on the concentration of globulin binding sex steroids (GSSB) and hemostasis parameters is less pronounced. In combination with dienogestrel, estradiol valerate shows an increase in high-density lipoproteins (HDL), while the concentration of low-density lipoprotein cholesterol (LDL) decreases slightly.
Dienogest is an oral progestagen characterized by additional partial antiandrogenic effects. Its estrogenic, anti-estrogenic and androgenic properties are insignificant. Due to its special chemical structure a spectrum of pharmacological action is provided which combines the most important advantages of 19-nor-progestagens and progesterone derivatives.

Indications

ContraceptionPeroral contraception.

Composition

One pink film-coated tablet:
Active ingredients: Estradiol valerate, micro 20 – 2,000 mg Dienogest, micro – 2,000 mg,
Excipients: lactose monohydrate, corn starch, corn starch pregelatinized, povidon-25, magnesium stearate
Shell: hypromellose, macrogol-6000, talc, titanium dioxide, iron oxide red dye.
Per one pale yellow film-coated tablet:
Active ingredients: estradiol valerate, micro 20 – 2,000 mg Dienogest, micro – 3,000 mg
Excipients: lactose monohydrate, corn starch, corn starch pregelatinized, povidon-25, magnesium stearate
Coating: hypromellose, macrogol-6000, talc, titanium dioxide, iron oxide yellow dye.
Per one red film-coated tablet:
Active ingredient: estradiol valerate, micro 20 – 1,000 mg
Excipients: lactose monohydrate, corn starch, corn starch pregelatinized, povidon-25, magnesium stearate
Shell: hypromellose, macrogol-6000, talc, titanium dioxide, iron oxide red dye.

How to take, the dosage

How and when to take Claira

Take the tablets daily in the order shown on the package, regardless of meals, at about the same time, with water if necessary. The tablets should be taken continuously. One tablet per day should be taken consecutively for 28 days. Each new pack of pills is started after the last tablet from the previous calendar pack has been taken. Menstrual bleeding usually begins when the last pills of the calendar pack are taken and may not end until the beginning of the next calendar pack. In some women, bleeding begins after taking the first pills of the new calendar pack.
If used correctly, the Perl Index (an indicator that reflects the frequency of pregnancy per 100 women during a year of contraceptive use) is less than 1. If the pill is missed or used incorrectly, the Perl Index may increase.

Package preparation

To help you keep track of your pills, the package comes with 7 stickers labeled with the names of the 7 days of the week.
Choose the label that starts on the day of the week you first start taking pills. For example, if you start on Wednesday, use the sticker that starts with the word “Wed”.
Place this sticker at the top of the fold-out package of Claira where it says “Put the day of the week sticker here,” so that the name of the first day is above the number “1” pill.
Now above each pill is the name of the corresponding day of the week and you can see whether the pill has already been taken on a particular day or not. Follow the direction of the arrow on the package-book until you have taken all 28 pills.
Usually, so-called menstrual bleeding begins while you are taking the second dark red or white pill and may not end before you start the next package. For some women, bleeding still continues after taking the first pills of the new pack.
Start the next package without a break, that is, the day after you finish the current package, even if bleeding has not stopped. This means that the next pack should be started on the same day of the week as the current pack, and that menstrual bleeding should fall on the same days of the week each month.
If you use Clyra as directed, you are protected from unwanted pregnancy even during those 2 days when you take the inactive pills.

How do I start taking pills from the first package?

• If you haven’t used hormonal contraception in the past month.
  Start your Claira on the first day of your cycle, the first day of your period.
• If you change to Claira from other OCs, a combined contraceptive vaginal ring or a patch.
  Start Klyra the day after you take the last active pill (the last pill with the active ingredients) of your current hormonal contraceptive package. If your previous contraceptive package contains inactive pills, discard them and continue from the first package of Claira without taking a break. If you used a combined contraceptive vaginal ring or patch previously, start taking Klaira on the day the ring/patch was removed or follow your doctor’s advice.
• If you switch from a pure progestagen method of contraception (mini-pills, injection, implant or progestagen-releasing intrauterine system (IUD)
  You may switch to taking Klaira from a pure progestagen method on any day (from an implant or IUD – on the day of their removal; from an injectable method – on the day for which the next injection is scheduled), but in all cases you must use additional contraceptive measures (such as condoms) during the first 9 days of taking the Klaira drug.
• After a miscarriage
  Consult your doctor.
• After childbirth
  If you have just had a baby, your doctor may advise you to wait until you have had your first normal period before starting Clyra. Sometimes it is possible to start earlier. Your doctor will advise you on what to do.
  If you had sexual intercourse after giving birth, make sure you are not pregnant or wait until your next period starts before starting Claire.
  If you are breastfeeding and want to take Claira, discuss the matter with your doctor first.
  If in doubt about when to start taking Claira, ask your doctor for advice.

If you have taken too many tablets of Claira

Severe adverse effects of an overdose of Claira have not been reported.
If you have taken several active pills at one time, you may develop nausea or vomiting. Vaginal bleeding may occur in young girls.
If you take too many pills of Claira, or if you find that a child has taken any number of pills, ask your doctor for advice.

Pills without active ingredients (placebos) are necessary if you miss pills

Pills without active ingredients (placebos): If you miss one of the white pills (2 white pills at the end of the package), you do not need to take it later because it does not contain any active ingredients and you are still protected from an unwanted pregnancy.
However, it is important that you discard the missed white pill (or pills) and continue with the next pill at the usual time. Otherwise, your protection against unwanted pregnancy may be reduced (as a result of inadvertently extending the period during which the active pills are not taken).
If you forget to take the last white pill of your current package, it is important that you still take the first pill of the next package at the correct time.

The following recommendations apply to skipping active pills (pills 1-26 in the book pack):

The active pills: Depending on the day of the menstrual cycle on which one active pill was missed, you may need to use additional contraceptive measures, such as a barrier method, such as condoms.
Take the pill according to the following principles. Also see the “Missed Pills” chart for more details.

• If there is a delay of less than 12 hours in taking any pill, the contraceptive effect of the drug is maintained. Take the pill as soon as you remember it, and take the other pills at the usual time.
• If there is a delay of more than 12 hours in taking the pill, the contraceptive reliability of the drug may decrease. Depending on the day of the menstrual cycle on which one pill was missed, use additional contraceptive measures, such as a barrier method, particularly condoms. See also the “Missed Pills” chart for more information.
• More than one pill was missed from the package
  Consult your doctor for advice.

Do not take more than 2 active pills in one day to make up for missed pills.

If you forget to start a new pack, or if you miss one or more pills from day 3 to day 9, there is a risk that you are already pregnant (if you had intercourse within 7 days before missing the pill). If this is the case, talk to your doctor. The more pills (especially those with a combination of the two active ingredients on days 3 to 24) you miss, and the closer they are to the inactive pill phase, the more likely you are to be pregnant. See also the Missed Pills chart for more details.

If you forget to take any of the active pills in a package and then you don’t bleed at the end of the package, you may be pregnant. Check with your doctor before starting a new pack.

What to do if you vomit or have severe diarrhea

If you vomit or have severe diarrhea after taking any of the 26 active tablets of Claira, the absorption of the active ingredients may not be complete. If vomiting occurs 3-4 hours after taking the pill, it is tantamount to missing the pill. Therefore follow the recommendations described in the section What to do if you miss a pill. If you have severe diarrhea, see your doctor. Vomiting or diarrhea on the days of the last 2 inactive pills has no effect on the effectiveness of contraception.

You want to stop taking Clyra

You can stop taking Clyra at any time. If you are not planning a pregnancy, ask your doctor about other contraceptive methods. If you want to get pregnant, stop taking Clara and wait for your natural menstrual bleeding before trying to get pregnant. This will help you calculate your expected due date.

If you have further questions about the use of this medication, talk to your doctor.

Interaction

The effect of other drugs on the active ingredients of Claira^®

The interaction of CRPS with other drugs may lead to breakthrough uterine bleeding and/or lack of contraceptive effect. The following types of interactions have been described in the CRP literature in general or have been studied during clinical trials of Clyra^®:

Isozyme inducers (CYP3A4 isoenzyme). There may be an interaction with drugs that induce microsomal enzymes (such as cytochrome P450 system), which may increase clearance of sex hormones (these drugs include phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, as well as preparations containing St. John’s wort). HIV protease inhibitors (e.g. ritonavir), non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and their combinations have also been reported to affect hepatic metabolism.

The effect on intestinal-hepatic recirculation. Against the background of taking certain groups of antibiotics (e.g., penicillin and tetracycline groups), enterohepatic circulation of estrogens may be reduced, which may lead to lower concentrations of estradiol.

Women who are treated with microsomal enzyme inducing drugs or antibiotics are advised to use a temporary barrier method of contraception in addition to Clyra^® or choose another contraceptive method. The barrier method of contraception should be used for the entire period of taking concomitant drugs and for another 28 days after their withdrawal.

Isoenzyme inhibitors (CYP3A4 isoenzyme). Concomitant administration of rifampicin with tablets containing estradiol valerate and dienogest resulted in a significant decrease in C_ss and systemic exposure to dienogest and estradiol. Systemic exposure of dienogest and estradiol at C_ss, as measured by AUC_0-24, decreased by 83% and 44%, respectively.

Known CYP3A4 inhibitors, such as azole antifungals, cimetidine, verapamil, macrolides, diltiazem, antidepressants and grapefruit juice, may increase plasma concentrations of dienogest. When concomitantly administered with the potent inhibitor ketoconazole, the AUC_0-24 at equilibrium was increased by 186% for dienogestol and by 57% for estradiol. When used concomitantly with the moderate inhibitor erythromycin, the AUC_0-24 values of dienogest and estradiol in equilibrium increased by 62% and 33%, respectively.

The effects of the drug Claira ^® in relation to other drugs: PDA can affect the metabolism of several other drugs (e.g. lamotrigine) that can lead to either higher or lower concentrations of these substances in blood plasma and tissues. However, based on the data of in vitro studies, inhibition of CYP enzymes when using the drug Clyra^® at a therapeutic dose is unlikely.

Note: For possible interactions, read the instructions for the concomitant medications.

Incompatibilities. None.

Special Instructions

If any of the diseases/conditions/risk factors listed below are currently present, the potential risks and expected benefits of Clyra^® should be carefully balanced on a case-by-case basis and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, intensify, or first appear, the woman should consult her doctor, who may decide if the drug should be discontinued.

Cardiovascular disease

Epidemiologic studies suggest a relationship between CPT use and increased rates of venous and arterial thrombosis and thromboembolism (such as DVT, TELA, MI, and cerebrovascular events). The risk of venous thromboembolism (VTE) is maximal in the first year of taking these drugs, mostly during the first 3 months. An increased risk is present after initial use of a PDA or renewed use of the same or different PDAs (after a break of 4 weeks or more between doses). The overall risk of VTE in patients taking low-dose CRPs (less than 50 mcg ethinylestradiol) is 2-3 times higher than in patients not taking CRPs, but the risk remains lower compared to the risk of VTE in pregnancy and childbirth. VTE can be fatal (1-2% of cases).

VTE, manifesting as DVT or TELA, can occur with any PDA. It is extremely rare for thrombosis of other blood vessels, such as hepatic, mesenteric, renal, cerebral arteries and veins, or retinal vessels, to occur with PDA use. There is no consensus on the relationship between the occurrence of these events and the use of CPT. Arterial thromboembolism can be fatal.

The risk of thrombosis (venous and/or arterial) and thromboembolism is increased:

– with age;

– in smokers (the risk increases with more cigarettes smoked or increased age, especially in women over 35);

In the presence of:

– a family history (e.g., venous or arterial thromboembolism ever in a close relative or parent at a relatively young age). If there is an inherited or acquired predisposition, the woman should be examined by an appropriate specialist to decide whether she can take Claire^®;

– obesity (body mass index more than 30 kg/m²);

– dyslipoproteinemia;

– arterial hypertension;

– migraine;

– heart valve disease;

– atrial fibrillation;

– prolonged immobilization; extensive surgery, any lower extremity surgery, or extensive trauma. In these situations, it is advisable to stop taking Clyra^® (at least 4 weeks before surgery if planned) and not to resume for 2 weeks after the end of immobilization.

The possible role of varicose veins and superficial thrombophlebitis in VTE remains controversial.

The increased risk of thromboembolism in the postpartum period should be considered. Peripheral circulatory disorders can also be noted in 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 and severity of migraine headaches during use of Clyra^® (which may precede cerebrovascular disorders) may be grounds for immediate discontinuation of this drug.

Biochemical factors indicating an inherited or acquired predisposition to arterial or venous thrombosis include: activated protein C resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipid antibodies, lupus anticoagulant).

When evaluating the risk-benefit ratio, consider that treatment of the condition may reduce the associated risk of thrombosis. It should also be considered that the risk of thrombosis and thromboembolism in pregnancy is higher than with low-dose oral contraceptives (ethinyl estradiol less than 50 mcg).

Tumors

The most significant risk factor associated with the development of cervical cancer is persistent papillomavirus infection (PVI). Some increased risk of cervical cancer has been reported with long-term use of CRPS. The association with PDA intake has not been proven. The possibility of a correlation with cervical disease screening and sexual behavior patterns (less frequent use of barrier methods of contraception) is being discussed.

A meta-analysis of 54 epidemiological studies found a small increase in the relative risk (OR = 1.24) of developing breast cancer in women currently taking CRC. The increased risk gradually disappears within 10 years of stopping these drugs. Because breast cancer is rare in women younger than 40 years of age, some increase in the number of breast cancers diagnosed in women currently or recently taking CRPs is small relative to their overall risk of the disease. It has not been shown to be associated with taking CRPS. The increased risk observed may also be a consequence of earlier diagnosis of breast cancer in women taking CRPS. Women who have ever used PDAs are found to have earlier stages of breast cancer than women who have never used them.

In rare cases, PDA use has resulted in benign, and in extremely rare cases, malignant liver tumors, which in some cases have led to life-threatening intra-abdominal bleeding. If severe upper abdominal pain, increased liver size, or signs of intra-abdominal bleeding occur in women taking CRP, liver tumors should be excluded in the differential diagnosis.

Other conditions

Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of pancreatitis while taking CRP.

While small increases in BP have been described in many women taking CRP, clinically significant increases have rarely been reported. However, if a persistent, clinically significant increase in BP develops while taking Klaira^®, the drug should be stopped and treatment for arterial hypertension started. The use of Claira^® can be resumed if necessary, if normal BP values can be achieved by hypotensive therapy.

The following conditions develop or worsen during pregnancy as well as with CPP, but their association with taking CPP has not been proven: jaundice and/or cholestatic pruritus, cholelithiasis, porphyria, systemic lupus erythematosus, hemolytic uremic syndrome, Sydingham chorea, herpes of pregnancy, otosclerosis-related hearing loss.

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

Acute or chronic liver function abnormalities may require withdrawal of Claira^® until liver function parameters return to normal. Recurrent cholestatic jaundice that develops for the first time during pregnancy or previous use of sex hormones requires discontinuation of Clyra^®.

While PDAs may affect insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients who use Claira^®. However, women with diabetes need careful monitoring while taking Claira^®.

Cases of Crohn’s disease and ulcerative colitis have also been described while taking Clara.

Chloasma may sometimes develop, especially in women with a history of pregnancy chloasma.

Women who are prone to developing chloasma should avoid sun exposure or UV radiation while taking Clyra^®.

Impact on laboratory tests. Taking Claira^® may affect the results of some laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, plasma concentrations of transport proteins such as CRP and lipid/lipoprotein fractions, parameters of carbohydrate metabolism, coagulation and fibrinolysis. These changes usually remain within laboratory norms.

Medical examinations. Before starting Claira^®, the contraindications for prescribing the drug should be carefully evaluated on the basis of a woman’s life history, family history, and general medical and gynecological examinations. The frequency and nature of these examinations should be based on existing standards of medical practice, taking into account the individual characteristics of each patient. As a rule, blood pressure is measured, breast, abdominal and pelvic examinations, including cervical cytology, are checked.

Women should be advised that the drug Claira^® does not protect against HIV infection (AIDS) or other sexually transmitted diseases.

Decreased efficacy. The effectiveness of Claira^® may be reduced if pills with active ingredients are missed (see recommendations for missed pills under “Dosage and administration”), gastrointestinal distress while taking pills with active ingredients (see “Dosage and administration”). recommendations for gastrointestinal disorders under “Dosage and administration”) or with concomitant medication (see “Interactions”).

Inadequate control of the menstrual cycle. The use of Clyra^®, especially during the first months of use, may cause irregular menstrual bleeding (oozing or breakthrough uterine bleeding). Therefore, any irregular menstrual-like bleeding should be evaluated only after a period of adjustment, which is approximately 3 menstrual cycles.

If irregular menstrual-like bleeding recurs or occurs for the first time after previous regular cycles, the possibility of non-hormonal causes should also be considered and a thorough exam should be performed to rule out malignancy or pregnancy. This might include a diagnostic curettage.

In some women, menstrual-like bleeding may not occur while taking the inactive white pill. If you took Claira^® in accordance with the rules listed in the “Dosage and administration” section, pregnancy is unlikely. However, if the pills were taken irregularly before the first absent menstrual bleeding or 2 consecutive menstrual bleedings are missing, you should not continue using Clyra^® until pregnancy is excluded.

Impact on the ability to drive a car or perform work requiring increased speed of physical and mental reactions. No adverse effect of Claira® has been noted on the ability to drive or operate machinery, but patients who have had episodes of dizziness and loss of concentration during adaptation (in the first 3 months of taking the drug) should be treated with caution.

Contraindications

The drug Claira^® should not be used if any of the conditions listed below are present. The drug must be stopped immediately if any of these conditions develop for the first time while taking it:

• high sensitivity to the active ingredients or any of the excipients;
• thrombosis (venous and arterial) and thromboembolism (current or history of thrombosis).
• Thrombosis (venous, arterial, or arterial thromboemboli, current or history of thrombosis, pulmonary embolism, myocardial infarction (MI), current or history of stroke
• Pre- thrombotic conditions (including, but not limited toч.
• Transient ischemic attacks, angina pectoris), current or history
• Acquired or hereditary
• acquired or hereditary predisposition to venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocystsinemia, antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant);
• presence of high risk of venous or arterial thrombosis (see “Special Indications.
• High risk of venous or arterial thrombosis (see “Special Precautions”);
• migraine with focal neurologic symptoms, including history;
• diabetes mellitus with vascular complications;
• pancreatitis with marked hypertriglyceridemia at present or in the history;
• Liver tumors (benign and malignant), current or history;
• detected hormone-dependent malignant tumors (includingч.
• pregnancy or suspicion of it;
• blooding from the vagina of unclear genesis;
• pregnancy or suspicion of it;
• breastfeeding period;
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

WARNING

• .If any of the diseases/conditions/risk factors listed below are currently present, the potential risks and expected benefits of Claira^® should be carefully balanced on a case-by-case basis:
• risk factors for thrombosis and thromboembolism (smoking; obesity; dyslipoproteinemia; arterial hypertension; migraine; heart valve disease; heart rhythm disorders; extensive surgery without prolonged immobilization);
• other diseases in which peripheral circulatory disorders may be noted (diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, Crohn’s disease and ulcerative colitis, sickle cell anemia);
• hereditary angioedema;
• hypertriglyceridemia;
• diseases first developed or aggravated during pregnancy or on previous use of sex hormones (e.g., cholestatic jaundice, cholestatic pruritus, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes of pregnancy, Sydenham’s chorea);
• Postpartum period.

.

Side effects

The following serious adverse events have been reported in women using PDAs (which include Claira^®) Arterial and venous thrombosis and thromboembolic complications; worsening of the course or triggering of symptoms of angioedema; liver tumors; acute pancreatitis

Overdose

Symptoms: No serious disorders have been reported with an overdose of Clyra^®. Based on the summarized experience of PDA use – symptoms that may be noted in case of overdose of active pills: nausea, vomiting, mastic bloody discharge or metrorrhagia.

Treatment: symptomatic.