Vendiol

INSTRUCTIONS for medical use of the medicinal product VENDIOL (VENDIOL)

Composition:

Active ingredients: gestodene, ethinylestradiol;

1 active tablet contains 0.060 mg micronized gestodene and 0.015 mg micronized ethinylestradiol;

Excipients: lactose monohydrate, microcrystalline cellulose (type 102), potassium polacrilin, magnesium stearate;

Film coating: Opadry II Yellow 31K32378, lactose monohydrate, hypromellose (type 2910), titanium dioxide (E 171), triacetin, quinoline yellow dye (E 104);

1 placebo tablet contains:

Active ingredients: absent;

Excipients: microcrystalline cellulose, anhydrous lactose, pregelatinized corn starch, magnesium stearate, colloidal anhydrous silicon dioxide;

Film coating: Opadry II Green 85F21389, polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, indigo carmine dye (E 132), quinoline yellow dye (E 104), iron oxide black dye (E 172), yellow sunset FCF dye (E 110).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

Active tablets: round, biconvex, film-coated tablets of yellow color;

engraving on one side: "G43", the other side without engraving;

Placebo tablets: round, biconvex, film-coated tablets of green color, diameter – approximately 6 mm.

Pharmacotherapeutic group. Sex gland hormones and drugs used in pathologies of the genital system. Progestogens and estrogens, fixed combinations. ATC code G03A A10.

Pharmacological properties.

Pharmacodynamics.

Monophasic combined oral contraceptive.

Pearl Index considering incorrect use: 0.24 (21,521 cycles), 95% confidence interval 0.04–0.57.

The contraceptive effect of Vindiol is achieved through three complementary mechanisms:

• effect on the hypothalamic-pituitary system by suppressing ovulation;
• effect on cervical mucus, making it impermeable to spermatozoa;
• effect on the endometrium, impairing conditions for implantation of the fertilized egg.

Pharmacokinetics.

Ethinylestradiol

Absorption

Orally administered ethinylestradiol is rapidly and completely absorbed. After a 15 mcg dose, maximum serum concentration of 30 pg/mL is reached within 1–1.5 hours. Ethinylestradiol undergoes a significant first-pass liver effect with high individual variability. Absolute bioavailability is approximately 45%.

Distribution

The apparent volume of distribution of ethinylestradiol is 15 L/kg, with plasma protein binding of approximately 98%. Ethinylestradiol induces the synthesis of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) in the liver. During treatment with 15 mcg ethinylestradiol, plasma SHBG concentration increases from 86 to approximately 200 nmol/L.

Metabolism

Ethinylestradiol is completely metabolized (plasma clearance of metabolites is approximately 10 mL/min/kg). Metabolites are excreted in urine (40%) and feces (60%).

Elimination

The elimination half-life of ethinylestradiol is approximately 15 hours. Only a small portion of ethinylestradiol is excreted unchanged. Ethinylestradiol metabolites are eliminated via urine and bile in a ratio of 4:6.

Steady state

Steady state is achieved in the second half of the cycle, when serum concentrations of ethinylestradiol increase by 1.4 to 2.1 times.

Gestodene

Absorption

Orally administered gestodene is rapidly and completely absorbed. Absolute bioavailability is approximately 100%. After a single 60 mcg dose, maximum serum concentration of 2 ng/mL is reached after approximately 1 hour. Plasma concentration strongly depends on SHBG levels.

Distribution

The apparent volume of distribution is 1.4 L/kg after a single 60 mcg dose. Approximately 30% of gestodene binds to plasma albumin, and 50–70% binds to SHBG.

Metabolism

Gestodene is completely metabolized. Metabolic clearance is approximately 0.8 mL/min/kg after a single 60 mcg dose. Inactive metabolites are excreted in urine (60%) and feces (40%).

Elimination

The expected elimination half-life is approximately 13 hours. The half-life increases to 20 hours when gestodene is administered together with ethinylestradiol.

Steady state

After repeated administration of the gestodene/ethinylestradiol combination, serum concentrations increase by 2 to 4 times.

Clinical characteristics.

Indications.

Hormonal oral contraception.

When deciding to prescribe Vendiola, it is necessary to consider current risk factors for the individual woman, especially risk factors for venous thromboembolism (VTE), and the extent to which the risk of VTE with Vendiola use compares to other combined hormonal contraceptives (see sections "Contraindications" and "Special precautions").

Contraindications.

Combined hormonal contraceptives (CHCs) must not be used in the following conditions. If any of these conditions occur during use of the CHC, the drug must be discontinued immediately:

• Hypersensitivity to the active substances or to any of the excipients of the product (see section "Composition");
• Presence of or risk for venous thromboembolism (VTE);
  • Venous thromboembolism – current VTE (anticoagulant therapy in use) or history of VTE (e.g., deep vein thrombosis [DVT] or pulmonary embolism [PE]);
  • Known hereditary or acquired predisposition to venous thromboembolism, e.g., activated protein C resistance (APC, including factor V Leiden), antithrombin-III deficiency, protein C deficiency, protein S deficiency;
  • Major surgery with prolonged immobilization (see section "Special precautions");
  • High risk of venous thromboembolism due to the presence of multiple risk factors (see section "Special precautions");
• Presence of or risk for arterial thromboembolism (ATE);
  • Arterial thromboembolism – current arterial thromboembolism, history of arterial thromboembolism (e.g., myocardial infarction) or prodromal condition (e.g., angina pectoris);
  • Cerebrovascular disease – current stroke, history of stroke, prodromal condition (e.g., transient ischemic attack [TIA]);
  • Known hereditary or acquired predisposition to arterial thromboembolism, e.g., hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);
  • History of migraine with focal neurological symptoms;
  • High risk of arterial thromboembolism due to multiple risk factors (see section "Special precautions") or presence of any of the following serious risk factors:
• Diabetes mellitus with vascular complications;
• Severe arterial hypertension;
• Severe dyslipidemia;
• Established pregnancy or suspected pregnancy;
• Presence of or suspicion of breast cancer;
• Endometrial carcinoma or presence of any other estrogen-dependent tumor or suspicion thereof;
• Presence of liver tumors (benign or malignant) or such tumors in history, severe liver disease (until liver function has recovered);
• Severe renal insufficiency or acute renal failure;
• Vaginal bleeding of unknown etiology;
• Presence of pancreatitis or history of pancreatitis if associated with severe hypertriglyceridemia.

Concomitant use of Vendiola and medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, as well as medicinal products containing glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir, is contraindicated (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Note: Information on the concomitantly used medicinal product should be reviewed to identify potential interactions.

Pharmacodynamic interactions

During clinical trials in patients receiving medications for treatment of hepatitis C virus (HCV) infection containing ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, elevations in alanine aminotransferase (ALT) greater than 5 times the upper limit of normal (ULN) were observed. This occurred more frequently in women receiving medications containing ethinylestradiol, including CHCs. Additionally, in women receiving treatment with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir, increases in ALT were observed when taking ethinylestradiol-containing medications such as CHCs (see section "Contraindications"). Therefore, women taking Vendiola should switch to an alternative method of contraception (e.g., progestogen-only contraception or non-hormonal methods) prior to initiating therapy with these combination regimens. Use of Vendiola may be resumed 2 weeks after completion of treatment with these combination regimens.

Pharmacokinetic interactions

Effect of other medicinal products on Vendiola

Interactions are possible with medicinal products that induce microsomal enzymes. This may lead to increased clearance of sex hormones, which may result in breakthrough bleeding and/or loss of contraceptive efficacy.

Therapy

Enzyme induction may be observed within a few days of starting treatment. Maximum enzyme induction generally occurs after several weeks. After discontinuation of the inducing agent, enzyme induction may persist for approximately 4 weeks.

Short-term treatment

Women taking enzyme-inducing medicinal products should temporarily use a barrier method or another contraceptive method in addition to the CHC. The barrier method should be used throughout the treatment period with the relevant drug and for an additional 28 days after discontinuation of the drug.

If treatment with an enzyme-inducing agent is initiated during the period of taking the last active tablets from the current pack, the placebo tablets should be discarded and the next pack of CHC tablets should be started immediately after finishing the previous pack.

Long-term treatment

Women undergoing long-term therapy with enzyme-inducing substances are advised to use another reliable non-hormonal contraceptive method.

The following interactions have been described in the literature.

Substances increasing clearance of CHCs (reduced CHC efficacy due to enzyme induction), e.g.: barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, and HIV drugs – ritonavir, nevirapine, and efavirenz; possibly also felbamate, griseofulvin, oxcarbazepine, topiramate, and products containing St John’s wort (Hypericum perforatum).

There is a risk of reduced contraceptive efficacy during treatment and for one cycle after discontinuation of modafinil.

Substances with variable effects on CHC clearance

When used concomitantly with CHCs, many combinations of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors, including combinations with HCV inhibitors, may increase or decrease plasma concentrations of estrogen or progestins. The net effect of such changes may be clinically significant in some cases.

Therefore, information on the medicinal product used for treatment of HIV/HCV should be reviewed to identify potential interactions and any related recommendations. In case of any doubt, women should additionally use a barrier method of contraception during therapy with protease inhibitors or non-nucleoside reverse transcriptase inhibitors.

Substances decreasing CHC clearance (enzyme inhibitors)

The clinical significance of potential interactions with enzyme inhibitors remains unclear.

Concomitant use of strong CYP3A4 inhibitors may increase plasma concentrations of estrogen, progestin, or both components.

Etoricoxib at doses of 60 to 120 mg/day has demonstrated an increase in ethinylestradiol plasma concentrations by 1.4–1.6 times, respectively, when used concomitantly with a combined hormonal contraceptive containing 0.035 mg ethinylestradiol.

Effect of Vendiola on other medicinal products

CHCs may affect the metabolism of certain other medicinal products. Consequently, plasma and tissue concentrations may increase (e.g., cyclosporine) or decrease (e.g., lamotrigine).

Clinical data indicate that ethinylestradiol inhibits the clearance of CYP1A2 substrates, resulting in mild (e.g., with theophylline) or moderate (e.g., with tizanidine) increases in their plasma concentrations.

Laboratory tests

Use of contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters of liver, kidney, thyroid and adrenal gland function, levels of (transport) plasma proteins such as corticosteroid-binding globulin, lipid/lipoprotein fractions, carbohydrate metabolism parameters, and coagulation and fibrinolysis parameters. Changes are usually within normal limits.

Special precautions for use.

With caution

If a woman has any of the conditions or risk factors listed below, the appropriateness of using the medicinal product Vendiola should be discussed with the patient. If any of the conditions or risk factors listed below worsen or appear, women are advised to consult their physician, who will decide whether treatment with Vendiola should be discontinued.

Disorders of circulation

Risk of venous thromboembolism (VTE)

The use of any combined oral contraceptive (COC) increases the risk of VTE compared to non-use. COCs containing levonorgestrel, norgestimate, or norethisterone are associated with a lower risk of VTE. Other COCs, such as Vendiola, may be associated with approximately twice the risk of VTE. The decision to use any COC instead of a product with a lower risk of VTE should only be made after discussing with the patient to ensure she understands the risk of VTE with COC use, appreciates how existing risk factors affect the likelihood of VTE, and recognizes that the risk of VTE is highest during the first year of COC use. There is also some evidence that this risk increases when COCs are restarted after a break of 4 weeks or more.

Approximately 2 out of 10,000 women who do not use COCs and are not pregnant will develop VTE over one year. However, in any individual woman, the risk may be considerably higher, depending on existing risk factors (see information below).

According to estimates,[1] 9–12 out of 10,000 women using COCs containing gestodene will develop VTE over one year; this can be compared to approximately 6 cases[2] among women using COCs containing levonorgestrel.

In both cases, the annual rate of VTE is lower than the rate expected during pregnancy or the postpartum period.

VTE can result in fatal outcomes in 1–2% of cases.

1These cases were identified in a widely used epidemiological study assessing different COCs containing levonorgestrel (relative risks used).

2Average rate in the range of 5–7 per 10,000 woman-years for COCs containing levonorgestrel, compared to a control group of 2.3–3.6.

Number of VTE cases per 10,000 women per year

Among women using COCs, thrombosis of other vessels (e.g., hepatic, mesenteric, renal, retinal veins, and arteries) has been observed very rarely.

Factors increasing VTE risk

The risk of venous thromboembolic complications in users of COCs may be substantially increased in the presence of additional risk factors, particularly when multiple risk factors are present (see Table 1).

The medicinal product Vendiola is contraindicated in women with multiple risk factors, as their presence indicates a high likelihood of venous thromboembolism (see section "Contraindications"). The presence of more than one risk factor may increase the likelihood of VTE more significantly than the sum of individual factors; in such cases, the probability of VTE should be carefully assessed. If the risk of complications outweighs the benefits of use, COCs should not be prescribed (see section "Contraindications").

Factors increasing VTE risk

Table 1

There is no consensus regarding the possible influence of varicose veins and superficial thrombophlebitis on the onset or progression of venous thrombosis.

The risk of thromboembolism should be considered during pregnancy, particularly during the 6-week period following childbirth (information regarding use during pregnancy or breastfeeding is provided in the section "Use during pregnancy or breastfeeding").

Signs and symptoms of venous thromboembolism (deep vein thrombosis and pulmonary embolism)

If symptoms occur, women are advised to seek immediate medical attention and inform their physician that they are taking a COC.

Symptoms of deep vein thrombosis (DVT) may include:

• Unilateral swelling of the leg and/or foot or a region along a vein in the leg;
• Pain or tenderness in the leg, which may occur only when standing or walking;
• A feeling of warmth in the affected leg;
• Redness or discoloration of the skin on the leg.

Symptoms of pulmonary embolism (PE) may include:

• Sudden unexplained shortness of breath or rapid breathing;
• Sudden cough, possibly with hemoptysis;
• Acute chest pain;
• Severe dizziness or lightheadedness;
• Rapid or irregular heartbeat.

Some of these symptoms (e.g., shortness of breath, cough) are nonspecific and may be incorrectly interpreted as more common or less serious conditions (e.g., respiratory tract infections).

Other signs of vascular occlusion may include: sudden pain, swelling, and development of a bluish discoloration of a limb.

Symptoms of occlusion in the eye vessels may vary from painless blurred vision, which may progress to vision loss. Sometimes, vision loss may occur almost instantaneously.

Risk of arterial thromboembolism (ATE)

Epidemiological studies have associated the use of COCs with an increased risk of arterial thromboembolism (myocardial infarction) or cerebrovascular events (e.g., transient ischemic attack, stroke). Arterial thromboembolic complications can be fatal.

Risk factors for ATE

The risk of arterial thromboembolic complications or cerebrovascular events among women taking COCs increases in those who have risk factors (see Table 2). The medicinal product Vendiolo is contraindicated if the patient has one serious risk factor or several ATE risk factors leading to a high risk of arterial thrombosis (see section "Contraindications"). If a woman has more than one risk factor, the increase in risk may be greater than the sum of the individual factors, so the overall ATE risk for the patient should be carefully evaluated. If the benefit-risk balance is considered unfavorable, COCs should not be prescribed (see section "Contraindications").

Risk factors for ATE

Table 2

Symptoms of ATE

If any symptoms occur, women are advised to seek immediate medical attention and inform their doctor that they are taking COCs.

Symptoms of cerebrovascular disorders may include:

• sudden numbness or weakness of the face, arm, or leg, especially on one side of the body;
• sudden difficulty walking, dizziness, loss of balance or coordination;
• sudden confusion, speech disturbances or difficulty understanding speech;
• sudden vision changes in one or both eyes;
• sudden, severe or prolonged headache of unknown cause;
• loss of consciousness or fainting with or without seizures.

Transient symptoms may indicate a transient ischemic attack (TIA).

Symptoms of myocardial infarction (MI) may include:

• pain, discomfort, tightness, pressure, or heaviness in the chest, arm, or below the sternum;
• discomfort radiating to the back, jaw, throat, arm, or stomach;
• sensation of fullness, indigestion, or shortness of breath;
• excessive sweating, nausea, vomiting, or dizziness;
• unusual weakness, anxiety, or breathlessness;
• rapid or irregular heartbeat.

Gynecological cancers

Some epidemiological studies suggest an increased risk of cervical cancer in women who have used COCs for a prolonged period (more than 5 years). However, data remain controversial regarding whether this risk is related to sexual behavior and other factors such as human papillomavirus (HPV).

A meta-analysis of 54 epidemiological studies indicates a slight increase in relative risk (RR = 1.24) of developing breast cancer in women using combined oral contraceptives. This increased risk gradually disappears within 10 years after discontinuation of COCs. Since breast cancer is rare in women under 40 years of age, the increase in diagnosed cases among women currently or recently using oral contraceptives is small relative to the overall lifetime risk of breast cancer. These studies do not provide evidence of a causal relationship. The observed increased risk may be explained by earlier diagnosis of breast cancer in COC users, a biological effect of combined oral contraceptives, or both. Breast cancers diagnosed in women who have ever used COCs tend to be less advanced clinically than in those who have never used COCs.

High-dose COCs (0.05 mg ethinylestradiol) have been associated with a reduced risk of endometrial and ovarian cancer. Whether this benefit extends to low-dose COCs remains to be determined.

Liver tumors

There have been reports of rare cases of benign liver tumors and even more rarely, malignant liver tumors in women using COCs. In isolated cases, these tumors have led to life-threatening intra-abdominal hemorrhage.

Headache

The onset or worsening of migraine, or the occurrence of unusual, recurrent, prolonged, or severe headache requires immediate discontinuation of treatment and evaluation of the underlying cause.

Other

Depressed mood and depression are common adverse reactions associated with hormonal contraceptives (see section "Adverse Reactions"). Depression can be severe and is a known risk factor for suicidal behavior and suicide. Women should be advised to seek medical help if they experience mood changes or symptoms of depression, even if these occur shortly after starting treatment.

Women with hypertriglyceridemia or a strong family history of hypertriglyceridemia who use COCs may be at increased risk of developing pancreatitis.

Although a slight increase in blood pressure has been reported in women using COCs, clinically significant changes are rare. Immediate discontinuation of COCs is justified only in such rare cases. If COCs are used in the presence of arterial hypertension and there is persistent or marked increase in blood pressure that is not adequately controlled by antihypertensive therapy, COC use should be discontinued. If appropriate, COC use may be resumed once normotensive levels are achieved with antihypertensive treatment.

Conditions such as jaundice and/or pruritus associated with cholestasis, gallstone formation, porphyria, systemic lupus erythematosus, hemolytic uremic syndrome, Sydenham's chorea, herpes gestationis, hearing loss associated with otosclerosis, may develop or worsen both during pregnancy and during COC use; however, a causal relationship with COC use has not been established.

Exogenous estrogens may induce or exacerbate symptoms of hereditary or acquired angioedema.

Acute illness or exacerbation of chronic liver disease may require discontinuation of COCs until liver function tests return to normal. Recurrent cholestatic jaundice that first occurred during a previous pregnancy or prior use of sex hormones necessitates discontinuation of COCs.

Although COCs may affect insulin resistance and glucose tolerance, there is generally no need to alter the therapeutic regimen in diabetic patients using low-dose COCs (< 0.05 mg ethinylestradiol). However, diabetic women should be closely monitored during COC use.

Exacerbation of endogenous depression, epilepsy, Crohn's disease, and ulcerative colitis has been reported during COC use.

Chloasma may occasionally occur, particularly in women with a history of chloasma of pregnancy. Women predisposed to chloasma should avoid direct exposure to sunlight or ultraviolet radiation during COC use.

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

Placebo tablets contain the yellow dye sunset yellow (E 110), which may cause allergic reactions.

Medical examination

Before initiating or resuming use of the medicine Vendiola, a thorough medical history (including family history) should be taken and pregnancy must be ruled out. Blood pressure should be measured and a complete medical examination performed, considering contraindications (see section "Contraindications") and warnings (see section "Special precautions for use"). The woman should be informed about venous and arterial thrombosis, including the risk associated with taking Vendiola compared to other COCs, symptoms of VTE and ATE, known risk factors, and actions to take in case of suspected thrombosis.

The woman should also carefully read the package leaflet and follow the provided recommendations. The frequency and nature of examinations should be based on current medical practice guidelines, taking into account individual patient characteristics.

The woman should be advised that hormonal contraceptives do not protect against HIV infection (AIDS) or other sexually transmitted infections.

Reduced efficacy

The efficacy of COCs may be reduced in the following situations: missed tablets (see section "Dosage and administration"), gastrointestinal disturbances (see section "Dosage and administration"), or concomitant use of other medicinal products (see section "Interaction with other medicinal products and other forms of interaction").

Menstrual cycle disturbances

With use of any oral contraceptive, intermenstrual bleeding (spotting or breakthrough bleeding) may occur, especially during the first few months. Therefore, evaluation of irregular intermenstrual bleeding should only be performed after an adaptation period of three cycles.

If irregular bleeding persists after this adaptation period or reappears after a period of regular cycles, non-hormonal causes of bleeding should be considered and appropriate diagnostic measures taken to exclude malignancy and pregnancy. Diagnostic measures may include curettage.

In some women, menstruation may not occur during the tablet-free interval.

If the COC is taken according to instructions in the section "Dosage and administration," pregnancy is unlikely. However, if the medication has been taken irregularly or if menstruation is absent for two consecutive cycles, pregnancy must be ruled out before continuing COC use.

Use during pregnancy or breastfeeding.

Pregnancy

The medicinal product Vendiola is contraindicated during pregnancy.

Clinically, unlike diethylstilbestrol, numerous epidemiological studies have not established a link between congenital malformations and the use of estrogens alone or in combination during early pregnancy.

Furthermore, risks to fetal sexual differentiation (particularly in female fetuses), described for older, highly androgenic progestogens, should not be extrapolated to modern progestogens (such as those in this medicinal product), which have significantly lower or no androgenic properties.

Therefore, discovery of pregnancy during use of a medicinal product containing estrogen and progestogen does not require termination of pregnancy.

The increased risk of VTE in the postpartum period should be considered when resuming use of Vendiola (see sections "Special precautions for use" and "Dosage and administration").

Breastfeeding period

COCs may affect lactation by reducing the quantity and altering the composition of breast milk. Use of this medicinal product is not recommended during breastfeeding, as estrogen and progestogen pass into breast milk and may adversely affect the infant.

If the patient wishes to continue breastfeeding, an alternative method of contraception should be recommended.

Ability to influence the speed of reactions when driving vehicles or operating machinery.

The medicinal product Vendiola has no effect or has a negligible effect on the ability to drive vehicles or operate machinery.

Dosage and Administration

How to take Vendiola

Tablets should be swallowed whole, without chewing, with a small amount of liquid if necessary, daily at approximately the same time and in the order indicated on the blister pack. One tablet should be taken daily (preferably at the same time each day) for 28 consecutive days (24 yellow tablets daily, followed by 4 green placebo tablets daily) without interruption between packs. Withdrawal bleeding usually begins 2–3 days after taking the last active tablet and may last until the start of the next pack.

How to start taking Vendiola

If no hormonal contraception was used in the previous month

Start taking tablets on the first day of the natural menstrual cycle (i.e., the first day of menstrual bleeding).

Switching from another combined hormonal contraceptive, vaginal ring, or transdermal patch

It is best to start taking Vendiola the day after the last active tablet (the last tablet containing active ingredients) of the previous contraceptive. In no case should it be later than the day following the usual tablet-free interval or after taking the placebo tablets of the previous contraceptive. When using a transdermal patch or vaginal ring, the woman should start taking Vendiola on the day of removal, but in no case later than the day when a new ring is to be inserted or a new patch applied.

Switching from progestogen-only contraceptives ("mini-pills", injections, implants), or an intrauterine system (IUS) releasing progestogen

Switching from "mini-pills" can occur at any time; from an implant or IUS – on the day of removal; from injections – on the day the next injection would have been due. However, in all these cases, an additional barrier method of contraception must be used for the first 7 days of taking Vendiola.

Use after first-trimester abortion

The woman may start taking the medication immediately. In this case, additional contraceptive methods are not required.

Use after childbirth or second-trimester abortion

Vendiola should be started between days 21 and 28 after childbirth or second-trimester abortion. If the woman starts later, an additional barrier method of contraception must be used for the first 7 days of tablet intake. However, if sexual intercourse occurred before starting the medication, pregnancy must be ruled out before initiating contraceptive use, or the woman should wait for her first menstrual period.

Missed tablet intake

Contraceptive efficacy may be reduced if a yellow tablet is not taken, especially at the beginning of the pack.

If a tablet is taken less than 12 hours late, contraceptive protection is not compromised. The tablet should be taken as soon as remembered, and the next tablet should be taken at the usual time.

If a yellow tablet is taken more than 12 hours late, contraceptive protection is not guaranteed.

In this case, the following two main rules should be followed:

1. Tablet intake should never be interrupted for more than 4 days.
2. A 7-day period of continuous tablet intake is required to adequately suppress the hypothalamic-pituitary-ovarian system.

Based on these rules, the following recommendations apply:

Days 1–7 of tablet intake

The woman should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. After that, tablets should be taken at the usual time. An additional barrier method of contraception (e.g., condom) should be used for the next 7 days. If the woman had sexual intercourse in the previous 7 days, the possibility of pregnancy should be considered. The greater the number of missed tablets and the closer the missed dose is to the tablet-free interval, the higher the risk of pregnancy.

Days 8–14 of tablet intake

The woman should take the last missed tablet immediately upon remembering, even if this means taking two tablets at once. After that, tablets should be taken at the usual time. If tablets were taken regularly during the 7 days prior to the first missed tablet, no additional contraceptive measures are needed. If the woman took tablets irregularly or missed more than one tablet, additional contraceptive measures are required for 7 days.

Days 15–24 of tablet intake

Due to the upcoming tablet-free interval, there is a high risk of reduced contraceptive reliability. However, despite this, reduced contraceptive protection can be prevented by adjusting the dosing schedule. According to the rules mentioned above, no additional contraceptive measures are needed if the woman took tablets correctly during the 7 days before the first missed tablet. Otherwise, the woman should follow the first recommendation and use additional contraceptive methods for 7 days.

1. The woman should take the last missed tablet as soon as she remembers, even if this means taking two tablets at once. After that, tablets should be taken at the usual time until the active tablets are finished. All 4 placebo tablets of the last row should not be taken. The woman should immediately start the next pack after finishing the previous one. Withdrawal bleeding is unlikely until the second pack is completed, but slight spotting or breakthrough bleeding may occur during tablet intake.
2. Alternatively, the woman may stop taking tablets from the current pack. In this case, she should take one placebo tablet daily for 4 days, including the days of missed doses, then start a new pack.

If the woman missed tablets during the placebo tablet period and no withdrawal bleeding occurs, pregnancy must be ruled out.

Use in gastrointestinal disturbances

If the woman experiences vomiting or diarrhea, absorption may be incomplete, and additional contraceptive measures should be used. If vomiting occurs within 3–4 hours after taking the tablet, an additional tablet should be taken as soon as possible, but no later than 12 hours after the usual intake time. If more than 12 hours have passed, follow the recommendations for missed tablets (see section "Dosage and Administration", "Missed tablet intake"). If the woman does not wish to alter her usual dosing schedule, she should take an additional tablet and begin a new pack.

Changing the start day of the menstrual cycle

If the woman wishes to delay the onset of menstruation, she should start the next pack of Vendiola without taking the placebo tablets. She may continue taking tablets from the next pack for as long as desired (until the pack is finished). Breakthrough bleeding or spotting may occur during this period. After taking the placebo tablets, the woman should resume regular intake of Vendiola.

If the woman wishes to shift the start of menstruation to another day of the week, she should shorten the placebo tablet interval by the number of days desired. The shorter this interval, the higher the risk of absent withdrawal bleeding and the occurrence of breakthrough bleeding or spotting during the second pack (similar to delayed menstruation).

Information for special patient groups

Elderly patients

Vendiola is not indicated after menopause.

Patients with hepatic impairment

Vendiola is contraindicated in women with severe hepatic impairment (see section "Contraindications").

Patients with renal impairment

Vendiola has not been studied in patients with renal impairment.

Administration method

Oral.

Children

The medication is not intended for use in children.

Overdose

No serious adverse effects have been observed following ingestion of large doses of combined oral contraceptives (COCs). Clinical experience with COCs indicates that such cases may be accompanied by symptoms such as nausea, vomiting, and in young girls, minor vaginal bleeding.

There is no specific antidote; therefore, treatment should be purely symptomatic.

Adverse reactions.

The following adverse reactions have been identified with the use of COCs.

Serious adverse reactions are listed in the section "Special warnings and precautions for use".

The use of any COCs increases the risk of VTE. Information on risks according to COC type and the risk of arterial thrombosis is provided in the section "Special warnings and precautions for use".

Amenorrhea was observed in 15% of patients in clinical studies (see section "Special warnings and precautions for use"). The most commonly reported adverse reactions in phase III clinical trials and the post-marketing period were headache, migraine, bleeding, and spotting.

The following adverse reactions have also been identified during the use of combined oral contraceptives:

* Combined oral contraceptives may worsen the course of gallstone disease and exacerbate cholestasis.

Description of individual adverse reactions

An increased risk of arterial/venous thrombotic and thromboembolic disorders, including myocardial infarction, stroke, transient ischemic attack, and pulmonary artery thromboembolism, has been observed in women taking COCs; see section "Special precautions" for details.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product's registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua/.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 30 °C, in the original packaging to protect from light and moisture.

Keep the medicinal product out of reach of children.

Packaging.

28 film-coated tablets per blister pack (24 yellow active tablets and 4 green placebo tablets); 1 or 3 blister packs, each blister pack in a laminated sachet with a flat cardboard holder for the blister pack and a weekly calendar sticker, all contained in a cardboard box.

Prescription status. Prescription only.

Manufacturer. JSC "Gedeon Richter".

Manufacturer's address and location of its business operations.

19-21 Demréi Street, Budapest, H-1103, Hungary