Logest®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LOGEST® (LOGEST®)

Composition:

Active substances: ethinylestradiol, gestodene;

One coated tablet contains 20 mcg of ethinylestradiol and 75 mcg of gestodene;

Excipients: lactose monohydrate; corn starch; povidone; magnesium stearate; sucrose; polyethylene glycol; calcium carbonate; talc; non-ionic emulsified wax.

Pharmaceutical form. Coated tablets.

Main physicochemical properties: white, round, coated tablets.

Pharmacotherapeutic group. Gonadal hormones and drugs used in disorders of the genital system. Hormonal contraceptives for systemic use.

ATC code G03A A10.

Pharmacological Properties

Pharmacodynamics

Combined monophasic "mini-pills" containing estrogen and progestin. Pearl Index corrected: 0.07 (19,095 cycles). The failure rate may increase in case of incorrect administration or missed doses.

The contraceptive effect of Logest® is based on three complementary mechanisms:

• Suppression of ovulation at the hypothalamic-pituitary axis level;
• Alteration of cervical mucus, making it impermeable to sperm migration;
• Endometrial changes rendering the endometrium unsuitable for implantation.

Safety data from preclinical studies

Toxicological studies were conducted with each active ingredient separately and in combination.

Acute toxicity studies in animals indicate no risk associated with accidental overdose.

Repeated-dose studies revealed no risk to human health. Long-term carcinogenicity studies with repeated dosing showed no carcinogenic potential; however, the influence of sex steroids on the growth of certain tissues in hormone-dependent tumors remains unknown.

Embryotoxicity, teratogenicity, and reproductive function studies revealed no specific risk with proper use of estrogens/progestins. However, treatment must be discontinued immediately if these agents are inadvertently administered during early pregnancy.

Mutagenicity studies in vitro and in vivo showed no mutagenic potential for ethinylestradiol or gestodene.

Pharmacokinetics

Ethinylestradiol

• Rapidly and completely absorbed from the gastrointestinal tract;
• Maximum plasma concentration is reached within 1–2 hours;
• First-pass effect results in a bioavailability of approximately 45%;
• Ethinylestradiol binds to albumin and increases the sex hormone-binding globulin (SHBG) binding capacity;
• Elimination half-life is approximately 28 hours;
• Initial metabolism occurs via aromatic hydroxylation, followed by methylation and hydroxylation into free metabolites and conjugates (glucuronides and sulfates);
• Conjugated derivatives undergo enterohepatic recirculation;
• Approximately 40% of metabolites are excreted in urine and about 60% in feces;
• In vitro, ethinylestradiol acts as a reversible inhibitor of CYP2C19, CYP1A1, and CYP1A2, and as an irreversible inhibitor of CYP3A4/5, CYP2C8, and CYP2J2.

Gestodene

• Rapidly and completely absorbed from the gastrointestinal tract;
• Maximum plasma concentration is achieved within 1–2 hours;
• No first-pass effect; bioavailability is complete;
• Gestodene is highly bound to SHBG;
• Elimination half-life is approximately 18 hours;
• The A-ring is reduced and subsequently conjugated into glucuronide form;
• Approximately 50% of gestodene is excreted in urine and about 33% in feces.

Clinical characteristics.

Indications.

Oral contraception.

Contraindications.

Combined hormonal contraceptives (CHCs) must not be used if any of the conditions or diseases listed below are present. If any of these conditions occur for the first time during use of CHCs, the drug should be discontinued immediately.

Presence of or risk of venous thromboembolism (VTE):

• Current venous thromboembolic events (anticoagulant therapy) or history thereof (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE));
• Known hereditary or acquired predisposition to thrombosis, venous thromboembolism (e.g., activated protein C resistance, including factor V Leiden), antithrombin III deficiency, protein C deficiency, protein S deficiency;
• Major surgical procedures with prolonged immobilization (see section "Special precautions");
• High risk of venous thromboembolism due to presence of multiple risk factors (see section "Special precautions").

Presence of or risk of arterial thromboembolism (ATE):

• Arterial thromboembolism – current or past history of arterial thromboembolic events (e.g., myocardial infarction (MI)) or presence of prodromal states (e.g., angina pectoris);
• Cerebrovascular disorders – current or past history of stroke or presence of prodromal states (e.g., transient ischemic attack (TIA));
• Known hereditary or acquired predisposition to arterial thromboembolism (e.g., hyperhomocysteinemia) or presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);
• History of migraine with focal neurological symptoms;
• High risk of arterial thromboembolism due to presence of multiple risk factors (see section "Special precautions") or presence of any serious risk factor such as diabetes mellitus with vascular involvement, severe arterial hypertension, severe dyslipoproteinemia;
• Current or past history of severe liver disease until liver function tests return to normal;
• Current or past history of liver tumors (benign or malignant);
• Known or suspected hormone-dependent malignant neoplasms (e.g., of genital organs or breast);
• Vaginal bleeding of unknown etiology;
• Hypersensitivity to the active substances or to any of the excipients of the drug.

Logest® is contraindicated for concomitant use with medicinal products containing St. John’s wort (see section "Interaction with other medicinal products and other forms of interaction").

Logest® is contraindicated for concomitant use with medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir/voxilaprevir (medicinal products for treatment of hepatitis C virus infection) (see sections "Special precautions" and "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Carefully review information on any concomitantly administered medicinal product to identify potential interactions.

Interactions between contraceptives containing estrogens and progestins and other medicinal products may lead to increased or decreased plasma concentrations of estrogen/progestin.

Reduced plasma levels of estrogen/progestin may result in increased frequency of intermenstrual bleeding, menstrual cycle disturbances, and potential reduction in contraceptive efficacy of estrogen- and progestin-containing contraceptives.

Enzyme induction may be observed within several days of treatment. Maximum enzyme induction is generally observed within the first few weeks. After discontinuation of treatment, enzyme induction may persist for approximately 4 weeks.

Contraindicated combinations

St. John’s wort. Reduced plasma concentration of hormonal contraceptives due to enzyme induction by St. John’s wort-containing products is associated with risk of reduced or even lost contraceptive efficacy, potentially leading to pregnancy.

Protease inhibitors (ombitasvir, paritaprevir, and dasabuvir).
Increased hepatotoxicity.

Concomitant use of medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin, may increase the risk of elevated ALT levels (see sections "Contraindications" and "Special precautions").

Similar increases in ALT levels have also been observed during treatment with hepatitis C virus (HCV) antiviral agents containing glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir.

Therefore, women using Logest® should temporarily switch to an alternative contraceptive method (e.g., progestogen-only contraceptives or non-hormonal methods) prior to initiation of therapy with the above-mentioned drug combinations. Logest® may be resumed 2 weeks after completion of therapy with these combinations.

Not recommended combinations

Enzyme inducers. Concomitant use of antiepileptic drugs (phenobarbital, phenytoin, fosphenytoin, primidone, carbamazepine, oxcarbazepine), as well as rifabutin, rifampicin, efavirenz, nevirapine, dabrafenib, enzalutamide with Logest® results in reduced contraceptive efficacy due to enhanced hepatic metabolism of hormonal contraceptives. During concomitant use, it is advisable to use additional contraceptive methods, including barrier methods, throughout the current and the following cycle.

Lamotrigine (see also below "Combinations to be used with caution"). There is a risk of reduced lamotrigine concentration and efficacy due to increased hepatic metabolism; therefore, use of oral contraceptives should be avoided during the lamotrigine dose titration period.

Modafinil. There is a risk of reduced contraceptive efficacy during treatment and throughout the following cycle after modafinil discontinuation due to its enzyme-inducing effect. Therefore, it is recommended to prefer oral contraceptives with standard dosing or to choose another contraceptive method.

Nelfinavir. There is a risk of reduced contraceptive efficacy due to decreased plasma concentrations of hormonal contraceptives. It is advisable to use alternative contraceptive methods, including barrier methods (condoms or intrauterine systems), during concomitant use and throughout the following cycle.

Elvitegravir. There is a risk of reduced contraceptive efficacy due to decreased ethinylestradiol concentration, and also increased progestin concentration. It is advisable to use an estrogen-progestin contraceptive containing at least 30 µg ethinylestradiol or alternative contraceptive methods, including barrier methods, during treatment and throughout the following cycle.

Protease inhibitors boosted with ritonavir. There is a risk of reduced contraceptive efficacy due to decreased plasma concentrations of hormonal contraceptives resulting from enhanced hepatic metabolism induced by ritonavir. It is advisable to use alternative contraceptive methods, including barrier methods (condoms or intrauterine systems), during concomitant use and throughout the following cycle.

Topiramate. When topiramate is prescribed at doses ≥ 200 mg/day, there is a risk of reduced contraceptive efficacy due to decreased estrogen concentration. It is advisable to use another contraceptive method, preferably a barrier method.

Vemurafenib. There is a risk of reduced estrogen/progestin concentrations, which may lead to reduced contraceptive efficacy.

Perampanel. When perampanel is used at doses ≥ 12 mg/day, there is a risk of reduced contraceptive efficacy. Another contraceptive method should be selected, preferably a barrier method.

Concomitant use of estrogen-progestin contraceptives and most medicinal products used for treatment of HIV (AIDS) or HCV (hepatitis C) infections (protease inhibitors and non-nucleoside reverse transcriptase inhibitors) may increase or decrease plasma concentrations of estrogen or progestin. In some cases, these changes may have clinical implications. It is necessary to review the prescribing information for each medicinal product used for treatment of HIV or HCV infections (protease inhibitors and non-nucleoside reverse transcriptase inhibitors) for specific recommendations.

Combinations to be used with caution

• Bosentan.* There is a risk of reduced contraceptive efficacy due to enhanced hepatic metabolism of hormonal contraceptives. Therefore, during concomitant use and throughout the following cycle, a reliable contraceptive method is recommended as an additional or alternative method.

• Griseofulvin.* There is a risk of reduced contraceptive efficacy due to increased hepatic metabolism of hormonal contraceptives. It is advisable to use another contraceptive method, including a barrier method, during concomitant use and throughout the following cycle.

• Lamotrigine.* There is a risk of reduced lamotrigine concentration and efficacy due to increased hepatic metabolism. Clinical monitoring and dose adjustment of lamotrigine are recommended at the initiation and discontinuation of oral contraceptive use.

• Rufinamide.* Moderate reduction in ethinylestradiol concentration. It is advisable to select another contraceptive method, preferably a barrier method.

Combinations requiring attention

• Etoricoxib.* Ethinylestradiol concentration increases when used in combination with etoricoxib. Etoricoxib at doses of 60 to 120 mg/day has been shown to increase plasma concentrations of ethinylestradiol by 1.4–1.6 times when used concomitantly with a combined hormonal contraceptive containing 0.035 mg ethinylestradiol.

Active substances that reduce COC clearance (enzyme inhibitors)

Concomitant use of strong or moderate CYP3A4 inhibitors, such as azole antifungals (e.g., itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g., clarithromycin, erythromycin), diltiazem, and grapefruit juice, may increase plasma concentrations of estrogen, progestin, or both components.

However, the clinical significance of potential interactions with enzyme inhibitors remains unclear.

Effect of combined oral contraceptives on other medicinal products

Oral contraceptives may affect the metabolism of certain medicinal products. Consequently, plasma and tissue concentrations of these drugs may either 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., theophylline) or moderate (e.g., tizanidine) increases in their plasma concentrations.

Laboratory tests. Use of estrogen/progestin combinations may affect results of certain laboratory tests, such as liver function biochemical parameters, thyroid, adrenal, and renal function, plasma concentrations of transport proteins such as corticosteroid-binding globulin, lipid/lipoprotein fractions, carbohydrate metabolism parameters, coagulation and fibrinolysis parameters. These changes are usually within normal limits.

Special precautions for use

The decision to prescribe Logest® should be made taking into account risk factors, including those for venous thromboembolism (VTE), as well as the risk of VTE associated with the use of Logest® compared to other combined hormonal contraceptives (CHCs) (see sections "Contraindications", "Special precautions for use").

If any of the conditions or risk factors listed below are present, the appropriateness of using Logest® should be discussed with the woman.

Women should be advised to consult their physician if they experience worsening or new onset of the symptoms or risk factors listed below, to determine whether use of Logest® should be discontinued.

Risk of venous thromboembolism (VTE)

The risk of VTE is increased in women using CHCs compared to women not using them. Contraceptives containing levonorgestrel, norgestimate, or norethisterone are associated with the lowest risk of VTE. The risk of VTE associated with other CHCs, such as Logest®, may be approximately doubled. The decision to prescribe any CHC other than those with the lowest VTE risk should be made only after discussion with the woman. It is important to ensure that she understands the risk of VTE associated with Logest®, the impact of her individual risk factors, and that the risk of VTE is highest during the first year of use. According to some data, the risk of VTE may increase when restarting CHC after a break of 4 weeks or longer.**

Among 10,000 women who do not use CHCs and are not pregnant, approximately 2 will develop VTE over a one-year period. However, for any individual woman, the risk may be significantly higher depending on her individual risk factors (see below).

It is estimated¹ that among 10,000 women using CHCs containing gestodene, 9–12 will develop VTE within one year; among women using CHCs containing levonorgestrel, this number is 6–7².

In both cases, the annual incidence of VTE is lower than that expected during pregnancy or the postpartum period. In 1–2% of cases, VTE may be fatal.

Number of VTE events per 10,000 women per year

¹ These estimates are based on data from epidemiological studies, taking into account relative risks associated with different CHCs compared to CHCs containing levonorgestrel.

² Average of 5–7 cases per 10,000 woman-years, calculated from the relative risk of CHCs containing levonorgestrel compared to non-users of CHCs (approximately 2.3–3.6 cases).

Very rare cases of thrombosis in other blood vessels—such as arteries and veins of the liver, kidneys, mesenteric vessels, or retinal vessels—have been reported in women using CHCs.

Risk factors for VTE

The risk of venous thromboembolic complications in women using CHCs may be substantially increased in the presence of other risk factors, especially multiple ones (see Table 1).

The use of Logest® is contraindicated in women with multiple risk factors that may increase the risk of venous 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 risks associated with each factor. Therefore, the overall risk of VTE should be considered. If the benefit-risk balance is unfavorable, CHCs should not be prescribed (see section "Contraindications").

Table 1

Risk factors for VTE

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

Particular attention should be paid to the increased risk of thromboembolism during pregnancy, especially within the 6 weeks following delivery (for information on pregnancy and lactation, see section "Use during pregnancy or breastfeeding").

Symptoms of VTE (venous thromboembolism: deep vein thrombosis and pulmonary embolism)

Women should be advised to seek immediate medical attention and inform their physician that they are taking a COC if any of the symptoms listed below occur.

Symptoms of deep vein thrombosis may include:

• Unilateral swelling of the leg and/or swelling along a vein in the leg;
• Pain or increased tenderness in the leg, which may occur only when standing or walking;
• A feeling of warmth in the affected leg, redness, or change in skin color.

Symptoms of pulmonary embolism may include:

• Sudden unexplained shortness of breath or rapid breathing;
• Sudden cough, possibly with hemoptysis (coughing up blood);
• Sudden chest pain;
• Pre-syncope or dizziness;
• Rapid or irregular heartbeat.

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

Other manifestations of vascular occlusion may include sudden pain, swelling, and mild cyanosis of a limb.

Ocular vascular occlusion may initially present with blurred vision without pain, which may progress to vision loss. In some cases, vision loss develops almost instantaneously.

Risk of arterial thromboembolism (ATE)

Epidemiological studies have shown that the use of any COC is associated with an increased risk of arterial thromboembolism (myocardial infarction) or cerebrovascular events (such as transient ischemic attack, stroke). Arterial thromboembolic events may be fatal.

Factors increasing the risk of ATE

When using COCs, the risk of arterial thromboembolic complications or cerebrovascular events increases in women with risk factors (see Table 2).

The use of Logest® is contraindicated in women who have either one serious or multiple risk factors that may increase the 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 risks associated with each individual factor; therefore, the overall risk should be considered. If the benefit-risk ratio is unfavorable, COCs should not be prescribed (see section "Contraindications").

Table 2

Factors increasing the risk of ATE

Arterial Thromboembolism (ATE) Symptoms

Women should be advised to seek immediate medical attention and inform their physician if they are using COCs should any of the following symptoms occur.

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 or language difficulties;
• sudden vision disturbance in one or both eyes;
• severe or prolonged headache of unknown origin; loss of consciousness or syncope with or without seizures.

Transient nature of symptoms may indicate transient ischemic attack (TIA).

Symptoms of myocardial infarction may include: chest pain, discomfort, pressure, heaviness, or tightness in the chest, arm, or behind the breastbone; discomfort radiating to the back, jaw, throat, arm, or stomach; sensation of fullness, indigestion, or heartburn; excessive sweating, nausea, vomiting, or dizziness; weakness, anxiety, or severe shortness of breath; rapid or irregular heartbeat.

Oncological Diseases

Results of some epidemiological studies suggest an increased risk of cervical cancer with long-term use of combined oral contraceptives (COCs) (>5 years). However, this assertion remains controversial, as it has not been definitively established to what extent study results account for confounding risk factors such as sexual behavior and human papillomavirus infection.

A meta-analysis based on 54 epidemiological studies indicates a slight increase in relative risk (RR = 1.24) of breast cancer in women using COCs. This increased risk gradually disappears within 10 years after discontinuation of COC use.

Since breast cancer is rare in women under 40 years of age, the increase in the number of diagnosed cases among women currently or recently using COCs is small relative to the overall risk of breast cancer.

These study results do not provide evidence of a causal relationship. The increased risk may be due to earlier diagnosis of breast cancer in COC users, a biological effect of COCs, or a combination of both factors. There is a trend that breast cancer detected in women who have ever used COCs tends to be clinically less advanced than in those who have never used COCs.

In rare cases, benign and even more rarely malignant liver tumors have been observed in women using COCs, which in some instances led to life-threatening intra-abdominal hemorrhage. In case of complaints of severe epigastric pain, hepatomegaly, or signs of intra-abdominal bleeding, the possibility of a liver tumor associated with COC use should be considered in differential diagnosis.

Use of oral contraceptives containing higher estrogen doses (50 mcg ethinylestradiol) reduces the risk of endometrial and ovarian cancer. These data are expected to be confirmed also for low-dose oral contraceptives.

Other Conditions

Women with hypertriglyceridemia or a family history of this disorder represent a risk group for developing pancreatitis during COC use.

A moderate increase in blood pressure has been reported in many women taking COCs; clinically significant hypertension is observed only in isolated cases. Immediate discontinuation of oral contraceptive therapy is required only in these rare cases.

In cases of persistent arterial hypertension or inability to control blood pressure with antihypertensive agents, COC use should be discontinued in women taking COCs.

If appropriate, COC use may be resumed after normotension has been achieved with antihypertensive therapy.

The following conditions have been reported to occur or worsen during pregnancy and during COC use, but their association with estrogen/progestin use has not been definitively established: cholestatic jaundice and/or pruritus, gallstone formation, porphyria, systemic lupus erythematosus, hemolytic-uremic syndrome, Sydenham's chorea, herpes gestationis, hearing loss associated with otosclerosis.

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

In case of acute or chronic liver function disorders, discontinuation of COC use may be necessary until liver function tests return to normal. COC use should be discontinued in case of recurrence of cholestatic jaundice and/or pruritus that first occurred during pregnancy or previous use of sex hormones.

COCs may affect peripheral insulin resistance and glucose tolerance. However, there is no need to alter the therapeutic regimen in diabetic women using low-dose COCs (<0.05 mg ethinylestradiol).

Women with diabetes should be carefully monitored during COC use, especially at the beginning of treatment.

Cases of exacerbation of endogenous depression, epilepsy, Crohn’s disease, and ulcerative colitis have also been observed during COC use.

Depressed mood and depression are well-known adverse effects that may occur during use of hormonal contraceptives (see section "Adverse Reactions"). Depression can be a serious condition and is a well-known risk factor for suicidal behavior and suicide. Women should be advised to consult a physician if mood changes or symptoms of depression occur, including soon after starting treatment.

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

This medicinal product contains lactose. In patients with rare hereditary conditions of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption, the use of Logest® is not recommended.

Logest® also contains sucrose. Its use is not recommended in patients with hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase/isomaltase deficiency.

Elevation of ALT Levels

In clinical trials involving patients receiving antiviral therapy for hepatitis C with drugs containing ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, elevations in transaminase levels (ALT) >5 times the upper limit of normal (ULN) were observed significantly more frequently in women using ethinylestradiol-containing drugs, such as combined hormonal contraceptives (CHCs) (see sections "Contraindications" and "Interaction with Other Medicinal Products and Other Forms of Interaction"). Similar ALT elevations have also been observed during treatment with hepatitis C drugs containing glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir.

Consultations/Medical Examination

Prior to initiation or resumption of Logest® use, a complete medical examination, including a comprehensive medical and family history, should be performed, and pregnancy should be ruled out. Blood pressure should be measured, and a medical examination should be conducted, considering contraindications (see section "Contraindications") and special precautions (see section "Special Precautions for Use"). Women should be informed about venous and arterial thrombosis, including the risk associated with Logest® compared to other CHCs, symptoms of VTE and ATE, known risk factors, and actions to take if thrombosis is suspected.

Patients should be advised to carefully read the package leaflet and follow the recommendations provided. The frequency and nature of follow-up examinations should depend on established treatment protocols and be adapted to each individual woman.

Patients should be informed that hormonal contraceptives do not protect against HIV infection (AIDS) or any other sexually transmitted diseases.

Reduced Efficacy

The efficacy of COCs may be reduced in case of missed tablet intake (see section "Dosage and Administration"), gastrointestinal disturbances (see section "Dosage and Administration"), or concomitant use with other medicinal products (see section "Interaction with Other Medicinal Products and Other Forms of Interaction").

Cycle Disturbances

Irregular bleeding (spotting or breakthrough bleeding) may occur during COC use, especially during the first months of use. If such bleeding persists beyond three menstrual cycles, it should be considered significant.

If irregular bleeding persists or occurs after a period of regular bleeding, non-hormonal causes of bleeding should be considered and appropriate diagnostic measures undertaken, including investigations to exclude malignancy and pregnancy. Diagnostic procedures may include curettage.

In some women, withdrawal bleeding may not occur during the tablet-free interval. If COCs have been taken according to the instructions in the section "Dosage and Administration," pregnancy is unlikely. However, if COCs were taken irregularly before the first missed withdrawal bleed, or if withdrawal bleeding is absent for two consecutive cycles, pregnancy must be ruled out before continuing COC use.

Use During Pregnancy or Breast-Feeding

Pregnancy. The drug is contraindicated during pregnancy. If pregnancy occurs during use of Logest®, treatment must be discontinued.

Results of numerous epidemiological studies do not indicate an increased risk of congenital malformations in children whose mothers used oral contraceptives prior to pregnancy. No teratogenic effects have been observed with accidental use of COCs in early pregnancy. When resuming use of Logest®, the increased risk of VTE in the postpartum period should be considered (see sections "Dosage and Administration" and "Special Precautions for Use").

Breast-Feeding. Use of Logest® is not recommended during breast-feeding, as estrogens/progestins pass into breast milk.

If a woman wishes to breast-feed, an alternative contraceptive method should be selected.

Ability to Influence Reaction Speed When Driving or Operating Machinery

Data not available.

Method of Administration and Dosage

Dosage

Take 1 tablet once daily, regularly at approximately the same time each day (swallowed with a small amount of liquid if necessary), for 21 consecutive days.

The tablets from the next pack should be started after completing the 7-day break from taking the medication. Withdrawal bleeding usually begins 2–3 days after the last tablet has been taken and may continue even after starting tablets from the next pack.

How to Start Taking Logest®

• No previous use of hormonal contraceptives

Take the first tablet on the first day of the menstrual cycle.

• Switching from another estrogen/progestin-containing contraceptive (combined oral contraceptive, COC), vaginal ring, or transdermal patch

It is recommended to start taking the first tablet of Logest® the day after taking the last active tablet of the previous contraceptive, or no later than the day following the usual tablet-free interval. When switching from a vaginal ring or transdermal patch, start taking Logest® on the day of device removal, but no later than the day when the next application of these products would normally be due.

• Switching from progestin-only contraceptives (‘mini-pills’, injections, or implants), or from an intrauterine system containing progestin

Switching from low-dose progestin-only contraceptives can occur at any time during the cycle. Treatment with Logest® should begin the day after discontinuation of the previous contraceptive. Switching from progestin-only contraceptives or intrauterine systems should occur the day after their removal; in the case of injections – instead of the next scheduled injection. In all such cases, the woman should use an additional barrier method of contraception for the first 7 days of taking Logest®.

• After first-trimester abortion

Treatment with Logest® may be started immediately. In this case, there is no need to use additional contraceptive methods.

• After childbirth or second-trimester abortion

Since the risk of thromboembolism is increased in the postpartum period, it is recommended to start using estrogen/progestin-containing oral contraceptives no earlier than 21–28 days after childbirth or second-trimester abortion. If treatment is initiated later than 28 days after childbirth or second-trimester abortion, an additional barrier method of contraception should be used for the first 7 days of tablet intake. If sexual intercourse has already occurred, pregnancy should be ruled out or the woman should wait for the onset of the first menstruation before starting estrogen-progestin oral contraceptives.

For breastfeeding women, see section "Use during Pregnancy or Breastfeeding".

Missed one or more tablets. Missing a tablet increases the risk of pregnancy.

Contraceptive reliability may decrease if tablets are missed, particularly if the missed dose extends the interval between the last tablet of the current blister pack and the first tablet of the next blister pack.

If the delay in taking a tablet does not exceed 12 hours, the missed tablet should be taken as soon as remembered. The next tablet should be taken at the usual time.

If the delay in taking the missed tablet exceeds 12 hours, contraceptive protection may be reduced. In this case, two main rules should be followed:

1. The interval between tablet intakes from two blister packs must never exceed 7 days.
2. Adequate suppression of the hypothalamus-pituitary-ovarian system is achieved by continuous tablet intake for 7 days.

Accordingly, in everyday practice, the following recommendations should be followed:

• Week 1

Take the last missed tablet as soon as remembered, even if this means taking two tablets at the same time.

Continue taking the tablets at the usual time thereafter. Additionally, use a barrier method of contraception (e.g., condom) for the next 7 days. If sexual intercourse occurred within the previous 7 days before the missed tablet, consider the possibility of pregnancy.

The greater the number of missed tablets and the closer the missed dose is to the start of a new pack, the higher the risk of pregnancy.

• Week 2

Take the last missed tablet as soon as remembered, even if this means taking two tablets at the same time. Then continue taking tablets at the usual time.

If the tablets have been taken correctly for the 7 days prior to the missed dose, no additional contraceptive methods are required. However, if more than one tablet is missed, women are advised to use additional contraceptive methods for the next 7 days.

• Week 3

The risk of reduced contraceptive efficacy increases as the 7-day tablet-free interval approaches. However, by following the dosing regimens described below, a reduction in contraceptive protection can be avoided.

• If the woman has taken tablets correctly for the 7 days preceding the missed dose, no additional contraceptive methods are required. Either of the following regimens may be followed.
• If this is not the case, the woman is advised to follow the first regimen below and use additional contraceptive methods for the next 7 days.

Regimen 1.

Take the last missed tablet as soon as remembered, even if this means taking two tablets at the same time. Then continue taking tablets at the usual time. Start taking tablets from the next pack immediately after finishing the previous one, i.e., there should be no break between packs. Withdrawal bleeding is unlikely to occur before completion of the second pack, although breakthrough bleeding or spotting may occur during tablet intake.

Regimen 2.

Alternatively, stop taking tablets from the current pack. In this case, the break before starting tablets from the next pack should be 7 days, including the days of missed doses.

If, after missing tablets, the expected withdrawal bleeding does not occur during the first normal tablet-free interval, pregnancy must be ruled out.

Recommendations in Case of Gastrointestinal Disorders

Gastrointestinal disturbances such as vomiting or diarrhea occurring within 3–4 hours after taking the medication may lead to temporary contraceptive failure due to reduced hormone absorption, and actions recommended for a delay of less than 12 hours should be taken. An active tablet from another blister pack should be taken. If such events recur over several days, follow the recommendations for a delay exceeding 12 hours. If such disturbances are prolonged, another reliable method of contraception should be used.

Information for Special Patient Groups

Patients with hepatic impairment. Logest® is contraindicated in women with severe hepatic impairment (see section "Contraindications").

Patients with renal impairment. Logest® has not been studied in patients with renal impairment.

Route of Administration

Oral.

Children

The drug is indicated for use by prescription only after the onset of regular menstruation.

Overdose

There are no reports of overdose with Logest®.

In case of COC overdose, symptoms such as nausea, vomiting, and withdrawal bleeding may occur. Withdrawal bleeding may occur in girls even before menarche if the drug is taken accidentally or unintentionally. There is no specific antidote; treatment is symptomatic.

Adverse reactions.

Description of individual adverse reactions.

An increased risk of venous or arterial thrombotic/thromboembolic events, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis, and pulmonary embolism, has been observed in women taking COCs, as described in more detail in the section "Special precautions for use".

The adverse reactions listed below have been observed with the use of estrogen/progestin-containing oral contraceptives. The most commonly reported adverse effects by patients (> 10%) during phase III clinical trials and post-marketing surveillance were headache, including migraine, and vaginal bleeding/spotting.

Other adverse reactions associated with the use of estrogen/progestin-containing oral contraceptives are listed in Table 3.

Table 3

The following serious adverse reactions have been observed in women using estrogen-progestin oral contraceptives, also described in section "Special precautions" (frequency unknown).

Tumors

• A slightly increased incidence of breast cancer diagnosis has been observed in women using estrogen-progestin OCs. Since breast cancer is rare in women under 40 years of age, the increase is small in relation to the overall risk of breast cancer. The relationship to the use of estrogen-progestin oral contraceptives is not known.

Other conditions

• Development or exacerbation of disorders for which the relationship to the use of estrogen-progestin oral contraceptives has not been definitively established: herpes gestationis, hearing loss associated with otosclerosis, epilepsy, Crohn's disease, ulcerative colitis.
• In women with hereditary predisposition to angioneurotic edema, exogenous estrogens may cause or exacerbate symptoms of angioneurotic edema.
• Disorders of liver function.

Interactions

Breakthrough bleeding and/or reduced contraceptive efficacy may occur due to interactions with other medicinal products (enzyme inducers) and oral contraceptives (see section "Interaction with other medicinal products and other forms of interaction").

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization is very important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report suspected adverse reactions.

Shelf life.

3 years.

Storage conditions.

Store in a place protected from light and inaccessible to children, at a temperature not exceeding 25 °C.

Packaging.

21 film-coated tablets in a blister with a calendar scale; 1 blister per carton.

Prescription category.

Prescription only.

Manufacturer

Bayer AG.

Manufacturer's address and location of operation.

Müllerstraße 178, 13353 Berlin, Germany.