Modelle^® Ovule (Tablets) Instructions for Use

Marketing Authorization Holder

Actavis Group PTC ehf. (Iceland)

Manufactured By

Laboratorios Leon Farma, S.A. (Spain)

Contact Information

TEVA (Israel)

ATC Code

G03AA09 (Desogestrel and Ethinylestradiol)

Active Substances

Ethinylestradiol (Rec.INN registered by WHO)

Desogestrel (Rec.INN registered by WHO)

Dosage Form

Modelle® Ovule

Film-coated tablets, 150 mcg+20 mcg: 21, 63, or 126 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex, engraved with “C” on one side and “5” on the other.

Excipients: lactose monohydrate – 54.91 mg, corn starch – 6.5 mg, povidone K30 – 2 mg, RRR-alpha-tocopherol* – 0.08 mg, colloidal hydrated silicon dioxide – 0.07 mg, colloidal anhydrous silicon dioxide – 0.65 mg, stearic acid – 0.65 mg.

Film coating composition (hypromellose 2910 – 1.326 mg, macrogol – 0.286 mg, titanium dioxide – 0.988 mg) – 2.6 mg.

* contains 67.2% D-alpha-tocopherol and 32.8% soybean oil.

21 pcs. – PVC/PVDC/AL blisters (1) – cardboard packs.
21 pcs. – PVC/PVDC/AL blisters (3) – cardboard packs.
21 pcs. – PVC/PVDC/AL blisters (6) – cardboard packs.

Clinical-Pharmacological Group

Monophasic oral contraceptive

Pharmacotherapeutic Group

Combined contraceptive agent (estrogen + gestagen)

Pharmacological Action

The contraceptive effect of the drug, like other combined oral contraceptives (COCs), is based on the interaction of various factors, the most important of which are suppression of ovulation and changes in cervical mucus secretion.

The gestagen Desogestrel suppresses the synthesis of gonadotropic hormones, primarily LH, thus preventing follicle maturation (blocks ovulation).

The estrogen component of the drug Ethinylestradiol is a synthetic analogue of the follicular hormone estradiol, regulating the menstrual cycle.

In addition to the indicated central and peripheral mechanisms that prevent the maturation of a fertilizable egg, the contraceptive effect is due to an increase in the viscosity of the cervical secretion, which impedes the penetration of sperm into the uterine cavity.

In addition to contraceptive properties, the drug has a number of effects that may be considered when choosing a contraceptive method. Menstrual-like reactions become more regular, less painful, and are accompanied by less pronounced bleeding. The latter circumstance leads to a reduction in the frequency of concomitant iron deficiency anemia.

Taking COCs with a high ethinylestradiol content (50 mcg) reduces the risk of developing ovarian and endometrial cancer. There are no data confirming this pharmacological effect for COC preparations with a lower ethinylestradiol content.

Pharmacokinetics

Ethinylestradiol

Absorption

After oral administration, Ethinylestradiol is rapidly and completely absorbed. Its C_max in blood plasma is 80 pg/ml and is reached 1-2 hours after administration. The absolute bioavailability of ethinylestradiol is about 60%.

Distribution

Ethinylestradiol non-specifically binds to blood plasma albumin (approximately 98.5%) and causes an increase in SHBG concentration in blood plasma. The apparent V_d of ethinylestradiol is about 5 L/kg.

Steady-state conditions. C_ss are reached after 3-4 days of administration, when the plasma concentration is 30-40% higher than the concentration after a single dose.

Metabolism

Ethinylestradiol undergoes presystemic metabolism, both in the small intestinal mucosa and in the liver. Ethinylestradiol is first metabolized by aromatic hydroxylation to form various hydroxylated and methylated metabolites, which are present both in free form and as conjugates with glucuronides and sulfates. The metabolic clearance rate of ethinylestradiol from plasma is about 5 ml/min/kg.

Excretion

The concentration of ethinylestradiol in plasma decreases in two phases. The terminal phase is characterized by a T_1/2 of about 24 hours. Ethinylestradiol is not excreted unchanged; ethinylestradiol metabolites are excreted by the kidneys and through the intestines in a 4:6 ratio. The T_1/2 of metabolites is about 24 hours.

Desogestrel

Absorption

When taken orally, Desogestrel is rapidly and completely absorbed and converted to etonogestrel. The C_max of etonogestrel in blood plasma is 2 ng/ml and is reached approximately 1.5 hours later. Bioavailability is 62-81%.

Distribution

Etonogestrel binds to blood plasma albumin and sex hormone-binding globulin (SHBG). Only 2-4% of the total plasma concentration of etonogestrel is present as free steroid, and 40-70% is specifically bound to SHBG. The increase in SHBG concentration caused by ethinylestradiol affects the distribution between blood plasma proteins, causing an increase in the SHBG-bound fraction and a decrease in the albumin-bound fraction. The apparent V_d of desogestrel is 1.5 L/kg.

Steady-state conditions. The pharmacokinetics of etonogestrel are influenced by the level of SHBG, the concentration of which increases 3-fold under the influence of ethinylestradiol. With daily administration, the plasma concentration of etonogestrel increases approximately 2-3 times, reaching a constant value in the second half of the drug administration cycle.

Metabolism

Etonogestrel is completely metabolized via known pathways of sex hormone metabolism. The metabolic clearance rate from plasma is about 2 ml/min/kg. No interaction of etonogestrel with concurrently administered ethinylestradiol was detected.

Excretion

The concentration of etonogestrel in plasma decreases in two phases. The distribution in the terminal phase is characterized by a T_1/2 of about 30 hours. Desogestrel and its metabolites are excreted by the kidneys and through the intestines in an approximate ratio of 6:4.

Indications

• Contraception.

ICD codes

Dosage Regimen

The tablets should be taken orally in the order indicated on the package, starting from the current day of the week, every day, at approximately the same time, with a small amount of water if necessary.

Take 1 tablet/day for 21 days. Taking tablets from the next package should be started 7 days after the end of the previous one. During these 7 days, menstrual-like bleeding occurs. It usually begins on the 2nd-3rd day after taking the last tablet and may not stop before starting the next package.

How to start taking the drug

If hormonal contraceptives have not been used in the last month, then taking the drug should be started on the 1st day of the menstrual cycle (i.e., on the first day of menstrual bleeding). You can start taking the drug on days 2-5 after the start of the menstrual cycle, but in this case, it is recommended to use an additional (non-hormonal) method of contraception during the first 7 days of taking the tablets in the first cycle.

Switching from combined hormonal contraceptives (COC, vaginal ring, or transdermal patch): it is advisable to start taking the drug the day after taking the last active tablet of the previously used drug (containing active substances), but no later than the day after the end of the usual tablet-free interval or the day after taking the last tablet not containing hormones. In the case of using a vaginal ring or transdermal patch, it is advisable to start taking the drug on the day of their removal, but no later than the day when a new ring should have been inserted or the next patch application should have been made.

If a woman has used the previous contraceptive method consistently and correctly, and if it is reliably known that she is not pregnant, in this case, she can switch to taking the drug MODELLE^® OVULE on any day of the cycle. It should be taken into account that the usual interval in the use of the previous contraceptive method should not exceed its recommended duration.

Switching from preparations containing only progestogen (“mini-pills”, injections, implant) or from a progestogen-releasing intrauterine system (IUD). A woman taking “mini-pills” can switch to taking the drug on any day without a break; switching from an implant or IUD – on the day of their removal; from an injectable contraceptive drug – on the day when the next injection is due; in all cases, it is recommended to use additional contraceptive methods during the first 7 days of taking the drug.

After a first-trimester abortion, a woman can start taking the drug immediately. There is no need to use any additional contraceptive methods.

After childbirth or a second-trimester abortion, it is recommended to start taking the drug no earlier than 21-28 days after childbirth, in the absence of breastfeeding, or termination of pregnancy in the second trimester. If starting the drug later, it is recommended to use barrier contraceptive methods during the first 7 days of taking the drug. In any case, if a woman has had sexual intercourse after childbirth or abortion before starting the drug, pregnancy must be ruled out or wait for the first menstruation.

In case of a missed dose

If the intake of the next tablet is delayed by less than 12 hours, contraceptive reliability is not reduced. The woman should take the tablet as soon as she remembers, and take the subsequent tablets at the usual time.

If the intake of the next tablet is delayed by more than 12 hours, contraceptive reliability may be reduced. In this case, the following rules should be followed

1. Tablet intake should never be interrupted for more than 7 days;
2. To adequately suppress the hypothalamic-pituitary-ovarian system, tablets must be taken for 7 consecutive days.

The cyclical nature of the drug intake implies 3 weeks of use. Therefore, the following recommendations can be given.

Week 1. The woman should take the missed tablet as soon as she remembers, even if this means taking 2 tablets at the same time. Then she should continue taking according to the usual schedule. Additionally, a barrier contraceptive method should be used for the next 7 days. If the woman had sexual intercourse during the previous 7 days, the possibility of pregnancy should be considered. The more tablets missed, and the closer the break in taking the drug is to the moment of sexual intercourse, the higher the risk of pregnancy.

Week 2. The woman should take the missed tablet as soon as she remembers, even if this means taking two tablets at the same time. Then she should continue taking according to the usual schedule. Provided that the woman took the tablets on time for 7 days preceding the first missed dose, there is no need to use additional (non-hormonal) contraceptive methods. Otherwise, or if the woman missed more than 1 tablet, it is recommended to use additional contraceptive methods for the next 7 days.

Week 3. Contraceptive reliability may be reduced due to the subsequent break in taking the drug. This can be avoided by adapting the drug intake regimen. If either of the two following schemes is used, there is no need to use additional contraceptive measures, provided that the woman took the tablets on time for 7 days preceding the first missed dose. Otherwise, it is recommended to use one of the two following schemes and also use additional contraceptive measures for the next 7 days.

1. The woman should take the missed tablet as soon as she remembers, even if this means taking 2 tablets at the same time. Then she should continue taking according to the usual schedule. Taking tablets from a new package should be started as soon as the current package is finished, i.e., no break should be made between packages. The likelihood of withdrawal bleeding occurring before the end of the second package is low, but some may experience spotting or heavy bleeding while still taking the drug.
2. It can be recommended to stop taking the drug from the current package. The woman should take a break in taking the drug for no more than 7 days, including the days when she forgot to take the tablets, and then start a new package.

If a dose is missed and subsequently there is no “withdrawal bleeding” in the nearest tablet-free interval, the possibility of pregnancy should be considered.

Recommendations in case of gastrointestinal disorders

In severe gastrointestinal disorders, absorption may be incomplete and additional contraceptive measures should be taken. If vomiting occurs within 3-4 hours after taking the drug, the recommendations regarding a missed dose should be followed. If the woman does not want to change her usual intake schedule, she can take an additional tablet from another package (the number of additional tablets is determined by an obstetrician-gynecologist during an in-person consultation).

How to change the timing of menstrual-like bleeding

To delay menstrual-like bleeding, continue taking tablets from another package of the drug without the usual break in intake. Menstrual-like bleeding can be delayed for any period until the tablets from the second package are finished. During this period, the woman may experience spotting or heavy bleeding. The usual drug intake schedule should be resumed after a 7-day interval in intake.

To move the day of onset of menstrual-like bleeding to another day, the usual break in intake can be shortened by as many days as necessary. The shorter the break, the higher the risk of absence of menstrual-like bleeding during the break and the occurrence of heavy or spotting bleeding while taking the drug from the second package.

Adverse Reactions

Possible adverse effects associated with taking the drug, which were noted when taking the combination Ethinylestradiol+Desogestrel or other COCs, are listed below.

Adverse effects noted in women taking COCs

Cardiac disorders: venous or arterial thrombosis or thromboembolism (including myocardial infarction, stroke, deep vein thrombosis, pulmonary embolism, thrombosis/embolism of hepatic, mesenteric, renal arteries and veins, retinal arteries); increased BP.

Nervous system disorders: dizziness, nervousness.

Benign, malignant and unspecified neoplasms (including cysts and polyps): benign and malignant liver tumors, hormone-dependent breast tumors.

Skin disorders: chloasma (especially in case of a history of chloasma during pregnancy), acne.

Gastrointestinal disorders: Crohn’s disease, ulcerative colitis.

Reproductive system disorders: acyclic bleeding (more often in the first months of use), candidal vulvovaginitis, absence of menstrual-like bleeding.

Other: occurrence or exacerbation of jaundice and/or pruritus associated with cholestasis, cholelithiasis, porphyria, systemic lupus erythematosus, hemolytic-uremic syndrome, Sydenham’s chorea, herpes gestationis, hearing loss due to otosclerosis, allergic reactions.

Contraindications

The drug MODELLE^® OVULE is contraindicated in the presence of any of the diseases/conditions/risk factors listed below. If any of them occur while taking the drug, it should be discontinued immediately

• Hypersensitivity to the components of the drug;
• Current or history of venous thrombosis (including deep vein thrombosis of the leg, pulmonary embolism);
• Current or history of arterial thrombosis (including myocardial infarction, stroke) or precursors of thrombosis (including transient ischemic attack, angina pectoris);
• Identified predisposition to venous or arterial thrombosis, including resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);
• Migraine with focal neurological symptoms in the medical history;
• Diabetes mellitus with diabetic angiopathy;
• Presence of multiple factors or a high degree of severity of one of the risk factors for the development of venous or arterial thrombosis, thromboembolism (see the “Special Precautions” section);
• Uncontrolled arterial hypertension (BP 160/100 mm Hg and higher);
• Pancreatitis (including in the medical history) accompanied by severe hypertriglyceridemia;
• Severe dyslipoproteinemia;
• Endometrial hyperplasia;
• Hepatic insufficiency, acute or severe liver diseases (until liver function parameters normalize), including in the medical history;
• Liver tumors (benign and malignant), including in the medical history;
• Hormone-dependent malignant neoplasms of the genital organs or mammary glands (including suspected);
• Vaginal bleeding of unknown etiology;
• Smoking at the age over 35 years (more than 15 cigarettes per day);
• Pregnancy (including suspected);
• Period of breastfeeding;
• Adolescent girls under 18 years of age (data on the efficacy and safety of the drug use are absent);
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

With caution

If any of the diseases/conditions/risk factors listed below are currently present, the potential risk and expected benefit of using the drug should be carefully weighed in each individual case

• Age over 35 years;
• Smoking;
• Presence of thromboembolic diseases in the family history (venous or arterial thrombosis/thromboembolism in brothers, sisters or parents at a young age);
• Overweight (BMI over 25 kg/m² and less than 30 kg/m²);
• Dyslipoproteinemia;
• Controlled arterial hypertension;
• Migraine without focal neurological symptoms;
• Uncomplicated valvular heart defects;
• Varicose veins, superficial thrombophlebitis;
• Postpartum period;
• Diabetes mellitus;
• Systemic lupus erythematosus;
• Hemolytic-uremic syndrome;
• Chronic inflammatory bowel diseases (Crohn’s disease or ulcerative colitis);
• Sickle cell anemia;
• Hypertriglyceridemia (including in the family history);
• Presence in the medical history of diseases that first occurred or worsened during a previous pregnancy or while taking sex hormones;
• Hereditary angioedema;
• Chloasma;
• Mild and moderate liver diseases in the medical history with normal liver function tests.

Use in Pregnancy and Lactation

The use of the drug during pregnancy is contraindicated. If pregnancy occurs while using the drug, its administration should be discontinued.

The drug may affect lactation, as combined oral contraceptives (COCs) reduce the amount and change the composition of breast milk. The use of the drug MODELL^® OVULE is contraindicated until breastfeeding is discontinued. A small amount of sex hormones and/or their metabolites may be excreted in breast milk.

Use in Hepatic Impairment

Contraindications: hepatic insufficiency, acute or severe liver diseases (until liver function parameters normalize), including in the medical history; liver tumors (benign and malignant), including in the medical history.

Special Precautions

In the presence of any of the diseases/conditions/risk factors listed below, the benefits and possible risks of taking the drug MODELL^® OVULE should be carefully weighed. This issue should be discussed with the patient before starting the drug. In case of exacerbation of diseases, worsening of the condition, or the appearance of the first symptoms of the aforementioned conditions or risk factors, the patient should immediately consult a doctor. The decision to discontinue the drug is made by the doctor individually.

Cardiovascular diseases

Epidemiological studies have established that there may be a connection between the use of COCs and an increased risk of arterial and venous thromboses and thromboembolisms, such as myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism. These diseases are observed extremely rarely.

The use of any COC is associated with an increased risk of venous thromboembolism (VTE), manifested as deep vein thrombosis and/or pulmonary embolism. The risk is higher in the first year of use than in women taking COCs for more than 1 year.

When taking the combination of desogestrel and ethinylestradiol, there is an increased (almost 2 times) risk of developing VTE compared to drugs containing levonorgestrel, norgestimate, or norethisterone as the progestogenic component.

Very rarely, thrombosis occurs in other blood vessels (for example, in the veins and arteries of the liver, mesentery, kidneys, brain, or retina).

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

If a hereditary predisposition to thromboembolic diseases is suspected, the woman should be referred for a specialist consultation before deciding to prescribe any hormonal contraceptives.

Risk factors for the development of venous and arterial thrombosis, thromboembolism

High-risk factors for the development of venous thrombosis are

• Age over 35 years;
• Air travel lasting more than 4 hours (especially in the presence of other risk factors);
• Overweight (BMI over 30 kg/m²); the risk of complications increases with increasing body mass index, and it is especially important to consider this in the presence of other risk factors;
• Prolonged immobilization; major surgical interventions; neurosurgical operations; surgical interventions in the pelvic area or on the lower limbs; severe trauma; in case of prolonged immobilization and the aforementioned surgical interventions, it is recommended to discontinue the use of the drug, for planned surgical interventions no later than 4 weeks before the operation, and not to resume administration for 2 weeks after full rehabilitation. To prevent unwanted pregnancy, other methods of contraception should be used. If the administration of the drug MODELL^® OVULE was not discontinued in advance, then antithrombotic therapy is indicated in this case;
• Presence of thromboembolic diseases in the family history (venous thrombosis/thromboembolism in brothers, sisters or parents at a young age);
• Other conditions/diseases associated with the development of venous thrombosis (oncological diseases, systemic lupus erythematosus, hemolytic-uremic syndrome, chronic inflammatory bowel diseases (Crohn’s disease or ulcerative colitis), sickle cell anemia).

The risk of developing venous thromboembolism is increased both with the primary use of COCs and with the resumption of COC use after a break of 4 weeks or more.

The development of venous thromboembolism can be fatal in 1-2% of cases.

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

Symptoms of deep vein thrombosis may include

• Unilateral swelling of the leg, including the foot, or along the affected vein;
• Pain in the leg or tenderness when touching the leg, which may be felt, including only when standing or walking;
• A feeling of warmth in the affected limb, redness or discoloration of the skin of the leg.

Symptoms of pulmonary embolism

• Sudden attack of difficulty breathing or rapid breathing of unknown etiology;
• Sudden attack of coughing, which may be accompanied by hemoptysis;
• Sharp pain in the chest;
• A feeling of severe weakness or dizziness;
• Rapid or irregular heart rhythm.

Some of these symptoms (for example, difficulty breathing, cough) are nonspecific, which may complicate the diagnosis. It is possible to diagnose a more common or less dangerous disease (for example, a respiratory tract infection).

Other signs of vessel occlusion: sudden pain, swelling, and bluish discoloration of the limb.

In case of occlusion of an eye vessel, symptoms can range from painless blurred vision, which can progress to complete loss of vision. Sometimes complete loss of vision can occur suddenly.

Epidemiological studies have revealed a connection between the use of COCs and an increased risk of developing arterial thrombosis (myocardial infarction) or cerebrovascular disorders (for example, transient ischemic attack, stroke). Arterial thromboembolism can be fatal.

High-risk factors for the development of arterial thrombosis are

• Age over 35 years;
• Smoking; women taking COCs are advised to refrain from smoking; women over 35 years of age who smoke should not take COCs;
• Arterial hypertension;
• Overweight (BMI over 30 kg/m²); the risk of complications increases with increasing BMI, and it is especially important to consider this in the presence of other risk factors;
• Presence of thromboembolic diseases in the family history (arterial thrombosis/thromboembolism in brothers, sisters or parents at a young age);
• Migraine; an increase in the frequency and intensity of migraine while taking COCs (which may be a sign of cerebrovascular disorders) is a reason to discontinue the drug MODELL^® OVULE;
• Other conditions/diseases associated with the development of vascular adverse events (diabetes mellitus, hyperhomocysteinemia, heart valve defect and atrial fibrillation, dyslipoproteinemia and systemic lupus erythematosus).

Symptoms of arterial thromboembolism

Symptoms of cerebrovascular disorders

• Sudden numbness or weakness of the facial muscles, arms, or legs, affecting one side or part of the body;
• Sudden gait disturbance, dizziness, loss of balance or coordination of movement;
• Sudden confusion, speech impairment or understanding;
• Sudden visual impairment in one or both eyes;
• Sudden severe or prolonged headache of unknown etiology;
• Loss of consciousness or severe weakness with or without convulsions.

Temporary symptoms may indicate the development of a transient ischemic attack.

Symptoms of myocardial infarction

• Pain, discomfort, feeling of pressure, heaviness or fullness in the chest; pain in the arm or below the sternum;
• Unpleasant sensation (discomfort) radiating to the back, jaw, throat, arm, stomach area;
• Feeling of stomach fullness, indigestion or feeling of suffocation;
• Sweating, nausea, vomiting or dizziness;
• Severe fatigue, anxiety or difficulty breathing;
• Rapid or irregular heart rhythm.

The risk of developing thromboembolic complications increases with a combination of several risk factors for these complications.

Biochemical indicators that may indicate a hereditary or acquired predisposition to venous or arterial thrombosis are: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

Tumors

The most important risk factor for cervical cancer is the persistence of human papillomavirus (HPV infection). Some epidemiological studies note an increased risk of cervical cancer in women who have been taking COCs for a long time, but to date there are controversies regarding the degree of influence on these data by confounding various factors, such as cervical screening and sexual behavior, including less frequent use of barrier methods of contraception, or their interrelation.

There is evidence that there is a small increase in the relative risk (1.24) of developing breast cancer in women using COCs. The increased risk gradually decreases within 10 years after discontinuation of COCs. Since breast cancer in women under 40 years of age is quite rare, the increase in the risk of developing breast cancer in women currently taking COCs or who have recently stopped using them is small relative to the baseline probability of developing cancer. These studies do not provide data on the etiology of cancer. The increased risk of developing breast cancer may be a consequence of medical supervision and earlier diagnosis of cancer in women taking COCs (they are diagnosed with earlier stages of cancer than women who have never taken COCs), the biological effect of COCs, or a combination of these two factors.

Very rarely, when using the combination Ethinylestradiol+Desogestrel, cases of benign, and even more rarely, malignant liver tumors have been observed. In some cases, these tumors led to life-threatening intra-abdominal bleeding. The doctor should consider the possibility of a liver tumor in the differential diagnosis of diseases in a woman taking the drug MODELL^® OVULE, if symptoms include acute pain in the upper abdomen, liver enlargement, or signs of intra-abdominal bleeding.

Other diseases

If a woman or her family members have been diagnosed with hypertriglyceridemia, then the risk of pancreatitis may increase when taking the drug MODELL^® OVULE.

If a woman taking the drug MODELL^® OVULE develops persistent clinically significant arterial hypertension, the doctor should discontinue the drug and prescribe treatment for arterial hypertension. In cases where antihypertensive therapy achieves normal blood pressure values, the doctor may consider it possible for the patient to resume taking the drug.

There are reports that jaundice and/or itching caused by cholestasis; gallstone formation, porphyria, systemic lupus erythematosus, hemolytic-uremic syndrome, Sydenham’s chorea (chorea minor), herpes gestationis, hearing loss due to otosclerosis, (hereditary) angioedema develop or worsen both during pregnancy and when taking COCs, however, evidence regarding the use of the combination Ethinylestradiol+Desogestrel is inconclusive.

Acute or chronic liver function disorders may be grounds for discontinuing the drug MODELL^® OVULE until liver function parameters normalize. Recurrence of cholestatic jaundice, observed earlier during pregnancy or when using sex hormone drugs, requires discontinuation of the drug MODELL^® OVULE.

Although taking the drug MODELL^® OVULE may affect peripheral insulin resistance and glucose tolerance, as a rule, adjustment of the dosage regimen of hypoglycemic drugs in patients with diabetes mellitus is not required. Nevertheless, careful monitoring of blood glucose concentration is necessary, especially during the first months of taking COCs.

There is evidence of a connection between taking COCs and Crohn’s disease and ulcerative colitis.

Sometimes, when taking the drug MODELL^® OVULE, skin pigmentation of the face (chloasma) may be observed, especially if it was present earlier during pregnancy. Women with a predisposition to chloasma should avoid direct sunlight and UV radiation from other sources while taking the drug MODELL^® OVULE.

Medical examinations/consultations

Before starting or resuming the use of the drug MODELL^® OVULE, the doctor should collect a detailed medical history (including family history) from the patient and conduct a thorough examination, taking into account contraindications and precautions. It is important to repeat periodic medical examinations because diseases that are contraindications to the use of the drug MODELL^® OVULE (for example, transient ischemic attack) or risk factors (for example, a family history of venous or arterial thrombosis) may first appear during the use of the drug.

The frequency and list of examinations should be based on generally accepted practice and selected individually for each woman (but not less than once every 6 months). In any case, special attention should be paid to measuring blood pressure, examining the mammary glands, abdominal and pelvic organs, including cytological examination of the cervix.

The woman should be informed that COCs do not protect against HIV (AIDS) and other sexually transmitted infections.

Reduced efficacy

The efficacy of the drug MODELL^® OVULE may decrease in case of missed doses, gastrointestinal disorders, or concomitant use of certain medications (see the “Drug Interactions” section).

Irregular bleeding

When taking the drug MODELL^® OVULE, especially in the first months of use, irregular spotting or heavy bleeding may occur. Therefore, the assessment of irregular bleeding should be carried out only after the end of the adaptation period, lasting 3 months.

If irregular bleeding persists or appears after previous regular cycles, possible non-hormonal causes of cycle disorders should be considered and appropriate examinations should be carried out to exclude malignant neoplasms or pregnancy. These measures may include diagnostic curettage.

Some women may not have menstrual-like bleeding during the break between taking the drug. If the drug MODELL^® OVULE was taken in accordance with the recommended dosage regimen, the likelihood of pregnancy is low. Otherwise, or if bleeding is absent 2 times in a row, the possibility of pregnancy should be excluded and a doctor should be consulted.

Laboratory tests

COCs may affect the results of some laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, the content of transport proteins in blood plasma, for example, corticosteroid-binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism, parameters of coagulation and fibrinolysis. Usually, these changes are within the normal laboratory values.

Effect on the ability to drive vehicles and mechanisms

No effect of the drug on the ability to drive vehicles and work with mechanisms has been noted.

Overdose

Symptoms: nausea, vomiting may occur, in young girls – spotting vaginal bleeding. No serious complications have been observed with an overdose of the Ethinylestradiol+Desogestrel combination.

Treatment: symptomatic therapy. There are no antidotes.

Drug Interactions

Hepatic metabolism: interactions may occur with inducers of hepatic microsomal enzymes, which may lead to an increase in the clearance of sex hormones (for example, hydantoins, barbiturates, primidone, carbamazepine, rifampicin; and possibly also oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, bosentan, modafinil, rifabutin and preparations containing St. John’s wort). Maximum induction of microsomal enzymes is not observed in the first 2-3 weeks of taking the Desogestrel+Ethinylestradiol combination, but may persist for at least 4 weeks after discontinuation of the drug. Impaired contraceptive effect has also been reported when taking the Desogestrel+Ethinylestradiol combination with antibiotics such as ampicillin and tetracyclines. The mechanism of this effect is unclear.

Concomitant use of atorvastatin and some combined oral contraceptives containing Ethinylestradiol increases the AUC of ethinylestradiol by approximately 20%.

Ascorbic acid may increase the plasma concentration of ethinylestradiol, which is possibly due to inhibition of conjugation.

The drug MODELL^® OVULE reduces the effectiveness of indirect anticoagulants, anxiolytics (diazepam), tricyclic antidepressants, theophylline, caffeine, hypoglycemic drugs, clofibrate, and glucocorticosteroids.

When used concomitantly with inducers of microsomal enzymes, an additional barrier method of contraception (for example, a condom) should be used throughout the entire course of treatment and for 28 days after discontinuation of treatment. If long-term use of inducing drugs is necessary, other effective non-hormonal methods of contraception should be considered. While taking antibiotics (except for rifampicin and griseofulvin, which are inducers of microsomal enzymes), it is necessary to use a barrier method of contraception throughout the entire course of treatment and for 7 days after the end of therapy. If the cycle of taking the drug MODELL^® OVULE ends before the end of therapy with the inducing drug, it is recommended to start taking tablets from a new package of the drug MODELL^® OVULE without the usual break.

Combined oral contraceptives can affect the metabolism of other drugs and, accordingly, change their concentrations in plasma and tissues: increase (for example, cyclosporine) or decrease (lamotrigine, salicylic acid, morphine).

When concomitantly using other drugs, the instructions for medical use of these drugs should be consulted to determine a possible interaction.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life is 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.