Novinet

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NOVYNETTE

Composition:

Active substances: desogestrel, ethinylestradiol;

One coated tablet contains 0.15 mg of desogestrel and 0.02 mg of ethinylestradiol;

Excipients: quinoline yellow (E 104), alpha-tocopherol (all-rac-α-tocopherol), magnesium stearate, colloidal anhydrous silicon dioxide, stearic acid, povidone, potato starch, lactose monohydrate;

Coating composition: propylene glycol, polyethylene glycol 6000, hypromellose.

Pharmaceutical form. Coated tablets.

Main physicochemical properties: pale yellow, round, biconvex coated tablets, approximately 6 mm in diameter, marked with «P9» on one side and «RG» on the other.

Pharmacotherapeutic group.

Hormonal contraceptives for systemic use, progestogens and estrogens.

ATC code G03A A09.

Pharmacological properties.

Pharmacodynamics.

The contraceptive effect of combined oral contraceptives (COCs) is based on the interaction of several factors, the most important of which are the suppression of ovulation and changes in cervical secretion. In addition to preventing pregnancy, COCs have certain beneficial effects, which, like adverse effects (see sections "Special precautions" and "Adverse reactions"), may be considered when choosing a method of fertility control. COCs promote regular menstrual cycles, and menstruation becomes less painful and is associated with reduced blood loss. This latter effect may reduce the incidence of iron deficiency.

Furthermore, there is evidence that high-dose COCs (0.05 mg ethinylestradiol) reduce the incidence of benign breast tumors, ovarian cysts, pelvic inflammatory disease, ectopic pregnancy, endometrial cancer, and ovarian cancer. However, it has not yet been confirmed whether this also applies to the use of low-dose COCs.

Pharmacokinetics.

Desogestrel

Absorption. Desogestrel, when administered orally, is rapidly and completely absorbed and converted into etonogestrel. Peak serum concentrations are reached within approximately 1.5 hours. Bioavailability ranges from 62% to 81%.

Distribution. Etonogestrel binds to serum albumin and sex hormone-binding globulin (SHBG). Only 2–4% of the total drug concentration in serum exists as free steroid, while 40–70% is specifically bound to SHBG. The ethinylestradiol-induced increase in SHBG affects the distribution among serum proteins, increasing the SHBG-bound fraction and decreasing the albumin-bound fraction. The volume of distribution of desogestrel is 5 L/kg.

Biological transformation. Etonogestrel is completely metabolized via well-known steroid metabolic pathways. The clearance rate of metabolites from serum is approximately 2 mL/min/kg. No interaction between etonogestrel and co-administered ethinylestradiol has been observed.

Elimination. Serum levels of etonogestrel decline in two phases. The terminal elimination phase is characterized by a half-life of approximately 30 hours. Desogestrel and its metabolites are excreted in urine and bile in a ratio of 6:4.

Steady state. The pharmacokinetics of etonogestrel are influenced by serum SHBG levels, which increase threefold during ethinylestradiol administration. With daily dosing, steady state is reached in the second half of the cycle, when serum concentrations of etonogestrel increase by 2–3 times.

Ethinylestradiol

Absorption. After oral administration, ethinylestradiol is rapidly and almost completely absorbed. Peak plasma concentrations are achieved within approximately 1–2 hours. Absolute bioavailability, due to presystemic conjugation and first-pass effect, is approximately 60%.

Distribution. Ethinylestradiol exhibits strong but non-specific binding to serum albumin (approximately 98.5%) and induces an increase in serum SHBG concentration. The expected volume of distribution is 5 L/kg.

Biological transformation. Ethinylestradiol undergoes presystemic conjugation in the mucosa of the small intestine and in the liver. It is primarily metabolized via aromatic hydroxylation, but numerous other hydroxylated and methylated metabolites are also formed, which are detected as free metabolites as well as conjugated sulfates and glucuronides. Metabolic clearance rate is approximately 5 mL/min/kg.

In vitro, ethinylestradiol is a reversible inhibitor of CYP2C19, CYP1A1, and CYP1A2, and an irreversible inhibitor of CYP3A4/5, CYP2C8, and CYP2J2.

Elimination. Serum levels of ethinylestradiol decline in a biphasic manner; the terminal elimination phase is characterized by a half-life of approximately 24 hours. Ethinylestradiol is not excreted unchanged; its metabolites are excreted in urine and bile in a ratio of 4:6. The elimination half-life of metabolites is approximately one day.

Steady state. Steady state is achieved within 3–4 days, when serum concentrations of the drug are approximately 30–40% higher than after a single dose.

Clinical characteristics.

Indications.

Oral contraception.

Before prescribing Novinet, individual risk factors present in a woman should be assessed, particularly those related to the risk of venous thromboembolism (VTE), and the risk of venous thromboembolic complications associated with Novinet should be compared with that of other combined hormonal contraceptives (CHCs) (see sections "Contraindications" and "Special precautions").

Contraindications.

Combined hormonal contraceptives (CHCs) must not be used in the conditions listed below. If any of these conditions occurs for the first time during CHC use, treatment should be discontinued immediately.

• Established or suspected pregnancy.
• Presence or risk of venous thromboembolism (VTE).
  • Current venous thromboembolism, including patients receiving anticoagulant therapy, or history of venous thromboembolism (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)).
  • Known hereditary or acquired predisposition to venous thromboembolism, such as activated protein C resistance (including factor V Leiden mutation), 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 or risk of arterial thromboembolism (ATE).
  • Current or past arterial thromboembolism (e.g., myocardial infarction) or prodromal conditions (e.g., angina pectoris).
  • Cerebrovascular disorders – current or past stroke, or prodromal conditions (e.g., transient ischemic attack (TIA)).
  • Established hereditary or acquired predisposition to arterial thromboembolism, such as hyperhomocysteinemia or presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
  • History of migraine with focal neurological symptoms.
  • High risk of ATE 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 dyslipoproteinemia.
• Current or past history of pancreatitis associated with severe hypertriglyceridemia.
• Current or past severe liver disease until liver function tests have returned to normal.
• Current or past liver tumors (benign or malignant).
• Known or suspected hormone-dependent malignant neoplasms (e.g., of genital organs or breast).
• Endometrial hyperplasia.
• Vaginal bleeding of unknown etiology.
• Hypersensitivity to the active substances or to any of the excipients of the drug.
• Novinet is contraindicated for concomitant use with medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, medicinal products containing glecaprevir/pibrentasvir, or sofosbuvir/velpatasvir/voxilaprevir (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Warning. To detect possible drug interactions, information contained in the instructions for medical use of other concurrently administered drugs should be considered.

Pharmacodynamic interactions.

During clinical trials involving patients receiving treatment for hepatitis C virus (HCV) infection with medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin, elevations in transaminase levels (ALT) more than 5 times the upper limit of normal (ULN) occurred significantly more frequently in women taking medicinal products containing ethinylestradiol, such as combined hormonal contraceptives (CHCs). Elevations in ALT levels were also observed when glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir were used in women taking ethinylestradiol-containing medicinal products, such as CHCs (see section "Contraindications"). Therefore, women taking Novinet should switch to an alternative method of contraception (e.g., progestogen-only contraception or non-hormonal methods) prior to starting therapy with these combination medicinal products. Novinet may be resumed 2 weeks after completion of treatment with these combination regimens.

Pharmacokinetic interactions

Effect of other medicinal products on Novinet

Interactions with enzyme-inducing drugs are possible, which may increase the clearance of sex hormones, potentially leading primarily to breakthrough bleeding and/or contraceptive failure.

Management

Enzyme induction may occur within a few days of starting treatment. Maximum enzyme induction is usually observed within several weeks. After discontinuation of the inducing drug, enzyme induction may persist for up to 4 weeks.

Short-term treatment

Women taking enzyme-inducing drugs should temporarily use a barrier method of contraception or another contraceptive method in addition to the COC. A barrier method should be used throughout the entire period of concomitant therapy and for an additional 28 days after its discontinuation. If the enzyme-inducing drug is still being taken after the last tablet of the current COC pack, the next pack should be started without the usual break.

Long-term treatment

Women undergoing long-term therapy with drugs that induce the hepatic enzyme system are advised to use another reliable non-hormonal method of contraception.

Interactions described in the literature.

Substances that increase COC clearance (reducing COC efficacy due to enzyme induction), e.g.: barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, and the HIV treatment drug ritonavir, nevirapine, and efavirenz, possibly also felbamate, griseofulvin, oxcarbazepine, topiramate, and products containing St. John's wort (Hypericum perforatum).

Substances with variable effects on COC clearance: when used concomitantly with COCs, many combinations of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors, including combinations with hepatitis C virus protease inhibitors, may increase or decrease plasma concentrations of estrogens or progestins. The effect of these changes may be clinically significant in some cases.

Therefore, to detect possible drug interactions and related recommendations, information contained in the instructions for medical use of concomitant drugs used for the treatment of HIV infection/hepatitis C should be considered. In case of any doubts, women receiving protease inhibitors or non-nucleoside reverse transcriptase inhibitors should use an additional barrier method of contraception.

Active substances that decrease the clearance of Novinet (enzyme inhibitors)

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

Concomitant use with strong (e.g., ketoconazole, itraconazole, clarithromycin) or moderate (e.g., fluconazole, diltiazem, erythromycin) CYP3A4 inhibitors may lead to increased serum concentrations of estrogens or progestins, including etonogestrel.

Etoricoxib at doses of 60 to 120 mg/day has been shown to increase plasma concentrations of ethinylestradiol by 1.4–1.6 times, respectively, when co-administered with a combined hormonal contraceptive containing 0.035 mg ethinylestradiol.

Effect of Novinet on other medicinal products

Oral contraceptives may affect the metabolism of other medicinal products. Consequently, their concentrations in plasma and tissues 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., with theophylline) or moderate (e.g., with tizanidine) increases in their plasma concentrations.

Other interactions

Laboratory tests

The use of steroid contraceptives may influence the results of certain laboratory tests, such as biochemical parameters of liver, thyroid, adrenal, and kidney function, as well as levels of plasma transport proteins such as corticosteroid-binding globulin and lipid/lipoprotein fractions, carbohydrate metabolism parameters, and coagulation and fibrinolysis parameters. Usually, these changes remain within normal laboratory reference ranges.

Special precautions.

Warning

If any of the conditions or risk factors listed below are present, the justification for using the drug Novinet should be discussed with a woman.

Women are advised to consult their physician and discuss the possibility of discontinuing Novinet if any of these conditions or risk factors worsen or manifest.

1. Cardiovascular system disorders

Risk of venous thromboembolism (VTE)

The use of combined hormonal contraceptives (CHCs) increases the risk of venous thromboembolism (VTE) in users compared to women who do not use these drugs.

The use of contraceptives containing levonorgestrel, norgestimate, or norethisterone is associated with a lower risk of VTE. Other drugs, such as Novinet, may double the risk of VTE development. The decision to use a drug that does not belong to the group with the lowest risk of VTE should be made only after a consultation with the woman. It is necessary to ensure that she understands the risk of VTE associated with the use of Novinet, the extent to which her individual risk factors may influence this risk, and the fact that the risk of VTE is highest during the first year of using the drug. In addition, data indicate that the risk increases when combined hormonal contraceptives are restarted after a break of 4 weeks or more.

VTE occurs in approximately 2 out of 10,000 non-pregnant women who do not use CHCs. However, a woman's individual risk may be significantly higher depending on her existing risk factors (see below).

According to estimates¹, among 10,000 women using CHCs containing desogestrel, 9–12 will develop VTE within a year (compared to approximately 62 cases among women using CHCs containing levonorgestrel).

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

¹ These frequency values were obtained by analyzing pooled data from epidemiological studies, using relative risks for different drugs compared to CHCs containing levonorgestrel.

² Median range of 5–7 per 10,000 woman-years is based on the relative risk of CHCs containing levonorgestrel compared to non-users, which is approximately 2.3–3.6.

Number of VTE cases per 10,000 women per year

In rare cases, there have been reports of thrombosis of other vessels (e.g., hepatic, mesenteric, renal, or retinal veins and arteries) in women using COCs.

Risk factors for venous thromboembolism (VTE)

The risk of developing venous thromboembolic complications while using COCs may increase substantially in women with additional risk factors, especially when multiple risk factors are present (see Table 1).

Novinet is contraindicated in women with multiple risk factors placing them at high risk of venous thrombosis (see section "Contraindications"). If a woman has more than one risk factor, the risk increase may be greater than the sum of the individual risks associated with each factor; in such cases, the overall risk of VTE should be considered. COCs should not be prescribed if the benefit-risk balance is considered negative (see section "Contraindications").

Table 1

Risk factors for venous thromboembolism (VTE)

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

It should also be considered that the risk of thromboembolic complications increases during pregnancy and in the first 6 weeks postpartum (see section "Use during pregnancy or breastfeeding").

Symptoms of venous thromboembolism (VTE)

Women should be informed that if symptoms of VTE occur, they should seek immediate medical attention and inform their healthcare provider about their use of COCs.

Symptoms of deep vein thrombosis (DVT) may include:

• Unilateral swelling of the leg and/or foot or 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 of unknown cause, possibly with hemoptysis;
• Acute chest pain;
• Syncope or dizziness;
• Rapid or irregular heartbeat.

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

Other signs of vascular embolism may include: sudden pain, swelling, and mild cyanosis of a limb.

In cases of ocular vascular embolism, symptoms may range from blurred vision (without pain), which may progress to vision loss. Sometimes, complete vision loss develops almost immediately.

Risk of arterial thromboembolism (ATE)

Epidemiological studies have shown an association between the use of COCs and an increased risk of arterial thromboembolic events (myocardial infarction) or cerebrovascular disorders (e.g., transient ischemic attack, stroke). Arterial thromboembolic events may be fatal.

Risk factors for arterial thromboembolism (ATE)

The risk of developing ATE or cerebrovascular disorders while using COCs increases in women with risk factors (see Table 2). Novinet is contraindicated in women with a single serious risk factor or multiple risk factors that place them in a high-risk category for arterial thromboembolism (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, so the overall risk of ATE should be considered. COCs should not be prescribed if the benefit-risk ratio is considered unfavorable (see section "Contraindications").

Table 2

Risk factors for arterial thromboembolism (ATE)

Arterial Thromboembolism (ATE) Symptoms

Women should be informed that if any of the symptoms listed below occur, they should seek immediate emergency medical attention and inform their healthcare provider about their use of COCs.

Symptoms of cerebrovascular accident (stroke) may include:

• sudden numbness of the face, weakness or numbness of extremities, especially on one side of the body;
• sudden difficulty walking, dizziness, loss of balance or coordination;
• sudden confusion, speech or comprehension disturbances;
• sudden vision impairment in one or both eyes;
• sudden severe or prolonged headache without apparent cause;
• loss of consciousness or syncope with or without seizures.

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

Symptoms of myocardial infarction may include:

• pain, discomfort, pressure, heaviness, squeezing or aching sensation in the chest, arm, or behind the breastbone;
• discomfort radiating to the back, lower jaw, throat, arm, or stomach;
• feeling of fullness, indigestion, or suffocation;
• excessive sweating, nausea, vomiting, or dizziness;
• severe weakness, restlessness, or shortness of breath;
• rapid or irregular heartbeat.

1. Tumors

Long-term use of oral contraceptives is known to be a risk factor for cervical cancer in women infected with human papillomavirus (HPV). However, this statement remains controversial, as it has not been definitively established to what extent study results account for the influence of confounding risk factors (e.g., differences in number of sexual partners or use of barrier contraceptive methods).

A meta-analysis of 54 international studies indicates a slight increase in relative risk (RR = 1.24) of developing breast cancer in women currently 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 current or recent users of COCs is small relative to the overall risk of breast cancer. The results of these studies do not provide evidence of a causal relationship. The increased risk may be due to earlier diagnosis of breast cancer in women using COCs, a biological effect of COCs, or a combination of both factors. A trend has been observed that malignant breast tumors detected in women who have ever used COCs are generally less clinically advanced than those in women who have never used COCs.

In rare cases, benign and even more rarely malignant liver tumors have been observed in women using COCs. In some cases, these tumors have 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 liver tumor should be considered in the differential diagnosis of women taking COCs.

1. Other conditions

Depressed mood and depression are common adverse reactions during use of hormonal contraceptives (see section "Adverse Reactions"). Depression can be severe and is a known risk factor for suicidal behavior and suicide. Women should be informed about the need to consult a physician if mood swings or symptoms of depression occur, even if they appear shortly after starting treatment.

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

In women with hypertriglyceridemia or a family history of hypertriglyceridemia, the possible increased risk of pancreatitis should be considered during COC use.

Although a slight increase in blood pressure has been observed in many women using COCs, clinically significant increases are rare. No association has been established between COC use and clinically significant hypertension. However, in cases of persistent clinically significant hypertension during COC use, discontinuation of COCs is advisable, and antihypertensive treatment should be initiated. COC use may be resumed if normal blood pressure values are achieved with antihypertensive therapy.

The occurrence or exacerbation of the following conditions has been reported during pregnancy and COC use, but their causal relationship with COC use has not been definitively proven: cholestatic jaundice and/or pruritus; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham's chorea; herpes gestationis; hearing loss associated with otosclerosis.

Acute or chronic liver function disorders may require discontinuation of COCs until liver function tests return to normal. Recurrence of cholestatic jaundice, which first occurred during pregnancy or previous use of sex steroid hormones, necessitates discontinuation of COCs.

Although COCs may affect peripheral insulin resistance and glucose tolerance, there are no data indicating the need to modify therapeutic regimens in women with diabetes who use COCs. However, diabetic women using COCs should be under close medical supervision.

An increased risk of developing nonspecific ulcerative colitis and Crohn's disease has been associated with COC use.

Chloasma may occasionally develop (especially in women with a history of chloasma during pregnancy). Women prone to chloasma should avoid exposure to sunlight or ultraviolet radiation during COC use.

The above information should be taken into account when choosing contraceptive method(s).

Medical examination/consultation

Before initiating or re-prescribing Novinet, a thorough medical history (including family history) should be taken and pregnancy should be ruled out. Blood pressure should be measured, and a physical examination should be performed, guided by information on contraindications (see section "Contraindications") and special warnings and precautions (see section "Special Warnings and Precautions").

It is important to inform women about the risk of venous and arterial thrombosis, including the risk associated with Novinet compared to other COCs, symptoms of VTE and ATE, established risk factors, and necessary actions in case of suspected thrombosis. Women should be advised to carefully read the package leaflet and follow the recommendations provided. The frequency and nature of follow-up examinations should be based on current medical practice guidelines, taking into account individual characteristics of each woman.

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

Reduced contraceptive efficacy

The effectiveness of COCs may be reduced in case of missed tablets, 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").

Due to the risk of decreased plasma concentration of Novinet and reduced clinical effects, concomitant use with herbal preparations containing St. John's wort (Hypericum perforatum) should be avoided (see section "Interaction with Other Medicinal Products and Other Forms of Interaction").

Menstrual cycle control

Irregular bleeding (spotting or breakthrough bleeding), particularly during the first months of use, may occur during use of any COCs. Therefore, evaluation of any irregular bleeding is meaningful only after an adaptation period of approximately three cycles.

If irregular bleeding recurs or develops after previous regular cycles, non-hormonal causes of these conditions should be considered and malignancies or pregnancy should be excluded. Diagnostic curettage may be performed.

In some women, withdrawal bleeding may not occur during the tablet-free interval of oral contraceptives. If the woman has used COCs according to the instructions described in the section "Dosage and Administration," pregnancy is unlikely. However, if COCs have been used irregularly before the absence of the first withdrawal bleeding, or if withdrawal bleeding is absent for two consecutive cycles, pregnancy must be excluded before continuing COC use.

Novinet contains lactose. Women with rare hereditary conditions such as galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption syndrome should not take this medicinal product.

Use during pregnancy or breastfeeding

Pregnancy

Novinet is not indicated during pregnancy. Before initiating Novinet, pregnancy must be excluded. If pregnancy occurs during use of Novinet, treatment should be discontinued immediately.

According to results of epidemiological studies, the frequency of congenital anomalies in newborns whose mothers took oral contraceptives before pregnancy does not exceed the normal rate. Moreover, no teratogenic effect has been observed when oral contraceptives were taken during early pregnancy.

When re-prescribing Novinet, the increased risk of VTE in the postpartum period should be taken into account (see sections "Dosage and Administration" and "Special Warnings and Precautions").

Lactation

Oral contraceptives may reduce the quantity and alter the composition of breast milk. Furthermore, this group of drugs passes into breast milk (although there is no evidence of adverse effects on infant health). Therefore, the use of Novinet in breastfeeding women is not recommended.

Small amounts of steroid hormones and/or their metabolites may pass into breast milk, but there is no evidence of adverse effects on infant health.

Ability to influence reaction speed when driving or operating machinery

No effect of COCs on the ability to drive or operate machinery has been observed.

Method of Administration and Dosage

Dosage

Begin taking tablets on the first day of the menstrual cycle, taking 1 tablet daily for 21 consecutive days, preferably at the same time each day. Then, a 7-day break should be taken, during which withdrawal bleeding usually occurs. On the day following the 7-day break (i.e., 4 weeks after starting the first tablet, on the same day of the week), resume taking the medication from the next blister pack, which also contains 21 tablets, even if bleeding has not stopped. This regimen should be followed continuously as long as contraception is needed. When instructions are followed correctly, contraceptive efficacy is maintained throughout the 7-day tablet-free interval.

Tablets must be taken orally, in the order indicated on the blister pack.

First Use of Novinet

If no hormonal contraceptives were used in the previous month

The first Novinet tablet should be taken on the first day of the menstrual cycle. In this case, additional contraceptive methods are not required.

Alternatively, tablet intake may begin on days 2 to 5 of menstruation. However, in this case, additional (barrier) contraceptive methods should be used during the first 7 days of tablet intake in the first cycle.

If more than 5 days have passed since the onset of menstruation, the start of Novinet should be postponed until the next menstrual period.

Switching from a combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring, or transdermal patch)

It is recommended that a woman start taking Novinet tablets the day after taking the last active tablet of the previous COC. In such cases, Novinet should not be started later than the day after the usual tablet-free interval or after taking the last inactive tablet of the previous COC. When switching from a vaginal ring or transdermal patch, Novinet should preferably be started on the day of removal of the previous product; in such cases, Novinet intake should not begin later than the scheduled replacement date.

If the previous contraceptive method was used correctly and pregnancy has been ruled out, switching methods can be done at any time during the cycle. However, the recommended tablet-free interval of the previously used contraceptive should not be exceeded.

Switching from other progestogen-only contraceptives (‘mini-pill’, injections, implants) or from an intrauterine system containing progestogen

A woman currently taking a ‘mini-pill’ (progestogen-only pill) may start taking Novinet at any time. For an implant or intrauterine system, Novinet should be started on the day of removal. For injectable contraceptives, Novinet should be started instead of the next scheduled injection. However, in all these cases, an additional contraceptive method should be used during the first 7 days of tablet intake.

After first-trimester abortion

Novinet should be started immediately on the same day as the procedure or miscarriage. In this case, additional contraceptive methods are not required.

After childbirth or second-trimester abortion

For women who are not breastfeeding, oral contraceptive use should begin on days 21–28 after childbirth or second-trimester abortion. Additional contraceptive methods are not required in this case.

If Novinet is started later than day 28, additional contraceptive methods should be used during the first 7 days of tablet intake.

If sexual intercourse has already occurred after childbirth, tablet intake should be postponed until the first menstrual period.

Note: Women who are breastfeeding should not take COCs, as this may reduce the quantity of breast milk (see section "Use during pregnancy or breastfeeding").

Missed tablets

If less than 12 hours have passed since a missed tablet, contraceptive protection is not reduced. The missed tablet should be taken as soon as possible, and then continue taking the tablets at the usual time.

If more than 12 hours have passed since a missed tablet, contraceptive efficacy may be reduced. In case of a missed tablet, two main rules should be observed:

1. Do not interrupt tablet intake for more than 7 days.
2. Seven consecutive days of uninterrupted use are required to adequately suppress the hypothalamic-pituitary-ovarian system.

Accordingly, the following recommendations should be followed:

Week 1

Take the missed tablet as soon as possible, even if this means taking two tablets at the same time. Then continue taking tablets at the usual time. In addition, a barrier method of contraception (e.g., condom) should be used for the next 7 days. If sexual intercourse occurred in the previous 7 days, the possibility of pregnancy should be considered. The greater the number of missed tablets and the closer the missed doses are to the tablet-free interval, the higher the risk of pregnancy.

Week 2

Take the missed tablet as soon as possible, even if this means taking two tablets at the same time. Then continue taking tablets at the usual time. If tablets were taken correctly during the 7 days prior to the missed tablet, no additional contraceptive measures are needed. However, if more than one tablet was missed or if the 7-day rule was not followed, an additional contraceptive method should be used for 7 days.

Week 3

The risk of reduced contraceptive efficacy is inevitable due to the proximity of the tablet-free interval. However, this can be prevented by adjusting the tablet-taking schedule. If all tablets were taken correctly during the 7 days prior to the missed tablet, no additional contraceptive measures are needed, provided one of the two options below is followed. Otherwise, the first option should be used, along with an additional contraceptive method for 7 days.

1. Take the missed tablet as soon as possible, even if this means taking two tablets at the same time. Then continue taking tablets at the usual time. Immediately after finishing the current blister pack, start a new one without a break. Menstrual bleeding during the second pack is unlikely, but spotting or breakthrough bleeding may occur during tablet intake.
2. Alternatively, the woman may stop taking tablets from the current blister pack. In this case, a 7-day break should be observed (including the days when tablets were missed), after which a new blister pack should be started.

If a woman misses tablets and withdrawal bleeding does not occur during the first tablet-free interval, pregnancy should be considered.

Recommendations in case of gastrointestinal disturbances

In case of severe gastrointestinal disturbances, absorption of the drug may be incomplete, and additional contraceptive methods should be used.

If vomiting occurs within 3–4 hours after taking a tablet, follow the recommendations for missed tablets outlined in the section "Missed tablets" (see above). If a woman does not wish to alter her usual tablet-taking schedule, she should take an additional tablet(s) from another blister pack.

Postponing or shifting the menstrual cycle

Delaying the menstrual cycle is not an approved indication for this drug. However, in exceptional cases where menstrual delay is desired, the woman should continue taking tablets from a new Novinet blister pack without the scheduled break. This delay can continue as long as desired, until the tablets in the second blister pack are finished. During this period, spotting or breakthrough bleeding may occur. After a planned 7-day break, regular use of Novinet can be continued.

To shift the onset of menstruation to another day of the week, it is recommended to shorten the tablet-free interval by the desired number of days. The shorter the break, the higher the risk that withdrawal bleeding will not occur, and spotting or breakthrough bleeding may occur during the next pack (during the delayed menstruation period).

Children. The safety and efficacy of desogestrel in adolescents under 18 years of age have not been established. No data are available.

Overdose

No serious adverse reactions have been reported with overdose of oral contraceptives. Possible symptoms may include nausea, vomiting, and slight vaginal bleeding in young girls. Overdose does not require specific treatment. However, if overdose is detected within 2–3 hours or if a large number of tablets have been ingested, gastric lavage may be performed. There is no specific antidote; symptomatic therapy should be administered.

Adverse reactions.

Description of selected adverse reactions

An increased risk of developing arterial and venous thrombotic and thromboembolic complications, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary embolism, has been observed in women using combined oral contraceptives. More detailed information is provided in the section "Special precautions".

In addition, other adverse events observed during use of COCs include arterial hypertension, hormone-dependent neoplasms (e.g., liver tumors, breast tumors), and chloasma, as described in detail in the section "Special precautions".

As with use of any COCs, changes in the pattern of menstrual bleeding may occur, particularly during the first month of use. Changes in frequency (complete cessation, decreased or increased frequency), intensity (decreased or increased), or duration of bleeding may be observed.

Adverse reactions reported in women taking COCs containing 0.15 mg desogestrel and 0.02 mg ethinylestradiol (as in the drug Novinet), as well as general adverse reactions associated with COCs, are listed in the table below³. All adverse reactions are classified by system organ class and frequency of occurrence: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), and frequency not known (cannot be estimated from available data).

3The most appropriate MedDRA term has been used to describe specific adverse reactions. Synonyms or conditions related to the adverse reaction are not listed, but should be considered.

Interactions

Breakthrough bleeding and/or contraceptive failure may result from interactions between oral contraceptives and other medicinal products that induce microsomal enzymes (see section "Interaction with other medicinal products and other forms of interaction").

Reporting of suspected adverse reactions

Reporting suspected adverse drug reactions after authorization is important, as it allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report any suspected adverse reactions via the national reporting system.

Shelf life.

3 years.

Storage conditions. Store at temperatures not above 30 °C .

Keep out of the reach of children.

Packaging. 21 (21×1) tablets in a blister; 1 (21×1) or 3 (21×3) blisters in a cardboard box. A flat cardboard case for storing the blister is included in the cardboard box.

Prescription status.

Prescription only.

Manufacturer.

JSC "Gedeon Richter".

Manufacturer's location and address of its place of business.

H-1103, Budapest, Dózsa György út 19–21, Hungary.

Marketing authorization holder.

JSC "Gedeon Richter".

Address of the marketing authorization holder.

H-1103, Budapest, Dózsa György út 19–21, Hungary.