Lactinet film-coated tablets 0.075 mg No. 28

Instructions for Lactinet film-coated tablets 0.075 mg No. 28

Composition

active ingredient: desogestrel;

1 film-coated tablet contains 0.075 mg of desogestrel;

excipients: alpha-tocopherol, colloidal anhydrous silicon dioxide, stearic acid, povidone K-30, potato starch, lactose monohydrate; shell composition: Opadry II 85F28751 white: talc, macrogol 3000, titanium dioxide, E 171, polyvinyl alcohol.

Dosage form

Film-coated tablets.

Main physicochemical properties: round biconvex tablets, film-coated, white or almost white in color, approximately 5.5 mm in diameter, marked “D” on one side and “75” on the other side.

Pharmacotherapeutic group

Hormonal contraceptives for systemic use, progestogens. ATC code G03A C09.

Pharmacological properties

Pharmacodynamics.

Mechanism of action

Lactinet®-Richter film-coated tablets are a contraceptive containing only the progestogen desogestrel. Like other progestogen-only contraceptives, Lactinet®-Richter can be used in women who cannot or do not want to take estrogens. In contrast to conventional progestogen-only contraceptives, the contraceptive effect of Lactinet®-Richter film-coated tablets is achieved mainly by inhibiting ovulation. Other effects include increasing the viscosity of cervical mucus.

Clinical efficacy and safety

In a study conducted over 2 cycles, where ovulation was confirmed by a progesterone level of more than 16 nmol/l for 5 consecutive days, ovulation was detected in 1% (1/103) with a 95% confidence interval of 0.02% to 5.29% in the group that started taking the drug (users and those for whom the method was unsuccessful). Suppression of ovulation was observed from the first cycle of use of the drug. In this study, after discontinuation of desogestrel 0.075 mg tablets, which were used for 2 cycles (56 consecutive days), ovulation was observed on average after the 17th day (range 7 to 30 days).

According to the comparative efficacy study (missed tablets allowed to be taken up to 3 hours after the usual time), in the group that started taking the drug, the Pearl index value for desogestrel tablets 0.075 mg was 0.4 (95% CI 0.09–1.2) compared to 1.6 for 30 μg levonorgestrel (95% CI 0.42–3.96).

Thus, the Pearl index for desogestrel 0.075 mg tablets is comparable to that established for COCs in the general COC-using population.

The use of desogestrel tablets 0.075 mg leads to a decrease in estradiol levels to values corresponding to the early follicular phase. No clinically significant effects on carbohydrate metabolism, lipid metabolism and hemostasis were detected.

Children

There are no clinical trial data on efficacy and safety in adolescents under 18 years of age.

Pharmacokinetics.

Absorption

After oral administration of Lactinet®-Richter, film-coated tablets of desogestrel are rapidly absorbed and metabolized to etonogestrel. At steady state, the maximum plasma concentration is reached 1.8 hours after tablet administration; the absolute bioavailability of etonogestrel is approximately 70%.

Distribution

Etonogestrel is 95.5 - 99% bound to plasma proteins, mainly to albumin and to a lesser extent to sex hormone binding globulin (SHBG).

Biotransformation

Desogestrel is metabolized by hydroxylation and dehydrogenation to the active metabolite etonogestrel. Etonogestrel is primarily metabolized by the cytochrome P450 3A isoenzyme (CYP3A) with subsequent formation of sulfate and glucuronide conjugates.

Breeding

The mean elimination half-life of etonogestrel is approximately 30 hours, regardless of whether it was administered repeatedly or once. Steady-state plasma levels are reached after 4 to 5 days. With intravenous administration of etonogestrel, plasma clearance is approximately 10 l/h. Etonogestrel and its metabolites are excreted in the form of free steroids or conjugates with urine and feces (in a ratio of 1.5:1). In lactating women, etonogestrel penetrates into breast milk at a ratio of 0.37 to 0.55 milk/blood plasma. Taking into account these data, as well as the fact that the child consumes 150 ml of milk per kg of body weight per day, she can receive about 0.01 to 0.05 micrograms of etonogestrel per day.

Special patient groups

Kidney dysfunction

Studies of the pharmacokinetics of desogestrel in patients with renal disease have not been conducted.

Liver dysfunction

The pharmacokinetics of desogestrel have not been studied in patients with liver disease. However, it should be borne in mind that the metabolism of steroid hormones may be impaired in patients with impaired liver function.

Ethnic groups

Comparison of desogestrel pharmacokinetics in different ethnic groups has not been performed.

Indication

Contraception.

Contraindication

Thromboembolic venous diseases in the active phase.

Past or present serious liver diseases until liver function tests normalize.

Diagnosed or suspected malignant hormone-dependent neoplasms.

Hypersensitivity to the active substance or to any of the excipients of Lactinet®-Richter.

Interaction with other medicinal products and other types of interactions

Interactions

Note: The information for the concomitant medicinal product should be consulted for potential interactions.

The effect of other drugs on Lactinet®-Richter.

Interaction with drugs that induce microsomal enzymes is possible, as a result of which the clearance of sex hormones may increase, which, in turn, will lead to "breakthrough" bleeding and/or loss of contraceptive effectiveness.

Therapy

Enzyme induction can be observed after a few days of administration. Maximum enzyme induction is generally observed after a few weeks. After drug withdrawal, enzyme induction may persist for up to 4 weeks.

Short-term treatment

Women taking medicinal and herbal remedies that induce liver enzymes should be informed that the effectiveness of Lactinet®-Richter may be reduced and should temporarily use a barrier method of contraception in addition to Lactinet®-Richter. The barrier method of contraception should be used throughout the entire period of treatment with the liver enzyme-inducing drug and for 28 days after its discontinuation.

Long-term treatment

Women on long-term therapy with drugs that induce liver enzymes are recommended to use another method of contraception that is not affected by drugs that induce liver enzymes.

Substances that increase the clearance of sex hormones (reduced contraceptive efficacy due to enzyme induction), e.g. barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, efavirenz and possibly felbamate, griseofulvin, oxcarbazepine, topiramate, rifabutin and preparations containing the herbal component St. John's wort (Hypericum perforatum).

Substances with inconsistent effects on the clearance of contraceptive hormones

When used concomitantly with hormonal contraceptives, many combinations of HIV protease inhibitors (e.g., ritonavir, nelfinavir) and non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine) and/or combinations with hepatitis C virus (HCV) drugs (e.g., boceprevir, telaprevir) may increase or decrease plasma concentrations of progestins. The net effect of these changes may be clinically significant in some cases.

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

Substances that reduce the clearance of sex hormones (enzyme inhibitors)

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

The effect of Lactinet®-Richter on other medicines.

Hormonal contraceptives can affect the metabolism of other drugs. Accordingly, their concentration in blood plasma and tissues can either increase (e.g., cyclosporine) or decrease (e.g., lamotrigine).

Application features.

Physical examination

Before prescribing the drug, it is necessary to carefully collect anamnesis and conduct a gynecological examination to exclude a possible pregnancy. Before prescribing, the causes of menstrual cycle disorders (oligomenorrhea and amenorrhea) should be clarified. The frequency of repeated examinations is determined by the doctor individually for each patient. If there is a possibility of influencing the course of a latent or overt disease during the administration of the drug (see the section "Peculiarities of use"), appropriate regular control examinations should be scheduled.

Despite regular use of Lactinet®-Richter, dysfunctional bleeding may occur. If bleeding occurs very frequently and irregularly, another method of contraception should be considered. If symptoms persist, functional disorders should be excluded.

Control of amenorrhea during treatment depends on adherence to pill instructions and may include a pregnancy test.

In case of pregnancy, the drug should be discontinued.

The woman should be warned that Lactinet®-Richter does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Warning.

In general, the risk of developing breast cancer increases with age. During the use of combined oral contraceptives (COCs), the risk of developing breast cancer is slightly increased. This increased risk gradually decreases during the 10 years after stopping COCs, but it is not related to the duration of COC use, but to the age of the woman taking the COC. The expected number of cases diagnosed per 10,000 women who used COCs (up to 10 years after stopping use) compared with those who had never used COCs during the same period has been calculated for the relevant age groups and is presented in the table below.

The risk in women taking progestogen-only oral contraceptives (COCs) such as Lactinet®-Richter is likely to be similar to that observed in women taking COCs. However, the data for COCs are inconclusive. Compared with the lifetime risk of developing breast cancer, the risk with COC use is low. In women taking COCs, cancer is usually diagnosed at an earlier stage than in non-users. The increased risk in women taking COCs may be explained by earlier diagnosis, the biological action of the pill, or a combination of both.

Since a biological effect of progestogen on the development of liver cancer cannot be excluded, the benefit/risk ratio should be assessed individually in women with liver cancer.

In case of acute or chronic liver dysfunction, the woman should be referred for examination and consultation with an appropriate specialist.

Epidemiological studies have shown that COC use is associated with an increased incidence of venous thromboembolism (VTE, deep vein thrombosis and pulmonary embolism). Although the clinical relevance of this finding for desogestrel, which is used in non-estrogenic contraceptives, is unknown, Lactinet®-Richter should be discontinued if thrombosis develops. Lactinet®-Richter should be discontinued in cases of prolonged immobilisation due to surgery or illness.

Women with a history of thromboembolic disease should be informed about possible recurrences.

Although progestogens may affect tissue insulin resistance and glucose tolerance, there is currently no evidence to suggest that diabetic patients taking progestogen-only contraceptives should be given a different treatment regimen. However, diabetic patients should be closely monitored during the first month of use.

If persistent arterial hypertension develops during the use of Lactinet®-Richter or if significantly elevated blood pressure does not decrease in response to antihypertensive therapy, discontinuation of Lactinet®-Richter should be considered.

Administration of Lactinet®-Richter results in a decrease in serum estradiol concentrations to levels corresponding to the early follicular phase. It is not yet known whether this decrease has a clinically significant effect on bone mineral density.

Progestogen-only contraceptives are not as effective in preventing ectopic pregnancy as combined oral contraceptives. This is because ovulation occurs more frequently with progestogen-only contraceptives. Despite the fact that Lactinet®-Richter consistently inhibits ovulation, the possibility of pregnancy should be considered in the differential diagnosis if a woman complains of amenorrhea or abdominal pain.

In rare cases, chloasma may occur, especially in women with a history of chloasma during pregnancy. Women prone to chloasma should avoid exposure to the sun and ultraviolet radiation while taking Lactinet®-Richter.

The following diseases have been reported both during pregnancy and during the use of sex steroid hormones, the relationship of which to the use of progestogens has not been established: jaundice and/or itching associated with cholestasis; gallstone formation; porphyria; systemic lupus erythematosus, hemolytic-uremic syndrome; Sydenham's chorea; herpes gestationis; hearing loss associated with otosclerosis; (hereditary) angioedema.

The effectiveness of Lactinet®-Richter may be reduced in the event of missed tablets (see section "Method of administration and dosage"), gastrointestinal disorders (see section "Method of administration and dosage") or with the simultaneous use of certain drugs that change the plasma concentration of etonogestrel, the active metabolite of desogestrel (see section "Interaction with other medicinal products and other types of interactions").

Lactinet®-Richter, film-coated tablets contain 52.34 mg of lactose monohydrate and should therefore not be used in patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Laboratory tests.

There have been reports of the effects of COCs on certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, serum levels of proteins (carriers) such as corticosteroid-binding globulin and lipid/lipoprotein fractions, and parameters of carbohydrate metabolism, coagulation and fibrinolysis. The changes usually remain within normal limits. It is not known to what extent this applies to progestogen-only contraceptives.

Use during pregnancy or breastfeeding

Pregnancy

Lactinet®-Richter is not indicated for use during pregnancy. If pregnancy occurs in women using Lactinet®-Richter, the drug should be discontinued immediately.

Animal studies have shown that very high doses of compounds with progestogenic activity can lead to masculinization of female offspring.

Extensive epidemiological studies have not revealed an increased risk of congenital malformations in children born to women who used COCs before pregnancy, nor a teratogenic effect in the event of inadvertent use of COCs in early pregnancy. Pharmacovigilance data on various COCs containing desogestrel also do not indicate any increased risk.

Breastfeeding period

According to clinical data, desogestrel tablets 0.075 mg do not affect the production of breast milk and its quality (protein, lactose or fat concentration). However, according to infrequent post-marketing reports, a decrease in breast milk production was observed during the use of desogestrel tablets 0.075 mg. Small amounts of etonogestrel (a metabolite of desogestrel) penetrate into breast milk. As a result, the child may receive 0.01-0.05 micrograms of the drug per kg of body weight per day (based on an approximate milk consumption of 150 ml/kg/day). Like other progestogen-only preparations, Lactinet®-Richter can be used during breastfeeding.

There are limited data from long-term studies on children whose mothers started taking desogestrel 0.075 mg tablets between 4 and 8 weeks postpartum. They were breastfed for up to 7 months and followed up for up to 1.5 years (n = 32) or 2.5 years (n = 14). Assessment of growth, physical and psychomotor development did not reveal any differences compared to infants whose mothers used a copper intrauterine system (IUD). Based on the available data, Lactinet®-Richter can be used during breastfeeding. However, the growth and development of the child whose mother uses Lactinet®-Richter should be closely monitored.

Fertility

Lactinet®-Richter is intended for the prevention of pregnancy. For information on restoring fertility (ovulation), see the Pharmacodynamics section.

Ability to influence reaction speed when driving vehicles or other mechanisms

The drug Lactinet®-Richter has no or negligible influence on the ability to drive and use machines.

Method of administration and doses

Dosage

To achieve effective contraception, Lactinet®-Richter should be used according to the instructions (see “How to take Lactinet®-Richter” and “How to start taking Lactinet®-Richter”).

Special patient groups

Kidney dysfunction

Clinical studies have not been conducted in patients with renal impairment.

Liver dysfunction

Clinical studies in patients with impaired liver function have not been conducted. In severe liver dysfunction, the metabolism of steroid hormones may be impaired, therefore, in such cases, Lactinet®-Richter should be prescribed only after normalization of liver function tests (see section "Contraindications").

Method of application.

Intended for oral administration.

How should you take Lactinet®-Richter?

The tablets should be taken every day, at about the same time, so that the interval between taking two tablets is always 24 hours. The first tablet should be taken on the first day of menstrual bleeding. Then you should continue to take one tablet per day, regardless of possible bleeding. A new blister pack should be started the day after the tablets from the previous pack are finished.

How should you start taking Lactinet®-Richter?

Tablet-taking should be started on the first day of the woman's natural menstrual cycle (the first day is the first day of menstrual bleeding). It is allowed to start taking the drug on the 2nd-5th day of the cycle, however, during the first cycle it is recommended to use a barrier method of contraception for the first 7 days of tablet-taking.

After an abortion in the first trimester.

It is recommended to start taking the pills immediately after an abortion in the first trimester. In this case, there is no need to use additional contraceptive methods.

After childbirth or abortion in the second trimester.

It is advisable to start taking the drug on the 21st-28th day after childbirth or termination of pregnancy in the 2nd trimester. Women who start taking the pills later should additionally use barrier methods of contraception during the first 7 days of taking the drug. If there was unprotected sexual intercourse before starting to take the drug, pregnancy must be excluded or wait for the first menstrual bleeding before taking the first tablet of Lactinet®-Richter. For additional information on the use of the drug during breastfeeding, see the section “Use during pregnancy or breastfeeding”.

How to start using Lactinet®-Richter after using other methods of contraception.

Switching from combined hormonal contraceptives (combined oral contraceptives (COCs), contraceptive vaginal rings or transdermal contraceptive patches).

The woman should start taking Lactinet®-Richter the day after taking the last active tablet of the COC (the last tablet containing the active substance) or on the day of removal of the contraceptive vaginal ring or transdermal contraceptive patch. In these cases, the use of additional methods of contraception is not required.

A woman can also start taking the drug no later than the day after the end of the break in taking contraceptive pills or using patches or rings, or after the placebo tablet period of her previous combined hormonal contraceptive, but it is recommended to additionally use a barrier method of contraception during the first 7 days of tablet-taking.

Switching from progestogen-only pills (mini-pills, injections, implants) or from a progestogen-releasing intrauterine system (IUD).

A woman can switch from the mini-pill on any day (from an implant or IUD on the day of their removal, from injectable forms of the drug on the day of the next scheduled injection).

Procedure in case of missing the time of drug administration.

Contraceptive protection may be reduced if more than 36 hours have passed between taking two tablets. If less than 12 hours have passed since the missed tablet, the woman should take the missed tablet as soon as she remembers, and the next tablet should be taken at the usual time. If more than 12 hours have passed since the missed tablet, the woman should use an additional method of contraception for the next 7 days. If the tablet was missed during the first week after starting Lactinet®-Richter and the woman had sexual intercourse during the week preceding the missed tablet, the possibility of pregnancy should be considered.

Recommendations in case of gastrointestinal disorders.

In case of severe gastrointestinal disorders, absorption of the active substance may be incomplete, therefore additional contraceptive measures must be taken.

If vomiting occurs within 3-4 hours of taking the tablet, the drug may not be fully absorbed. Since this situation is similar to missing a dose, in such situations the instructions for taking missed tablets given in the section "What to do if you miss a dose" should be followed.

Children.

The safety and efficacy of Lactinet®-Richter in adolescents under 18 years of age have not been established. There are no data on the use of the drug in this age group.

Overdose

There have been no reports of serious adverse effects from overdose. In case of overdose, the following symptoms are observed: nausea, vomiting, and in young girls - slight vaginal bleeding. There is no antidote, symptomatic treatment is recommended.

Adverse reactions

In clinical trials, the most frequently reported adverse reaction was irregular bleeding. Approximately 50% of women using desogestrel, tablets 0.075 mg, reported acyclic bleeding. Since desogestrel, tablets 0.075 mg, unlike other progestogen-only contraceptives, leads to ovulation suppression in almost 100% of cases, irregular bleeding occurs more often with its use than with other progestogen-only contraceptives. In 20-30% of women, bleeding becomes more frequent, while in another 20% it becomes less frequent or may even stop altogether. Vaginal bleeding may also become longer.

In clinical trials with desogestrel 0.075 mg tablets, the most commonly reported adverse reactions (>2.5%) were acne, mood changes, breast pain, nausea and weight gain. The adverse reactions are listed in the table below.

Adverse reactions are classified by frequency and system organ class: common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (<1/1000) and frequency unknown (cannot be estimated from the available data).

The following side effects may occur when using Lactinet®-Richter: breast discharge and rarely ectopic pregnancy (see section "Special precautions for use"). In addition, exacerbation of hereditary angioedema is possible (see section "Special precautions for use").

A number of (serious) adverse reactions have been reported in women taking (combined) oral contraceptives. These include venous and arterial thromboembolism, hormone-dependent neoplasms (e.g. liver tumours, breast cancer) and chloasma, some of which are discussed in detail in the section "Special warnings and precautions for use".

Breakthrough bleeding and/or loss of contraceptive efficacy may occur due to the interaction of other drugs (microsomal enzyme inducers) with hormonal contraceptives (see section "Interaction with other drugs and other types of interactions").

Reporting of suspected adverse reactions

It is important to receive reports of suspected adverse reactions after a medicinal product has been authorised. This allows monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national adverse reaction reporting system.

Expiration date

2 years.

Storage conditions

The medicine does not require special temperature storage conditions.

Store in the original packaging to protect from light and moisture.

Keep the medicine out of the reach of children!

Packaging

28 film-coated tablets in a blister; each blister is placed in a laminated aluminum foil bag; 1 or 3 laminated bags together with a cardboard case for storing the blister in a cardboard box with instructions for medical use.

Vacation category

According to the recipe.

Producer

JSC "Gedeon Richter".

Location of the manufacturer and address of its place of business.

H-1103, Budapest, Demrei Street 19-21, Hungary.

Address

H-1103, Budapest, Demrei Street 19-21, Hungary.