Desirette film-coated tablets 0.075 mg blister No. 28

Instructions for Desirette film-coated tablets 0.075 mg blister No. 28

Composition

active ingredient: desogestrel;

1 tablet contains desogestrel 0.075 mg;

excipients: lactose monohydrate, corn starch, povidone, α-tocopherol, colloidal anhydrous silicon dioxide, colloidal aqueous silicon dioxide, stearic acid;

shell: hypromellose, polyethylene glycol, titanium dioxide (E 171).

Dosage form

Film-coated tablets.

Main physicochemical properties: round, smooth white tablets.

Pharmacotherapeutic group

Hormonal contraceptives for systemic use.

ATX code G03A C09.

Pharmacological properties

Pharmacodynamics.

Mechanism of action

DESIRETTE is a contraceptive that contains only the progestogen desogestrel. Like other progestogen-only contraceptives, DESIRETTE can be used in women who cannot or do not want to use estrogens. Unlike conventional progestogen-only contraceptives, the contraceptive effect of DESIRETTE is achieved primarily by inhibiting ovulation. Other effects include increasing the viscosity of cervical mucus.

Pharmacokinetics.

Absorption. After oral administration, desogestrel is rapidly absorbed and converted to its biologically active metabolite etonogestrel. After reaching steady state, peak serum levels are reached 1.8 hours after oral administration. The absolute bioavailability of etonogestrel is approximately 70%.

Distribution: Etonogestrel is 95.5-99% bound to serum proteins (mainly albumin) and to a lesser extent to sex hormone binding globulin.

Metabolism: Desogestrel is metabolized by hydroxylation and dehydrogenation to the active metabolite etonogestrel. Etonogestrel is metabolized primarily by the cytochrome P450 3A isoenzyme (CYP3A), followed by conjugation to form sulfate and glucuronide conjugates.

Elimination. The half-life of etonogestrel is approximately 30 hours after both single and multiple doses. Steady-state plasma levels are reached after 4-5 days. Serum clearance after intravenous administration of etonogestrel is approximately 10 liters per hour. Etonogestrel and its metabolites are excreted in urine and feces, both as free steroid and as conjugates (in a ratio of 1.5:1). In lactating women, etonogestrel is excreted in breast milk at a ratio of 0.37-0.55 milk/plasma. Based on these data and an estimated milk intake of 150 ml/kg/day, the infant may receive 0.01-0.05 micrograms of etonogestrel.

Certain patient groups

Patients with renal impairment

Studies of the effect of renal disease on the pharmacokinetics of desogestrel have not been conducted.

Patients with liver dysfunction

Studies on the effect of liver disease on the pharmacokinetics of desogestrel have not been conducted. However, in women with impaired liver function, the metabolism of sex hormones may be impaired.

Ethnic groups

Pharmacokinetic studies in ethnic groups have not been conducted.

Indication

Oral contraception.

Contraindication

Hypersensitivity to any component of the drug.

Established or suspected pregnancy.

Acute venous thromboembolic disorders.

Severe liver disease (current or history, until liver function tests normalize).

Known or suspected malignant tumors sensitive to sex hormones.

Vaginal bleeding of unknown etiology.

Interaction with other medicinal products and other types of interactions

Remark

It is necessary to carefully read the instructions for use of the concomitant medication to identify possible interactions.

Interactions between hormonal contraceptives (HCs) and other medicinal products may lead to breakthrough bleeding and/or loss of contraceptive protection. The following interactions have been reported (mainly with combined oral contraceptives (COCs), but sometimes also with progestogen-only contraceptives).

Hepatic metabolism

Interactions may occur with drugs or herbal products that induce microsomal enzymes, particularly P450 (CYP) enzymes, leading to increased clearance of sex hormones and may reduce the effectiveness of oral contraceptives (OCs), including DESIRETTE. These drugs include phenytoin, phenobarbital, primidone, bosentan, carbamazepine, rifampicin, oxicarbazepine, topiramate, felbamate, griseofulvin, some HIV protease inhibitors (e.g. ritonavir), non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz) and drugs containing the herbal component St. John's wort Hypericum perforatum.

When used concomitantly with PC, many combinations of HIV protease inhibitors (e.g. nelfinavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine), combinations with anti-hepatitis C virus drugs (e.g. boceprevir, telaprevir) may increase or decrease plasma concentrations of progestins, including etonogestrel, the active metabolite of desogestrel. The net effect of these changes may be clinically significant in some cases. Therefore, the prescribing information for the concomitant medicinal product for the treatment of HIV or hepatitis C virus infection should be consulted to assess the potential for interactions and to make any appropriate recommendations. In case of any doubt, women receiving treatment with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor should use an additional barrier method of contraception.

Women taking any of these drugs or herbal remedies that induce liver enzymes should be aware that the effectiveness of DESIRETTE may be reduced. When taking drugs that stimulate microsomal enzymes, a barrier method should be used in addition to DESIRETTE throughout the entire period of use of the drug that stimulates microsomal enzymes and for 28 days after its discontinuation.

In case of long-term treatment with enzyme-stimulating drugs, an alternative method of contraception that is not affected by them should be considered.

Concomitant use of DESIRETTE 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.

When activated charcoal is used, the absorption of the steroid contained in the tablet may be reduced, which may reduce the contraceptive efficacy of the drug. In this case, the recommendations for missing tablets should be followed (see "What to do if you miss a tablet").

GCs may affect the metabolism of other drugs. Accordingly, plasma and tissue concentrations may increase (e.g., cyclosporine) or decrease (e.g., lamotrigine).

Application features

Medical examination

Before prescribing the drug, a gynecological examination should be performed to exclude 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 the drug, 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.

Treatment of amenorrhea during the contraceptive pill period depends on adherence to the pill instructions and may include a pregnancy test. In case of pregnancy, the pill should be discontinued.

Women should be informed that DESIRETTE does not protect against HIV infections (AIDS) and other sexually transmitted diseases.

Warning

If any of the conditions/risk factors listed below occur, the benefits of using a progestogen should be weighed against the possible risks for each individual woman and discussed with her before she decides to start taking DESIRETTE. In the event of worsening, exacerbation of the disease or the first occurrence of any of these conditions, the woman should consult her doctor about possible discontinuation of the drug.

The risk of breast cancer generally increases with age. The risk of breast cancer being diagnosed is somewhat increased during the use of combined oral contraceptives. This increased risk gradually disappears within 10 years after stopping combined oral contraceptives and is not related to the duration of previous use but depends on the age at which the woman started using combined oral contraceptives. For the relevant age groups, the expected number of cases of breast cancer diagnosed among 10,000 women who used combined oral contraceptives (during the period up to 10 years after stopping their use) compared with women who had never used them (during the same period) has been calculated. The number of these cases is shown in Table 1.

Table 1

The risk in users of progestogen-only COCs may be similar to that in users of combined COCs. However, the data for progestogen-only COCs are inconclusive. The risk of breast cancer associated with COC use is small compared with the lifetime risk of breast cancer. Breast cancer diagnosed in women who have used COCs may grow less rapidly than cancer diagnosed in women who have never used COCs. The increased risk in women who use COCs may be due to earlier diagnosis, the biological effects of the drug, or a combination of these two factors.

Since a biological effect of progestogens on liver cancer cannot be excluded, the individual risk-benefit ratio for women with liver cancer must be considered.

In case of acute or chronic liver dysfunction, a woman should consult a specialist for examination and consultation.

If persistent hypertension develops while taking DESIRETTE or if a significant increase in blood pressure does not adequately respond to antihypertensive therapy, discontinuation of the drug should be considered.

Epidemiological studies have associated the use of combined oral contraceptives with an increased incidence of venous thromboembolism (VTE, deep vein thrombosis and pulmonary embolism). Although the clinical significance of these findings for desogestrel used as a contraceptive that does not contain an estrogen component is unknown, the drug should be discontinued if thrombosis develops. Discontinuation of the drug should also be considered in the event of prolonged immobilization due to surgery or illness. Women with a history of thromboembolic disorders should be warned about the possibility of recurrence.

Although progestogens may affect peripheral insulin resistance and glucose tolerance, there is no evidence that there is a need to change the therapeutic regimen in diabetic patients using progestogen-only pills. However, diabetic women should be closely monitored during the first month of use.

The use of DESIRETTE leads to a decrease in serum estradiol levels to levels corresponding to the early follicular phase. It is not yet known whether this decrease has any clinically significant effect on bone mineral density.

Prevention of ectopic pregnancy with traditional progestogen-only pills is not as effective as with COCs, as ovulation often occurs with traditional progestogen-only pills. Although DESIRETTE effectively inhibits ovulation, in the case of amenorrhea and abdominal pain, ectopic pregnancy should be excluded in the differential diagnosis.

Chloasma may occasionally occur, especially in women with a history of chloasma. Women with a tendency to chloasma should avoid exposure to sunlight or ultraviolet radiation while using DESIRETTE.

Mood swings and depression are well-known side effects of GCs (see section 4.8). Depression can be serious and is a known risk factor for suicidal behaviour and suicide. Women should seek medical advice if they experience mood swings and depressive symptoms, including shortly after starting treatment.

The following conditions have been reported both during pregnancy and during the use of GCs: jaundice and/or pruritus associated with cholelithiasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham's chorea; herpes gestationis; hearing loss associated with otosclerosis; angioedema (hereditary), but their relationship to the use of progestogens has not been established.

The effectiveness of DESIRETTE may be reduced in case of missed tablets, gastrointestinal disorders or concomitant medications that reduce the plasma concentration of etonogestrel, which is the active metabolite of desogestrel.

DESIRETTE contains 55 mg of lactose. Women with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Decreased efficiency

The effectiveness of progestogen-only pills may be reduced in case of missed pills (see "What to do if you miss a pill"), gastrointestinal disorders (see "Recommendations in case of digestive tract disorders") or when taken in combination with other medicines (see section "Interaction with other medicines and other types of interactions").

Worsening menstrual cycle control

If irregular bleeding persists or occurs after previously regular cycles, non-hormonal causes should be considered and adequate diagnostic measures, including curettage, should be prescribed to exclude pregnancy or malignancy.

Some women may not have withdrawal bleeding during the tablet-free interval. If the COCs have been used according to the recommendations given in the section "Method of administration and dosage", the possibility of pregnancy is low. However, if these recommendations were violated before the first absence of withdrawal bleeding during the tablet-free interval or if withdrawal bleeding is absent twice in a row, pregnancy should be excluded before continuing COC use.

Laboratory tests

There have been reports of effects of contraceptive steroids on some laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma protein levels such as corticosteroid-binding globulin, lipid/lipoprotein fractions, carbohydrate metabolism parameters and coagulation and fibrinolysis parameters. The changes generally remain within normal limits. It is not known to what extent this applies to progestogen-only contraceptives.

Use during pregnancy or breastfeeding

Pregnancy

DESIRETTE is contraindicated for use during pregnancy. If pregnancy occurs during use of the drug, further use of the drug should be discontinued.

Animal studies suggest that very high doses of progestogen may cause masculinization of the fetus.

However, epidemiological studies do not indicate an increased risk of birth defects in children born to women who took COCs before pregnancy, nor does they indicate a teratogenic effect if COCs are inadvertently taken in early pregnancy. Pharmacovigilance data collected from various combined COCs containing desogestrel also do not indicate an increased risk.

Breastfeeding DESIRETTE does not affect the lactation process or the composition of breast milk (protein, lactose or fat content). However, small amounts of etonogestrel are excreted in breast milk. As a result, the child receives 0.01 - 0.05 mcg of etonogestrel per kilogram of body weight per day (based on an estimated milk intake of 150 ml/kg/day).

There are data on long-term follow-up of children whose mothers started taking desogestrel during the 4th-8th week after delivery. They were breastfed for 7 months and were followed 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 an intrauterine system (IUS). Based on the available data, DESIRETTE can be used during breastfeeding. However, the growth and development of the child should be carefully monitored.

Reproductive function

The drug is intended for the prevention of pregnancy. For information on the restoration of reproductive function (ovulation), see the section "Pharmacological properties".

Ability to influence reaction speed when driving vehicles or other mechanisms

Based on the pharmacodynamic profile of the drug, it is considered that DESIRETTE has no or very minor influence on the ability to drive and use machines.

Method of administration and doses

The tablets should be taken in the order indicated on the package, every day, at about the same time, if necessary with a small amount of liquid. One tablet should be taken every day for 28 days. The next package is started immediately after the previous package is finished.

How to start taking DESIRETTE

In the absence of previous use of GC (within the last month)

The use of tablets should be started on the 1st day of the menstrual cycle (on the 1st day of menstrual bleeding). It is allowed to start taking on the 2nd-5th day, but then during the first cycle during the first 7 days of taking the tablets it is recommended to use a barrier method of contraception.

After abortion during the first trimester

After an abortion during the first trimester, it is recommended to start using the drug immediately; an additional method of contraception is not required.

After childbirth or abortion during the second trimester

The woman should be advised to start taking the drug on the 21st-28th day after childbirth or abortion during the second trimester. If taking the drug is started later, the woman should additionally use a barrier method during the first 7 days of taking the tablets. However, if the woman has already had sex after childbirth or abortion before starting taking DESIRETTE, then before starting taking the drug, pregnancy should first be excluded or the woman should wait for the first menstruation.

How to start taking DESIRETTE when switching from other methods of contraception

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

If the drug is started the day after the last active COC tablet (the last tablet containing the active substances) or the day of removal of the vaginal ring or patch, the woman should use an additional barrier method for the first 7 days of tablet-taking.

Switching from other progestogen-only preparations (mini-pills, injections or progestogen-releasing intrauterine systems [IUDs])

A woman can switch to DESIRETTE any day after stopping the mini-pill (in the case of an implant – on the day of its removal, in the case of an injection – instead of the next injection), there is no need for an additional method of contraception.

What to do if you miss a pill

Contraceptive protection may be reduced if the interval between taking two tablets is more than 36 hours. If the delay in taking the tablet is less than 12 hours, the missed tablet should be taken as soon as the woman remembers, and the next tablet should be taken at the usual time. If the delay in taking the tablet is more than 12 hours, the woman should use an additional method of contraception for the next 7 days. If the drug was missed during the first week of its use and sexual intercourse took place during the week preceding the missed tablet, then in this case the possibility of pregnancy should be assumed.

Recommendations in case of digestive tract disorders

In case of severe gastrointestinal disorders, absorption may be incomplete, so additional contraceptive measures should be taken. If vomiting occurs within 3-4 hours after taking the tablet, absorption may be incomplete. In this case, the recommendations for missed tablets given in the relevant section should be followed (see "What to do if you miss a tablet").

Children.

DESIRETTE is not prescribed for children.

Overdose

No serious adverse effects have been reported from overdose. Symptoms that may occur include nausea, vomiting, and in young girls, slight vaginal bleeding. There is no antidote, and further treatment should be symptomatic.

Side effects

The most common adverse reaction reported during use of the drug was menstrual irregularities, as DESIRETTE inhibits ovulation by approximately 100%. In 20-30% of women, bleeding may become more frequent, but in another 20% it may be less frequent or stop altogether. Vaginal bleeding may be longer. After several months of use, bleeding becomes less frequent. Information, counseling and a diary in which all bleeding episodes are recorded will help the woman to correctly perceive the characteristics of the bleeding.

The most common adverse reactions (>2.5%) were: menstrual disorders, acne, mood changes, breast pain, nausea and weight gain. The adverse reactions listed in Table 2 below were assessed by the investigators as having an established, probable or possible relationship to treatment. All adverse reactions are listed by system organ class and frequency: common (≥1/100), uncommon (≥1/1000 to <1/100), rare (<1/1000) and not known (cannot be estimated from the available data).

Table 2

* MedDRA (MedDRA) version 9.0.

Angioedema and/or exacerbation of hereditary angioedema may occur. Serious adverse reactions such as venous and arterial thromboembolic disorders, hormone-dependent tumours (e.g. breast cancer) and chloasma have been reported in women using combined oral contraceptives, some of which are described in more detail in the section "Special warnings and precautions for use".

Interactions between GCs and other drugs (enzyme inducers) may lead to breakthrough bleeding and/or reduced contraceptive efficacy.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after the registration of a medicinal product is an important measure. This allows for continuous monitoring of the benefit/risk balance of the medicinal product. Physicians are asked to report any suspected adverse reactions.

Expiration date

3 years

Storage conditions

Does not require special storage conditions.

Keep out of reach of children.

Packaging

28 tablets in a blister, 1 or 3 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

Laboratorios Leon Pharma, S.A.

Location.

S/La Vallina s/n, Polígono Industrial Navategera, Villaquilambre, 24193 León, Spain.