Charosette, 75 mcg 28 pcs

Charosetta is a gestagen-containing oral contraceptive. Like other gestagen-containing oral contraceptives (“mini-pills”) Charosette is best suited for use during breastfeeding and for women who are contraindicated or who do not want to take estrogens. Unlike the “mini-pill,” Charosette’s contraceptive effects are achieved mainly by suppressing ovulation. Other effects include an increase in cervical mucus viscosity.

When using Charosette for the first 56 days, the rate of ovulation is less than 1%; after discontinuing the 56-day drug, ovulation occurs in 7 to 30 days (averaging 17 days).

In a comparative efficacy study (in which missed pills were allowed for a maximum of 3 hours), Charosette’s overall Perl index (a measure of the frequency of pregnancy in 100 women during one year of contraceptive use) was 0.4 in the group of all patients enrolled in the study.

The Charosette Perl Index is comparable to the Perl Index of combined oral contraceptives in the general population of oral contraceptive users. Administration of Charosette leads to a decrease in serum estradiol levels to values characteristic of the early follicular phase. No clinically significant changes in carbohydrate, lipid metabolism and hemostasis parameters were found.

Pharmacokinetics

Inabsorption

. After oral administration of Charosette, desogestrel is rapidly absorbed and converted to the active metabolite etonogestrel. After reaching steady state C_max etonogestrel is reached 1.8 h after taking the next tablet. The absolute bioavailability of etonogestrel is approximately 70%.

Distribution

C_ss in plasma are reached after 4-5 days of administration.

Etonogestrel binds 95.5-99% to serum proteins, predominantly albumin and to a lesser extent to sex hormone-binding globulin.

Etonogestrel is excreted with breast milk at a milk/serum ratio of 0.37-0.55, so for an approximate milk intake of 150 ml/kg/day a newborn can receive 0.00001-0.00005 mg of etonogestrel.

Metabolism

Desogestrel is converted by hydroxylation and dehydrogenation to the active metabolite etonogestrel. Etonogestrel is metabolized through the formation of sulfate and glucuronide conjugates.

Elimation

Atonogestrel is eliminated with a T_1/2 of approximately 30 h by both single and course administration of the drug. Serum clearance after intravenous administration of etonogestrel is approximately 10 L/h. Excretion of etonogestrel and its metabolites occurs both as free steroids and as conjugates in the urine and feces (1.5/1 ratio).

Indications

Contraception.
If Charozetta is used correctly, according to the instructions (without missing tablets), the likelihood of pregnancy is very low.
Charozette can be taken by women who are intolerant to estrogens, as well as by nursing mothers.

Pharmacological effect

Charozetta is a gestagen-containing oral contraceptive. Like other progestin-containing oral contraceptives (“mini-pills”), Charozette is best suited for use during breastfeeding and for women who are contraindicated or who do not want to take estrogens. Unlike the mini-pill, the contraceptive effect of Charozetta is achieved mainly by suppressing ovulation. Other effects include an increase in the viscosity of cervical mucus.

When using the drug Charozetta in the first 56 days, the frequency of ovulation does not exceed 1%; after stopping the 56-day drug intake, ovulation occurs after 7-30 days (on average after 17 days).

In a comparative effectiveness study (in which missed pills were allowed to be taken within a maximum of 3 hours), the overall Pearl index (an indicator reflecting the pregnancy rate in 100 women during a year of contraceptive use) of Charozetta was 0.4 in the group of all patients included in the study.

The Pearl index of Charozetta is comparable to the Pearl index of combined oral contraceptives in the general population taking oral contraceptives. Taking the drug Charozetta leads to a decrease in the level of estradiol in the serum, to values ​​​​characteristic of the early follicular phase. At the same time, no clinically significant changes were detected in carbohydrate, lipid metabolism and hemostasis parameters.

Pharmacokinetics

Suction

After taking Charozetta orally, desogestrel is rapidly absorbed and converted into the active metabolite etonogestrel. After reaching a steady state, Cmax of etonogestrel is achieved 1.8 hours after taking the next tablet. The absolute bioavailability of etonogestrel is approximately 70%.

Distribution

Css in blood plasma are achieved after 4-5 days of administration.

Etonogestrel is 95.5-99% bound to serum proteins, predominantly albumin and to a lesser extent sex hormone-binding globulin.

Etonogestrel is excreted in breast milk in a milk/serum ratio of 0.37-0.55, therefore, with an approximate volume of milk consumed of 150 ml/kg/day, a newborn can receive 0.00001-0.00005 mg of etonogestrel.

Metabolism

Desogestrel is converted by hydroxylation and dehydrogenation to the active metabolite etonogestrel. Etonogestrel is metabolized through the formation of sulfate and glucuronide conjugates.

Removal

Etonogestrel is eliminated from T1/2 in approximately 30 hours with both single and course administration of the drug. Serum clearance after intravenous administration of etonogestrel is approximately 10 L/h. Excretion of etonogestrel and its metabolites occurs both in the form of free steroids and in the form of conjugates with urine and feces (in a ratio of 1.5/1).

Special instructions

Medical examinations/consultations: before prescribing the drug, a woman should carefully collect anamnesis and conduct a thorough gynecological examination to exclude pregnancy. Before prescribing the drug, the cause of menstrual irregularities, for example, oligomenorrhea and amenorrhea, should be established. The interval between control medical examinations is determined by the doctor in each individual case (the frequency of examinations is at least once a year). If the prescribed drug may affect a latent or existing disease, an appropriate schedule of follow-up medical examinations should be drawn up.

Despite taking Charozetta regularly, irregular bleeding may sometimes occur. If bleeding is very frequent and irregular, you should consider using another method of contraception. If the above symptoms are persistent, then in this case it is necessary to exclude organic pathology. Management of amenorrhea while using the drug depends on whether the tablets were taken as directed and may include a pregnancy test. In case of pregnancy, the drug should be discontinued. In case of acute or chronic liver dysfunction, a woman should contact a specialist for examination and consultation. Women should be informed that Charosette does not protect against HIV infection (AIDS) or other sexually transmitted diseases.

Reduced effectiveness: The effectiveness of progestin-containing oral contraceptives may be reduced if pills are missed, gastrointestinal disorders, or when taking other medications.

Changes in menstrual patterns: While using progestin-containing contraceptives, some women may experience vaginal bleeding more frequently or for a longer period of time, while for other women this bleeding may become less frequent or stop altogether. These changes are often the reason that a woman refuses this method of contraception, or ceases to strictly follow the doctor’s instructions. In detailed consultation with women who decide to start taking Charozetta, the doctor should discuss the possibility of such changes in the nature of the menstrual cycle. Evaluation of vaginal bleeding should be based on clinical presentation and may include testing to rule out malignancy or pregnancy.

Follicular development: When taking all low-dose hormonal contraceptives, follicular development occurs, and occasionally the size of the follicle can reach sizes exceeding those in a normal cycle. In general, these enlarged follicles disappear spontaneously. Often, this occurs without symptoms; in some cases there is mild pain in the lower abdomen. Surgery is rarely required.

Laboratory tests: Data obtained with combined oral contraceptives have shown that the use of hormonal contraceptives may affect the results of some laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, serum levels of (transport) proteins, such as corticosteroid binding globulin, lipid/lipoprotein fractions, carbohydrate metabolism parameters and blood clotting and fibrinolysis. Usually these changes remain within normal limits. It is not known to what extent this also applies to progestogen-only contraceptives.

Breast cancer: The risk of breast cancer increases with age. While using combined oral contraceptives, the risk that a woman will be diagnosed with breast cancer increases slightly. This increased risk gradually disappears over 10 years after stopping oral contraceptives and is not related to duration of use but depends on the woman’s age at the time of combined oral contraceptive use.

The risk in women using progestogen-only oral contraceptives, such as Charozetta, may be similar to those using combined oral contraceptives. However, the data for progestogen-only oral contraceptives are less clear. Compared with the lifetime risk of breast cancer, the increase in risk associated with combined oral contraceptives is small. Breast cancer diagnosed in women using combined oral contraceptives tends to be less clinically advanced than cancer diagnosed in women who have never used combined oral contraceptives. The increased risk in women using combined oral contraceptives may be due to earlier diagnosis, biological effects of the drug, or a combination of these two factors.

Venous thromboembolism: Epidemiological studies have established an association between the use of combined oral contraceptives and an increased incidence of venous thromboembolism (VTE, deep vein thrombosis and pulmonary embolism). Although the clinical significance of these data for desogestrel, a contraceptive that does not contain an estrogen component, is unknown, the use of Charozetta should be discontinued if thrombosis develops. Discontinuation of Charozetta should be considered in case of prolonged immobilization associated with surgery or illness.

Diabetes mellitus: Although progestins may affect peripheral insulin resistance and glucose tolerance, there is no evidence that there is a need to change the therapeutic regimen in patients with diabetes mellitus using progestogen-containing oral contraceptives. However, women with diabetes should be closely monitored during the first months of using the drug.

Bone Mineral Density: The use of Charozetta leads to a decrease in serum estradiol levels to levels corresponding to the early follicular phase. It is currently unknown whether this decrease has any clinically significant effect on bone mineral density.

Prevention of ectopic pregnancy with traditional gestagen-containing oral contraceptives (“mini-pills”) is not as effective as with combined oral contraceptives, since ovulation often occurs when using “mini-pills.” Although Charozetta effectively suppresses ovulation, in the case of amenorrhea or abdominal pain, ectopic pregnancy should be excluded in the differential diagnosis.

Charozetta contains no more than 65 mg of lactose, so women with rare hereditary disorders associated with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should refrain from taking the drug.

Impact on the ability to drive vehicles and operate machinery:

Based on the pharmacodynamic profile, it is believed that the drug does not affect the ability to drive vehicles and operate machinery.

Active ingredient

Desogestrel

Composition

1 film-coated tablet contains:

Desogestrel 0.075 mg.

Excipients:

Corn starch;
Povidone;
α-tocopherol;
Stearic acid;
Colloidal silicon dioxide;
Lactose monohydrate.

Shell composition:

Hypromellose;
Macrogol 400;
Talc;
Titanium dioxide

Pregnancy

During pregnancy, the use of the drug is contraindicated.

The results of preclinical studies have shown that very high doses of gestagens can cause masculinization of the female fetus.

Extensive epidemiological studies have found neither an increased risk of birth defects in children whose mothers took oral contraceptives before pregnancy, nor a teratogenic effect from unintentional use of oral contraceptives in early pregnancy. Charosette does not affect the quantity or quality (protein, lactose or fat concentrations) of breast milk. However, small amounts of etonogestrel are excreted in breast milk. As a result, the baby may receive 0.01-0.05 mcg of etonogestrel per kg of body weight per day (based on consumption of 150 ml/kg/day of breast milk).

There is limited long-term follow-up data from children whose mothers started taking Charozetta within 4 to 8 weeks postpartum. The duration of breastfeeding was 7 months, and the children were monitored until they reached the age of 1.5 (n=32) or 2.5 years (n=14). Assessment of growth, physical and psychomotor development did not reveal any differences with babies whose mothers used IUDs containing copper. Available evidence suggests that Charosetta can be used during lactation. However, the development and growth of an infant whose mother is taking Charozetta should be carefully monitored.

Contraindications

Hypersensitivity to the active substance or any excipient of the drug.
Established or suspected pregnancy.
The presence or history of venous thromboembolism (including deep vein thrombosis of the leg, pulmonary embolism).
Current or past history of severe liver disease (until liver function tests return to normal).
Liver failure, incl. in the anamnesis.
Established or suspected malignant hormone-dependent tumors.
Bleeding from the vagina of unknown etiology.
Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

With caution

Side Effects

The most common adverse effect reported in clinical studies was irregular menstruation. Up to 50% of women using desogestrel experienced acyclic bleeding: in 20–30% of women, menstruation becomes more frequent, while in another 20% it becomes less frequent or may even stop completely. Menstruation may also become longer.

After several months of taking the drug, menstruation tends to become less frequent. Informing the doctor, monitoring by the doctor, and using a menstrual diary can increase compliance with drug treatment.

The following are undesirable effects that have an established, probable or possible connection with the use of the drug.

If any of the following conditions/risk factors are observed, the expected benefits and risks of using contraception should be carefully weighed in consultation with your doctor throughout the entire period of contraception. If any of the following conditions/risk factors appear, intensify, or change, the patient should immediately consult a doctor to decide on the possibility of further use of the drug.

Often – acne, nausea, mood changes, decreased libido, breast tenderness, menstrual irregularities, headache, weight gain.

Uncommon: alopecia, fatigue, vomiting, discomfort when wearing contact lenses, vaginitis, dysmenorrhea, ovarian cysts.

Rarely – redness of the skin, rash, urticaria, erythema nodosum.

Although a reliable connection with the intake of gestagens has not been established, when taking them, cholestatic jaundice, skin itching, cholelithiasis, chorea, herpes of pregnant women, otosclerosis, deafness, and the development of hemolytic-uremic syndrome are possible.

Interaction

Interactions between oral contraceptives and other drugs may result in breakthrough bleeding and/or decreased contraceptive effectiveness. The following interactions have been reported in the literature (mainly with combined contraceptives, but sometimes also reported with progestin-containing contraceptives).

Interactions may occur with drugs that induce microsomal enzymes, which leads to an increase in the clearance of sex hormones (hydantoins /e.g. phenytoin/, barbiturates /e.g. phenobarbital/, primidone, carbamazepine, rifampicin, oxcarbazepine, rifabutin, topiramate, felbamate, ritonavir, nelfinavir, griseofulvin, preparations containing St. John’s wort). Women using any of these drugs should temporarily use a barrier method in addition to Charozetta or choose another method of contraception. A barrier method of contraception should be used while using these medications and for 28 days after stopping them. For women receiving long-term treatment with liver enzyme inducers, the use of a non-hormonal method of contraception should be considered.

When using activated charcoal, the absorption of desogestrel contained in the tablet may be reduced and, therefore, contraceptive effectiveness may be reduced. In this case, you should act in accordance with the recommendations regarding missed pills.
Hormonal contraceptives may affect the metabolism of other drugs. Accordingly, drug concentrations in plasma and tissues can either increase (for example, cyclosporine) or decrease.
To identify possible interactions, you should read the instructions for use of these medications.

Overdose

No serious side effects have been reported as a result of overdose.

Symptoms: nausea, vomiting and, in young girls, slight vaginal bleeding.

Treatment: there is no specific antidote. Symptomatic therapy is carried out.

Storage conditions

The drug should be stored out of the reach of children, in a dry place, protected from light, at a temperature of 2° to 30°C.

Shelf life

3 years.

Manufacturer

N.V.Organon, Netherlands