Menopur® [Menotropin]

Pharmacological properties

menopur contains menotropin (hmg), which consists of FSH and lg. in addition, menopur contains human chorionic gonadotropin (hhg), isolated from the urine of women in the postmenopausal period, which contributes to the activity of lh. Menotropin, which has both FSH and LH activity, stimulates the growth and development of follicles, as well as the production of sex steroid hormones in women without primary ovarian dysfunction. FSH is the main factor that determines the replenishment of the follicular population and growth at the beginning of folliculogenesis, while LH is important for steroidogenesis in the ovaries and advanced follicular maturation. FSH can stimulate follicular growth in the complete absence of LH (for example, with hypogonadotropic hypogonadism), but as a result, follicles develop abnormally, which is associated with low levels of estradiol and can cause insufficient follicular maturation.

In accordance with the action of LH in relation to increasing the production of sex steroid hormones, the estradiol level associated with Menopur treatment is higher than with recombinant FSH in the preparation of regulated in vitro fertilization cycles by insemination (IVF ICSI). This question should be considered when monitoring patient response based on estradiol levels. No difference in estradiol levels was found when using low-dose ovulation induction protocols in anovulatory patients.

Pharmacokinetics The pharmacokinetic profile of FSH in Menopur is documented. After 7 days of repeated injections of 150 IU Menopur for inhibitory regulation in healthy female volunteers_max FSH in the blood plasma (with basic correction mean ± SD) was 8.9 ± 3.5 and 8.5 ± 3.2 IU / L for subcutaneous and intramuscular administration, respectively. WITH_max FSH was achieved within 7 hours for both methods of their use. After repeated administration, FSH was excreted with T_½ (mean ± SD) 30 ± 11 and 27 ± 9 h for subcutaneous and intramuscular administration, respectively. Although individual curves of LH concentration versus time show an increase in LH concentration after taking Menopur, the existing data were infrequent, therefore, they are not suitable for pharmacokinetic analysis. Menotropin is secreted mainly by the kidneys. The pharmacokinetics of menopur in patients with renal or hepatic insufficiency have not been investigated.

Indications

• Female infertility due to anovulation (in particular as a result of polycystic ovary) in women who cannot be treated with clomiphene; with controlled ovarian hyperstimulation to induce multiple follicular formation during drug treatment programs for infertility (including in vitro fertilization / embryonic transfer, in-tube gamete transfer (HPV) and intracytoplasmic sperm injection (Icis)).

Application

Menopur is intended for SC or IM administration. the powder is diluted immediately before administration using the solvent that is provided. in 1 ml of solvent, up to 3 bottles of menopur powder can be diluted. do not use an opaque solution or if particles are detected in it.

Dosage regimens are identical for subcutaneous and intramuscular administration.

The individual reaction of the ovaries to exogenous gonadotropins varies significantly, which does not allow the use of standardized dosing regimens. In view of this, the doses are selected individually, depending on the reaction of the ovaries to the treatment. Menopur can be used both separately and in combination with gonadotropin-RF (its agonist or antagonist in order to control ovarian hyperstimulation). The recommended dosage and duration of treatment may vary depending on the individual treatment regimen.

Anovulation (including polycystic ovary): The goal of Menopur treatment is to form one Graaf follicle from which the oocyte is released as a result of hCG.

Menopur should be started during the first 7 days of the menstrual cycle. The recommended starting dose is 75–150 IU / day for 7 days. Based on the results of clinical monitoring (including ovarian ultrasound alone or in combination with estradiol control), subsequent dosing must be individualized depending on the response. The dose can be corrected no more than 1 time in 7 days. The recommended single dose increase is 37.5 IU and should not exceed 75 IU. The maximum daily dose should not exceed 225 IU. If there is no result for 4 weeks, the course of treatment should be discontinued, in the future, treatment should begin with higher doses compared to those used in the interrupted cycle.

After achieving the optimal result, a single dose of hCG of 5000-10,000 IU should be administered the day after the last dose of Menopur. On the day of hCG administration and the next day, it is recommended to have sex. An alternative way is to carry out artificial intrauterine fertilization. In case of an increased reaction to Menopur, treatment should be discontinued, and patients should refrain from sexual intercourse or use barrier methods of contraception until the beginning of the next month cycle.

Controlled ovarian hyperstimulation to induce multiple follicular formation during assisted reproductive technology (ART) programs

An example protocol for the use of Menopur with gonadotropin-RF agonists. In clinical trials that included regulation using gonadotropin-RF, treatment with Menopur should be started approximately 2 weeks after the start of treatment with an agonist. The recommended initial dose of Menopur is 150–225 IU / day for at least the first 5 days of treatment. Based on clinical observations (including ultrasound alone or in combination with estradiol determination), subsequent dosing should be individualized, but not exceed 150 IU with each dose adjustment. The maximum daily dose should not exceed 450 IU, and in most cases, the duration of treatment longer than 20 days is not recommended.

In regimens that do not provide for regulation (inhibition), treatment with Menopur should begin on the 2nd – 3rd day of the menstrual cycle. The recommended size and dosage regimen are the same as those proposed for the above protocols using chorionic gonadotropin hormone agonists for regulation.

Having achieved the optimal reaction of the body, a single dose of 5000-10,000 IU of hCG is administered to patients to induce the final maturation of the follicle and prepare for the release of the oocyte. Patients should be closely monitored for at least 2 weeks after hCG administration. In case of an increased reaction to Menopur, treatment should be discontinued, and patients should refrain from sexual intercourse or use barrier methods of contraception until the beginning of the next month cycle.

Preparation of the solution (Menopur 600 IU and 1200 IU). The powder should be dissolved only with the solvent contained in the package.

Attach the dissolution needle into the pre-filled syringe. Insert all solvent into a powder vial. The powder should dissolve quickly until a clear solution is obtained. Otherwise, carefully rotate the bottle in your hands until a clear solution is obtained. Vigorous shaking should be avoided.

Syringes for injection, graduated in units of FSH / LH from 37.5 to 600 IU, are supplied in Menopur packaging with needles. Select the prescribed dose of the resulting solution from the vial into the syringe for injection. 1 ml of the finished solution contains 600 IU FSH and LH.

Each bottle of dissolved Menopur 600 IU or 1200 IU is for individual use.

Select the exact dose of the prepared solution from the vial into the syringe for injection and immediately enter the solution.

Incompatibility. Menopur should not be administered in the same injection with other drugs except for urofollitropin Bravel 75 IU manufactured by Ferring. Studies have shown that the simultaneous administration of Menopur and urofollitropin does not significantly change the expected bioactivity.

Contraindications

The drug is contraindicated in women:

• with pituitary or hypothalamic tumors;
• with carcinoma of the ovary, uterus or breast;
• with gynecological bleeding of unknown etiology;
• with hypersensitivity to any of the components of the drug;
• with cysts or an increase in ovarian size, which is not associated with polycystic ovary.

In the cases described below, a positive result of treatment is not expected, therefore, the drug should not be prescribed for:

• primary insufficiency of ovarian function;
• genital abnormalities incompatible with pregnancy;
• fibroid neoplasms of the uterus, incompatible with pregnancy.

Side effects

In the treatment of a drug in clinical trials, adverse reactions were most often reported: abdominal pain, headache, reactions and pain at the injection site with a frequency of up to 10%. the table shows the most common adverse reactions from organs and systems obtained during clinical trials.

According to clinical trials, typical symptoms of digestive tract associated with OHSS were discomfort and bloating, nausea, and vomiting. A common complication of OHSS is venous thromboembolic disorder and ovarian twisting.

Allergic reactions have been reported with the use of gonadotropin preparations: local skin reactions and general reactions, including anaphylaxis.

Treatment of hMG often leads to unwanted multiple pregnancy. Pregnancies that have occurred during treatment with bsplodia with gonadotropins are more likely to end in abortion compared to conventional pregnancies.

Hypersensitivity reactions (fever, skin rashes), swelling, pain, or itching at the injection site rarely develop.

In some cases, with prolonged use of the drug, the formation of antibodies is possible, which leads to the ineffectiveness of the therapy.

Treatment with hMG drugs can cause ovarian hyperstimulation, which clinically manifests itself after administration for the purpose of ovulating hCG. This can lead to the formation of large ovarian cysts. In addition, with severe ovarian hyperstimulation, ascites, hydrothorax, oliguria, arterial hypotension, and thromboembolism can occur.

Perhaps the development of flu-like symptoms.