Alterpur, lyophilizate 75 me 1 ml 1pc.

The product contains highly purified follicle stimulating hormone (FSH) derived from the urine of postmenopausal women, with a small admixture of luteinizing hormone (LH).

The LH content in the final product is minimized by a chromatographic purification procedure. Stimulates the growth and maturation of follicles, causing an increase in estrogen concentration and endometrial proliferation.

FSH binds to receptors on the surface of granulosa cells of small follicles in the ovaries.

Indications

Anovulation (including polycystic ovary syndrome (PCOS) when clomiphene therapy is ineffective);
Controlled ovarian hyperstimulation to induce the growth of multiple follicles during assisted reproductive technologies (ART)

Pharmacological effect

The drug contains highly purified follicle-stimulating hormone (FSH), obtained from the urine of postmenopausal women, with a slight admixture of luteinizing hormone (LH).

The LH content in the final product is minimized due to the chromatographic purification procedure. Stimulates the growth and maturation of follicles, causing an increase in estrogen concentrations and endometrial proliferation.

FSH binds to receptors on the surface of granulosa cells in small follicles in the ovaries.

Special instructions

Treatment should be carried out under the supervision of a doctor experienced in treating infertility.

Before starting to use the drug Alterpur, it is recommended to conduct an examination to identify hypothyroidism, adrenal insufficiency, hyperprolactinemia, tumors of the pituitary gland or hypothalamus; as well as appropriate specific treatment.

OHSS
OHSS is a syndrome distinct from uncomplicated ovarian enlargement, the manifestations of which depend on the severity. It includes significant ovarian enlargement, high serum estrogen concentrations, and increased vascular permeability, which can lead to fluid accumulation in the abdominal, pleural, and, rarely, pericardial cavities (in severe OHSS). In moderate OHSS, symptoms include abdominal pain, bloating, significant ovarian enlargement, weight gain, shortness of breath, oliguria, and gastrointestinal symptoms including nausea, vomiting, and diarrhea. In severe OHSS, hypovolemia, hemoconcentration, electrolyte disturbances, ascites, hemoperitoneum, hydrothorax, acute respiratory distress syndrome and thromboembolic complications develop.

Excessive ovarian response to gonadotropin administration rarely leads to the development of OHSS unless hCG is administered to stimulate ovulation. Therefore, in case of ovarian hyperstimulation, hCG should not be administered, and the patient should be warned to abstain from sexual intercourse or use barrier methods of contraception for at least 4 days. OHSS can progress rapidly (over 24 hours to several days) to become a serious medical complication, so patients should be monitored for at least 2 weeks after hCG administration. Compliance with the recommended doses of Alterpur, the administration regimen and careful monitoring of therapy can minimize cases of ovarian hyperstimulation and multiple pregnancies. When performing ART, aspiration of the contents of all follicles before ovulation can reduce the risk of developing OHSS.

OHSS may be more severe and protracted as pregnancy progresses. Most often, OHSS develops after cessation of treatment with gonadotropins and reaches maximum severity within 7-10 days after the end of treatment. OHSS usually resolves spontaneously after the onset of menstruation.

For moderate to severe OHSS, the patient is hospitalized and specific therapy is started.
OHSS occurs with high frequency in patients with polycystic ovary syndrome.

Multiple pregnancy

Multiple pregnancies are associated with an increased risk of adverse maternal and perinatal outcomes. When using urofollitropins, multiple pregnancies develop more often than with natural conception. In the case of in vitro fertilization (IVF), the likelihood of a multiple pregnancy depends on the number of embryos introduced, their quality and the age of the patient. The patient should be warned about the potential risk of multiple pregnancy before starting treatment.

Complications of pregnancy

The frequency of spontaneous abortions during pregnancy occurring after treatment with Alterpur is higher than in healthy women.

Ectopic pregnancy

With a history of fallopian tube diseases, both during natural conception and during infertility treatment, women have a high risk of ectopic pregnancy. The prevalence of ectopic pregnancy after IVF is 2% to 5%, compared to 1% to 1.5% in the general population.

Neoplasms of the reproductive system

There are reports of neoplasms of the ovaries and other organs of the reproductive system, both benign and malignant, in women who have undergone infertility treatment using several ART techniques. It has not yet been established whether treatment with gonadotropins increases the baseline risk of these tumors in infertile women.

Congenital defects

The prevalence of congenital malformations of the fetus using ART is slightly higher than with natural conception. It is believed that this may be due to the individual characteristics of the parents (mother’s age, sperm characteristics) and multiple pregnancies.

Thromboembolic complications

Women with known risk factors for thromboembolic complications, such as personal or family history, obesity (body mass index > 30 kg/m2) or thrombophilia, may have an increased risk of venous or arterial thromboembolic complications during or after treatment with gonadotropins. In such cases, the benefit of their use must outweigh the risk. It should be borne in mind that pregnancy itself also increases the risk of thromboembolic complications.

Impact on the ability to drive vehicles and machinery

The drug Alterpur does not affect the ability to drive vehicles and machines.

Active ingredient

Urofollitropin

Composition

1 bottle of lyophilisate contains:

Active ingredient – urofollitropin 75 IU, 150 IU

Auxiliary components – lactose monohydrate 10.00 mg

Pregnancy

The drug is contraindicated during pregnancy and breastfeeding.

Contraindications

· Hypersensitivity to urofollitropin and other components of the drug.

Tumors of the pituitary gland or hypothalamus.

· Decompensated diseases: hypothyroidism, adrenal insufficiency, hyperprolactinemia.

· Age up to 18 years.

· Persistent enlargement of the ovaries, ovarian cysts (not caused by PCOS).

· Anomalies in the development of the genital organs, incompatible with pregnancy.

· Uterine fibroids, incompatible with pregnancy.

· Bleeding from the vagina of unknown etiology.

· Estrogen-dependent tumors (ovarian cancer, uterine cancer or breast cancer).

· Primary ovarian failure.

· Pregnancy and breastfeeding period.

With caution

The presence of risk factors for thromboembolic complications, such as individual or family predisposition, severe obesity (body mass index >30 kg/m2) or thrombophilia, since in this case there is an increased risk of developing venous or arterial thrombosis and thromboembolism during or after the use of gonadotropins. In this case, the benefits of treatment with gonadotropins should outweigh the risks of their use.

Side Effects

Adverse adverse reactions were classified as follows:

very frequent – (> 1/10); frequent – (from > 1/100 to 1/1000 to 1/10000 to < 1/1000); very rare - (< 1/10000).

Organ system

Frequency

Adverse reaction

Endocrine system

infrequently

hyperthyroidism

Psychic sphere

infrequently

mood lability, depression

Nervous system

often

infrequently

headache

lethargy, dizziness

Respiratory system

infrequently

shortness of breath, nosebleeds

Gastrointestinal tract

often

infrequently

constipation, bloating, nausea, abdominal pain, dyspepsia

Skin and subcutaneous tissues

infrequently

erythema, itching

Kidneys and urinary tract

infrequently

cystitis

Genital organs and mammary gland

often

infrequently

ovarian hyperstimulation syndrome

breast enlargement, breast tenderness, hot flashes

General and administration site disorders

often

infrequently

rarely

pain

fatigue

hyperemia and hematoma at the injection site

Laboratory and instrumental data

infrequently

increased duration of bleeding

In rare cases, arterial thromboembolism has occurred in association with human urofollitropin/hCG treatment.

The incidence of pregnancy loss with the use of gonadotropins is comparable to that in women with other fertility disorders. A small risk of ectopic pregnancy and multiple pregnancies has been recorded.

Interaction

Alterpur can be prescribed alone or in combination with gonadotropin releasing hormone (GnRH) agonists or antagonists.

Alterpur should not be mixed in the same syringe with other medications.

It is assumed that the combined use of Alterpur and clomiphene may lead to increased follicular growth, although there is no clinical data on the combined use of these drugs. When prescribing a GnRH agonist to reduce the intrinsic activity of the pituitary gland, the drug should be prescribed in higher doses to achieve the desired follicular response.

Overdose

In case of overdose, the development of OHSS and thromboembolic complications is possible.

Symptoms of OHSS are ovarian enlargement, lower abdominal pain, nausea, vomiting, diarrhea, weight gain, oliguria, ascites, hydrothorax, hemoperitoneum, hemoconcentration, shortness of breath.

Symptoms of mild to moderate OHSS usually do not require additional treatment and resolve on their own within 2-3 weeks.

In case of severe OHSS, hospitalization in the intensive care units of specialized gynecological hospitals is necessary for complex treatment.

Recommendations for use

The drug can be administered intramuscularly or subcutaneously. The subcutaneous route of administration is preferable, as it ensures the greatest absorption of the drug. The injection solution is prepared immediately before administration.

Treatment with the drug should only be carried out under the supervision of a physician with appropriate specialization and experience in the treatment of infertility. The dose of the drug described below is the same for both subcutaneous and intramuscular routes of administration. The dose should be adjusted individually depending on the response of the ovaries. This requires monitoring the ovarian response to therapy in the form of ultrasound in combination with determining the concentration of estradiol in the blood plasma.

Anovulation (including PCOS if clomiphene therapy is ineffective)

The recommended initial dose is 75-150 IU/day. Alterpur can be administered daily. The use of the drug should begin during the first 7 days of the menstrual cycle. In the absence of a sufficient ovarian response, the dose is gradually increased. The recommended interval for dose escalation should be at least 7 days (preferably 14 days) to achieve an adequate rather than excessive ovarian response. The recommended increasing dose is 37.5 IU, but not more than 75 IU. The maximum daily dose usually does not exceed 225 IU. Adequate ovarian development is usually observed after 7-14 days of therapy. If the therapeutic effect is not achieved within 4 weeks of treatment, Alterpur injections are stopped and then a new cycle is started with a higher dose of the drug.

When an adequate ovarian response is achieved, 24-48 hours after the last injection of Alterpur, 5000-10000 IU of human chorionic gonadotropin (hCG) is administered once to induce ovulation. The patient is recommended to have sexual intercourse on the day of hCG administration and the day after administration. As an alternative method, intrauterine insemination is possible.
In case of an excessive reaction of the ovaries (a large number of follicles more than 14 mm in diameter or an increase in the concentration of estradiol by more than 2 times a day for 2-3 days in a row), the administration of Alterpur should be stopped and the administration of hCG should be discontinued. The patient is recommended to use barrier methods of contraception or abstain from sexual intercourse until menstruation occurs.

Treatment should be resumed in the next cycle at a lower dose than in the previous cycle.

· Controlled ovarian hyperstimulation to induce the growth of multiple follicles during BPT.

A widely used protocol for hyperstimulation involves administering 150-225 IU of Alterpur daily, starting on days 2 or 3 of the menstrual cycle and continuing until sufficient follicular size is achieved. The daily dose is adjusted according to the patient’s response to therapy. The daily dose should not exceed 450 IU FSH daily.

24-48 hours after the last injection of the drug Alterpur, one injection of hCG is prescribed at a dose of 5000 IU-10000 IU to induce the final maturation of the follicles.

To prevent the release of endogenous LH, gonadotropin releasing hormone agonists (GnRH agonists) are now widely used. In this case, the use of Alterpur should be started approximately two weeks after the start of treatment with GnRH agonists. In the future, both drugs continue to be used together until an adequate level of follicle development is achieved. The dose of Alterpur is adjusted according to the reaction from the patient’s ovaries.

Patients should be closely monitored for two weeks after hCG administration. If there is an excessive reaction to treatment with the drug, therapy should be discontinued, the administration of hCG should be discontinued and barrier methods of contraception should be used until the onset of the next menstruation.

Functional features

After a single subcutaneous administration of a dose of 300 IU, the time to reach the maximum concentration of the drug in plasma (Tmax) is 21.33±9.18 hours, the maximum concentration (Cmax) is 5.74±0.95 IU/l. The area under the curve (AUC0-∞) is 541.22±113.83 IU/l x h.

The half-life of the drug is approximately 50 hours.

Bioavailability after intramuscular administration is approximately 70%

Storage conditions

In a place protected from light, at a temperature not exceeding 25 °C

Shelf life

2 years

Manufacturer

IBSA Institute Biokimik S.A., Switzerland