Coriphyltropin alfa - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Hormones of the hypothalamus, pituitary gland, gonadotropins and their antagonists

Included in the formulation

Elonva®

solution PC

Organon, N.V. Netherlands

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

АТХ:

G.03.G.A.09 Coriphlitropin alfa

Pharmacodynamics:

Coriphyltropin alfa is a glycoprotein, which is formed by Chinese hamster ovary cells using recombinant DNA technology.

Coriphyltropin alfa is a stimulant for the growth of follicles of prolonged action, which, according to its pharmacodynamic properties, is comparable to a recombinant follicle-stimulating hormone, but has a much longer action. The drug causes and supports the growth of follicles within a week, so one subcutaneous injection of the recommended dose of the drug can replace 7 daily injections of any drugs recombinant follicle-stimulating hormone with controlled ovarian stimulation. An increase in the duration of follicle-stimulating activity was achieved by the addition of a carboxyterminal beta-subunit peptide human chorionic gonadotropin to the beta chain of the human follicle-stimulating hormone.

Coriphyltropin alfa does not have luteinizing hormone activity and human chorionic gonadotropin.

Pharmacokinetics:

After a single subcutaneous injection of the drug, the maximum serum concentrations were reached after 44 hours (34-57 hours). Absolute bioavailability was 58% (48-70%), the volume of distribution was 9.2 l (6.5-13.1 l) and the clearance in the equilibrium state was 0.13 l / h (0.10-0.18 l / h ), respectively. The pharmacokinetics of coryphol- lthropin alfa did not depend on the dose over a wide range of doses (7.5-240 μg). The half-life of coryphallitropin alfa is 69 h (59-79 h). After the administration of the recommended dose, the serum concentrations of coryphallitropine alpha are sufficient to support multiple growth of the follicles throughout the week.

Exposure of coryphallitropine alpha depends on body weight. In clinical studies, serum concentrations of corypholtroline alpha were similar after administration of the drug at doses of 100 μg and 150 μg to women with a body weight ≤ 60 kg and ≥ 60 kg, respectively.

The distribution, metabolism and excretion of coryphallitropine alpha are similar to those of other gonadotropins, such as follicle-stimulating hormone, human chorionic gonadotropin and luteinizing hormone.After absorption into the blood coryphallitropine alpha is distributed mainly in the ovaries and kidneys and is excreted mainly by the kidneys. The ability to excrete can be reduced in patients with renal impairment. Hepatic disorders contribute to an insignificant increase in the time of excision of coryphallitropine alpha. Although there is no data on patients with hepatic impairment, it is unlikely that liver damage will affect the pharmacokinetic profile of coryphol- lthropine alpha.

Indications:

Controlled ovarian stimulation in combination with GnRH antagonists to form multiple follicles in women participating in the assisted reproduction program.

ICD-10

XXI.Z30-Z39.Z31.1 Artificial insemination

Contraindications:

Tumors of the ovaries, breast, uterus, pituitary or hypothalamus; bleeding and spotting from the genital tract (not associated with menstruation) of an unknown cause; primary failure of the ovaries; ovarian cysts or ovarian enlargement; ovarian hyperstimulation syndrome in the anamnesis; in the event that the previous cycle of controlled ovarian stimulation led to the growth of more than 30 follicles to a size of not less than 11 mm,revealed by ultrasound; the number of basal antral follicles more than 20, revealed by ultrasound examination; fibroid tumors of the uterus, in which the onset and further bearing of pregnancy is difficult; malformations of reproductive organs, in which pregnancy is impossible; pregnancy; lactation period (breastfeeding); increased sensitivity to coryphallitropin alfa.

Carefully:

In patients with renal insufficiency, there may be a disruption of the excision of coryphallitropine alpha, so the use in such patients is not recommended.

In women with risk factors for thromboembolic complications (history of thromboembolism, family history, obesity (body mass index> 30 kg / m²) or thrombophilia) treatment with gonadotropins may further increase this risk. In such cases, the risk and benefit of using gonadotropins should be assessed. It should be noted that pregnancy itself increases the risk of developing thrombosis.

Pregnancy and lactation:

Category FDA not determined.

Contraindicated in pregnancy and lactation (breastfeeding).

After controlled stimulation of the ovaries by gonadotropins, there was no teratogenic effect in clinical practice. Clinical data do not allow excluding the teratogenic effect of coryphallitropine alpha in case of its unintentional introduction during pregnancy.

In pre-clinical studies, there was no teratogenic effect of coryphol- lythropin alfa.

Dosing and Administration:

Enter subcutaneously (preferably under the skin of the abdomen) in accordance with special schemes.

Recommended doses were established only when combined with a GnRH antagonist.

Women with a body weight of less than 60 kg once injected 100 mcg.

Women with a body weight of more than 60 kg once injected 150 mcg.

Side effects:

From the nervous system: often - headache; infrequently - dizziness.

From the digestive system: often - nausea; infrequently - abdominal pain, vomiting, diarrhea, constipation, bloating.

On the part of the reproductive system: often - ovarian hyperstimulation syndrome, pain and discomfort in the pelvic region, complaints from the mammary glands; infrequently - torsion of the ovary. In addition, ectopic pregnancy is described,miscarriage and multiple pregnancies, which are considered complications of assisted reproduction methods.

Common reactions: often fatigue.

Overdose:

Not described.

Interaction:

It is not recommended to apply coryphallitropine alpha in combination with the GnRH agonist, as well as in women with polycystic ovary syndrome.

During the first 7 days after the administration of coryphallitropine alpha, rFSH should not be administered.

Special instructions:

Before starting treatment, the couple should be properly examined, a diagnosis of infertility is made and possible contraindications are taken into account. In particular, the patient should be examined for hypothyroidism, adrenal insufficiency, hyperprolactinaemia and tumors of the pituitary or hypothalamus, if appropriate, to prescribe appropriate treatment.

Coriphyltropin alfa is intended only for single subcutaneous administration. During the same cycle, no additional injections of the drug should be prescribed.

It is recommended that careful monitoring of possible ovarian hyperstimulation in the first stimulation cycle in patients with unspecified risk factors syndrome of ovarian hyperstimulation.

When all gonadotropin drugs were used, there were cases of multiple pregnancies and the birth of twins. Before starting treatment, the woman and her partner should be informed of the possible risk to the mother (complications of pregnancy and childbirth) and newborns (low body weight). In the treatment of assisted reproductive technologies, the risk of multiple pregnancies mostly depends on the number of embryos transferred.

In women with infertility, who are offered treatment by assisted reproductive technologies, especially in vitro fertilization, the pathology of the fallopian tubes is common, which can lead to an increased risk of ectopic pregnancy. In this regard, in early pregnancy should be an ultrasound to confirm the presence of uterine or ectopic pregnancy.

The frequency of congenital malformations after assisted reproductive technologies is slightly higher than after natural fertilization. This is associated with the individual characteristics of the parents (for example, the age of the woman, the sperm count) and the increased frequency of multiple pregnancies.

Coriphyltroline alpha may cause dizziness.Patients should be warned that with dizziness should not engage in driving vehicles or use sophisticated technology.

Instructions

Coriphlitropin alfa (Corifollitropinum alfa)