Cetrorelix

When ATH:
H01CC02

Characteristic.

Cetrorelix acetate is a synthetic decapeptide with antagonistic activity against gonadotropin releasing hormone. (GnRG), natural analogue of GnRH to substitutions of amino acids in 1, 2, 3, 6 and 10 positions. Soluble in water. Molecular weight 1431,06.

Pharmacological action.
Antigonadotropnoe.

Application.

Prevention of premature ovulation during the treatment period, aimed at controlled ovarian stimulation, followed by oocyte fence, and carrying out assisted reproductive activities.

Contraindications.

Hypersensitivity to cetrorelix acetate, exogenous peptide hormones, GnRG, GnRH analogues, pregnancy (suspected or confirmed), lactation, postmenopausal, kidney and / or liver failure.

Restrictions apply.

Not intended for use by women 65 and older.

Pregnancy and breast-feeding.

Cetrorelix acetate, administered to rats in the first seven days of gestation at doses up to 38 mg / kg (about one-time recommended therapeutic dose for humans, designed for body surface area), no effect on the development of the fertilized egg implanted. However, the dose 139 mg / kg (approximately four-fold the human dose) It led to resorption of the ovum and postimplantation losses 100% cases.

When administered cetrorelix acetate from the 6th day of pregnancy and, about, until the time of delivery to rats at a dose 4,6 mg / kg (0,2-fold the human dose) and rabbit in a dose 6,8 mg / kg (0,4-fold the human dose) observed very early gestational sac resorption and complete miscarriage (pervasive post-implantation loss). Fetal resorption in animals is a logical consequence of changes in hormonal levels, related to cetrorelix acetate antigonadotropnym properties, Consequently, and possible loss of the fetus in humans. Animals, who kept the pregnancy, increase in the incidence of fetal abnormalities was observed.

Contraindicated in confirmed or suspected pregnancy (before starting treatment pregnancy should be excluded).

FDA Fetal Action Category — X (Animal tests or clinical trials revealed a violation of the fetus and / or there is evidence of the risk of adverse effects on the human fetus, obtained in research or practice; risk, associated with the use of drugs in pregnancy, greater than the potential benefits.)

Unknown, whether cetrorelix acetate penetrates into breast milk. Because many drugs are excreted in human breast milk, and the effects of cetrorelix acetate on lactation and / or children, are fed on breast milk, We have not been studied, appoint him nursing women should not.

Side effects.

Security cetrorelix acetate was evaluated in controlled clinical trials 949 patients, treated with, directed to controlled ovarian stimulation, aged 19-40 years (average age 32 year), 94% of which are white. Cetrorelix acetate is administered in a dose of 0,1 mg 5 mg once or several times. Systemic side effects of treatment of cetrorelix acetate to confirm the pregnancy using ultrasound, observed in ≥1% of patients: moderate to severe ovarian hyperstimulation syndrome (a sense of tension and pain in the abdomen, vomiting, diarrhea, difficulty breathing) - 3,5% (n = 33), nausea - 1,3% (n = 12), headache - 1,1% (n = 10).

Local reactions (usually transient, medium intensity, short): redness, эritema, subcutaneous hemorrhage, itch, swelling. During post-marketing studies have been rare cases of hypersensitivity reactions, including anaphylactoid reactions.

In the study, as indicated by, not related to infertility (ovarian cancer), one patient after 7 months of treatment in a dose of Cetrorelix acetate 10 mg / day was observed severe anaphylactic reaction to the appearance of cough, rash, gipotenzii.

In Phase 3 clinical trials of cetrorelix acetate were 2 case mertvorozhdeniya.

Congenital anomalies

According to the results of completed clinical trials in 316 newborns from mothers, primenyavshih cetrorelix acetate, We revealed the following anomalies: one of the twins had anencephaly (died 4 days after birth), second born normal; one child was born with a ventricular septal defect and one child with bilateral congenital glaucoma.

In four cases, the pregnancy ended in a medical abortion in Phase 2 and Phase 3 treatment studies, directed to controlled ovarian stimulation (there were major anomalies: diaphragmatic hernia, of trisomy 21 pair of chromosomes, Klinefelter's syndrome, multiple malformations, of trisomy 18 pair of chromosomes). In three of the four cases was performed intracellular sperm injection, the fourth was used IVF.

Small congenital anomalies included: extra nipples, Bilateral strabismus, imperforated hymen, birthmark, hemangioma and long QT syndrome. The causal link between the described anomalies and taking Cetrorelix acetate is unknown. Multiple factors, genetic and other (includes treatment, aimed at stimulating the ovaries, IVF, gonadotropin and progesterone and not only these factors) create difficulties in determining the cause.

Cooperation.

Studies in vitro marked by low probability of interaction with drugs, metabolized by the cytochrome P450 or reacted conjugation, however, completely rule out the possibility of such an interaction can not be.

Overdose.

Data on overdose of cetrorelix acetate 0,25 and 3 mg people have no. Single doses up 120 mg were well tolerated, treated for indications, not related to infertility.

Dosing and Administration.

P /, the lower portion of the abdominal wall, in the area around the navel (To avoid local irritation at repeated dosing regimen should be chosen for the different parts of the injection). Appointed 1 once a day, through 24 no, in the morning or evening, dose 0,25 mg once or during the transition from early to mid follicular phase, at a dose of 3 mg.

The single dosing regimen cetrorelix 3 mg appointed to the 7th day of ovarian stimulation (within 5-9 days) when appropriate response stimulation serum estradiol levels. If during the 4 days after injection at a dose of Cetrorelix acetate 3 mg of injected human CG, should be every day until the day of the appointment of the human HCG administered cetrorelix acetate 0,25 mg.

In a multiple dosing regimen of cetrorelix acetate 0,25 mg appointed to the 5th day of ovarian stimulation (in the morning or evening) or on day 6 (morning), daily, until the day of the appointment of the human CG.

Precautions.

Cetrorelix acetate is to be assigned a doctor with experience treating reproductive disorders. Before initiation of therapy the patient should be advised of the duration of treatment, the need for monitoring procedures and the risk of possible adverse reactions. Careful monitoring of the patients with hypersensitivity to GnRH after the first injection.

In the case of ovarian hyperstimulation syndrome symptomatic treatment (recreation, in / with the introduction of electrolytes or colloids, holding heparin).

Support of the luteal phase (event, aimed at supporting pregnancy) It should be carried out in accordance with common practice of reproductive events.

Due to insufficient clinical experience of re-stimulation of ovulation using the drug with repeated courses of treatment should be used with caution and only after careful evaluation of the degree of doctor the potential risks and the effectiveness of treatment.