Cetrotide^® (Lyophilisate) Instructions for Use

ATC Code

H01CC02 (Cetrorelix)

Active Substance

Cetrorelix (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Gonadotropin-releasing hormone antagonist

Pharmacotherapeutic Group

Pituitary and hypothalamic hormones and their analogues; hypothalamic hormones; antigonadotropin-releasing hormones

Pharmacological Action

GnRH antagonist. Exerts a competitive effect on the binding of endogenous GnRH to the receptors of pituitary cell membranes. Due to this, Cetrorelix controls the secretion of gonadotropins (LH and FSH). Causes a dose-dependent inhibition of LH and FSH secretion by the pituitary gland.

In the absence of prior stimulation, the onset of inhibition of pituitary secretory function occurs almost immediately after the administration of cetrorelix. In women, it causes a delay in the LH surge and, consequently, ovulation.

The duration of action depends on the magnitude of the applied dose.

The effect of cetrorelix is completely reversible after discontinuation of treatment.

Pharmacokinetics

Cetrorelix is rapidly absorbed after s/c injection, the absolute bioavailability is about 85%. Pharmacokinetic parameters after a single s/c administration of 0.25 mg and multiple administration (over 14 days), respectively: C_max – 4.17-5.92 ng/ml and 5.18-7.96 ng/ml; T_max – 0.5-1.5 h and 0.5-2 h; AUC – 23.4-42 ng/h/ml and 36.7-54.2 ng/h/ml. V_d is 1.1 l/kg. T_1/2 is 2.4-48.8 h and 4.1-179.3 h after single and multiple (over 14 days) s/c administration of a 0.25 mg dose, respectively. Cetrorelix is excreted by the kidneys.

Indications

Prevention of premature ovulation in patients undergoing treatment aimed at achieving controlled ovarian stimulation, followed by oocyte retrieval and assisted reproductive technologies.

ICD codes

Dosage Regimen

Administer Cetrotide^® as a single daily subcutaneous injection at a dose of 0.25 mg.

Initiate treatment on day 5 or 6 of ovarian stimulation (approximately 120 hours after starting gonadotropins).

Continue treatment daily until the day of final follicular maturation is achieved, as determined by your physician.

Alternatively, administer a single 3 mg dose subcutaneously.

For this regimen, administer the 3 mg dose on day 7 of ovarian stimulation (approximately 144 hours after starting gonadotropins).

If ovulation induction with hCG has not occurred within 4 days after the 3 mg dose, administer a supplementary daily dose of 0.25 mg until the day of hCG administration to prevent a premature LH surge.

Reconstitute the lyophilisate immediately before use with 0.9% Sodium Chloride solution.

Inject the solution subcutaneously, preferably into the lower abdominal wall; rotate injection sites daily.

Follow your physician’s instructions precisely regarding the timing and duration of treatment.

Adverse Reactions

Immune system disorders: uncommon – systemic allergic or pseudoallergic reaction, including life-threatening anaphylaxis.

Nervous system disorders: uncommon – headache.

Gastrointestinal disorders: uncommon – nausea.

Reproductive system and breast disorders: common – mild or moderate ovarian hyperstimulation syndrome (OHSS) – grade I-II according to WHO classification; uncommon – severe OHSS – grade III according to WHO classification.

Local reactions common – redness, swelling, itching at the injection site, usually transient and mild.

Contraindications

Hypersensitivity to cetrorelix or exogenous peptide hormones; moderate or severe renal failure, moderate or severe hepatic failure; postmenopausal period; pregnancy, lactation (breastfeeding).

With caution

In the presence of signs and symptoms of an active allergic process or a history of predisposition to allergies.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindicated in moderate or severe hepatic impairment.

Use in Renal Impairment

Contraindicated in moderate or severe renal impairment.

Special Precautions

If OHSS develops, symptomatic therapy should be carried out (including rest, intravenous administration of electrolytes or colloid solutions, heparin therapy).

Luteal phase support should be carried out in accordance with the generally accepted practice of reproductive procedures.

Caution should be exercised when using cetrorelix in the presence of signs and symptoms of an active allergic process or a history of predisposition to allergies; in women with severe allergic conditions, the use of cetrorelix should be avoided.

To date, experience with repeated ovarian stimulation using cetrorelix is limited. For repeated courses of treatment, Cetrorelix should be used after assessing the degree of potential risk and treatment effectiveness.

Drug Interactions

A low likelihood of drug interactions has been demonstrated when cetrorelix is administered concomitantly with drugs metabolized by cytochrome P450, or undergoing glucuronidation or any other conjugation reactions.

Although there is no evidence of interaction with other widely used drugs, in particular with gonadotropins and drugs that potentially induce histamine release in patients with a predisposition to allergies, the possibility of drug interaction when used concomitantly with cetrorelix cannot be completely excluded.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.