Cetrotide® (Cetrotid®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceCetrorelixCetrorelix
Similar drugsTo uncover
  • Cetrotide®
    lyophilizate PC 
    Merck Serono Juorope Limited     United Kingdom
    • Dosage form: & nbspLyophilizate for the preparation of a solution for subcutaneous administration.
    Composition:

    In one bottle with a drug in a dose of 0.25 mg contains:

    Active substance:

    Cetrorelix acetate, in terms of cetrorelix - 0.25 mg.

    Excipient:

    Mannitol - 54.8 mg.


    In one bottle with a drug in a dose of 3 mg contains:

    Active substance:

    Cetrorelix acetate, in terms of cetrorelix, 3.0 mg.

    Excipient:

    Mannitol - 164.4 mg.

    In one pre-filled syringe with a solvent for a dose of 0.25 mg is contained

    Water for injection -1,0 ml.

    In one pre-filled syringe with a solvent for a dose of 3 mg contains:

    Water for injection - 3.0 ml.

    Description:Preparation: powder or mass (in the form of a flat cake) white or almost white.
    Solvent: Clear, colorless liquid.
    Pharmacotherapeutic group:Gonadotropin-releasing hormone analog.
    ATX: & nbsp

    H.01.C.C.02   Cetrorelix

    Pharmacodynamics:Cetrorelix, being an analogue of gonadotropin-releasing hormone (GnRH), binds to the receptors of membranes of pituitary cells and competitively inhibits the binding of endogenous GnRH to these receptors. Cetrorelix dose-dependent inhibits the secretion of gonadotropins by the pituitary gland - luteinizing (LH) and follicle-stimulating (FSH) hormones. In the absence of preliminary stimulation, the onset of oppression of the secretory function of the pituitary gland occurs virtually immediately after the administration of the drug, the duration of action of cetrorelix depends on the dose administered. Among women cetrorelix causes a delay in raising the level of LH and, therefore, ovulation. After a single injection of 3 mg of cetrorelix, the drug continues for at least 4 days (on the 4th day after administration, the secretory function is inhibited by 70%). Regular administration of cetrorelix by 0.25 mg every 24 hours maintains the effect of the drug. The action of cetrorelix is ​​completely reversible after discontinuation of treatment.
    Pharmacokinetics:

    Suction and distribution

    Quickly absorbed after a subcutaneous injection, the absolute bioavailability is about 85%. The volume of distribution is 1.1 l / kg.

    Pharmacokinetic parameters after a single subcutaneous injection of 0.25 mg and repeated administration (for 14 days), respectively: the maximum concentration - (CmOh) in plasma - 4,17-5,92 ng / ml and 5,18-7,96 ng / ml; time to reach CmOh (TFROMmOh) 0.5-1.5 hours and 0.5-2 hours; area under the concentration-time curve (AUC) - 23.4-42 ng / h / ml and 36.7-54.2 ng / h / ml.

    Excretion

    The half-life (T1 / 2) is 2.4-48.8 hours and 4.1-179.3 hours after a single and multiple (within 14 days) subcutaneous dose of 0.25 mg, respectively. With subcutaneous administration of single doses of cetrorelix (0.25 to 3 mg), as well as with daily administration for 14 days, the pharmacokinetics of the drug shows a linear relationship.

    The mean final half-life after intravenous and subcutaneous administration is 12 and 30 hours, respectively, indicating absorption at the site of administration. Cetrorelix is excreted by the kidneys. The total plasma and renal clearance is 1.2 ml / min x kg and 0.1 ml / min x kg, respectively. The final half-life after intravenous and subcutaneous administration is, respectively, an average of about 12 and 30 hours.

    Indications:Prevention of premature ovulation in patients with controlled stimulation of ovulation for the production of eggs and assisted reproductive technologies.
    Contraindications:
    - Hypersensitivity to cetrorelix acetate, any other structural analogues of GnRH and other exogenous peptide hormones, mannitol;
    - pregnancy and lactation;
    - postmenopausal period;
    - renal or hepatic insufficiency of moderate or severe degree.
    Carefully:In the presence of signs and symptoms of an active allergic process or predisposition to an allergy in an anamnesis.
    Pregnancy and lactation:Cetrotide is contraindicated for use during pregnancy and during lactation.
    Dosing and Administration:

    Cetrotide can be prescribed only by a gynecologist. To achieve maximum effectiveness of treatment with Cetrotide, you should carefully read these recommendations.

    After the first injection, a patient of 30 minutes should be under the supervision of a physician to make sure that there is no allergic or pseudo-allergic reaction to administer the drug. All tools and drugs to stop such a reaction should be available.

    Cetrotide 0.25 mg

    The contents of 1 vial (0.25 mg cetrorelix) should be administered once a day every 24 hours in the morning or evening.

    Drug administration in the morning: Cetrotide treatment should be started on the 5th or 6th day of ovarian stimulation (approximately 96-120 hours after the onset of stimulation) with a gonadotropin preparation,recombinant or excreted from urine, and continue throughout the period of gonadotropin stimulation, including the day of administration of the ovulatory dose of chorionic gonadotropin (CG).

    Administration of the drug in the evening: Cetrotide treatment should be started on day 5 of ovarian stimulation (approximately 96-108 hours after the onset of stimulation) with a gonadotropin drug recombinant or excreted from urine and continue for the entire period of gonadotropin stimulation, including the evening preceding the day of administration of the ovulatory dose of CG.

    Cetrotide 3.0 mg

    The contents of 1 vial (3.0 mg of cetrorelix) should be given on the 7th day of ovarian stimulation (approximately 132-144 hours after the onset of stimulation) with a gonadotropin preparation, recombinant or isolated from urine.

    After a single injection of 3.0 mg cetrorelix, the drug continues for at least 4 days. If at 5 day after the introduction of Cetrotide 3.0 mg, the size of the follicles does not allow the appointment of ovulation induction, 0.25 mg of cetrorelix (Cetrotid 0.25 mg) should be additionally administered once a day, beginning 96 hours after the administration of Cetrotide 3.0 mg and including the day of administration of the ovulatory dose of HG.

    Recommendations for the self-administration of the drug Zetrothid 0.25 mg and 3.0 mg (information for the patient).

    The first injection should be done by a specialist doctor. After receiving the appropriate instructions from the doctor about the symptoms that may indicate the occurrence of an allergic reaction, the consequences of such a reaction and the need for its treatment, the patient can independently enter Cetrotide.

    The cetrotide is injected subcutaneously into the lower part of the anterior abdominal wall, preferably into the area around the navel. To avoid the appearance of local irritation with repeated administration of the drug, the injection site should be changed daily.

    Cetrotide should be diluted only in the attached solvent. During the dissolution, the vial should be shaken gently. To avoid the formation of bubbles, do not use vigorous shaking to accelerate dissolution. Do not use the solution if it is opaque or contains undissolved particles.

    From the vial should be typed in a syringe all its contents. This will allow to enter a dose of cetrorelix no less than 0.23 mg with the use of Zetrothid 0.25 mg and at least 2.82 mg with the use of Cetrotide 3.0 mg.The solution should be administered immediately after its preparation.

    With the self-introduction of Cetrotide, you must perform the following actions:

    1. Wash your hands. It is very important that the hands and all the necessary devices for injection are clean.

    2. On a clean surface, arrange everything you need for injection (one vial, one syringe with thinner, one needle with yellow marking, one needle with a gray marking and two impregnated sponge tampons).

    3. Open the flip cover on the vial. Wipe with one swab with alcohol, an aluminum ring and a rubber stopper.

    4. Take a needle with a yellow marking and remove the wrapper from it. Remove the syringe with the solvent from the package. Put the needle on the syringe with the solvent and remove the protective cap from it.


    5. Insert the needle into the center of the vial of the vial. Insert the solution from the syringe into the vial slowly pressing the plunger.


    6. Without removing the needle from the bottle, gently shake the bottle until the powder is completely dissolved. Avoid vigorous shaking so that no bubbles form during dissolution.

    7. Type the entire contents of the vial into the syringe.If there is a solution in the vial, turn the vial and pull the needle out so that its opening is immediately below the stopper. If you look from the side to the inside of the plug, you can control the movement of the needle and fluid. It is very important to fill the contents of the vial with a syringe.


    8. Remove the needle from the syringe and place the syringe. Take a needle with a gray marking and remove the wrapper from it. Put the needle on the syringe and remove the protective cap from it.

    9. Turn the syringe upside down and press the plunger until all the air bubbles come out of the syringe. Do not touch the needle or allow it to come into contact with any surface.


    10. Choose the place of administration of the drug in the lower part of the anterior abdominal wall, preferably in the area around the navel. Take a second swab impregnated with alcohol, and wipe the skin at the site of the intended introduction. Hold the syringe in one hand. With the second hand, squeeze gently - the skin surrounding the insertion site, and firmly fix it between the fingers.


    11. Take the syringe the way you normally hold a pencil, and at a 45-degree angle, completely insert the needle into the skin.


    12. After completely inserting the needle, stop squeezing the skin.

    13. Carefully pull the plunger of the syringe back. If blood appears in the syringe, proceed as described in point 14. If there is no blood, slowly inject the solution, pressing the plunger. After the administration of the entire solution, slowly remove the needle and gently press the alcohol-impregnated swab onto the skin at the injection site. Remove the needle from the skin at the same angle at which it was inserted.

    14. If blood appears in the syringe, remove the needle from the skin and press it gently with a swab at the point where the needle is inserted. For repeated injection, this solution can not be used, pour the contents of the syringe into the sink. Start all over from point 1.

    15. The syringe and needles can only be used once. Immediately after use, discard them (to prevent injury, put protective caps on the needles).
    Side effects:
    The most frequent reactions at the injection site, such as reddening, itching and swelling, are generally mild and passing. In clinical trials, these events were observed at a frequency of 9.4% after multiple injections of Cetrotide at a dose of 0.25 mg.
    In the procedure for stimulation of ovulation by gonadotropins, the syndrome of ovarian hyperstimulation (OSS) from mild to moderate severity (grade I-II according to WHO classification) was relatively common.On its appearance may indicate symptoms such as a feeling of tension and abdominal pain, nausea, vomiting, diarrhea, weight gain, increased ovaries (see section "Special instructions"). On the other hand, severe SWC (grade III - according to the WHO classification) was infrequent (hypersensitivity, ascites, hypovolemia,
    hemoconcentration, electrolyte imbalance, pleural effusions, accumulation
    fluid in the pericardial cavity, oliguria, acute respiratory distress syndrome and thromboembolic disorders).
    Hypersensitivity reactions, including pseudoallergic / anaphylactoid reactions (similar in symptoms with allergic, but without the development of antibodies, and usually manifested to varying degrees in the form of redness of the skin, heat, urticaria, headache, difficulty breathing) were noted infrequently.

    Below are the data on all the undesirable reactions observed with the application of Cetrotide, in accordance with the generally accepted system-organ classification, which, depending on the incidence, are divided into very frequent (>1/10 applications), frequent (>1/100 and <1/10), infrequent (>1/1000 and <1/100), the rare (>1/10000 and <1/1000) and very rare (<1/10000).

    Immune system disorders

    Infrequently: systemic allergic or pseudo-allergic reaction, including life-threatening anaphylaxis.

    Disturbances from the nervous system

    Infrequently: a headache.

    Disorders from the gastrointestinal tract

    Infrequently: nausea.

    Violations of the genitals and mammary gland

    Often: mild or moderate SWC (I-II Art. according to WHO classification);

    Infrequently: severe SWC (grade III according to WHO classification).


    General disorders and disorders at the site of administration

    Often: reactions at the injection site (redness, swelling, pruritus) are usually transient and mild.

    Overdose:Overdose of the drug Cetrotide may lead to an increase in the duration of its action, however, this is not accompanied by acute toxicity effects (in case of an overdose, no special measures are required).
    Interaction:In vitro studies, a low probability of drug interactions was demonstrated with simultaneous administration of Cetrotide with drugs metabolized with cytochrome P450, or undergoing glucuronization or some other conjugation.Although there is no evidence of interaction with other widely used drugs, in particular gonadotropins and drugs potentially inducing histamine release in patients with a predisposition to allergy, the likelihood of drug interaction can not be completely ruled out, while they can be used with Cetrotide. It is necessary to inform the attending physician about all medications taken shortly before the beginning of treatment by Cetrotide or taken at the present time.
    Special instructions:Cetrotide 0.25 mg is best administered regularly every 24 hours. If you miss a regular injection of the drug, you can inject at any other time during the same day.
    Care should be taken when using the drug in the presence of signs and symptoms of an active allergic process or predisposition to an allergy in an anamnesis; in women with severe allergic conditions, the use of the drug should be avoided, and therefore it is very important for the patient to inform the attending physician of all the manifestations of allergy present in her.During or after the stimulation of ovulation, CHD may occur, in which case appropriate therapy is performed. The occurrence of HNS is regarded as an inherent risk in the procedure for stimulating ovulation by gonadotropins. For gonadotropin prescribing regimens in combination with GnRH antagonists, a correlation was observed with a shorter period of stimulation, as well as smaller doses of gonadotropins and lower concentrations of estradiol. These observations may indicate a reduction in the risk of the occurrence of an acute hypoglycemic event when GnRH antagonists are used. HSH can rapidly progress (from days to several days) to a severe condition, so after the administration of HG it is necessary to observe for at least two weeks.
    To minimize the risk of CHD, ultrasound and estrogen concentrations in the blood plasma are regularly used.
    In the development of severe CHD, gonadotropin therapy, if it continues, should be discontinued. The patient should be hospitalized and prescribed a specific treatment for CHD.
    Support for the luteal phase should be carried out in accordance with the generally accepted practice of assisted reproductive technologies.
    To date, the experience of repeated carrying out of stimulation of ovulation with the use of Cetrotide is limited. Therefore, the drug with repeated courses of treatment should be used after assessing the degree of potential risk and the effectiveness of treatment.
    Effect on the ability to drive transp. cf. and fur:Cetrotide does not affect the ability to drive a car and other mechanical means.
    Form release / dosage:
    Lyophilizate for the preparation of a solution for subcutaneous administration 0.25 mg.
    Packaging:
    For 0.25 mg of cetrorelix in a vial of colorless clear glass type I (Hebrew F.), sealed with a rubber stopper, sealed on top by an aluminum cap with a detachable plastic cap of the "flip-off" type.
    For 1.0 ml of water for injection in a pre-filled glass type I syringe (Hebrew F./F. USA) equipped with a polypropylene rod-piston with a rubber seal and a cap of
    polypropylene.
    The kit includes:
    1 bottle with lyophilizate;
    1 pre-filled syringe with solvent;
    1 needle (20G) in individual packing made of paper and polymer film;
    1 needle (27G) in individual packing made of paper and polymer film;
    2 tampons of nonwoven material impregnated with 70% isopropyl alcohol, in a two-layer package of laminated foil.
    For 1 or 7 sets (0.25 mg only) in a contoured cell pack of plastic sealed with a paper lid, together with instructions for use in a pack of cardboard.
    Storage conditions:Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
    Shelf life:
    Lyophilizate - 2 years. Solvent - 3 years.
    Do not use after the expiry date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:П N014978 / 01
    The owner of the registration certificate:Merck Serono Juorope LimitedMerck Serono Juorope Limited United Kingdom
    Manufacturer: & nbsp
    Representation: & nbspARES TRADING SAARES TRADING SARussia
    Information update date: & nbsp16.10.2015
    Illustrated instructions
    Instructions
    Up