Composition, form of production and packaging
Liofilizate for the preparation of a solution for s / c injection in the form of powder or mass (in the form of a flat cake) white or almost white.
1 f.
cetrorelix (in the form of acetate) 250 Ојg
Excipients: mannitol - 54.8 mg.
Solvent: water d / u - 1 ml.
Vials of colorless glass (1) complete with a solvent (syringes 1 pc.), Needles (1 needle No. 20 for the introduction of solvent into the vial, 1 needle No. 27 for injection) and tampons with alcohol (2 pcs.) - Contour (1) - packs cardboard.
Vials of colorless glass (1) complete with a solvent (syringes 1 pc.), Needles (1 needle No. 20 for the introduction of solvent into the vial, 1 needle No. 27 for injection) and tampons with alcohol (2 pcs.) - Contour (7) - packs cardboard.
Liofilizate for the preparation of a solution for s / c injection in the form of powder or mass (in the form of a flat cake) white or almost white.
1 f.
cetrorelix (in the form of acetate) 3 mg
Excipients: mannitol - 164.4 mg.
Solvent: water q / u - 3 ml.
Vials of colorless glass (1) complete with a solvent (syringes 1 pc.), Needles (1 needle No. 20 for the introduction of solvent into the vial, 1 needle No. 27 for injection) and tampons with alcohol (2 pcs.) - Contour (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
Analog GnRH. Cetrorelix binds to receptors of membranes of pituitary cells and competitively inhibits the binding of endogenous GnRH to these receptors. Cetrorelix dosozavisimo inhibits the secretion of the pituitary gland gonadotropins - LH and FSH. 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. In women, cetrorelix causes a delay in raising the level of LH and, therefore, ovulation.
After a single administration of cetrorelix at a dose of 3 mg, the effect of the drug continues for at least 4 days (on the 4th day after administration, the secretory function is inhibited by 70%). Regular administration of 250 Ојg every 24 hours maintains the effect of the drug.
The action of cetrorelix is ​​completely reversible after discontinuation of treatment.
PHARMACOKINETICS
Suction and distribution
After the injection of cetrorelix rapidly absorbed, bioavailability - 85%. Pharmacokinetic parameters after a single sc administration at a dose of 250 Ојg and repeated administration (within 14 days), respectively: C max - 4.17-5.92 ng / ml and 5.18-7.96 ng / ml; T max is 0.5-1.5 h and 0.5-2 h; AUC was 23.4-42 ng h / ml and 36.7-54.2 ng h / ml.
With the introduction of cetrorelix in single doses (from 250 Ојg to 3 mg), as well as with daily administration for 14 days, the linear kinetics of the drug is noted.
V d is equal to 11.1 l / kg.
Excretion
After a single SC administration at a dose of 250 Ојg and repeated administration (within 14 days), T 1/2 is 2.4-48.8 hours and 4.1-179.3 hours, respectively. It is excreted by the kidneys. The total plasma and renal clearance is 1.2 ml / min, respectively? kg and 0.1 ml / min? kg. The final T 1/2 after IV and SC administration is an average of about 12 hours and 30 hours, respectively.
INDICATIONS
- Prevention of premature ovulation with controlled stimulation of ovulation for the production of eggs and assisted reproductive technologies.
DOSING MODE
Treatment Cetrotide can be performed only by a gynecologist with clinical experience of using this drug.
After the first injection, a clinical control is necessary for 30 min to detect symptoms of a possible allergic or pseudo-allergic reaction to the drug administration. At the same time, it is necessary to provide conditions and facilities for stopping such reactions.
Cetrotide in a dose of 250 mcg (1 vial) should be administered 1 time / day every 24 hours in the morning or in the evening.
Administration of the drug 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 drug recombinant or excreted from urine and continue for the entire period of gonadotropin stimulation, including the day of the ovulatory dose of the chorionic gonadotropin (HG).
Administration of the drug in the evening: Cetrotide treatment should be started on the 5th day 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 ovulatory dose administration HG.
Cetrotide at a dose of 3 mg (1 vial) should be administered 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 administration of Cetrotide in a dose of 3 mg, the effect of the drug continues for at least 4 days. If on the 5th day after the introduction of Cetrotide at a dose of 3 mg, the size of the follicles does not allow the induction of ovulation, Cetrotide should be additionally administered at a dose of 250 Ојg (1 vial) 1 time / day, starting 96 hours after the administration of Cetrotide at a dose of 3 mg and including day the introduction of an ovulatory dose of CG.
Rules for the preparation of injection solutions and drug administration
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.
Cetrotid should be injected s / c into the lower part of the anterior abdominal wall, preferably in the area around the navel. To avoid the appearance of local irritation with the repeated administration of the drug, the injection site should be changed daily.
Cetrotide should be dissolved only with the help of the applied solvent. During the dissolution, the vial should be gently shaken. 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 the syringe all its contents. This will introduce a dose of cetrorelix of at least 230 Ојg when using Zetrothid 250 Ојg and at least 2.82 mg with the use of Zetrothid 3 mg.
The solution should be administered immediately after its preparation.
With self-introduction of Cetrotide, the following recommendations must be fulfilled:
1. Wash your hands. It is very important that the hands and all the necessary adaptations are clean.
2. Place on the clean surface what is necessary for the injection (1 bottle, 1 syringe with solvent, 1 needle with yellow marking, 1 needle with gray marking and 2 alcohol impregnated swabs).
3. Open the flip cover on the vial. Wipe with one swab with alcohol, an aluminum ring and a rubber stopper.
4. Remove the wrapper from the needle with the yellow marking. Remove the syringe with 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, you should gently rock 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 the solution remains in the vial, you should 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 put the syringe. Remove the wrapper from the needle with a gray marking. Put this needle on the syringe and remove the protective cap from it.
9. Turn the syringe with the needle upwards and press down on the piston until all air bubbles leave the syringe. Do not touch the needle or allow it to come into contact with any surface.
10. Place of injection - 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. In one hand, you should hold a syringe, with the second hand gently squeeze the skin surrounding the injection site, and firmly fix it between the fingers.
11. Take the syringe the way you normally hold a pencil, and at a 45 В° angle completely insert the needle into the skin.
12. After completely inserting the needle, the skin should be released.
13. Carefully pull the syringe piston back. If blood appears in the syringe, then you should act in accordance with clause 14. In the absence of blood, slowly inject the solution by 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 the injection site lightly with a swab. For repeated injection, this solution can not be used, so the contents of the syringe should be poured. Then start the procedure first with step 1.
15. The syringe and needles can only be used once. Immediately after use, they should be discarded (to avoid injury, wear protective caps on the needle).
SIDE EFFECT
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 with a frequency of 9.4% after multiple injections of Cetrotide at a dose of 250 Ојg.
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. On the other hand, severe SWC (grade III according to WHO classification) was infrequent (shortness of breath, ascites, hypovolemia, hemoconcentration, electrolyte imbalance, pleural effusion, accumulation of 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, feelings of heat, hives, headaches, difficulty breathing) were noted infrequently.
The data on all the undesirable reactions observed with the use of Cetrotide are given below, in accordance with the generally accepted system-organ classification, which, depending on the incidence, are divided into very frequent (? 1/10 cases), frequent (? 1/100 and <1 / 10), infrequent (? 1/1000 and <1/100), rare (? 1/10 000 and <1/1000) and very rare (<1/10 000).
From the immune system: infrequently - a systemic allergic or pseudoallergic reaction, including life-threatening anaphylaxis.
From the nervous system: infrequently - a headache.
From the side of the digestive system: infrequently - nausea.
On the part of the genitals: often - easy or moderate HSH (I-II degree according to WHO classification); infrequently - severe SWC (grade III according to WHO classification).
Local reactions: often - reactions at the injection site (redness, swelling, pruritus), usually transient and mild.
CONTRAINDICATIONS
- moderate or severe renal failure;
- hepatic insufficiency of moderate or severe degree;
- the period of postmenopause;
- Pregnancy;
- lactation;
- Hypersensitivity to cetrorelix acetate, any other structural analogues of GnRH, other exogenous peptide hormones, mannitol.
Caution should be applied to the drug 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.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated use of the drug for renal failure of moderate or severe degree.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated use of the drug for hepatic insufficiency of moderate or severe degree.
APPLICATION FOR CHILDREN
Not applicable.
APPLICATION IN ELDERLY PATIENTS
Not applicable.
SPECIAL INSTRUCTIONS
Cetrotide at a dose of 250 mcg 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.
Cetrotide is not recommended for women prone to severe allergic reactions, so before using the drug should carefully collect anamnesis to clarify all the existing manifestations of allergies.
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. OCG can rapidly progress (from days to several days) to a severe condition, so after the administration of HC it is necessary to observe for at least 2 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.
Impact on the ability to drive vehicles and manage mechanisms
Cetrotide does not affect the ability to drive vehicles and other mechanical means.
OVERDOSE
Overdosing of the drug Cetrotide may lead to an increase in the duration of its action, but this is not accompanied by symptoms of acute toxicity.
In the event of an overdose, no special measures are required.
DRUG INTERACTION
In vitro studies, a low probability of drug interaction was demonstrated when combined with the administration of Cetrotid with drugs metabolized with the participation of cytochrome P450 isoenzymes or subjected to conjugation reactions.
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 warn the patient about the need to inform the doctor about any medications that she takes or expects to take against the background of Cetrotide therapy.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 2 years, solvent - 3 years.
