Cetrotide

Cetrorelix acetate.

Each vial contains cetrorelix acetate 0.26-0.27 mg equivalent to 0.25mg cetrorelix.
It also contains the following excipients: Mannitol and water for injections 1 mL.

Pharmacotherapeutic Group: LHRH-Antagonist. ATC Code: G03X.
Pharmacology: Cetrotide inhibits the effects of a natural hormone, called luteinising hormone (LHRH). LHRH regulates the secretion of another hormone, called luteinising hormone (LH), which induces ovulation during the menstrual cycle. Cetrotide inhibits premature ovulation which is undesirable during hormone treatment for ovarian stimulation as only mature egg cells are suitable for fertilization.
Pharmacodynamics: Cetrorelix is a luteinising hormone releasing hormone (LHRH) antagonist. LHRH binds to membrane receptors on pituitary cells.
Cetrorelix competes with the binding of endogenous LHRH to these receptors. Due to this mode of action, cetrorelix controls the section of gonadtropins (LH and FSH).
Cetrorelix dose-dependently inhibits the secretion of LH and FSH from the pituitary gland. The onset of supression is virtually immediate and is maintained by continuous treatment, without initial stimulatory effect.
In females, cetrorelix delays the LH surge and consequently ovulation. In women undergoing ovarian stimulation the duration of action of cetrorelix is dose dependent. Following a single dose of cetrorelix 3 mg a duration of action of at least 4 days has been evaluated.
On day 4 the supression was approximately 70%. At a dose of 0.25 mg per injection repeated injections every 24 hrs will maintain the effect of cetrorelix.
In animals as well as humans, the antagonistic hormonal effects of cetrorelix were fully reversible after termination of treatment.
Pharmacokinetics: The absolute bioavialability of cetrorelix after SC administration is about 85%.
The total plasma clearance and the renal clearance are 1.2 mL x min^-1 kg^-1 and 0.1 mL x min^-1 x kg^-1, respectively. The volume of distribution (Vd/area) is 1.1 l x kg^-1. The mean terminal half-lives following IV and SC administration are about 12 hrs and 30 hrs, respectively, demonstrating the effect of absorption processes at the injection site. The SC administration of a single dose (cetrorelix 0.25-3 mg) and also daily dosing over 14 days show linear kinetics.

Prevention of premature ovulation in patients undergoing a controlled ovarian stimulation, followed by oocyte pick-up and assisted reproductive techniques. In clinical trials, Cetrotide was used with human menopausal gonadotropin (HMG), however, limited experience with recombinant FSH suggested similar efficacy.

Cetrotide should only be prescribed by a specialist experienced in this field.
Administration: Cetrotide is for SC injection into the lower abdominal wall. The 1st administration of Cetrotide should be performed under the supervision of a physician and under conditions where treatment of possible pseudoallergic reactions is immediately available. The following injections may be self-administered as long as the patient is made aware of the signs and symptoms that may indicate hypersensitivity, the consequences of such a reaction and the need for immediate medical intervention.
The contents of 1 vial (cetrorelix 0.25 mg) are to be administered once daily, at 24 hrs intervals, either in the morning or in the evening. Following the 1st administration, it is advised that the patient be kept under medical supervision for 30 min to ensure there is no allergic/pseudoallergic reaction to the injection. Facilities for the treatment of such reactions should be immediately available.
Administration in the Morning: Treatment with Cetrotide should commence on day 5 or 6 of ovarian stimulation (approximately 96-120 hrs after start of ovarian stimulation) with urinary or recombinant gonadotropins and is to be continued throughout the gonadotropin treatment period including the day of ovulation induction.
Administration in the Evening: Treatment with Cetrotide should commence on day 5 of ovarian stimulation (approximately 96-108 hrs after start of ovarian stimulation) with urinary or recombinant gonadotropins and is to be continued throughout the gonadotropin treatment period until the evening prior to the day of ovulation induction.
Missed a Dose: If you missed to administer Cetrotide on one day, please contact your doctor immediately and ask for advice. Ideally Cetrotide should be administered at 24 hrs intervals. But if you missed to administer Cetrotide at the right time it is no problem to administer this dose at a different time on the same day.

Overdosage in humans may result in a prolonged duration of action but is unlikely to be associated with acute toxic effects. Therefore, in case of overdosage no specific measures are required.
In acute toxicity studies in rodents, nonspecific toxic symptoms were observed after intraperitoneal administration of cetrorelix doses >200 times higher than pharmacologically effective doses after SC administration.

Hypersensitivity to any structural analogues of gonadotropin-releasing hormone (GnRH) or mannitol; postmenopausal women; moderate to severe renal and hepatic impairment. Pregnancy and lactation.

During or following ovarian stimulation an ovarian hyperstimulation syndrome can occur. This event must be considered as an intrinsic risk of the stimulation procedure with gonadotropins.
An ovarian hyperstimulation syndrome should be treated symptomatically eg, with rest, IV electrolytes/colloids and heparin therapy.
Luteal phase support should be given according to the reproductive medical centre's practice.
There is limited experience up to now with the administration of Cetrotide during a repeated ovarian stimulation procedure. Therefore, Cetrotide should be used in repeated cycles only after a careful risk/benefit evaluation.
Effects on the Ability to Drive or Operate Machinery: Due to its pharmacological profile, cetrorelix is unlikely to impair the patient's ability to drive or to operate machinery.
Use in pregnancy & lactation: Cetrotide is not intended to be used during pregnancy and lactation (see Contraindications).
Studies in animals have indicated that cetrorelix exerts a dose related influence on fertility, reproductive performance and pregnancy. No teratogenic effects occurred when the drug was administered during the sensitive phase of gestation.

Cetrotide is not intended to be used during pregnancy and lactation.
Studies in animals have indicated that cetrorelix exerts a dose related influence on fertility, reproductive performance and pregnancy. No teratogenic effects occurred when the drug was administered during the sensitive phase of gestation.

Mild and transient reactions at the injection site eg, erythema, itching and swelling.
Occasionally systemic side effects eg, nausea and headache have been reported. In addition, a single case of pruritus have been reported during treatment with cetrorelix.
A sever hypersensitivity reaction associated with cough, rash and hypotension, was observed in one patient after 7 months of treatment of ovarian cancer with cetrorelix (10 mg daily). The patient recovered completely within 20 min. A casual relation could not be excluded.
Occasionally an ovarian hyperstimulation syndrome (OHSS) can occur which is an intrinsic risk of the stimulation procedure (see Precautions).
Symptoms like abdominal pain, tension, nausea, vomiting, diarrhoea and breathing difficulties may indicate an OHSS.
Inform the physician immediately, if such symptoms occur. If any unwanted effect not mentioned in the leaflet is noticed or if unsure about the effect of the medicine, please inform the physician or pharmacist.

In vitro investigations have shown that interactions are unlikely with medications that are metabolised by cytochrome P-450 or glucuronised or conjugated in some other way. However, the possibility of interactions with commonly used medicinal products can not entirely be excluded.

Cetrotide is for injection under the skin of the lower abdominal wall, preferably around the navel. To minimise local irritation, please select a diff erent injection site each day.
Dissolve Cetrotide only with the water contained in the pre-filled syringe. Do not use Cetrotide solution if it contains particles or if it is not clear.
Before administration, please read the following instructions clearly.
1. Wash hands well with soap and water.
2. On a clean surface, lay out everything needed (1 vial, 1 pre-filled syringe, 1 injection needle with a yellow mark, 1 injection needle with a grey mark and 2 alcohol wipes).
3. Flip off the plastic cover of the vial. Wipe the aluminum ring and the rubber stopper with an alcohol wipe.
4. Take the injection needle with the yellow mark and remove the wrapping. Take the pre-filled syringe and remove the cover. Put the needle on the syringe and remove the cover of the needle.
5. Push the needle through the center of the rubber stopper of the vial. Inject the water into the vial by slowly pushing the plunger of the syringe.
6. Leave the syringe on the vial. Gently shake the vial until the solution is clear and without residue. Avoid forming bubbles during dissolution.
7. Draw the total contents of the vial into the syringe. If liquid is left in the vial, invert the vial, pull back the needle until the opening of the needle is just inside the stopper. Look from the side through the gap in the stopper to control the movement of the needle and the liquid. It is important to withdraw the entire contents of the vial.
8. Detach the syringe from the needle and lay down the syringe. Take the injection needle with the grey mark and remove its wrapping. Put the needle on the syringe and remove the cover of the needle.
9. Invert the syringe and push the plunger until all air bubbles have been pushed out. Do not touch the needle or allow the needle to touch any surface.
10. Choose an injection site at the lower abdominal wall, preferably around the belly button. If on a multiple dose (0.25-mg) regimen, choose a different injection site each day to minimize local irritation. Take the 2nd alcohol wipe, clean the skin at the injection site, and keep the wipe. Hold the syringe in one hand. Gently pinch up the skin surrounding the site of injection and hold firmly with the other hand.
11. Hold the syringe like holding a pencil, insert the needle completely into the skin at an upward angle of about 45°.
12. Once the needle have been inserted completely, release grasp of the skin.
13. Gently pull back the plunger of the syringe to check the correct positioning of the needle. If no blood appears, inject the entire solution by slowly pushing the plunger forward. After all of the solution has been injected, take out the needle at the same angle as it was inserted. Gently press the alcohol wipe on the injection site.
14. If blood appears, withdraw the needle with the syringe and gently press the alcohol wipe on the injection site. Do not use the medicine. Dispose the syringe and the medicine. Use a new packaged tray of Cetrotide to repeat the procedure.
15. Use the syringe and needles only once. Dispose of the syringe and needles immediately after use (put the covers on the needles to avoid injury). If available, a medical waste container should be used for disposal.

Store below 25ºC. Protect it from light.
The powder in the vial and solvent in the pre-filled syringe have the same expiry date. It is printed on the labels and on the carton. Do not use the Cetrotide 0.25 mg powder or the solvent after this date.
The solution should be used immediately after preparation.

Trophic Hormones & Related Synthetic Drugs

H01CC02 - cetrorelix ; Belongs to the class of anti-gonadotropin-releasing hormones. Used in hypothalamic hormone preparations.

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