Cetrotide

Package leaflet: Information for the user

Cetrotide 0.25 mg powder and solvent for injectable solution

cetrorelix
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Cetrotide is and what it is used for
2. What you need to know before using Cetrotide
3. How to use Cetrotide
4. Possible side effects
5. How to store Cetrotide
6. Contents of the pack and other information
   How to mix and inject Cetrotide

1. What Cetrotide is and what it is used for

What Cetrotide is
Cetrotide contains an active substance called "cetrorelix". This medicine blocks the release of an egg from the ovary (ovulation) during the menstrual cycle. Cetrotide belongs to a family of medicines known as "gonadotropin-releasing hormone antagonists".

What Cetrotide is used for
Cetrotide is one of the medicines used during "assisted reproductive techniques" to help achieve pregnancy. It prevents the premature release of eggs (premature ovulation), because if the eggs are released too early, your doctor cannot retrieve them.

How Cetrotide works
Cetrotide blocks a natural hormone in the body called LHRH (luteinizing hormone-releasing hormone).

• LHRH controls another hormone called LH (luteinizing hormone).
• LH stimulates ovulation during the menstrual cycle.

This means that Cetrotide interrupts the chain of events leading to the release of an egg from the ovary. When the eggs are ready to be collected, you will be given another medicine that triggers their release (induction of ovulation).

2. What you should know before using Cetrotide

Do not use Cetrotide

• if you are allergic to cetrorelix or to any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to medicines similar to Cetrotide (any other peptide hormone);
• if you are pregnant or breastfeeding;
• if you have severe kidney disease.

Do not use Cetrotide if any of the above apply to you. If you are unsure, consult your doctor before using this medicine.

Warnings and precautions

Allergies
If you currently have an allergy or have had allergies in the past, inform your doctor before taking Cetrotide.

Ovarian Hyperstimulation Syndrome (OHSS)
Cetrotide is used together with other medicines that stimulate the ovaries to produce a greater number of oocytes ready for release. During or after taking these medicines, Ovarian Hyperstimulation Syndrome (OHSS) may occur. OHSS happens when follicles develop excessively, becoming large cysts.
For possible side effects to monitor and what to do if they occur, see section 4, "Possible side effects".

Use of Cetrotide for more than one cycle
Experience with the use of Cetrotide for more than one treatment cycle is limited. If you need to use Cetrotide for more than one cycle, your doctor will carefully evaluate the benefits and risks.

Liver disease
Inform your doctor before using Cetrotide if you have liver disease. Cetrotide has not been studied in patients with hepatic disease.

Kidney disease
Inform your doctor before using Cetrotide if you have kidney disease. Cetrotide has not been studied in patients with renal disease.

Children and adolescents
Cetrotide is not intended for use in children and adolescents.

Other medicines and Cetrotide
Inform your doctor if you are currently taking, have recently taken, or might take any other medicines.

Pregnancy and breastfeeding
Do not use Cetrotide if you are pregnant, suspect you may be pregnant, or are breastfeeding.

Driving and using machines
Cetrotide is not expected to affect your ability to drive or operate machinery.

3. How to use Cetrotide

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.
Use of this medicine
This medicine is intended only for abdominal injection just beneath the skin surface (subcutaneous). To avoid skin irritation, choose a different area of the abdomen each day.

• The first administration must be performed under the supervision of your doctor. Your doctor or nurse will show you how to prepare and inject the medicine.
• You may perform subsequent administrations yourself, once your doctor has informed you about the symptoms that may indicate allergic reactions and about possible severe or life-threatening consequences requiring immediate treatment (see section 4 "Possible side effects").
• Read carefully and follow the instructions described in the section at the end of this document.

Instructions for mixing and injecting Cetrotide

• Treatment cycle day 1 will begin using another medication. You will start using Cetrotide a few days later. (See section “How much medicine to use”.)

How much medicine to use
Inject the contents of one vial of Cetrotide once daily. It is recommended to administer the medicine at the same time each day, with an interval of 24 hours between doses.
You may choose to give the injection either every morning or every evening.

• If you choose morning administration, start injections on day 5 or 6 of the treatment cycle. Depending on ovarian response, your doctor may decide to start on a different day. Your doctor will inform you of the exact date and time. You will continue using this medicine until the morning of oocyte retrieval (ovulation induction).

OR

• If you have chosen evening administration: start injections on day 5 of the treatment cycle. Depending on ovarian response, your doctor may decide to start on a different day. Your doctor will inform you of the exact date and time. You will continue using this medicine until the evening before oocyte retrieval (ovulation induction).

If you use more Cetrotide than you should
No serious effects are expected if you accidentally inject a higher dose of this medicine than intended. The effect of the medicine will simply last longer. Therefore, specific measures are generally not required.

If you forget to use Cetrotide

• If you forget a dose, inject it as soon as you remember and contact your doctor.
• Do not inject a double dose to make up for the missed dose.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

• Feeling of warmth, skin redness, itching (often in the groin or armpits), red, itchy raised areas (urticaria), runny nose, rapid or irregular heartbeat, swelling of the tongue and throat, sneezing, wheezing or severe breathing difficulties, or dizziness. You may experience a serious or life-threatening allergic reaction to this medicine. This reaction is uncommon (may affect up to 1 in 100 women). If you notice any of these side effects, stop using Cetrotide immediately and inform your doctor straight away.

Ovarian hyperstimulation syndrome (OHSS)
This may occur as a result of other medicines you are using to stimulate the ovaries.

• Symptoms of OHSS may include lower abdominal pain with a feeling of illness (nausea) or actual illness (vomiting). This may indicate that the ovaries have over-responded to treatment and that large ovarian cysts have developed. This is a common occurrence (may affect up to 1 in 10 women).
• OHSS may become severe, with markedly enlarged ovaries, reduced urine output, weight gain, difficulty breathing, or fluid accumulation in the abdomen or chest. This is an uncommon occurrence (may affect up to 1 in 100 women). If you notice any of these side effects, inform your doctor immediately.

Other side effects
Common (may affect up to 1 in 10 women):

• Mild, short-lived skin irritation at the injection site, such as redness, itching, or swelling.

Uncommon (may affect up to 1 in 100 women):

• Feeling unwell (nausea)
• Headache.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cetrotide

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton, on the vial, and on the
prefilled syringe after Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze and do not place near the freezer compartment or
cooling packs.
Keep in the original packaging to protect the medicine from light.
The unopened product may be stored in the original packaging at room temperature (not exceeding
30°C) for up to three months.
The solution should be used immediately after preparation.
Do not use this medicine if you notice that the white powder in the vial has changed in appearance. Do not use the prepared solution in the vial if it is not clear and colourless or if it contains particles.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Cetrotide contains

• The active substance is cetorelix. Each vial contains 0.25 mg of cetorelix (as acetate).
• The other components are:
  • In the powder: mannitol.
  • In the solvent: water for injections.

Description of the appearance of Cetrotide and package contents
Cetrotide is a powder and solvent for injectable solution. The white powder is contained in a
glass vial with a rubber stopper. The solvent is a clear, colourless solution contained in a pre-filled syringe.
The powder vial contains 0.25 mg of cetorelix and the pre-filled syringe contains 1 ml of
solvent.
It is available in packs containing 1 vial and 1 pre-filled syringe or packs containing 7 vials and 7 pre-filled syringes (not all pack sizes may be marketed).
In addition, for each vial, the package contains:

• a needle for injection with a yellow mark for introducing sterile water into the vial and withdrawing the prepared medicine from the vial
• a needle for injections with a grey mark for injecting the medicine into the abdomen

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
Manufacturer
Merck Healthcare KGaA, Frankfurter Straße 250, D-64293 Darmstadt, Germany
More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu .
HOW TO MIX AND INJECT CETROTIDE

• This section describes how to mix the powder with sterile water (solvent) and inject the medicine.
• Before starting to use this medicine, read these instructions completely and carefully.
• This medicine is for your use only; no one else should use it.
• The needle, vial, and syringe are for single use only.

Before you begin

1. This medicine must be brought to room temperature before injection.

Remove it from the refrigerator approximately 30 minutes before use.

2. Wash your hands

• It is important that the hands and all objects used are as clean as possible.

3. Place all required items on a clean surface:

• a vial containing the powder
• a pre-filled syringe with sterile water (solvent)
• a yellow-marked needle, for injecting sterile water into the vial and withdrawing the prepared medication
• a grey-marked needle, for injecting the medication into the abdomen
• two alcohol wipes (not provided in the package).

Mixing the powder with sterile water to prepare the medication

1. Remove the closure cap from the vial

• Underneath there is a rubber stopper; keep it on the vial.
• Clean the rubber stopper and the metal ring with an alcohol-impregnated wipe.

2. Adding the water from the pre-filled syringe to the powder in the vial

• Remove from the packaging the needle with the yellow mark.
• Remove the cap from the pre-filled syringe and screw on the yellow needle. Remove the cap from the needle.
• Insert the yellow needle through the center of the rubber stopper of the vial.
• Inject the water into the vial by slowly pushing the syringe plunger. Do not use any other type of water.
• Leave the syringe in the rubber stopper.

3. Mixing the powder with water in the vial

• Carefully holding the syringe and the vial, gently rotate them to mix the powder with the water. Once mixed, the solution should appear clear, without particles.
• Do not shake, to avoid creating bubbles in the medicine.

4. Reconstituting the syringe with the medicine from the vial

• Invert the vial. Then, gently pull back the plunger to draw the medicine from the vial into the syringe. Be careful not to completely remove the plunger with the attached rubber stopper. If the plunger with the rubber stopper is accidentally removed, discard the dose, as it is no longer sterile, and prepare a new one (starting again from step 1).
• If some medicine remains in the vial, slowly retract the yellow needle until its tip is just inside the rubber stopper. By viewing sideways through the slit, you can monitor the needle movements and the solution.
• Make sure all the medicine has been drawn from the vial.

• Replace the cap onto the yellow needle. Unscrew the yellow needle from the syringe and place the syringe on a flat surface.

Preparing the injection site and administering the medicine

1. Removing air bubbles

• Remove from the package the needle marked grey. Screw the grey needle onto the syringe and remove the needle cap.
• Hold the syringe with the grey needle pointing upwards and check for the presence of air bubbles.
• To remove air bubbles, gently tap the syringe until all air bubbles rise to the top; then gently push the plunger to expel the air from the syringe.
• Do not touch the grey needle and prevent the grey needle from coming into contact with any surface.

2. Cleaning the injection site

• Select the injection site on the abdomen, preferably around the navel. To reduce skin irritation, choose a different area of the abdomen each day.
• Clean the skin at the selected injection site using the second alcohol wipe, moving in circular motions.

3. Skin puncture

• Hold the syringe in one hand as if it were a pencil.
• With the other hand, gently pinch the skin around the area where you intend to inject the medication and hold it firmly.
• Push the grey needle completely and slowly into the skin at an angle of 45–90 degrees, then release the skin.

4. Injection of the medicinal product

• Gently pull back the syringe plunger. If blood appears, proceed as described in point 5.
• If no blood appears, slowly push the plunger to inject the medicinal product.
• When the syringe is empty, slowly withdraw the grey needle at the same angle.
• After completing the injection, apply light pressure to the injection site using the second alcohol-soaked swab.

5. If blood appears:

• slowly withdraw the grey needle at the same angle
• apply light pressure on the injection site with the second alcohol swab
• empty the medicine into a container and proceed as described in point 6
• wash hands and restart with a new vial and a new pre-filled syringe.

6. Disposal

• The needle, vial, and syringe are for single use only.
• Replace the cap on the needles so they can be safely discarded.
• Ask your pharmacist how to safely dispose of used needles, vials, and syringes.