Zivafert

Patient Information Leaflet

Warning! Keep this leaflet! Information on the immediate packaging is in a foreign language.
Zivafert
5000 IU, powder and solvent for solution for injection
Gonadotrophinum chorionicum
▼ This medicinal product will be subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience after using this medicine. For information on how to report side effects – see section 4.
Please read this leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.
• In this leaflet, the medicine Zivafert 5000 IU powder and solvent for solution for injection is referred to as Zivafert.

Table of Contents

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

1. What Zivafert is and what it is used for

What Zivafert is:
Zivafert contains highly purified human chorionic gonadotropin, a hormone derived from human urine, belonging to the family of "gonadotropins", which are natural hormones responsible for reproduction and fertility.
When Zivafert is used:
Zivafert is used:

• to support the development and maturation of several follicles (each containing an egg cell) in women undergoing assisted reproductive technologies (procedures that may help achieve pregnancy), such as in vitro fertilization;
• to support the release of an egg from the ovary (induction of ovulation) in women who do not produce egg cells ("anovulation") or who produce too few egg cells ("oligoovulation").

This medicine should be used under the supervision of a doctor, unless otherwise advised by the doctor.

2. Important information before using Zivafert

When not to use Zivafert:

• if the patient is allergic to human chorionic gonadotropin or any of the other ingredients of this medicine (listed in section 6);
• if the patient has untreated diseases of the thyroid, pituitary gland, or adrenal glands;
• if the patient has cancer of the ovary, uterus, or breast;
• if the patient has a condition that prevents normal pregnancy, such as ovarian failure, absence of the uterus, premature menopause, blocked fallopian tubes, uterine fibroids, or other abnormalities of the reproductive organs;
• if the patient has recently experienced unexplained vaginal bleeding.

Tell your doctor or pharmacist if any of the above conditions apply to you, as this medicine may not be suitable.

Warnings and precautions

Before starting treatment, the doctor should check that the patient's reproductive organs are normal.
Before using Zivafert, discuss with your doctor if you have or have previously had any of the following conditions:

• abnormalities of the reproductive organs;
• chronic diseases (such as diabetes, cardiovascular disorders, etc.);
• vascular complications (i.e. increased risk of blood clots, history of blood clots in the patient or in the patient's family, overweight).

Medical tests

Up to 10 days after administration of Zivafert, a pregnancy test may give a false positive result.

During treatment with Zivafert, the following may occur:

Ovarian hyperstimulation syndrome (OHSS)

Treatment with gonadotropin hormones such as Zivafert may cause ovarian hyperstimulation syndrome. This is a serious condition in which the ovaries are overstimulated and developing ovarian follicles become too large. In rare cases, severe OHSS can be life-threatening. Therefore, it is very important that the patient remains under close medical supervision. The doctor will perform an ultrasound scan (USG) of the ovaries to monitor the treatment effects. Blood hormone levels may also be checked (see also section 4).

In ovarian hyperstimulation syndrome, fluid rapidly accumulates in the abdominal cavity and chest cavity. Blood clots may also form. Seek immediate medical attention if you experience:

• significant abdominal swelling and abdominal pain;
• nausea;
• vomiting;
• rapid weight gain due to fluid accumulation;
• diarrhea;
• reduced urine output;
• breathing difficulties.

Ovarian torsion

Ovarian torsion is a condition in which the ovary twists, potentially cutting off its blood supply.

Before starting treatment with this medicine, inform your doctor if:

• the patient has ever been diagnosed with ovarian hyperstimulation syndrome;
• the patient is pregnant or suspects she may be pregnant;
• the patient has ever had abdominal surgery;
• the patient has ever been diagnosed with ovarian torsion;
• the patient currently or previously had ovarian cysts or polycystic ovaries.

Blood clots (thrombosis)

Pregnancy increases the risk of blood clots.
If the patient has risk factors for blood clots (e.g. overweight or family history of blood clots), the risk of developing blood clots in blood vessels may increase during in vitro fertilization (IVF) treatment.
Blood clots can lead to serious conditions such as:

• pulmonary embolism (blockage in the lung arteries);
• stroke;
• heart attack;
• reduced blood flow to vital organs, which may lead to organ damage;
• reduced blood flow (deep vein thrombosis) to arms or legs, which may lead to amputation.

Multiple births, birth defects, miscarriage, or pregnancy complications

Pregnancies following treatment with Zivafert are more likely to be twin or multiple pregnancies.
Multiple pregnancies are associated with increased risks for both mother and baby during pregnancy and childbirth.
Women undergoing infertility treatment have a slightly increased risk of miscarriage or ectopic pregnancy (pregnancy outside the uterus). Therefore, the doctor should perform an early ultrasound scan to rule out ectopic pregnancy. The likelihood of multiple births is higher if the patient is also using other ovulation-stimulating medicines (e.g. hMG).
It is not known whether in vitro fertilization treatment causes congenital malformations in the baby or increases the risk of certain reproductive organ tumors.

Children and adolescents

Zivafert is not indicated for use in children and adolescents.

Zivafert with other medicines

Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including over-the-counter medicines. This is particularly important if you are taking medicines that:

• stimulate ovulation (e.g. hMG);
• contain cortisone, especially in high doses.

Pregnancy and breastfeeding

Do not use Zivafert if the patient is pregnant or breastfeeding. If the patient suspects she may be pregnant, she should consult her doctor before using this medicine.

Driving and operating machinery

Zivafert has no effect on the ability to drive or operate machinery.

Zivafert contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per injection, meaning the medicine is considered "sodium-free".

3. How to use Zivafert

Zivafert is a powder that must be dissolved in a liquid (diluent) before use and is administered by subcutaneous or intramuscular injection. The solution is prepared by combining the diluent with the powder and must be used immediately after preparation.
This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.

How to administer Zivafert:

Zivafert is administered by subcutaneous or intramuscular injection. Each vial must be used only once, and the injection should be performed immediately after preparing the solution.

The recommended dose of Zivafert is 5,000 IU or 10,000 IU. The medicine should be administered within 24–48 hours after achieving optimal follicular stimulation.

After appropriate counseling and training, your doctor may recommend that you self-administer Zivafert.

Before your first self-injection, your doctor will:

• explain how to prepare the correct dose of the medicine;
• demonstrate how to prepare the injection solution;
• indicate possible injection sites;
• allow you to practice performing subcutaneous injections.

Before self-administering Zivafert, carefully read the instructions below.

How to prepare the Zivafert solution from 1 vial of powder:

The solution should be prepared immediately before injection. Each vial is for single use only.

Zivafert must only be prepared using the diluent provided in the package, following the instructions below:

Step 1
Wash your hands before preparing the solution. Use a clean surface. It is important that your hands and materials are as clean as possible.

Step 2
Lay out all the following items on a clean surface:

• two alcohol swabs (not included in the pack);
• one vial containing Zivafert powder;
• one pre-filled syringe with diluent;
• one long needle for reconstitution and intramuscular injection;
• one short needle for subcutaneous injection.

Step 3

Remove only the cap from the pre-filled syringe.

• Attach the reconstitution needle (long needle) with its protective cap to the syringe and check that the needle is securely attached to prevent leakage. If leakage occurs, try adjusting the needle connection by gently rotating it.
• Carefully place the syringe on a clean surface.
• Avoid touching the needle.

Step 4

• Remove the colored plastic cap from the Zivafert vial by gently pressing it upwards.

• Wipe the rubber stopper with an alcohol swab and allow it to dry.

Step 5

• Pick up the syringe, remove the protective cap from the needle, and insert the needle through the rubber stopper at the top of the Zivafert vial.
• Firmly press the plunger and slowly inject the entire diluent into the vial containing the powder.
• DO NOT SHAKE. Gently rotate the vial between your hands until the powder is completely dissolved, taking care not to create foam.

Step 6

After the powder has dissolved (which usually happens immediately),
slowly draw the solution into the syringe as described below:

• With the needle still inserted, turn the vial upside down.
• Ensure the needle tip is below the fluid level.
• Gently pull back the plunger to draw all the Zivafert solution into the syringe.
• Check that the reconstituted solution is clear and colourless.

Preparing higher doses using more than one vial of powder:

If your doctor has prescribed a higher dose of 10,000 IU, this can be achieved using two vials of powder and one pre-filled syringe with diluent.

When preparing two vials of Zivafert, at the end of Step 3 above, draw the reconstituted solution from the first vial into the syringe and slowly inject it into the second vial.

Repeat Steps 4 to 6 for the second vial.

The solution must be clear and colourless.

Intramuscular injection:

For intramuscular injection, your doctor or nurse will prepare and administer Zivafert into the thigh or buttock.

Subcutaneous injection:

• Once the syringe contains the correct dose, place the protective cap on the long needle. Remove the long needle from the syringe and replace it with the short subcutaneous injection needle, which has its protective cap attached. Check that the needle is securely attached by firmly pushing the short needle onto the syringe barrel and gently twisting it to ensure it is fully secured to prevent leakage.

Remove the protective cap from the needle. Hold the syringe with the needle pointing upwards and gently tap the side of the syringe to move any air bubbles to the top.

• Press the plunger until a drop of liquid appears at the needle tip.
• DO NOT USE the solution if it contains any particles or appears cloudy.

Injection site:

• Remove the colored plastic cap from the Zivafert vial by gently pressing it upwards.
• Wipe the rubber stopper with an alcohol swab and allow it to dry.
• Your doctor or nurse will advise you on the appropriate injection site on the body. Typical sites include the thigh or the lower abdomen (abdominal area) below the navel.
• Clean the injection site with an alcohol swab.
• Firmly pinch the skin. With the other hand, insert the needle with a steady motion at a 45° or 90° angle.

Administering the solution:

• Inject the solution under the skin as instructed by your doctor.
• Do not inject the solution directly into a blood vessel.
• Slowly and steadily push the plunger to ensure proper injection and to avoid tissue damage.

Take as much time as needed to inject the prescribed volume of solution.

Removing the needle:

• Quickly withdraw the syringe and press gently on the injection site.
• Gently massage the injection site while maintaining light pressure. This helps disperse the Zivafert solution and reduces discomfort.

Disposal of used materials:

After completing the injection, all needles and empty syringes must be disposed of in an appropriate sharps container. Any unused solution or waste must be discarded in accordance with local regulations.

Use of a higher than recommended dose of Zivafert:

The effects of overdosing with Zivafert are not known; however, ovarian hyperstimulation syndrome may be expected (see “Possible side effects”). If you have used more than the prescribed dose of Zivafert, contact your doctor or pharmacist immediately.

Missed dose of Zivafert:

If you miss a dose of Zivafert, contact your doctor immediately.

Stopping treatment with Zivafert:

If you decide not to continue using this medicine, consult your doctor.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicinal product may cause adverse reactions, although not everyone experiences them.
If any of the following serious adverse reactions occur,
treatment with Zivafert must be discontinued and medical advice must be sought immediately –
urgent medical assistance may be required:

• Mild or moderate ovarian hyperstimulation (ovarian hyperstimulation syndrome), which manifests as enlarged ovaries, ovarian cysts, abdominal pain with nausea and vomiting (see also section 2. "Ovarian hyperstimulation syndrome"). This is a common adverse reaction (may occur in up to 1 in 10 people).
• Severe ovarian hyperstimulation (ovarian hyperstimulation syndrome) characterized by pelvic pain, nausea, vomiting, weight gain, accumulation of fluid in the abdominal cavity (ascites) or in the chest cavity (pleural effusion). This is an uncommon adverse reaction (may occur in up to 1 in 100 people).
• Rupture of an ovarian cyst (as a rare complication of severe ovarian hyperstimulation syndrome, may occur in up to 1 in 1,000 people).
• Formation of blood clots in blood vessels (thromboembolic events), as a complication of ovarian hyperstimulation syndrome. This is a rare adverse reaction (may occur in up to 1 in 1,000 people).
• Severe generalized allergic reactions, which may include: swelling of the face, eyes, lips, throat or tongue, difficulty breathing, wheezing, skin rash. This is a rare adverse reaction (may occur in up to 1 in 1,000 people).

Other adverse reactions:
Common adverse reactions (may occur in up to 1 in 10 people):

• reaction at the injection site, which may include redness, bruising, swelling, itching or pain at the injection site;
• swelling;
• mood changes;
• headache;
• breast tenderness.

Uncommon adverse reactions (may occur in up to 1 in 100 people):

• anxiety (restlessness);
• fatigue.

Rare adverse reactions (may occur in up to 1 in 1,000 people):

• swelling in the deep layers of the skin, often associated with urticaria;
• generalized skin rashes.

If any of the rare adverse reactions listed above occur,
medical advice must be sought immediately. The physician will assess whether treatment with Zivafert should be discontinued
or whether immediate transfer to the nearest hospital emergency department is required.
Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed
in this leaflet, inform a doctor or pharmacist. Adverse reactions can
be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to gather further information on the safety of the medicine.

5. How to store Zivafert

Keep the medicine out of the sight and reach of children.
Store below 25°C. Keep the vial and the ampoule-syringe in the original packaging to protect from light.
Use the solution immediately after preparation.
Do not use this medicine after the expiry date stated on the packaging. If the expiry date is given as month/year, the expiry date refers to the last day of the stated month.
Do not use this medicine if the solution is not clear (cloudy or contains visible particles). After preparation, the solution must be clear and colourless.
Do not dispose of medicines via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Zivafert contains

• The active substance is human chorionic gonadotropin.
• The other ingredients are:
• vial with powder: monohydrate lactose;
• pre-filled syringe with solvent (0.9% sodium chloride solution): water for injections, sodium chloride.

Each vial contains: 5000 IU human chorionic gonadotropin, obtained from human urine.
What Zivafert looks like and contents of the pack
Zivafert is available as:
Powder in vial: a lyophilized powder, white to almost white in colour.
Solvent in pre-filled syringe (0.9% sodium chloride solution): a clear, colourless solution.
One single pack contains:
A plastic tray containing a vial of powder made of colourless glass type I, closed with a bromobutyl rubber stopper and an aluminium flip-off cap.
1 mL of solvent in a pre-filled syringe made of colourless glass type I, with a plunger made of chlorobutyl rubber, a tip cap made of isoprene and bromobutyl, and two needles: one for reconstitution and intramuscular injection, and one for subcutaneous injection.
The outer pack (10+10) contains 10 plastic trays as described above.
For further information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in the Czech Republic, the country of export:
IBSA Slovakia s.r.o.
Mýtna 42
811 07 Bratislava
Slovakia
Manufacturer:
IBSA Farmaceutici Italia srl
Via Martiri di Cefalonia, 2
26900 Lodi
Italy
Parallel importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Repackaged by:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Marketing authorisation number in the Czech Republic, the country of export: 56/402/19-C
Parallel import authorisation number: 389/25
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
AT: Zivafert
DK: Gonasi Set
CZ: Zivafert
EL: Zivafert
ES: Gonasi Kit
FI: Gonasi Set
FR: GONADOTROPHINE CHORIONIQUE IBSA
HU: Zivafert Kit
NL: Gonasi
NO: Gonasi Set
PL: Zivafert
SE: Gonasi Set
SK: Gonasi Kit