Gonasi HP

Patient Information Leaflet

GONASI HP 250 IU/1 ml powder and solvent for injectable solution, 1,000 IU/1 ml powder and solvent for injectable solution, 2,000 IU/1 ml powder and solvent for injectable solution, 5,000 IU/1 ml powder and solvent for injectable solution

Chorionic Gonadotropin
Please read this leaflet carefully before using this medicine as 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 other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What GONASI HP is and what it is used for

GONASI HP is a powder to be dissolved in a liquid (solvent) before use; it is administered by subcutaneous injection (under the skin) or intramuscular injection (into a muscle).
The powder contains chorionic gonadotropin, a hormone derived from human urine, belonging to the family of "gonadotropins", natural hormones involved in reproduction and fertility. The chorionic gonadotropin contained in GONASI HP is highly purified.
This medicinal product promotes the production of sex hormones responsible for testicular maturation in children, sperm production (spermatogenesis) in men, and ovulation in women.
GONASI HP is used:
in CHILDREN with:

• undescended testicle (cryptorchidism);
• inadequate testicular function (hypogonadism, hypogonadotropic eunuchoidism);

in WOMEN with:

• absence of menstruation (primary or secondary amenorrhea);
• incomplete or underdeveloped ovaries (ovarian hypoplasia);
• vaginal bleeding (menometrorrhagia);
• history of recurrent miscarriage (habitual abortion), threatened abortion;
• infertility due to lack of oocytes (anovulatory infertility);
• sterility due to failure in oocyte production (ovogenesis deficit);

in MEN with:

• absence of spermatozoa (azoospermia) or reduced sperm count (oligoasthenospermia);
• reduced sperm motility (asthenospermia) due to a condition called hypogonadotropic hypogonadism, and in combination with FSH-containing medications.

Treatment with GONASI HP must be initiated and carried out only under strict medical supervision; the physician will determine the dosage and frequency of administration.
The safety and efficacy of chorionic gonadotropin have not been established in children under 4 years of age.

2. What you should know before taking GONASI HP

Do not take GONASI HP if:

• you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
• you suffer from precocious puberty;
• you have hypertrophy (enlargement) or a tumor of the pituitary gland (a gland located in the brain);
• you have ovarian, prostate or testicular cancer, or any other tumor that grows under the influence of male hormones (so-called androgen-dependent tumors);
• you have a condition that makes normal pregnancy impossible, e.g. ovarian or testicular insufficiency, absence of the uterus, premature menopause, tubal occlusion; (unless you are undergoing in vitro fertilization programs);
• you have inflammation of the veins with blood clot formation (thrombophlebitis).

Warnings and precautions
Before taking this medicine, inform your doctor if:

• you have heart or vascular diseases, for example high blood pressure;
• you have kidney disease;
• you have asthma;
• you suffer from headaches (migraine);
• you suffer from epilepsy.

Before starting treatment with GONASI HP, the following conditions should be evaluated to determine
whether additional treatments may be required:

• reduced thyroid (hypothyroidism) or adrenal gland function;
• high levels of a hormone called prolactin in the blood (hyperprolactinemia).

Women
During treatment with GONASI HP, the following may occur:

• ovarian hyperstimulation syndrome (see section 4). If you are taking other medications that promote ovulation (such as hMG), ovarian hyperstimulation may occur, characterized by: enlarged ovaries and abdominal pain. More serious symptoms may also occur, such as fluid accumulation in the abdomen (ascites), lung problems (pleural reactions), rupture of ovarian cysts, reduced volume of circulating blood (hypovolemia), and formation of blood clots in blood vessels (thromboembolic events).
• multiple pregnancies. These conditions are more likely if you are taking other medications that promote ovulation (such as hMG).
• menorrhagia (vaginal bleeding).

If you notice any of the above reactions, contact your doctor immediately. The doctor will evaluate whether
treatment with GONASI HP should be discontinued.

Children
During treatment with GONASI HP, you may notice signs of precocious puberty, which manifest as:

• in boys: development of axillary, pubic and facial hair, penile growth and masculine appearance;
• in girls: onset of menstruation, breast development, and appearance of pubic and axillary hair.

If you notice any of the above conditions, contact your doctor immediately. The doctor will evaluate whether
treatment with GONASI HP should be discontinued.

Other medicines and GONASI HP
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines,
including those not requiring a prescription. This is particularly important if you are taking medicines
that:

• promote ovulation (such as hMG);
• contain cortisone, especially at high doses.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding,
please consult your doctor before taking this medicine.
In particular, if you are being treated with GONASI HP because your pregnancy is at risk or you have had frequent miscarriages, always follow your doctor’s instructions carefully.
As a hormone of human placental origin, it is not contraindicated during pregnancy.
There are no indications for the use of hCG during breastfeeding.

Driving and using machines
GONASI HP does not affect the ability to drive or operate machinery.

GONASI HP contains sodium.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is practically ‘sodium-free’.
For individuals engaged in sports: using this medicine without a therapeutic need constitutes doping and may lead to a positive result in anti-doping tests.

3. How to take GONASI HP

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Administer the prescribed dose as a single injection, either under the skin (subcutaneous route) or into a muscle (intramuscular route).

IN WOMEN in case of:

• Absence of menstruation (primary and secondary amenorrhea) or menstrual cycles without ovulation (anovulatory cycles): the dose of GONASI HP ranges between 5,000 and 10,000 IU (for the 10,000 IU dose, reconstitute 2 vials of Gonasi HP 5,000 IU), to be administered after adequate estrogen levels have been achieved with other therapies;
• Incomplete or reduced ovarian development (ovarian hypoplasia): the dose of GONASI HP is 500 to 1,000 IU, administered 3–5 times per month;
• Vaginal bleeding (menometrorrhagia): the dose of GONASI HP is 500 to 1,000 IU administered on alternate days until bleeding stops. Afterwards, once weekly until menstrual cycles normalize;
• Recurrent miscarriage (habitual abortion): the dose of GONASI HP is 5,000 IU administered on alternate days during the first 3 months of pregnancy. Subsequently, 1,000 IU on alternate days for an additional 2 months;
• Threatened miscarriage: the dose of GONASI HP is 5,000 IU, administered up to twice daily until symptoms of threatened miscarriage resolve, followed by 1,000 IU every 3 days, as long as deemed appropriate by the physician based on the clinical picture;
• Infertility due to lack of egg production (deficient oogenesis): after stimulation with human menopausal gonadotropin (hMG), the dose of GONASI HP is 5,000 IU or 10,000 IU (for the 10,000 IU dose, reconstitute 2 vials of Gonasi HP 5,000 IU), administered 24 hours after the last dose of human menopausal gonadotropin (HMG).

IN MEN in case of:

• Absence of spermatozoa (azoospermia) or reduced sperm count (oligoasthenospermia): the dose of GONASI HP is 500 IU administered on alternate days for 3–4 months;
• Reduced sperm motility (asthenospermia): the dose of GONASI HP ranges between 1,000 and 2,000 IU (for the 2,000 IU dose, it is also possible to reconstitute 2 vials of Gonasi HP 1,000 IU), administered every 4 days for 3 months.

IN CHILDREN in case of:

• Undescended testicle (cryptorchidism): the dose of GONASI HP is 250, 500, or 1,000 IU, administered 2 or 3 times per week for periods of 40 days. This treatment may be repeated after a 30-day break, until the testicle descends into the scrotal sac and/or as deemed appropriate by the physician;
• Impaired testicular function (hypogonadism, hypogonadotropic eunuchoidism): the dose of GONASI HP is between 250 and 500 IU, administered 2–3 times per week for the first 6 months. Afterwards, the physician will reassess the therapy every 6 months based on testosterone levels and may increase the dose up to a maximum of 1,000 IU three times per week, until adequate testosterone levels are achieved. Treatment must be adjusted according to age, pubertal development stage, and desired blood testosterone levels.

Method of administration
Administer GONASI HP by subcutaneous (under the skin) or intramuscular (into a muscle) injection.
Prepare the solution immediately before use by dissolving the powder in the vial with the clear liquid (solvent) provided in the pre-filled syringe within the package. Use GONASI HP only if the solution is clear and free of particles.
Each vial must be used only once; discard any unused solution remaining after reconstitution.
For instructions on how to administer GONASI HP, carefully read and follow the directions at the end of this leaflet.
GONASI HP must not be mixed with other medicines in the same syringe.

If you take more GONASI HP than you should
Contact your doctor immediately. Overdose of chorionic gonadotropin in prepubertal children may induce precocious puberty and growth arrest.

If you forget to take GONASI HP
Do not take a double dose to make up for the missed dose. Inform your doctor as soon as you realize you have missed a 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 everyone gets them.

Common side effects (may affect up to 1 in 10 people)

• reaction at the injection site;
• swelling (oedema);
• altered mood, headache, emotional instability (irritability);
• abdominal pain.

Uncommon side effects (may affect up to 1 in 100 people)

• allergic reactions which may present as widespread skin rash, urticaria, itching, swelling of the face, eyes, lips, throat, accompanied by breathing difficulties;
• restlessness (agitation), fatigue.

WOMEN
Very common side effects (may affect more than 1 in 10 people)
Common side effects (may affect up to 1 in 10 people)

• excessive stimulation of the ovaries (ovarian hyperstimulation syndrome), mild or moderate, manifested by ovarian enlargement, abdominal pain, nausea and vomiting.

Rare side effects (may affect up to 1 in 1,000 people)

• severe ovarian hyperstimulation syndrome, characterized by lower abdominal (pelvic) pain, nausea, vomiting, weight gain, fluid accumulation in the abdomen (ascites) or in the chest (pleural effusion); blood clot formation in blood vessels (thromboembolic events), as a complication of ovarian hyperstimulation syndrome.

MEN
Side effects with unknown frequency (frequency cannot be estimated from the available data)

• breast enlargement (gynaecomastia).

CHILDREN
Side effects with unknown frequency (frequency cannot be estimated from the available data)

• growth arrest (premature fusion of epiphyses);
• precocious puberty, presenting as:
  • in boys: development of axillary, pubic and facial hair, penile growth and masculine appearance;
  • in girls: onset of menstruation, breast development, and appearance of pubic and axillary hair.

If you notice any of the conditions listed above, contact your doctor immediately, who will assess whether
treatment with GONASI HP should be stopped.

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 at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store GONASI HP

Keep this medicine out of the sight and reach of children.
Store GONASI HP at a temperature not exceeding +25 °C. Keep the medicine in the original packaging to protect it from light.
Do not use this medicine after the expiry date stated on the packaging. If the expiry date is stated as month/year, the expiry date refers to the last day of that month.
Take GONASI HP immediately after preparation.
Do not use GONASI HP if the solution does not appear clear.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What GONASI HP contains
The active substance is: choriogonadotropin.
The excipients are:

• in the vial of powder: lactose
• in the pre-filled syringe of solvent: water for injections, sodium chloride.

Each vial of 250, 1,000, 2,000 and 5,000 IU contains: 250, 1,000, 2,000 and 5,000 IU of choriogonadotropin in powder form.
Each pre-filled syringe contains 1 ml of solvent.

Description of the appearance of GONASI HP and contents of the pack
GONASI HP 250 IU/1 ml is available in the following pack sizes:

• 1 vial of powder and 1 pre-filled syringe of solvent;
• 3 vials of powder and 3 pre-filled syringes of solvent.

GONASI HP 1,000 IU/1 ml is available in the following pack sizes:

• 1 vial of powder and 1 pre-filled syringe of solvent;
• 3 vials of powder and 3 pre-filled syringes of solvent.

GONASI HP 2,000 IU/1 ml is available in the following pack sizes:

• 1 vial of powder and 1 pre-filled syringe of solvent;
• 3 vials of powder and 3 pre-filled syringes of solvent.

GONASI HP 5,000 IU/1 ml is available in the following pack size:

• 1 vial of powder and 1 pre-filled syringe of solvent.

Each pre-filled syringe is equipped with a back-stop device and is supplied with 2 needles: a 21 gauge needle with green cap (for reconstitution of the solution and intramuscular administration), and a 27 gauge needle with grey cap (for subcutaneous administration).

Marketing Authorisation Holder and Manufacturer
IBSA Farmaceutici Italia S.r.l., Via Martiri di Cefalonia, 2, 26900 Lodi.

INSTRUCTIONS FOR USE OF GONASI HP
Each vial is intended for single use only.
Wash your hands thoroughly. Ensure that all accessories are clean and placed on a clean surface.

1. 1. Preparation of solvent in pre-filled syringe: Remove the cap from the pre-filled syringe. Attach the 21 gauge needle (green cap) suitable for reconstitution of the solution.

Place the syringe on a clean surface, taking care not to touch the needle.

1. 2. Reconstitution of the solution
   • Remove the aluminium protective cap from the vial containing the powder and clean the surface of the rubber stopper with an alcohol swab;
   • slowly inject the solvent into the vial through the rubber stopper;

• to completely dissolve the powder, gently rotate the vial (without removing the syringe). Do not shake to avoid formation of bubbles. If the solution is not clear or contains particles, it must be discarded;
• once the powder has dissolved (this should occur immediately), invert the vial and slowly draw the solution back into the syringe.

Preparation of the 10,000 IU dose
If your doctor has prescribed a dose of 10,000 IU, this can be obtained by using two vials of 5,000 IU powder and one single solvent syringe.
To reconstitute two 5,000 IU vials of Gonasi HP, draw into the syringe the contents of the first 5,000 IU vial previously reconstituted by strictly following the steps described in this section, and then slowly inject it into a second 5,000 IU vial, repeating the same steps.
Discard the unused pre-filled solvent syringe remaining after the reconstitution procedure.

Preparation of the 2,000 IU dose
If your doctor has prescribed a dose of 2,000 IU, this can also be obtained by using two vials of 1,000 IU powder and one single solvent syringe.
To reconstitute two 1,000 IU vials of Gonasi HP, draw into the syringe the contents of the first 1,000 IU vial previously reconstituted by strictly following the steps described in this section, and then slowly inject it into a second 1,000 IU vial, repeating the same steps.
Discard the unused pre-filled solvent syringe remaining after the reconstitution procedure.

1. 3. Administration If you wish to administer GONASI HP via intramuscular injection, it is not necessary to change the needle.

If you wish to administer GONASI HP subcutaneously, you must discard the needle used for reconstitution and replace it with the fine needle suitable for subcutaneous administration (if using pre-filled syringes, this needle is included in the package: 27 gauge needle with grey cap). Your doctor will advise you on the injection site (e.g. abdomen, front of thigh).
Before administration, remove any air bubbles by holding the syringe vertically with the needle pointing upwards, gently tapping the syringe until the air bubbles rise to the top, then gently pushing the plunger to expel the air until liquid appears at the tip of the needle.

Inject the solution immediately after preparation.
To minimize skin irritation, choose a different injection site each day.
Clean the injection site with an alcohol swab. Firmly pinch the skin at the intended injection site and insert the needle at an angle between 45° and 90°.

GONASI HP must not be administered directly into a vein. To rule out intravenous injection, pull back on the plunger to check for blood. If blood appears, withdraw the syringe and repeat the procedure at another site.
Inject the entire solution subcutaneously or intramuscularly by slowly pressing the plunger.
Immediately remove the needle and clean the injection site with an alcohol swab using a circular motion.
After completing the injection, immediately dispose of used needles and empty glass vials safely, preferably in a sharps disposal container.