Gonal-f

Package leaflet: Information for the user

GONAL-f 75 UI powder and solvent

for injectable solution
follitropin alfa
Please read all of this leaflet carefully before you start 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 other people, even if they have the same symptoms as yours, because 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 GONAL-f is and what it is used for
2. What you need to know before using GONAL-f
3. How to use GONAL-f
4. Possible side effects
5. How to store GONAL-f
6. Contents of the pack and other information
   How to prepare and use GONAL-f powder and solvent

1. What GONAL-f is and what it is used for

What GONAL-f is
GONAL-f contains an active substance called "follitropin alfa". Follitropin alfa is a "follicle-stimulating hormone" (FSH), belonging to a family of hormones known as "gonadotropins". Gonadotropins are involved in reproduction and fertility.
What GONAL-f is used for
In adult women, GONAL-f is used

• to stimulate the release of an egg from the ovary (ovulation) in women who do not ovulate and who have not responded to treatment with a medicine called "clomiphene citrate".
• in combination with another medicine called "lutropin alfa" ("luteinizing hormone" or LH) to stimulate the release of an egg from the ovary (ovulation) in women whose bodies produce very low levels of gonadotropins (FSH and LH).
• to promote the development of multiple follicles (each containing an egg) in women undergoing assisted reproductive techniques (procedures that may help achieve pregnancy), such as "in vitro fertilization", "gamete intrafallopian transfer", or "zygote intrafallopian transfer".

In adult men, GONAL-f is used

• in combination with another medicine called "human chorionic gonadotropin" (hCG) to stimulate sperm production in infertile men due to low levels of certain hormones.

2. What you should know before using GONAL-f

Before starting treatment, a doctor experienced in the management of fertility disorders should thoroughly evaluate your couple's fertility.
Do not use GONAL-f

• if you are allergic to follicle-stimulating hormone or to any of the other ingredients of this medicine (listed in section 6).
• if you have a tumour of the hypothalamus or pituitary gland (both parts of the brain).
• if you are a woman
  • with enlarged ovaries or fluid-filled sacs in the ovary (ovarian cysts) of unknown origin
  • with vaginal bleeding of unknown origin
  • with cancer of the ovary, uterus or breast
  • with a condition that usually prevents a normal pregnancy, such as ovarian failure (premature menopause) or malformations of the reproductive system.
• if you are a man
  • with irreversible damage to the testicles.

Do not use GONAL-f if you have any of these conditions. If you have any doubts, consult your doctor before using this medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using GONAL-f.
Porphyria
Inform your doctor before starting treatment if you or a family member has porphyria (an inability to break down porphyrins, which may be inherited from parents).
Immediately inform your doctor if:

• your skin becomes fragile and easily develops blisters, especially in areas frequently exposed to sunlight, and/or
• you have stomach, arm, or leg pain.

In such cases, your doctor may advise you to stop treatment.
Ovarian hyperstimulation syndrome (OHSS)
If you are a woman, this medicine increases the risk of OHSS. In this condition, ovarian follicles develop excessively and turn into large cysts. Immediately inform your doctor if you experience lower abdominal pain, rapid weight gain, nausea or vomiting, or difficulty breathing; your doctor may ask you to stop taking the medicine (see section 4).
If you are an anovulatory patient and the recommended dosage and administration schedule are properly followed, the risk of OHSS is less likely.
Treatment with GONAL-f rarely causes severe OHSS if a medicine (containing human chorionic gonadotropin – hCG) is not administered to induce ovulation. If you are developing OHSS, your doctor may decide not to administer hCG during this treatment cycle and may advise you to avoid sexual intercourse or to use a barrier contraceptive method for at least four days.
Multiple pregnancy
When using GONAL-f, the chance of a multiple pregnancy is higher than with natural conception, most commonly twins. Multiple pregnancy may lead to complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of GONAL-f at the correct time. In assisted reproductive procedures, the risk of multiple pregnancy is related to age, quality, and number of fertilized eggs or embryos transferred.
Miscarriage
If you undergo assisted reproductive procedures or ovarian stimulation for egg production, the risk of miscarriage is higher than in other women.
Blood clotting disorders (thromboembolic events)
If you have had, or recently had, blood clots in your legs or lungs, a heart attack, or a stroke, or if such events occurred in your family, your risk of developing or worsening these problems during treatment with GONAL-f may increase.
Men with excessively high FSH levels in blood
If you are a man, excessively high FSH levels in the blood may indicate testicular damage. In such cases, GONAL-f is generally ineffective.
If your doctor decides to attempt treatment with GONAL-f, they may ask you to provide sperm samples for follow-up testing 4–6 months after starting treatment.
Children and adolescents
The use of GONAL-f is not indicated in children and adolescents under 18 years of age.
Other medicines and GONAL-f
Inform your doctor if you are taking, have recently taken, or might take any other medicines.

• If you use GONAL-f together with other medicines that promote ovulation (such as hCG or clomiphene citrate), this may enhance the follicular response.
• If you use GONAL-f simultaneously with a gonadotropin-releasing hormone (GnRH) agonist or antagonist (medicines that reduce sex hormone levels and block ovulation), you may require a higher dose of GONAL-f to produce follicles.

Pregnancy and breastfeeding
Do not use GONAL-f during pregnancy or breastfeeding.
Driving and using machines
This medicine is not expected to affect your ability to drive or use machinery.
GONAL-f contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is essentially "sodium-free".

3. How to use GONAL-f

Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.

How to use the medicine

• GONAL-f is administered by subcutaneous injection (just under the skin).
• The first injection of GONAL-f must be given under the supervision of a doctor.
• Your doctor or nurse will show you how to inject GONAL-f before you self-administer it.
• If you are self-injecting GONAL-f, carefully read and follow the instructions at the end of this leaflet titled “How to prepare and use the powder and solution of GONAL-f”.

What dose to use
Your doctor will determine the dose and frequency of administration. The doses listed below are expressed in International Units (IU).

Women

If you do not ovulate and have irregular or absent menstrual cycles

• GONAL-f is usually administered daily.
• If you have irregular menstrual cycles, start using GONAL-f within the first 7 days of your cycle. If you do not have menstrual cycles, you may start treatment on any day.
• The initial dose of GONAL-f is usually individualized and may be gradually adjusted.
• The daily dose of GONAL-f should not exceed 225 IU.
• When the desired response is achieved, a single injection of 250 micrograms of recombinant hCG (“r-hCG”, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG will be administered 24–48 hours after the last GONAL-f injection. The most suitable days for sexual intercourse are the day of hCG injection and the following day.

If your doctor does not observe the desired response, continuation of that treatment cycle with GONAL-f should be evaluated and managed according to standard clinical practice.
If your body responds excessively, treatment will be stopped and hCG will not be administered (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). In the next treatment cycle, your doctor will administer a lower dose of GONAL-f.

If you have been diagnosed with very low levels of FSH and LH hormones

• The usual initial dose of GONAL-f is between 75 and 150 IU, together with 75 IU of lutropin alfa.
• You will need to use both medicines daily for up to five weeks.
• The dose of GONAL-f may be increased every 7 or 14 days by 37.5–75 IU until the desired response is achieved.
• When the desired response is achieved, a single injection of 250 micrograms of recombinant hCG (“r-hCG”, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG will be administered 24–48 hours after the last injection of GONAL-f and lutropin alfa. The most suitable days for sexual intercourse are the day of hCG injection and the following day. Alternatively, intrauterine insemination or another assisted reproductive procedure may be performed, at the discretion of your doctor.

If your doctor observes no response after 5 weeks, that treatment cycle with GONAL-f should be discontinued. In the next treatment cycle, your doctor may prescribe a higher initial dose of GONAL-f.
If your body responds excessively, treatment will be stopped and hCG will not be administered (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). In the next cycle, your doctor will administer a lower dose of GONAL-f.

If you need to stimulate the development of multiple oocytes for assisted reproductive techniques

• The initial dose of GONAL-f is usually individualized and may be gradually adjusted up to a maximum of 450 IU per day.
• Treatment continues until the oocytes have reached a certain stage of development. Your doctor will determine the appropriate timing using blood tests and/or ultrasound monitoring.
• When the oocytes have developed sufficiently, a single injection of 250 micrograms of recombinant hCG (“r-hCG”, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG will be administered 24–48 hours after the last GONAL-f injection. This prepares the oocytes for retrieval.

Men

• The usual dose of GONAL-f is 150 IU together with hCG.
• You must use both medicines three times a week for at least 4 months.
• If you do not respond to treatment after 4 months, your doctor may recommend continuing treatment with both medicines for up to 18 months.

If you use more GONAL-f than you should
No adverse effects due to overdose of GONAL-f have been reported. However, Ovarian Hyperstimulation Syndrome (OHSS) may occur, as described in section 4. Nevertheless, OHSS can only occur if hCG has also been administered (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”).

If you forget to use GONAL-f
If you forget to use GONAL-f, 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 will experience them.

Serious side effects in women

• Pelvic pain in combination with nausea or vomiting may be symptoms of ovarian hyperstimulation syndrome (OHSS). This may indicate that the ovaries are over-responding to treatment and that large ovarian cysts have developed (see also section 2, “Ovarian hyperstimulation syndrome (OHSS)”). This side effect is common (may affect up to 1 in 10 people).
• OHSS may become severe, with markedly enlarged ovaries, reduced urine output, weight gain, breathing difficulties, and/or possible accumulation of fluid in the abdomen or chest. This side effect is not common (may affect up to 1 in 100 people).
• Rarely, complications of OHSS such as ovarian torsion or blood clots may occur (may affect up to 1 in 1,000 people).
• Very rarely, serious blood clotting complications (thromboembolic events) may occur, sometimes independent of OHSS (may affect up to 1 in 10,000 people). These may cause chest pain, shortness of breath, stroke, or heart attack (see also section 2, “Blood clotting disorders”).

Serious side effects in men and women

• Occasionally, allergic reactions such as rash, redness, urticaria, facial swelling with breathing difficulties may be severe. This side effect is very rare (may affect up to 1 in 10,000 people).

If you experience any of the side effects listed above, contact your doctor immediately, who may
instruct you to stop using GONAL-f.

Other side effects in women
Very common (may affect more than 1 in 10 people):

• Fluid-filled sacs in the ovary (ovarian cysts)
• Headache
• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Abdominal pain
• Nausea, vomiting, diarrhoea, abdominal cramps and bloating

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as rash, skin redness, urticaria, facial swelling with breathing difficulties may occur. These reactions may be severe.
• Asthma may worsen.

Other side effects in men
Very common (may affect more than 1 in 10 people):

• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Swelling of the veins located above and behind the testicles (varicocele)
• Enlargement of the breast gland, acne or weight gain

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as rash, skin redness, urticaria, facial swelling with breathing difficulties may occur. These reactions may be severe.
• Asthma may worsen.

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 GONAL-f

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial after "Exp". The expiry date refers to the last day of that month.
Do not store above 25°C.
Keep in the original packaging to protect the medicine from light.
Do not use GONAL-f if you notice any visible signs of deterioration, if the liquid contains particles, or if it is not clear.
The medicine must be administered immediately after preparation.
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.
GONAL-f must not be administered mixed with other medicines in the same injectable preparation, except for lutropin alfa. Studies have shown that these two medicines can be mixed and injected together without either being altered in any way.

6. Contents of the pack and other information

What GONAL-f contains

• The active substance is follitropin alfa.
• Each vial contains 5.5 micrograms of follitropin alfa.
• After reconstitution, each millilitre of the final injectable solution contains 75 IU (5.5 micrograms) of follitropin alfa.
• The other components are sucrose, monosodium phosphate monohydrate, disodium phosphate dihydrate, methionine, polysorbate 20, and concentrated phosphoric acid and sodium hydroxide for pH adjustment.
• The solvent is water for injections.

Description of the appearance of GONAL-f and contents of the pack

• GONAL-f is supplied as a powder and solvent used to prepare an injectable solution.
• The powder is a white pellet in a glass vial.
• The solvent is a clear, colourless liquid in pre-filled syringes, each containing 1 mL.
• GONAL-f is available in packs containing 1, 5 or 10 vials of powder with the corresponding number of pre-filled solvent syringes. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
Manufacturer
Merck Serono S.p.A., Via delle Magnolie 15, 70026 Modugno (Bari), Italy
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.
HOW TO PREPARE AND USE GONAL-f POWDER AND SOLVENT

• This section describes the preparation and use of GONAL-f powder and solvent.
• Before starting preparation, read these instructions completely.
• Administer the injection at the same time each day.

1. Wash your hands and find a clean surface

• It is important to ensure that your hands and equipment are clean.
• Suitable places include a clean table or clean kitchen countertop.

2. Prepare and lay out on a surface all the necessary items:

• 1 pre-filled syringe containing the solvent (the clear liquid)
• 1 vial containing GONAL-f (the white powder)
• 1 needle for preparation
• 1 fine needle for subcutaneous injection

Not supplied in the package:

• 2 alcohol-impregnated cotton swabs
• 1 sharps container for disposal of used needles

3. Prepare the solution

• Remove the protective closure cap from the vial containing the powder and from the pre-filled syringe.
• Attach the preparation needle to the pre-filled syringe, insert it into the vial of powder, and slowly inject all of the solvent. Gently rotate the vial without removing the syringe. Do not shake.
• Check that the resulting solution is clear and free from particles.
• Turn the vial upside down and slowly withdraw the solution back into the syringe by pulling the plunger.
• Remove the syringe from the vial and place it down carefully. Do not touch the needle and avoid contact with any surface.

(If more than one vial of GONAL-f has been prescribed, slowly re-inject the solution into another vial of powder, repeating this step until the number of vials prescribed have been dissolved in the solution. If lutropin alfa has been prescribed in addition to GONAL-f, you may mix the two medicines together instead of injecting them separately. After dissolving the lutropin alfa powder, withdraw the solution back into the syringe and re-inject it into the vial containing GONAL-f. Once the powder is fully dissolved, withdraw the solution back into the syringe. Check for the presence of particles and do not use the solution if it is not clear. Up to 3 powder vials can be dissolved in 1 mL of solvent.)

4. Prepare the syringe for injection

• Replace the needle with the thin needle for subcutaneous injections.
• Remove any air bubbles: if there are air bubbles in the syringe, hold it vertically with the needle pointing upwards, and gently tap until the air bubbles rise to the top. Then, gently push the plunger to expel the air.

5. Inject the dose

• Inject the solution immediately: your doctor or nurse has already informed you about the injection site (e.g., abdomen, front of the thigh). To minimize skin irritation, choose a different injection site each day.
• Clean the injection area with alcohol using a circular motion.
• Firmly pinch the skin at the injection site and insert the needle at an angle between 45° and 90° with a quick, dart-like motion.
• Inject the solution subcutaneously by slowly pushing the plunger as instructed. Do not inject directly into a vein. Make sure to inject the entire solution.
• Remove the needle immediately and clean the injection site with alcohol using a circular motion.

6. After the injection

Disposal of used items: immediately after the injection, safely dispose of used needles and empty glass vials, preferably in a sharps container.
Any unused solution must also be discarded.

Package leaflet: Information for the user

GONAL-f 1050 UI/1.75 mL powder and solvent

for injectable solution
follitropin alfa
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, consult 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, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What GONAL-f is and what it is used for

What GONAL-f is
GONAL-f contains an active substance called "follitropin alfa". Follitropin alfa is a "follicle-stimulating hormone" (FSH), belonging to a family of hormones known as "gonadotropins". Gonadotropins are involved in reproduction and fertility.

What GONAL-f is used for

In adult women, GONAL-f is used

• to stimulate the release of an egg from the ovary (ovulation) in women who do not ovulate and who have not responded to treatment with a medicine called "clomiphene citrate".
• in combination with another medicine called "lutropin alfa" ("luteinizing hormone" or LH) to stimulate the release of an egg from the ovary (ovulation) in women whose bodies produce very low levels of gonadotropins (FSH and LH).
• to promote the development of multiple follicles (each containing an egg) in women undergoing assisted reproductive procedures (procedures that may help achieve pregnancy), such as in vitro fertilization, gamete intrafallopian transfer, or zygote intrafallopian transfer.

In adult men, GONAL-f is used

• in combination with another medicine called "human chorionic gonadotropin" (hCG) to stimulate sperm production in infertile men due to low levels of certain hormones.

2. What you need to know before using GONAL-f

Before starting treatment, a doctor experienced in the management of infertility disorders should have thoroughly evaluated your couple's fertility.
Do not use GONAL-f

• if you are allergic to follicle-stimulating hormone or to any of the other ingredients of this medicine (listed in section 6).
• if you have a tumour of the hypothalamus or pituitary gland (both parts of the brain).
• if you are a woman
  • with enlarged ovaries or fluid-filled sacs in the ovary (ovarian cysts) of unknown origin
  • with vaginal bleeding of unknown origin
  • with ovarian, uterine or breast cancer
  • with a condition that usually makes a normal pregnancy impossible, such as ovarian failure (premature menopause) or malformations of the reproductive system.
• if you are a man
  • with irreversible testicular damage.

Do not use GONAL-f if you have any of these conditions. If you have any doubts, consult your doctor before using this medicine.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before using GONAL-f.
Porphyria
Inform your doctor before starting treatment if you or a family member suffer from porphyria (inability to break down porphyrins, which can be inherited from parents to children).
Immediately inform your doctor if:

• your skin becomes fragile and easily develops blisters, particularly in areas frequently exposed to sunlight, and/or
• you have stomach, arm or leg pain.

In these cases, your doctor may recommend that you stop treatment.
Ovarian hyperstimulation syndrome (OHSS)
If you are a woman, this medicine increases the risk of OHSS. In this condition, ovarian follicles develop excessively and turn into large cysts. Immediately inform your doctor if you experience lower abdominal pain, rapid weight gain, nausea or vomiting, or difficulty breathing; your doctor may ask you to stop taking the medicine (see section 4).
If you are an anovulatory patient and the recommended dosage and administration schedule are properly followed, the risk of OHSS is less likely.
Treatment with GONAL-f alone rarely causes severe OHSS if a medicine (containing human chorionic gonadotropin – hCG) is not administered to induce ovulation. If you are developing OHSS, your doctor may decide not to administer hCG during this treatment cycle and may recommend that you avoid sexual intercourse or use a barrier contraceptive method for at least four days.
Multiple pregnancy
When using GONAL-f, there is a higher risk of multiple pregnancy compared to natural conception, usually twins. Multiple pregnancy may lead to complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of GONAL-f at the correct time. In assisted reproductive procedures, the risk of multiple pregnancy is related to age, quality and number of fertilized oocytes or embryos transferred.
Miscarriage
If you undergo assisted reproductive procedures or ovarian stimulation for egg production, the risk of miscarriage is higher than in other women.
Blood clotting disorders (thromboembolic events)
If you have previously or recently had blood clots in your legs or lungs, a heart attack or stroke, or if such events have occurred in your family, your risk of developing or worsening these problems during treatment with GONAL-f may increase.
Men with excessively high FSH levels in blood
If you are a man, excessively high FSH levels in blood may indicate testicular damage. In such cases, GONAL-f is generally ineffective.
If your doctor decides to attempt treatment with GONAL-f, 4–6 months after starting treatment, you may be asked to provide semen samples for follow-up testing.
Children and adolescents
The use of GONAL-f is not indicated in children and adolescents under 18 years of age.
Other medicines and GONAL-f
Inform your doctor if you are taking, have recently taken or might take any other medicines.

• If you use GONAL-f together with other medicines that promote ovulation (such as hCG or clomiphene citrate), this may enhance the follicular response.
• If you use GONAL-f simultaneously with a gonadotropin-releasing hormone (GnRH) agonist or antagonist (these medicines reduce sex hormone levels and block ovulation), you may require a higher dose of GONAL-f to produce follicles.

Pregnancy and breastfeeding
Do not use GONAL-f during pregnancy or breastfeeding.
Driving and using machines
This medicine is not expected to affect the ability to drive or use machinery.
GONAL-f contains sodium, benzyl alcohol and latex
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially “sodium-free”.
Once reconstituted with the solvent provided, this medicine contains 1.23 mg of benzyl alcohol per 75 UI dose, equivalent to 9.45 mg/mL. Benzyl alcohol may cause allergic reactions.
The needle shield of the pre-filled syringe containing the solvent for reconstitution contains latex (dry natural rubber), which may cause severe allergic reactions.
A formulation (GONAL-f 75 UI powder and solvent for solution for injection) without benzyl alcohol and latex is available if you are allergic to these components.

3. How to use GONAL-f

Use this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor or pharmacist.

How to administer the medicine

• GONAL-f is given as an injection just under the skin (subcutaneous route). The prepared solution can be used for several injections.
• The first injection of GONAL-f must be administered under the supervision of a doctor.
• Your doctor or nurse will show you how to inject GONAL-f before you start self-injecting.
• If you are self-administering GONAL-f, carefully read and follow the instructions at the end of this leaflet titled “How to prepare and use the powder and solution of GONAL-f”.

What dose to use
Your doctor will decide how much medicine you should take and how often. The doses listed below are expressed in International Units (IU), the unit of measurement indicated on the syringes provided in the package for administration.
If you use a different syringe marked in millilitres (mL) instead of IU, you can determine the correct volume to inject, expressed in mL, from the following table:

Women
If you do not ovulate and have irregular or absent menstrual cycles

• GONAL-f is usually administered daily.
• If you have irregular menstrual cycles, start using GONAL-f within the first 7 days of your cycle. If you do not have menstrual cycles, you may start using the medicine on any day.
• The starting dose of GONAL-f is usually individualized and may be gradually adjusted.
• The daily dose of GONAL-f must not exceed 225 IU.
• When the desired response is achieved, you will receive a single injection of 250 micrograms of “recombinant hCG” (r-hCG, an hCG produced in the laboratory using a specific DNA technique) or 5,000–10,000 IU of hCG, 24–48 hours after the last injection of GONAL-f. The most suitable days for sexual intercourse are the day of hCG injection and the following day.

If your doctor does not observe the desired response, continuation of that treatment cycle with GONAL-f should be evaluated and managed according to standard clinical practice.
If your body responds excessively, treatment will be stopped and hCG will not be administered (see section 2, “Ovarian hyperstimulation syndrome (OHSS)”). In the next treatment cycle, your doctor will administer a lower dose of GONAL-f.

If you have been diagnosed with very low levels of FSH and LH hormones

• The usual starting dose of GONAL-f ranges between 75 and 150 IU together with 75 IU of lutropin alfa.
• You must use these two medicines daily for up to five weeks.
• The dose of GONAL-f may be increased every 7 or 14 days by 37.5–75 IU until the desired response is achieved.
• When the desired response is achieved, you will receive a single injection of 250 micrograms of “recombinant hCG” (r-hCG, an hCG produced in the laboratory using a specific recombinant DNA technique) or 5,000–10,000 IU of hCG, 24–48 hours after the last injection of GONAL-f and lutropin alfa. The most suitable days for sexual intercourse are the day of hCG injection and the following day. Alternatively, intrauterine insemination or another medically assisted reproduction procedure may be performed, according to your doctor’s judgment.

If your doctor observes no response after 5 weeks, that treatment cycle with GONAL-f must be discontinued. In the next treatment cycle, your doctor will administer a higher starting dose of GONAL-f.
If your body responds excessively, treatment will be stopped and hCG will not be administered (see section 2, “Ovarian hyperstimulation syndrome (OHSS)”). In the next cycle, your doctor will administer a lower dose of GONAL-f.

If you need to develop several oocytes for assisted reproductive techniques

• The starting dose of GONAL-f is usually individualized and may be gradually adjusted up to a maximum of 450 IU per day.
• Treatment continues until the oocytes have reached a certain stage of development. Your doctor will determine the appropriate timing using blood tests and/or ultrasound.
• When the oocytes have developed, you will receive a single injection of 250 micrograms of “recombinant hCG” (r-hCG, an hCG produced in the laboratory using a specific recombinant DNA technique) or 5,000–10,000 IU of hCG, 24–48 hours after the last injection of GONAL-f. This prepares the oocytes for retrieval.

Men

• The usual dose of GONAL-f is 150 IU together with hCG.
• You must use these two medicines three times a week for at least 4 months.
• If, after 4 months, you have not responded to treatment, your doctor may suggest continuing the use of both medicines for at least 18 months.

If you use more GONAL-f than you should
Effects due to an overdose of GONAL-f have not been reported. However, ovarian hyperstimulation syndrome (OHSS) may occur, as described in section 4. However, OHSS can only occur if hCG has also been administered (see section 2, “Ovarian hyperstimulation syndrome (OHSS)”).

If you forget to use GONAL-f
If you forget to use GONAL-f, 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 the use of 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.

Serious side effects in women

• Pelvic pain in combination with nausea or vomiting may be symptoms of ovarian hyperstimulation syndrome (OHSS). This may indicate that the ovaries are over-responding to treatment and that large ovarian cysts have developed (see also section 2, "Ovarian hyperstimulation syndrome (OHSS)"). This side effect is common (may affect up to 1 in 10 people).
• OHSS may become severe, with markedly enlarged ovaries, reduced urine production, weight gain, breathing difficulties and/or possible accumulation of fluid in the abdomen or chest. This side effect is not common (may affect up to 1 in 100 people).
• Rarely, complications of OHSS such as ovarian torsion or blood clotting (thromboembolic events) may occur (may affect up to 1 in 1,000 people).
• Very rarely, serious complications of blood clotting (thromboembolic events), sometimes independent of OHSS, may occur (may affect up to 1 in 10,000 people). These may cause chest pain, shortness of breath, stroke or heart attack (see also section 2, "Disorders of blood clotting").

Serious side effects in men and women

• Occasionally, allergic reactions such as rash, redness, hives, facial swelling with breathing difficulties, may be serious. This side effect is very rare (may affect up to 1 in 10,000 people).

If you notice any of the side effects listed above, contact your doctor immediately, who may
ask you to stop using GONAL-f.

Other side effects in women
Very common (may affect more than 1 in 10 people):

• Fluid-filled sacs in the ovary (ovarian cysts)
• Headache
• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Abdominal pain
• Nausea, vomiting, diarrhoea, abdominal cramps and bloating

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as rash, skin redness, hives, facial swelling with breathing difficulties may occur. These reactions may be serious.
• Asthma may worsen.

Other side effects in men
Very common (may affect more than 1 in 10 people):

• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Swelling of the veins located above and behind the testicles (varicocele)
• Enlargement of the breast gland, acne or weight gain

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as rash, skin redness, hives, facial swelling with breathing difficulties may occur. These reactions may be serious.
• Asthma may worsen.

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

5. How to store GONAL-f

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial or carton, following "Exp". The expiry date refers to the last day of that month.
Before reconstitution, do not store above 25 °C.
Store in the original packaging to protect the medicine from light.
Do not use GONAL-f if you notice visible signs of deterioration, if the liquid contains particles, or if it is not clear.
The prepared solution can be stored for up to 28 days.

• Write the date of solution preparation on the GONAL-f vial.
• Do not store above 25 °C. Do not freeze.
• Store in the original container to protect the medicine from light.
• Do not use the GONAL-f solution remaining in the vial after 28 days. At the end of treatment, any unused solution must be discarded.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
GONAL-f 1050 UI/1.75 mL powder must not be mixed with other medicines in the same injectable preparation.
GONAL-f 1050 UI/1.75 mL powder must not be mixed with other GONAL-f vials or containers in the same vial or syringe.

6. Contents of the pack and other information

What GONAL-f contains

• The active substance is follitropin alfa.
• Each vial contains 1,200 UI of follitropin alfa.
• After reconstitution, 1.75 mL of solution contains 1,050 UI (77 micrograms) of follitropin alfa, so each millilitre of solution contains 600 UI (44 micrograms).
• The other ingredients are sucrose, monobasic sodium phosphate monohydrate, dibasic sodium phosphate dihydrate, and concentrated phosphoric acid and sodium hydroxide to adjust pH.
• The solvent contains water for injections and benzyl alcohol.

Description of the appearance of GONAL-f and contents of the pack

• GONAL-f is supplied as a powder and solvent to be used for preparing an injectable solution.
• The powder is a white pellet in a multi-dose glass vial.
• The solvent is a clear, colourless solution in a pre-filled syringe containing 2 mL.
• GONAL-f is supplied in packs containing 1 vial of powder, 1 pre-filled syringe of solvent, and 15 single-use syringes graduated in International Units (FSH IU).

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
Manufacturer
Merck Serono S.p.A., Via delle Magnolie 15, 70026 Modugno (Bari), Italy
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu
HOW TO PREPARE AND USE GONAL-f POWDER AND SOLVENT

• This section describes the preparation and use of GONAL-f powder and solvent.
• Before starting, read these instructions completely.
• Administer the injection at the same time each day.

1. Wash your hands and find a clean surface

• It is important to make sure that your hands and equipment are clean.
• Suitable places are a clean table or clean kitchen countertop.

2. Prepare and lay out all necessary items on a surface

• 2 alcohol-soaked cotton swabs
• the pre-filled syringe containing the solvent (the clear liquid)
• the vial containing GONAL-f (the white powder)
• an empty syringe for the injection (see the following figure)

3. Prepare the solution

• Remove the protective caps from the vial containing the powder and from the pre-filled syringe.
• Take the pre-filled syringe, insert the needle into the powder vial, and slowly inject all the solvent into the vial containing the powder.
• Remove the syringe from the vial and discard it (cover the needle with the protective cap to avoid injury).
• This vial contains several doses of GONAL-f. You will need to keep it for several days and withdraw only the prescribed dose each day.

4. Prepare the syringe for injection

• Gently shake the vial containing GONAL-f prepared in step 3; do not agitate. Check that the solution is clear and free of particles.
• Take the injection syringe and fill it with air by pulling the plunger to the correct dose expressed in International Units (IU FSH).
• Insert the needle into the vial, turn the vial upside down, and inject the air into the vial.
• Draw the prescribed dose of GONAL-f into the syringe by pulling the plunger to the correct dose expressed in IU FSH.

5. Remove air bubbles

• If you see air bubbles in the syringe, hold it vertically with the needle pointing upwards and gently tap the syringe until all the air collects at the top. Push the plunger until the bubbles are expelled.

6. Inject the dose

• Inject the solution immediately: your doctor or nurse should have already instructed you on the injection site (e.g., abdomen, front of the thigh). To minimize skin irritation, choose a different injection site each day.
• Clean the injection area with alcohol using a circular motion.
• Firmly pinch the skin and insert the needle at an angle between 45° and 90° with a quick, dart-like motion.
• Inject the solution subcutaneously by slowly pushing the plunger, as you have been taught. Do not inject into a vein. Take all the time needed to inject the entire solution.
• Immediately remove the needle and clean the injection site with an alcohol swab using a circular motion.

7. After injection

• After the injection is complete, immediately dispose of the used syringes carefully, preferably into a sharps container.
• Store the glass vial containing the prepared solution in a safe place. You may need it again. The prepared solution is intended only for you and must not be given to other patients.
• For subsequent injections with the prepared GONAL-f solution, repeat steps 4 to 7.

Package leaflet: Information for the user

GONAL-f 450 UI/0.75 mL powder and solvent

for injectable solution
follitropin alfa
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, consult 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 could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What GONAL-f is and what it is used for

What GONAL-f is
GONAL-f contains an active substance called "follitropin alfa". Follitropin alfa is a "follicle-stimulating hormone" (FSH), belonging to a family of hormones known as "gonadotropins". Gonadotropins are involved in reproduction and fertility.

What GONAL-f is used for

In adult women, GONAL-f is used

• to stimulate the release of an egg from the ovary (ovulation) in women who do not ovulate and who have not responded to treatment with a medicine called "clomiphene citrate".
• in combination with another medicine called "lutropin alfa" ("luteinizing hormone" or LH) to stimulate the release of an egg from the ovary (ovulation) in women whose bodies produce very low levels of gonadotropins (FSH and LH).
• to promote the development of multiple follicles (each containing an egg) in women undergoing assisted reproductive procedures (procedures that may help achieve pregnancy), such as in vitro fertilization, gamete intrafallopian transfer, or zygote intrafallopian transfer.

In adult men, GONAL-f is used

• in combination with another medicine called "human chorionic gonadotropin" (hCG) to stimulate sperm production in infertile men due to low levels of certain hormones.

2. What you need to know before using GONAL-f

Before starting treatment, a doctor experienced in the treatment of fertility disorders should thoroughly evaluate your couple's fertility.
Do not use GONAL-f

• if you are allergic to follicle-stimulating hormone or to any of the other ingredients of this medicine (listed in section 6).
• if you have a tumor of the hypothalamus or pituitary gland (both parts of the brain).
• if you are a woman
  • with enlarged ovaries or fluid-filled sacs in the ovary (ovarian cysts) of unknown origin
  • with vaginal bleeding of unknown origin
  • with cancer of the ovary, uterus, or breast
  • with a condition that usually makes normal pregnancy impossible, such as ovarian failure (premature menopause) or malformations of the reproductive system.
• if you are a man
  • with irreversible damage to the testicles.

Do not use GONAL-f if you have any of these conditions. If you have any doubts, consult your doctor before using this medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using GONAL-f.
Porphyria
Inform your doctor before starting treatment if you or a family member has porphyria (inability to break down porphyrins, which can be inherited from parents).
Immediately inform your doctor if:

• your skin becomes fragile and easily develops blisters, especially in areas frequently exposed to sunlight, and/or
• you have stomach, arm, or leg pain.

In such cases, your doctor may advise you to stop treatment.
Ovarian hyperstimulation syndrome (OHSS)
If you are a woman, this medicine increases the risk of OHSS. In this condition, follicles develop excessively and turn into large cysts. Immediately inform your doctor if you experience lower abdominal pain, rapid weight gain, nausea or vomiting, or difficulty breathing; your doctor may ask you to stop taking the medicine (see section 4).
If you are anovulatory and follow the recommended dosage and administration schedule correctly, the risk of OHSS is less likely.
Treatment with GONAL-f rarely causes severe OHSS if a medicine (containing human chorionic gonadotropin – hCG) to induce ovulation is not administered. If you are developing OHSS, your doctor may decide not to administer hCG in this treatment cycle and may recommend avoiding sexual intercourse or using a barrier contraceptive method for at least four days.
Multiple pregnancy
When using GONAL-f, your risk of multiple pregnancy is higher than with natural conception, most commonly twins. Multiple pregnancy may lead to complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of GONAL-f at the correct time. In assisted reproductive procedures, the risk of multiple pregnancy is related to age, quality, and number of fertilized eggs or embryos transferred.
Miscarriage
If you undergo assisted reproductive procedures or ovarian stimulation to produce eggs, your risk of miscarriage is higher than in other women.
Blood clotting disorders (thromboembolic events)
If you have had or recently had blood clots in your legs or lungs, a heart attack, or a stroke, or if these events occurred in your family, your risk of these problems occurring or worsening during treatment with GONAL-f may increase.
Men with excessively high FSH levels in blood
If you are a man, excessively high FSH levels in blood may indicate testicular damage. In such cases, GONAL-f is generally ineffective.
If your doctor decides to attempt treatment with GONAL-f, they may ask you to provide sperm samples for follow-up testing 4–6 months after starting treatment.
Children and adolescents
The use of GONAL-f is not indicated in children and adolescents under 18 years of age.
Other medicines and GONAL-f
Inform your doctor if you are taking, have recently taken, or might take any other medicines.

• If you use GONAL-f together with other medicines that promote ovulation (such as hCG or clomiphene citrate), this may enhance the follicular response.
• If you use GONAL-f simultaneously with a gonadotropin-releasing hormone (GnRH) agonist or antagonist (these medicines reduce sex hormone levels and block ovulation), you may require a higher dose of GONAL-f to produce follicles.

Pregnancy and breastfeeding
Do not use GONAL-f during pregnancy or breastfeeding.
Driving and using machines
This medicine is not expected to affect your ability to drive or operate machinery.
GONAL-f contains sodium, benzyl alcohol, and latex
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is essentially "sodium-free".
Once reconstituted with the provided solvent, this medicine contains 1.23 mg of benzyl alcohol per 75 IU dose, equivalent to 9.45 mg/mL. Benzyl alcohol may cause allergic reactions.
The needle shield of the pre-filled syringe containing the solvent for reconstitution contains latex (dry natural rubber), which may cause severe allergic reactions.
A formulation (GONAL-f 75 IU powder and solvent for injectable solution) without benzyl alcohol and latex is available if you are allergic to these components.

3. How to use GONAL-f

Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.

How to use the medicine

• GONAL-f is administered by injection just under the skin (subcutaneously). The prepared solution can be used for several injections.
• The first GONAL-f injection must be given under the supervision of a doctor.
• Your doctor or nurse will show you how to inject GONAL-f before you self-administer it.
• If you are self-administering GONAL-f, carefully read and follow the instructions at the end of this leaflet titled "How to prepare and use the powder and solution of GONAL-f".

What dose to use
Your doctor will decide how much medicine you should use and how often. The doses listed below are expressed in International Units (IU), the unit of measurement indicated on the syringes provided in the package for administration.
If you are using a different syringe marked in millilitres (mL) instead of IU, you can determine the correct volume to inject, in mL, from the following table:

Women
If you do not ovulate and have irregular or absent menstrual cycles

• GONAL-f is generally administered every day.
• If you have irregular menstrual cycles, start using GONAL-f within the first 7 days of your cycle. If you do not have menstrual cycles, you may start using the medicine on any day.
• The starting dose of GONAL-f is usually individualized and may be gradually adjusted.
• The daily dose of GONAL-f must not exceed 225 IU.
• When the desired response is achieved, you will receive a single injection of 250 micrograms of "recombinant hCG" (r-hCG, a laboratory-produced hCG using a specific DNA technique) or 5,000–10,000 IU of hCG, 24–48 hours after the last injection of GONAL-f. The most suitable days for sexual intercourse are the day of the hCG injection and the following day.

If your doctor does not observe the desired response, continuation of that treatment cycle with
GONAL-f should be evaluated and managed according to standard clinical practice.
If your body responds excessively, treatment will be stopped and you will not be given hCG
(see section 2, "Ovarian hyperstimulation syndrome (OHSS)"). In the next treatment cycle, your doctor
will administer a lower dose of GONAL-f.
If you have been diagnosed with very low levels of FSH and LH hormones

• The usual starting dose of GONAL-f ranges between 75 and 150 IU together with 75 IU of lutropin alfa.
• You will need to use these two medicines every day for up to five weeks.
• The dose of GONAL-f may be increased every 7 or 14 days by 37.5–75 IU until the desired response is achieved.
• When the desired response is achieved, you will be given a single injection of 250 micrograms of "recombinant hCG" (r-hCG, a laboratory-produced hCG using a specific recombinant DNA technique) or 5,000–10,000 IU of hCG, 24–48 hours after the last injection of GONAL-f and lutropin alfa. The most suitable days for sexual intercourse are the day of the hCG injection and the following day. Alternatively, intrauterine insemination or another medically assisted reproduction procedure may be performed, based on your doctor’s judgment.

If your doctor observes no response after 5 weeks, that treatment cycle with GONAL-f
should be discontinued. In the next treatment cycle, your doctor will administer a higher
starting dose of GONAL-f.
If your body responds excessively, treatment will be stopped and you will not be given
hCG (see section 2, "Ovarian hyperstimulation syndrome (OHSS)"). In the next cycle, your
doctor will administer a lower dose of GONAL-f.
If you need to develop several eggs to be retrieved for assisted reproductive techniques

• The starting dose of GONAL-f is usually individualized and may be gradually adjusted up to a maximum of 450 IU per day.
• Treatment continues until the eggs have reached a certain stage of development. Your doctor will determine the appropriate time using blood tests and/or ultrasound.
• When the eggs have developed, you will receive a single injection of 250 micrograms of "recombinant hCG" (r-hCG, a laboratory-produced hCG using a specific recombinant DNA technique) or 5,000–10,000 IU of hCG, 24–48 hours after the last injection of GONAL-f. This prepares the eggs for retrieval.

Men

• The usual dose of GONAL-f is 150 IU together with hCG.
• You will need to use these two medicines three times a week for at least 4 months.
• If, after 4 months, you have not responded to treatment, your doctor may recommend continuing treatment with both medicines for at least 18 months.

If you use more GONAL-f than you should
Effects due to overdose of GONAL-f have not been reported. However, ovarian hyperstimulation
syndrome (OHSS) may occur as described in section 4. However, OHSS can occur only if hCG
has also been administered (see section 2, "Ovarian hyperstimulation syndrome (OHSS)").
If you forget to use GONAL-f
If you forget to use GONAL-f, 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 everybody gets them.

Serious side effects in women

• Pelvic pain in combination with nausea or vomiting may be symptoms of ovarian hyperstimulation syndrome (OHSS). This may indicate that the ovaries are reacting excessively to treatment and that large ovarian cysts have developed (see also section 2 under "Ovarian hyperstimulation syndrome (OHSS)"). This side effect is common (may affect up to 1 in 10 people).
• OHSS may become severe, with markedly enlarged ovaries, reduced urine production, weight gain, breathing difficulties and/or possible accumulation of fluid in the abdomen or chest. This side effect is not common (may affect up to 1 in 100 people).
• Rarely, complications of OHSS such as ovarian torsion or blood clotting may occur (may affect up to 1 in 1,000 people).
• Very rarely, serious complications related to blood clotting (thromboembolic events) may occur, sometimes independent of OHSS (may affect up to 1 in 10,000 people). This may cause chest pain, shortness of breath, stroke or heart attack (see also section 2 under "Blood clotting disorders").

Serious side effects in men and women

• Occasionally, allergic reactions such as skin rash, redness, urticaria, facial swelling with breathing difficulties, may be severe. This side effect is very rare (may affect up to 1 in 10,000 people).

If you experience any of the side effects listed above, contact your doctor immediately, who may
instruct you to stop using GONAL-f.

Other side effects in women
Very common (may affect more than 1 in 10 people):

• Fluid-filled sacs in the ovary (ovarian cysts)
• Headache
• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Abdominal pain
• Nausea, vomiting, diarrhoea, abdominal cramps and bloating

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as skin rash, redness of the skin, urticaria, facial swelling with breathing difficulties may occur. These reactions may be severe.
• Asthma may worsen.

Other side effects in men
Very common (may affect more than 1 in 10 people):

• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Swelling of the veins located above and behind the testicles (varicocele)
• Enlargement of the breast gland, acne or weight gain

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as skin rash, redness of the skin, urticaria, facial swelling with breathing difficulties may occur. These reactions may be severe.
• Asthma may worsen.

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 listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store GONAL-f

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial or carton, following "Exp." The expiry date refers to the last day of that month.
Before reconstitution, do not store above 25 °C.
Store in the original packaging to protect the medicine from light.
Do not use GONAL-f if you notice any visible signs of deterioration, if the liquid contains particles, or if it is not clear.
The prepared solution can be stored for up to 28 days.

• Write the date of solution preparation on the GONAL-f vial.
• Do not store above 25 °C. Do not freeze.
• Store in the original container to protect the medicine from light.
• Do not use any remaining GONAL-f solution in the vial after 28 days. At the end of treatment, any unused solution must be discarded.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.
The powder for GONAL-f 450 UI/0.75 mL must not be mixed with other medicines in the same injectable preparation.
The powder for GONAL-f 450 UI/0.75 mL must not be mixed with other GONAL-f vials in the same vial or syringe.

6. Package contents and other information

What GONAL-f contains

• The active substance is follitropin alfa.
• Each vial contains 600 IU of follitropin alfa.
• After reconstitution, 0.75 mL of solution contains 450 IU (33 micrograms) of follitropin alfa, so each millilitre of solution contains 600 IU (44 micrograms).
• The other components are sucrose, monobasic sodium phosphate monohydrate, dibasic sodium phosphate dihydrate, and concentrated phosphoric acid and sodium hydroxide used to adjust the pH.
• The solvent contains water for injections and benzyl alcohol.

Description of the appearance of GONAL-f and contents of the pack

• GONAL-f is presented as a powder and solvent used to prepare an injectable solution.
• The powder is a white pellet in a multi-dose glass vial.
• The solvent is a clear, colourless solution in a pre-filled syringe containing 1 mL.
• GONAL-f is supplied in packs containing 1 vial of powder, 1 pre-filled syringe of solvent, and 6 single-use syringes graduated in International Units (FSH IU).

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
Manufacturer
Merck Serono S.p.A., Via delle Magnolie 15, 70026 Modugno (Bari), Italy
More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu.
HOW TO PREPARE AND USE GONAL-f POWDER AND SOLVENT

• This section describes the preparation and use of GONAL-f powder and solvent.
• Before starting, read these instructions completely.
• Administer the injection at the same time each day.

1. Wash your hands and find a clean surface

• It is important to make sure that your hands and all equipment are clean.
• Suitable places are a clean table or a clean kitchen worktop.

2. Prepare and lay out on a surface all the necessary items

• 2 alcohol-soaked cotton balls
• the pre-filled syringe containing the solvent (the clear liquid)
• the vial containing GONAL-f (the white powder)
• an empty syringe for the injection (see the following figure)

3. Prepare the solution

• Remove the protective caps from the vial containing the powder and from the pre-filled syringe.
• Take the pre-filled syringe, insert the needle into the vial of powder, and slowly inject all of the solvent into the vial containing the powder.
• Remove the syringe from the vial and dispose of it (cover the needle with the protective cap to avoid injury).
• This vial contains several doses of GONAL-f. You will need to keep it for several days and withdraw only the prescribed dose each day.

4. Prepare the syringe for injection

• Gently shake the vial containing GONAL-f prepared in step 3; do not agitate. Check that the solution is clear and does not contain any particles.
• Take the injection syringe and fill it with air by pulling the plunger to the correct dose indicated in International Units (IU FSH).
• Insert the needle into the vial, turn the vial upside down, and inject the air into the vial.
• Draw the prescribed dose of GONAL-f into the syringe by pulling the plunger to the correct dose indicated in IU of FSH.

5. Remove air bubbles

• If you see air bubbles in the syringe, hold it vertically with the needle pointing upwards and gently tap the syringe until all the air collects at the top. Push the plunger until all the air bubbles are expelled.

6. Inject the dose

• Inject the solution immediately: your doctor or nurse should have already instructed you on the injection site (e.g., abdomen, front of the thigh). To minimize skin irritation, choose a different injection site each day.
• Clean the injection area with alcohol using a circular motion.
• Firmly pinch the skin and insert the needle at an angle between 45° and 90° with a quick, dart-like motion.
• Inject the solution subcutaneously by slowly pushing the plunger, as you have been taught. Do not inject into a vein. Take all the time needed to inject the entire solution.
• Immediately remove the needle and clean the injection site with an alcohol swab using a circular motion.

7. After injection

• After completing the injection, immediately dispose of the used syringes carefully, preferably into a sharps disposal container.
• Store the glass vial containing the prepared solution in a safe place. You may need it again. The prepared solution is intended only for you and must not be given to other patients.
• For subsequent injections with the prepared GONAL-f solution, repeat steps 4 to 7.

Package leaflet: information for the user

GONAL-f 150 UI/0.24 mL solution for injection in pre-filled pen

follitropin alfa
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 others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What GONAL-f is and what it is used for
2. What you need to know before using GONAL-f
3. How to use GONAL-f
4. Possible side effects
5. How to store GONAL-f
6. Package contents and other information
   Instructions for use

1. What GONAL-f is and what it is used for

What GONAL-f is
GONAL-f contains an active substance called "follitropin alfa". Follitropin alfa is a "follicle-stimulating hormone" (FSH), belonging to the family of hormones known as "gonadotropins". Gonadotropins are involved in reproduction and fertility.

What GONAL-f is used for

In adult women, GONAL-f is used

• to stimulate the release of an egg from the ovary (ovulation) in women who do not ovulate and who have not responded to treatment with a medicine called "clomiphene citrate".
• in combination with another medicine called "lutropin alfa" ("luteinizing hormone" or LH) to stimulate the release of an egg from the ovary (ovulation) in women whose bodies produce very low levels of gonadotropins (FSH and LH).
• to promote the development of multiple follicles (each containing an egg) in women undergoing assisted reproductive procedures (procedures that may help achieve pregnancy), such as "in vitro fertilization", "gamete intrafallopian transfer", or "zygote intrafallopian transfer".

In adult men, GONAL-f is used

• in combination with another medicine called "human chorionic gonadotropin" (hCG) to stimulate sperm production in infertile men due to low levels of certain hormones.

2. What you should know before using GONAL-f

Before starting treatment, a doctor experienced in the treatment of fertility disorders should thoroughly evaluate your couple's fertility.
Do not use GONAL-f

• if you are allergic to follicle-stimulating hormone or to any of the other ingredients of this medicine (listed in section 6).
• if you have a tumor of the hypothalamus or pituitary gland (both parts of the brain).
• if you are a woman
  • with enlarged ovaries or fluid-filled sacs in the ovary (ovarian cysts) of unknown origin
  • with vaginal bleeding of unknown origin
  • with cancer of the ovary, uterus, or breast
  • with a condition that usually prevents a normal pregnancy, such as ovarian failure (premature menopause) or malformations of the reproductive system.
• if you are a man
  • with irreversible testicular damage.

Do not use GONAL-f if you have any of these conditions. If you are in doubt, consult your doctor before using this medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using GONAL-f.
Porphyria
Tell your doctor before starting treatment if you or a family member has porphyria (an inability to break down porphyrins, which can be inherited from parents to children).
Immediately inform your doctor if:

• your skin becomes fragile and easily develops blisters, especially in areas frequently exposed to sunlight, and/or
• you have stomach, arm, or leg pain.

In such cases, your doctor may advise you to stop treatment.
Ovarian hyperstimulation syndrome (OHSS)
If you are a woman, this medicine increases the risk of OHSS. In this condition, ovarian follicles develop excessively and turn into large cysts. Immediately inform your doctor if you experience lower abdominal pain, rapid weight gain, nausea or vomiting, or difficulty breathing; your doctor may ask you to stop taking the medicine (see section 4).
If you are anovulatory and follow the recommended dosage and administration schedule correctly, the risk of OHSS is less likely.
Treatment with GONAL-f rarely causes severe OHSS if a medicine (containing human chorionic gonadotropin – hCG) is not administered to induce ovulation. If you are developing OHSS, your doctor may decide not to administer hCG in this treatment cycle and may advise you to avoid sexual intercourse or to use a barrier contraceptive method for at least four days.
Multiple pregnancy
When using GONAL-f, there is an increased risk of multiple pregnancy compared to natural conception, most commonly twins. Multiple pregnancy may lead to complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of GONAL-f at the correct time. In assisted reproductive procedures, the risk of multiple pregnancy is related to age, quality, and number of fertilized eggs or embryos transferred.
Miscarriage
If you undergo assisted reproductive procedures or ovarian stimulation for egg production, the risk of miscarriage is higher than in other women.
Blood clotting disorders (thromboembolic events)
If you have previously or recently had blood clots in your legs or lungs, a heart attack, or a stroke, or if these events occurred in your family, your risk of developing or worsening these problems during treatment with GONAL-f may increase.
Men with high levels of FSH in the blood
If you are a man, high levels of FSH in the blood may indicate testicular damage. In such cases, GONAL-f is generally ineffective.
If your doctor decides to attempt treatment with GONAL-f, you may be asked to provide sperm samples for follow-up tests 4–6 months after starting treatment.
Children and adolescents
The use of GONAL-f is not indicated in children and adolescents under 18 years of age.
Other medicines and GONAL-f
Inform your doctor if you are taking, have recently taken, or might take any other medicines.

• If you use GONAL-f together with other medicines that promote ovulation (such as hCG or clomiphene citrate), this may enhance the follicular response.
• If you use GONAL-f simultaneously with a gonadotropin-releasing hormone (GnRH) agonist or antagonist (medicines that reduce sex hormone levels and block ovulation), you may require a higher dose of GONAL-f to produce follicles.

Pregnancy and breastfeeding
Do not use GONAL-f during pregnancy or breastfeeding.
Driving and using machines
This medicine is not expected to affect your ability to drive or operate machinery.
GONAL-f contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is essentially "sodium-free".

3. How to use GONAL-f

Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.

How to use the medicine

• GONAL-f is administered by subcutaneous injection (just under the skin). The pre-filled pen may be used for multiple injections.
• The first injection of GONAL-f must be given under the supervision of a doctor.
• Your doctor or nurse will show you how to use the pre-filled GONAL-f pen to inject the medicine.
• If you are self-administering GONAL-f, carefully read and follow the “Instructions for Use”.

Which dose to use
Your doctor will decide how much medicine you should take and how often. The doses listed below are expressed in International Units (IU).

Women

If you do not ovulate and have irregular or absent menstrual cycles

• GONAL-f is usually administered daily.
• If you have irregular menstrual cycles, start using GONAL-f within the first 7 days of your cycle. If you do not have menstrual cycles, you may start treatment on any day.
• The initial dose of GONAL-f is usually individualized and may be gradually adjusted.
• The daily dose of GONAL-f must not exceed 225 IU.
• When the desired response is achieved, you will receive a single injection of 250 micrograms of recombinant “hCG” (r-hCG, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last GONAL-f injection. The most suitable days for sexual intercourse are the day of the hCG injection and the following day.

If your doctor does not observe the desired response, continuation of that treatment cycle with GONAL-f should be evaluated and managed according to standard clinical practice.
If your body responds excessively, treatment will be stopped and you will not receive hCG (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). In the next cycle, your doctor will administer a lower dose of GONAL-f.

If you have been diagnosed with very low levels of FSH and LH hormones

• The usual initial dose of GONAL-f is between 75 and 150 IU, together with 75 IU of lutropin alfa.
• You will need to use these two medicines daily for up to five weeks.
• The dose of GONAL-f may be increased every 7 or 14 days by 37.5–75 IU until the desired response is achieved.
• When the desired response is achieved, you will receive a single injection of 250 micrograms of recombinant “hCG” (r-hCG, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last injection of GONAL-f and lutropin alfa. The most suitable days for sexual intercourse are the day of the hCG injection and the following day. Alternatively, intrauterine insemination or another medically assisted reproduction procedure may be performed, according to your doctor’s judgment.

If your doctor observes no response after 5 weeks, that treatment cycle with GONAL-f should be discontinued. In the next treatment cycle, your doctor will administer a higher initial dose of GONAL-f.
If your body responds excessively, treatment will be stopped and you will not receive hCG (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). In the next cycle, your doctor will administer a lower dose of GONAL-f.

If you need to stimulate the development of several eggs for assisted reproductive techniques

• The initial dose of GONAL-f is usually individualized and may be gradually adjusted up to a maximum of 450 IU per day.
• Treatment continues until the eggs have reached a certain stage of development. Your doctor will determine the appropriate timing using blood tests and/or ultrasound.
• When the eggs have developed, you will receive a single injection of 250 micrograms of recombinant “hCG” (r-hCG, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last GONAL-f injection. This prepares the eggs for retrieval.

Men

• The usual dose of GONAL-f is 150 IU together with hCG.
• You will need to use these two medicines three times a week for at least 4 months.
• If you have not responded after 4 months, your doctor may recommend continuing treatment with both medicines for up to 18 months.

If you use more GONAL-f than you should
No effects due to overdose of GONAL-f have been reported. However, Ovarian Hyperstimulation Syndrome (OHSS) may occur, as described in section 4. Nevertheless, OHSS can only occur if hCG has also been administered (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”).

If you forget to use GONAL-f
If you forget to use GONAL-f, 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 questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Serious side effects in women

• Pelvic pain in combination with nausea or vomiting may be symptoms of ovarian hyperstimulation syndrome (OHSS). This may indicate that the ovaries are over-responding to treatment and that large ovarian cysts have developed (see also section 2 under "Ovarian hyperstimulation syndrome (OHSS)"). This side effect is common (may affect up to 1 in 10 people).
• OHSS may become severe, with markedly enlarged ovaries, reduced urine output, weight gain, breathing difficulties and/or possible accumulation of fluid in the abdomen or chest. This side effect is not common (may affect up to 1 in 100 people).
• Rarely, complications of OHSS such as ovarian torsion or blood clotting (thromboembolic events) may occur (may affect up to 1 in 1,000 people).
• Very rarely, serious complications of blood clotting (thromboembolic events), sometimes independent of OHSS, may occur (may affect up to 1 in 10,000 people). These may cause chest pain, shortness of breath, stroke or heart attack (see also section 2 under "Blood clotting disorders").

Serious side effects in men and women

• Occasionally, allergic reactions such as rash, redness, hives, or facial swelling with breathing difficulties may be severe. This side effect is very rare (may affect up to 1 in 10,000 people).

If you notice any of the side effects described, contact your doctor immediately, who may instruct you
to stop using GONAL-f.

Other side effects in women
Very common (may affect more than 1 in 10 people):

• Fluid-filled sacs in the ovary (ovarian cysts)
• Headache
• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Abdominal pain
• Nausea, vomiting, diarrhoea, abdominal cramps and bloating

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as rash, skin redness, hives, facial swelling with breathing difficulties may occur. These reactions may be severe.
• Asthma may worsen.

Other side effects in men
Very common (may affect more than 1 in 10 people):

• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Swelling of the veins located above and behind the testicles (varicocele)
• Enlargement of the breast gland, acne or weight gain

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as rash, skin redness, hives, facial swelling with breathing difficulties may occur. These reactions may be severe.
• Asthma may worsen.

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

5. How to store GONAL-f

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the cartridge label or the carton after "Exp". The expiry date refers to the last day of that month.
Store in the refrigerator (2 °C–8 °C). Do not freeze.
Before first use and within the shelf life, the product may be stored outside the refrigerator at a maximum temperature of 25 °C for a single period of up to 3 months; it must be discarded if not used within these 3 months.
Keep the cap on the pen to protect the medicine from light.
Do not use GONAL-f if you notice visible signs of deterioration, if the liquid contains particles, or if it is not clear.
After first use, the pen should be stored for a maximum of 28 days at a temperature between 2 °C and 25 °C. Do not use the medicine remaining in the pre-filled pen after 28 days.
At the end of treatment, any unused solution must be disposed of.
Do not dispose of medicines 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 GONAL-f contains

• The active substance is follitropin alfa.
• Each pre-filled multidose pen contains 150 IU (11 micrograms) of follitropin alfa in 0.24 mL of solution.
• The other components are poloxamer 188, sucrose, methionine, monobasic sodium phosphate monohydrate, dibasic sodium phosphate dihydrate, m-cresol, and concentrated phosphoric acid and sodium hydroxide to adjust pH, and water for injections.

Description of the appearance of GONAL-f and contents of the pack

• GONAL-f is a clear, colourless injectable liquid in a pre-filled pen.
• It is supplied in packs containing 1 pre-filled pen and 4 disposable needles.

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
Manufacturer
Merck Serono S.p.A., Via delle Magnolie 15, 70026 Modugno (Bari), Italy
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu .

Instructions for use

GONAL-f PREFILLED PEN 150 UI/0.24 mL

Injectable solution in a prefilled pen
Follitropin alfa
Important information about the GONAL-f prefilled pen

• Read the Instructions for Use and the Package Leaflet before using the prefilled pen

GONAL-f.

• Always follow all instructions provided in these Instructions for Use and given by your healthcare provider, as they may differ from those used previously. These instructions will help you avoid treatment errors, infections from needlestick injuries, or injuries from broken glass.
• The GONAL-f prefilled pen is intended for subcutaneous injection only.
• Use the GONAL-f prefilled pen only if a healthcare provider has shown you how to use it correctly.
• Your healthcare provider will tell you how many GONAL-f prefilled pens you need to complete your treatment.
• Administer the injection at the same time every day.
• The numbers shown in the dose control window indicate the dose of follitropin alfa in International Units (IU). Your healthcare provider will tell you how many IU of follitropin alfa you must inject each day.
• The numbers displayed in the dose control window will help you:

a. Set the prescribed dose (Figure 1).

b. Verify that the injection has been
completed (Figure 2).

c. Read the remaining dose to be injected with
a second pen (Figure 3).

• Remove the needle from the pen immediately after each injection.

Do not reuse needles.
Do not share the pen and/or needles with other people.
Do not use the GONAL-f prefilled pen if it has been dropped or if the pen is cracked or damaged, as
you may be injured.

How to use the GONAL-f prefilled pen treatment diary
A treatment diary is attached at the end of these Instructions for Use. Use the treatment diary to record the amounts injected.
Injecting incorrect amounts of medication may affect your treatment.

• Record the treatment day (column 1), date (column 2), time of injection (column 3), and volume remaining in the pen (column 4).
• Record the prescribed dose (column 5).
• Check that the dose is correctly set before injection (column 6).
• After the injection, read the number shown in the dose control window.
• Confirm administration of a complete injection (column 7), or record the number shown in the dose control window if it is not “0” (column 8).
• If necessary, administer an injection with a second pen, setting the remaining dose that was recorded in the column “Amount to select for second injection” (column 8).
• Record this remaining dose in the next column “Amount to inject” (column 6).

By using the treatment diary to record your daily injection(s), you can verify each day that you have received the full prescribed dose.
Example of a treatment diary:

Become familiar with the GONAL-f prefilled pen

Needle*:
Prefilled pen:
Step 1 Prepare the necessary items

1.1 Allow the prefilled pen to reach room temperature
for at least 30 minutes before use, so that the
medication reaches room temperature.
Do not use a microwave or other heating devices to warm the pen.
1.2 Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.

1.3 Additional required materials (not included in the
package):

• Alcohol wipes and a sharps disposal container (Figure 4).
  1.4 Wash your hands thoroughly with soap and water, then dry them completely (Figure 5).
  1.5 Remove the GONAL-f prefilled pen from the

package using one hand.
Do not use tools or other devices, as they may damage
the pen.
1.6 Check that the name printed on the prefilled pen
is GONAL-f.
1.7 Check the expiration date on the pen label
(Figure 6).
Do not use the GONAL-f prefilled pen if the
expiration date has passed or if the prefilled pen does not
say GONAL-f.

Step 2 Prepare for injection

2.1 Remove the pen cap (Figure 7).
2.2 Make sure the medication appears clear, colorless, and
free of particles.
Do not use the prefilled pen if
the medication is cloudy or has changed color, as this may lead to infection.
2.3 Make sure the dose control window displays “0”
(Figure 8).

Choose an injection site:
2.4 A healthcare provider will instruct you on the appropriate injection sites on the abdominal area
(Figure 9). To minimize skin irritation, select a different injection site each day.
2.5 Clean the skin at the injection site with an alcohol wipe.
Do not touch or cover the cleaned skin.

Step 3 Attach the needle
Important: Always use a new needle for each injection. Reusing a needle may cause infection.
3.1 Take a new needle. Use

only the “single-use” needles supplied
in the package.
3.2 Check that the outer needle cap is not damaged.
3.3 Hold the outer needle cap firmly.
3.4 Check that the tear-off tab on the outer needle cap is
not damaged or loose, and that the expiration date has not passed (Figure 10).
3.5 Remove the tab (Figure 11).
Do not use the needle if it is damaged or expired,
or if the outer needle cap or tear-off tab is damaged or loose.
Using an expired needle or one with a damaged tear-off tab or outer cap
can lead to infection. Dispose of it in a sharps container and take a new needle.
3.6 Screw the outer needle cap onto the threaded tip of the GONAL-f prefilled pen
until you feel slight resistance (Figure 12).
Do not overtighten the needle; otherwise, it may be difficult to remove after injection.
3.7 Remove the outer needle cap by gently pulling it off (Figure 13).
3.8 Set it aside for later use (Figure 14).
Do not discard the outer needle cap,
as it will be needed later to prevent needlestick injuries and infections when removing the needle from the prefilled pen.
3.9 Hold the GONAL-f prefilled pen with the needle pointing upward (Figure 15).
3.10 Carefully remove and discard the inner protective cap (Figure 16).

Do not replace the inner protective cap onto the needle. You could injure yourself and develop an infection.
3.11 Carefully examine the needle tip and check for one or more small drops of liquid (Figure 17).

If one or more small drops of liquid are not observed at or near the needle tip the first time a new pen is used:

1. Gently rotate the dose selector knob forward until the dose display window shows “25” (Figure 18).
   • If you go past “25”, you may turn the dose knob back.

2. Hold the pen with the needle pointing upward.
3. Lightly tap the cartridge holder (Figure 19).
4. Press the dose selector knob fully in. A small drop of liquid should appear at the needle tip (Figure 20).
5. Check that the dose display window shows “0” (Figure 21).
6. Proceed to Step 4 Set the Dose.

If no drop of liquid appears, contact your healthcare provider.
Step 4 Set the Dose
Note: The pen contains 150 IU of follitropin alfa. The maximum single dose that can be set on the 150 IU pen is 150 IU. The minimum single dose is 12.5 IU, and doses can be increased in 12.5 IU increments.
4.1 Rotate the dose selector knob until the prescribed dose appears in the dose display window.

• Example: If the prescribed dose is 150 IU, ensure that the number “150” is displayed in the dose window (Figure 22). Injecting incorrect amounts of medication may affect your treatment.

4.2 Confirm that the dose display window shows the full prescribed dose before proceeding to the next step.
Step 5 Inject the Dose
Important: Inject the dose according to the instructions provided by your healthcare provider.
5.1 Slowly insert the entire needle into the skin (Figure 24).
5.2 Place your thumb in the center of the dose selector knob.
Press the dose knob slowly and completely in and keep it pressed to complete the injection (Figure 25).
Note: The higher the dose, the longer the injection will take.

5.3 Keep the dose knob pressed for at least 5 seconds before removing the needle from the skin (Figure 26).

• The number in the dose display window will return to “0”.

• After at least 5 seconds, while keeping the dose selector knob pressed, remove the needle from the skin (Figure 27).

• Once the needle has been removed from the skin, release the dose selector knob.

Do not release the dose knob until the needle has been removed from the skin.
Step 6 Remove the Needle After Each Injection

6.1 Place the outer needle cap on a flat surface.
6.2 Hold the GONAL-f pre-filled pen firmly in one hand and place the needle into the outer cap.
6.3 Press the needle, now covered by its cap, against a hard surface until you hear a “click” (Figure 29).
6.4 Grasp the outer needle cap and unscrew the needle by turning it in the opposite direction (Figure 30).

6.5 Dispose of the used needle safely in a sharps container (Figure 31). Handle the needle with care to avoid needle-stick injuries.
Do not reuse or share used needles.
Step 7 After the Injection

7.1 Check that a complete injection has been administered:

• Verify that the dose display window shows “0” (Figure 32). If “0” appears in the dose display window, the full dose has been delivered. If the dose display window shows a number greater than “0”, the GONAL-f pre-filled pen is empty. The full prescribed dose has not been administered, and you must perform step 7.2 below.

7.2 Complete a partial injection (only if necessary):

• The dose display window indicates the remaining amount to be injected using a new pen. In the example shown, the remaining amount to administer is 50 IU (Figure 33).
• To complete the dose with a second pen, repeat steps 1 through 8.

Step 8 Store the GONAL-f Pre-filled Pen

8.1 Replace the pen cap to prevent infection (Figure 34).
8.2 Store the pen with the cap on in a safe place as indicated in the Package Leaflet.
8.3 When the pen is empty, ask your healthcare provider how to dispose of it properly.
Do not store the pen with the needle still attached, as this may lead to infection.
Do not reuse the GONAL-f pre-filled pen if it has been dropped or if the pen is cracked or damaged, as you may be injured.
If you have any questions, contact your healthcare provider.
Treatment Diary for the GONAL-f Pre-filled Pen

These Instructions for Use were last updated on: {MM/YYYY}.

Package leaflet: Information for the user

GONAL-f 300 UI/0.48 mL solution for injection in a pre-filled pen

follitropin alfa
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 could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What GONAL-f is and what it is used for

What GONAL-f is
GONAL-f contains an active substance called “follitropin alfa”. Follitropin alfa is a “follicle-stimulating hormone” (FSH), belonging to a family of hormones known as “gonadotropins”. Gonadotropins are involved in reproduction and fertility.

What GONAL-f is used for
In adult women, GONAL-f is used

• to stimulate the release of an egg from the ovary (ovulation) in women who do not ovulate and who have not responded to treatment with a medicine called “clomiphene citrate”.
• in combination with another medicine called “lutropin alfa” (“luteinizing hormone” or LH) to stimulate the release of an egg from the ovary (ovulation) in women whose bodies produce very low levels of gonadotropins (FSH and LH).
• to stimulate the development of multiple follicles (each containing an egg) in women undergoing assisted reproductive procedures (procedures that can help achieve pregnancy), such as “in vitro fertilization”, “gamete intrafallopian transfer”, or “zygote intrafallopian transfer”.

In adult men, GONAL-f is used

• in combination with another medicine called “human chorionic gonadotropin” (hCG) to stimulate sperm production in infertile men due to low levels of certain hormones.

2. What you need to know before using GONAL-f

Before starting treatment, a doctor experienced in the treatment of fertility disorders should have thoroughly evaluated your couple's fertility.
Do not use GONAL-f

• if you are allergic to follicle-stimulating hormone or to any of the other ingredients of this medicine (listed in section 6).
• if you have a tumor of the hypothalamus or pituitary gland (both parts of the brain).
• if you are a woman
  • with enlarged ovaries or fluid-filled sacs in the ovary (ovarian cysts) of unknown origin
  • with vaginal bleeding of unknown origin
  • with cancer of the ovary, uterus, or breast
  • with a condition that usually makes normal pregnancy impossible, such as ovarian failure (premature menopause) or malformations of the reproductive system.
• if you are a man
  • with irreversible testicular damage.

Do not use GONAL-f if you have any of these conditions. If you have any doubts, consult your doctor before using this medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using GONAL-f.
Porphyria
Inform your doctor before starting treatment if you or a family member has porphyria (an inability to break down porphyrins, which can be inherited from parents to children).
Immediately inform your doctor if:

• your skin becomes fragile and blisters easily, especially in areas frequently exposed to sunlight, and/or
• you have stomach, arm, or leg pain.

In these cases, your doctor may recommend that you stop treatment.
Ovarian hyperstimulation syndrome (OHSS)
If you are a woman, this medicine increases the risk of OHSS. In this condition, ovarian follicles develop excessively and turn into large cysts. Immediately inform your doctor if you experience lower abdominal pain, rapid weight gain, nausea or vomiting, or difficulty breathing; your doctor may ask you to stop taking the medicine (see section 4).
If you are an anovulatory patient and the recommended dosage and administration schedule are properly followed, the risk of OHSS is less likely.
Treatment with GONAL-f rarely causes severe OHSS if a medicine (containing human chorionic gonadotropin – hCG) is not administered to induce ovulation. If you are developing OHSS, your doctor may decide not to administer hCG in this treatment cycle and may recommend that you avoid sexual intercourse or use a barrier contraceptive method for at least four days.
Multiple pregnancy
When using GONAL-f, you have a higher risk of multiple pregnancy—most commonly twins—compared to natural conception. Multiple pregnancy may lead to complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of GONAL-f at the appropriate time. In assisted reproductive procedures, the risk of multiple pregnancy is related to age, quality, and number of fertilized eggs or embryos transferred.
Miscarriage
If you undergo assisted reproductive procedures or ovarian stimulation for egg production, the risk of miscarriage is higher than in other women.
Blood clotting disorders (thromboembolic events)
If you have had, or recently had, blood clots in your legs or lungs, a heart attack, or a stroke, or if these events have occurred in your family, your risk of these problems occurring or worsening during treatment with GONAL-f may increase.
Men with excessively high FSH levels in blood
If you are a man, excessively high FSH levels in the blood may indicate testicular damage. In such cases, GONAL-f is generally ineffective.
If your doctor decides to attempt treatment with GONAL-f, they may ask you to provide sperm samples for follow-up testing 4–6 months after starting treatment.
Children and adolescents
The use of GONAL-f is not indicated in children and adolescents under 18 years of age.
Other medicines and GONAL-f
Inform your doctor if you are taking, have recently taken, or might take any other medicines.

• If you use GONAL-f together with other medicines that promote ovulation (such as hCG or clomiphene citrate), this may enhance the follicular response.
• If you use GONAL-f simultaneously with a gonadotropin-releasing hormone (GnRH) agonist or antagonist (these medicines reduce sex hormone levels and block ovulation), you may require a higher dose of GONAL-f to produce follicles.

Pregnancy and breastfeeding
Do not use GONAL-f during pregnancy or breastfeeding.
Driving and using machines
This medicine is not expected to affect the ability to drive or use machinery.
GONAL-f contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is essentially “sodium-free”.

3. How to use GONAL-f

Use this medicine exactly as directed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
How to use the medicine

• GONAL-f is administered by injection just under the skin (subcutaneously). The pre-filled pen may be used for multiple injections.
• The first injection of GONAL-f must be given under the supervision of a doctor.
• Your doctor or nurse will show you how to use the GONAL-f pre-filled pen to inject the medicine.
• If you are self-administering GONAL-f, read carefully and follow the “Instructions for use”.

Which dose to use
Your doctor will decide how much medicine you should use and how often. The doses listed below
are expressed in International Units (IU).
Women
If you do not ovulate and have irregular or absent menstrual cycles

• GONAL-f is generally given every day.
• If you have irregular menstrual cycles, start using GONAL-f within the first 7 days of your cycle. If you do not have menstrual cycles, you may start using the medicine on any day.
• The starting dose of GONAL-f is usually individualized and may be gradually adjusted.
• The daily dose of GONAL-f should not exceed 225 IU.
• When the desired response is achieved, you will be given a single injection of 250 micrograms of “recombinant hCG” (r-hCG, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last GONAL-f injection. The most suitable days for sexual intercourse are the day of the hCG injection and the following day.

If your doctor does not observe the desired response, continuation of that treatment cycle with
GONAL-f should be evaluated and managed according to standard clinical practice.
If your body responds excessively, treatment will be stopped and you will not be given hCG (see section 2, “Ovarian hyperstimulation syndrome (OHSS)”). In the next cycle, your doctor will administer a lower dose of GONAL-f.
If you have been diagnosed with very low levels of FSH and LH hormones

• The usual starting dose of GONAL-f is between 75 and 150 IU together with 75 IU of lutropin alfa.
• You will need to use these two medicines every day for up to five weeks.
• The dose of GONAL-f may be increased every 7 or 14 days by 37.5–75 IU until the desired response is achieved.
• When the desired response is achieved, you will be given a single injection of 250 micrograms of “recombinant hCG” (r-hCG, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last injection of GONAL-f and lutropin alfa. The most suitable days for sexual intercourse are the day of the hCG injection and the following day. Alternatively, intrauterine insemination or another assisted reproductive procedure may be performed, depending on your doctor’s judgment.

If your doctor observes no response after 5 weeks, that treatment cycle with GONAL-f
should be discontinued. In the next treatment cycle, your doctor will administer a higher starting
dose of GONAL-f.
If your body responds excessively, treatment will be stopped and you will not be given
hCG (see section 2, “Ovarian hyperstimulation syndrome (OHSS)”). In the next cycle, your
doctor will administer a lower dose of GONAL-f.
If you need to stimulate the development of multiple eggs for assisted reproductive techniques

• The starting dose of GONAL-f is usually individualized and may be gradually adjusted up to a maximum of 450 IU per day.
• Treatment continues until the eggs have reached a certain stage of development. Your doctor will determine the appropriate timing using blood tests and/or ultrasound.
• When the eggs have developed, you will be given a single injection of 250 micrograms of “recombinant hCG” (r-hCG, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last GONAL-f injection. This prepares the eggs for retrieval.

Men

• The usual dose of GONAL-f is 150 IU together with hCG.
• You will need to use these two medicines three times a week for at least 4 months.
• If, after 4 months, you have not responded to treatment, your doctor may recommend continuing treatment with both medicines for at least 18 months.

If you use more GONAL-f than you should
Effects due to an overdose of GONAL-f have not been reported. However, ovarian hyperstimulation syndrome (OHSS) may occur as described in section 4. However, OHSS can occur only if hCG has also been administered (see section 2, “Ovarian hyperstimulation syndrome (OHSS)”).
If you forget to use GONAL-f
If you forget to use GONAL-f, 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 everybody will experience them.
Serious side effects in women

• Pelvic pain in combination with nausea or vomiting may be symptoms of ovarian hyperstimulation syndrome (OHSS). This may indicate that the ovaries are overreacting to treatment and that large ovarian cysts have developed (see also section 2 under “Ovarian hyperstimulation syndrome (OHSS)”). This side effect is common (may affect up to 1 in 10 people).
• OHSS may become severe, with markedly enlarged ovaries, reduced urine production, weight gain, breathing difficulties and/or possible accumulation of fluid in the abdomen or chest. This side effect is not common (may affect up to 1 in 100 people).
• Rarely, complications of OHSS may occur, such as ovarian torsion or blood clotting (may affect up to 1 in 1,000 people).
• Very rarely, serious blood clotting complications (thromboembolic events) may occur, sometimes independent of OHSS (may affect up to 1 in 10,000 people). This may cause chest pain, shortness of breath, stroke or heart attack (see also section 2 under “Blood clotting disorders”).

Serious side effects in men and women

• Occasionally, allergic reactions such as rash, redness, hives, or facial swelling with breathing difficulties may be serious. This side effect is very rare (may affect up to 1 in 10,000 people).

If you experience any of the side effects described, contact your doctor immediately. Your doctor may
ask you to stop using GONAL-f.
Other side effects in women
Very common (may affect more than 1 in 10 people):

• Fluid-filled sacs in the ovary (ovarian cysts)
• Headache
• Local reactions at the injection site such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Abdominal pain
• Nausea, vomiting, diarrhoea, abdominal cramps and bloating

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions may occur, such as rash, skin redness, hives, facial swelling with breathing difficulties. These reactions may be serious.
• Asthma may worsen.

Other side effects in men
Very common (may affect more than 1 in 10 people):

• Local reactions at the injection site such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Swelling of the veins located above and behind the testicles (varicocele)
• Enlargement of the breast gland, acne or weight gain

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions may occur, such as rash, skin redness, hives, facial swelling with breathing difficulties. These reactions may be serious.
• Asthma may worsen.

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 listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store GONAL-f

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cartridge label or on the box after "Exp". The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C–8 °C). Do not freeze.
Before first use and during its shelf life, the product may be stored outside the refrigerator at a maximum temperature of 25 °C for a single period of up to 3 months; if not used within these 3 months, it must be discarded.
Keep the cap on the pen to protect the medicine from light.
Do not use GONAL-f if you notice any visible signs of deterioration, if the liquid contains particles, or if it is not clear.
After first use, the pen must be stored for a maximum of 28 days at a temperature between 2 °C and 25 °C. Do not use any remaining medicine in the pre-filled pen after 28 days.
At the end of treatment, any unused solution must be discarded.
Do not dispose of medicines 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 GONAL-f contains

• The active substance is follitropin alfa.
• Each pre-filled pen with a multi-dose cartridge contains 300 IU (22 micrograms) of follitropin alfa in 0.48 mL of solution.
• The other components are poloxamer 188, sucrose, methionine, monobasic monohydrate sodium phosphate, dibasic dihydrate sodium phosphate, m-cresol, and concentrated phosphoric acid and sodium hydroxide used to adjust pH, as well as water for injections.

Description of the appearance of GONAL-f and contents of the pack

• GONAL-f is a clear, colourless injectable liquid in a pre-filled pen.
• It is supplied in packs of 1 pre-filled pen and 8 single-use needles.

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
Manufacturer
Merck Serono S.p.A., Via delle Magnolie 15, 70026 Modugno (Bari), Italy
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu .

Instructions for use

GONAL-f FOLLITROPIN ALFA PEN 300 UI /0.48 mL

Prefilled pen injection solution
Follitropin alfa
Important information about the GONAL-f prefilled pen

• Read the Instructions for Use and the Package Leaflet before using the prefilled pen

GONAL-f.

• Always follow all the instructions provided in these Instructions for Use and given by your healthcare provider, as they may differ from those used previously. These instructions will help you avoid treatment errors, infections from needlestick injuries, or injuries caused by broken glass.
• The pre-filled GONAL-f pen is intended for subcutaneous injection only.
• Use the pre-filled GONAL-f pen only if a healthcare professional has shown you how to use it correctly.
• Your healthcare provider will tell you how many pre-filled GONAL-f pens you need to complete your treatment.
• Inject at the same time each day.
• The numbers shown in the dose control window indicate the dose of follitropin alfa in International Units (IU). Your healthcare provider will tell you how many IU of follitropin alfa you must inject daily.

The numbers displayed in the dose control window will help you:

a. Set the prescribed dose (Figure 1).

b. Verify that the injection has been completed (Figure 2).

c. Read the remaining dose to be injected using a second pen (Figure 3).

• Remove the needle from the pen immediately after each injection.

Do not reuse needles.
Do not share the pen and/or needles with other people.
Do not use the pre-filled GONAL-f pen if it has been dropped or if the pen is cracked or damaged, as you may get injured.

How to use the treatment diary with the pre-filled GONAL-f pen
A treatment diary is attached at the end of these Instructions for Use. Use the treatment diary to record the doses injected.
Injecting incorrect amounts of medication may affect your treatment.

• Record the treatment day (column 1), date (column 2), time of injection (column 3), and volume remaining in the pen (column 4).
• Record the prescribed dose (column 5).
• Check that the dose has been correctly set before injection (column 6).
• After the injection, read the number shown in the dose control window.
• Confirm administration of a complete injection (column 7), or record the number shown in the dose control window if it is not “0” (column 8).
• If necessary, administer an injection using a second pen, setting the remaining dose recorded in the column “Amount to select for second injection” (column 8).
• Record this remaining dose in the next column “Amount to inject” (column 6).

By using the treatment diary to record your daily injection(s), you can verify each day that you have received the full prescribed dose.
Example of a treatment diary:

Become familiar with the pre-filled GONAL-f pen

Needle*:
Pre-filled pen:
Step 1 Prepare the necessary items

1.1 Allow the pre-filled pen to reach room temperature for at least 30 minutes before use.
Do not use a microwave or other heating devices to warm the pen.
1.2 Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.

1.3 Additional required materials (not included in the package):

• Alcohol wipes and a sharps disposal container (Figure 4).
  1.4 Wash your hands thoroughly with soap and water, then dry them completely (Figure 5).
  1.5 Remove the pre-filled GONAL-f pen from the

package using one hand.
Do not use tools or other devices, as they may damage the pen.
1.6 Check that the name printed on the pre-filled pen is GONAL-f.
1.7 Check the expiration date on the pen label (Figure 6).
Do not use the pre-filled GONAL-f pen if the expiration date has passed or if the pen does not have “GONAL-f” printed on it.

Step 2 Prepare for injection

2.1 Remove the pen cap (Figure 7).
2.2 Make sure the medication appears clear, colorless, and free of particles.
Do not use the pre-filled pen if the medication is cloudy or has changed color, as this may cause infection.
2.3 Ensure the dose control window displays “0” (Figure 8).

Choose an injection site:
2.4 A healthcare professional will instruct you on suitable injection sites on the abdominal area (Figure 9). To minimize skin irritation, select a different injection site each day.
2.5 Clean the skin at the injection site with an alcohol wipe.
Do not touch or cover the cleaned skin.

Step 3 Attach the needle
Important: Always use a new needle for each injection. Using a previously used needle may cause infection.
3.1 Take a new needle. Use only the “single-use” needles supplied in the package.
3.2 Check that the outer needle cap is not damaged.
3.3 Hold the outer needle cap firmly.
3.4 Check that the pull-tab on the outer needle cap is not damaged or loose, and that the expiration date has not passed (Figure 10).
3.5 Remove the pull-tab (Figure 11).
Do not use the needle if it is damaged or expired, or if the outer needle cap or pull-tab is damaged or loose. Using an expired needle or one with a damaged pull-tab or cap may lead to infection. Dispose of it in a sharps container and take a new needle.
3.6 Screw the outer needle cap onto the threaded tip of the pre-filled GONAL-f pen until you feel slight resistance (Figure 12).
Do not overtighten the needle, as it may become difficult to remove after injection.
3.7 Remove the outer needle cap by pulling gently (Figure 13).
3.8 Set it aside for later use (Figure 14).
Do not discard the outer needle cap, as it will be needed later to prevent needlestick injuries and infections when removing the needle from the pre-filled pen.
3.9 Hold the pre-filled GONAL-f pen with the needle pointing upward (Figure 15).
3.10 Carefully remove and discard the inner needle cover (Figure 16).

Do not reattach the inner needle cover to the needle. You may injure yourself and develop an infection.
3.11 Carefully examine the needle tip and check for one or more small drops of liquid (Figure 17).

If you do not see one or more small drops of liquid at or near the needle tip the first time you use a new pen:

1. Gently turn the dose selector knob forward until the dose display window shows “25” (Figure 18).
   • If you go past “25”, you may turn the dose knob back.

2. Hold the pen with the needle pointing upward.
3. Lightly tap the cartridge holder (Figure 19).
4. Press fully down the dose selector knob. A small drop of liquid should appear at the needle tip (Figure 20).
5. Check that the dose display window shows “0” (Figure 21).
6. Proceed to Step 4 Set the dose.

If no drop of liquid appears, contact your healthcare provider.
Step 4 Set the dose
Note: The pen contains 300 IU of follitropin alfa. The maximum single dose that can be set on the 300 IU pen is 300 IU. The minimum single dose is 12.5 IU, and the dose can be increased in 12.5 IU increments.
4.1 Turn the dose selector knob until the prescribed dose appears in the dose display window.

• Example: if the prescribed dose to be injected is “150” IU, ensure that the number “150” appears in the dose display window (Figure 22). Injecting incorrect amounts of medication may affect your treatment.

4.2 Check that the dose display window shows the full prescribed dose before proceeding to the next step.
Step 5 Inject the dose
Important: inject the dose according to the instructions provided by your healthcare provider.
5.1 Slowly insert the entire needle into the skin (Figure 24).
5.2 Place your thumb in the center of the dose selector knob. Press slowly and fully down the dose knob and keep it pressed to complete the injection (Figure 25).
Note: the higher the dose, the longer the injection will take.

5.3 Keep the dose knob fully pressed for at least 5 seconds before removing the needle from the skin (Figure 26).

• The number shown in the dose display window will return to “0”.
• After at least 5 seconds, while keeping the dose selector knob fully pressed, remove the needle from the skin (Figure 27).
• Once the needle has been removed from the skin, release the dose selector knob.

Do not release the dose knob until the needle has been removed from the skin.
Step 6 Remove the needle after each injection

6.1 Place the outer needle cap on a flat surface.
6.2 Hold the GONAL-f pre-filled pen firmly in one hand and place the needle into the outer cap.
6.3 Now press the needle, covered by its cap, against a hard surface until you hear a click (Figure 29).
6.4 Grasp the outer needle cap and unscrew the needle by turning it in the opposite direction (Figure 30).

6.5 Dispose of the used needle safely in a sharps container (Figure 31). Handle the needle carefully to avoid needle-stick injuries.
Do not reuse or share a used needle.
Step 7 After the injection

7.1 Check that you have completed the full injection:

• Check that the dose display window shows “0” (Figure 32). If the dose display window shows “0”, this means the full dose has been administered. If the dose display window shows a number higher than “0”, the GONAL-f pre-filled pen is empty. The full prescribed dose has not been administered, and you must perform step 7.2 below.

7.2 Complete a partial injection (only if necessary):

• The dose display window shows the remaining amount that needs to be injected using a new pen. In the example shown, the amount still to be administered is “50” IU (Figure 33).
• To complete the dose with a second pen, repeat steps 1 to 8.

Step 8 Store the GONAL-f pre-filled pen

8.1 Replace the pen cap to prevent infection (Figure 34).
8.2 Store the pen with the cap on, in a safe place as indicated in the Package Leaflet.
8.3 When the pen is empty, ask your healthcare provider how to dispose of it.
Do not store the pen with the needle still attached, as this may lead to infection.
Do not reuse the GONAL-f pre-filled pen if it has been dropped or if the pen is cracked or damaged, as you may be injured.
If you have any questions, contact your healthcare provider.
Treatment diary for the GONAL-f pre-filled pen

These Instructions for Use were last updated on: {MM/YYYY}.

Package leaflet: information for the user

GONAL-f 450 UI/0.72 mL solution for injection in a pre-filled pen

follitropin alfa
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 other people, even if their symptoms are similar to yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What GONAL-f is and what it is used for

What GONAL-f is
GONAL-f contains an active substance called "follitropin alfa". Follitropin alfa is a "follicle-stimulating hormone" (FSH), belonging to a family of hormones known as "gonadotropins". Gonadotropins are involved in reproduction and fertility.

What GONAL-f is used for

In adult women, GONAL-f is used

• to stimulate the release of an egg from the ovary (ovulation) in women who do not ovulate and who have not responded to treatment with a medicine called "clomiphene citrate".
• in combination with another medicine called "lutropin alfa" ("luteinizing hormone" or LH), to stimulate the release of an egg from the ovary (ovulation) in women whose bodies produce very low levels of gonadotropins (FSH and LH).
• to promote the development of multiple follicles (each containing an egg) in women undergoing assisted reproductive procedures (procedures that can help achieve pregnancy), such as "in vitro fertilization", "gamete intrafallopian transfer", or "zygote intrafallopian transfer".

In adult men, GONAL-f is used

• in combination with another medicine called "human chorionic gonadotropin" (hCG), to stimulate sperm production in infertile men due to low levels of certain hormones.

2. What you need to know before using GONAL-f

Before starting treatment, a doctor experienced in the management of fertility disorders should have thoroughly evaluated your couple's fertility.
Do not use GONAL-f

• if you are allergic to follicle-stimulating hormone or to any of the other ingredients of this medicine (listed in section 6).
• if you have a tumor of the hypothalamus or pituitary gland (both parts of the brain).
• if you are a woman
  • with enlarged ovaries or fluid-filled sacs in the ovary (ovarian cysts) of unknown origin
  • with vaginal bleeding of unknown origin
  • with cancer of the ovary, uterus, or breast
  • with a condition that usually makes normal pregnancy impossible, such as ovarian failure (premature menopause) or malformations of the reproductive system.
• if you are a man
  • with irreversible testicular damage.

Do not use GONAL-f if you have any of these conditions. If you are in doubt, consult your doctor before using this medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using GONAL-f.
Porphyria
Inform your doctor before starting treatment if you or a family member has porphyria (an inability to break down porphyrins, which can be inherited from parents to children).
Immediately inform your doctor if:

• your skin becomes fragile and easily develops blisters, especially in areas frequently exposed to sunlight, and/or
• you have stomach, arm, or leg pain.

In these cases, your doctor may recommend that you stop treatment.
Ovarian hyperstimulation syndrome (OHSS)
If you are a woman, this medicine increases the risk of OHSS. In this condition, ovarian follicles develop excessively and turn into large cysts. Inform your doctor immediately if you experience lower abdominal pain, rapid weight gain, nausea or vomiting, or difficulty breathing; your doctor may ask you to stop taking the medicine (see section 4).
If you are an anovulatory patient and the recommended dosage and administration schedule are properly followed, the risk of OHSS is less likely.
Treatment with GONAL-f alone rarely causes severe OHSS if a medicine (containing human chorionic gonadotropin – hCG) to induce ovulation is not administered. If you are developing OHSS, your doctor may decide not to administer hCG during this treatment cycle and may recommend that you avoid sexual intercourse or use a barrier contraceptive method for at least four days.
Multiple pregnancy
When using GONAL-f, your chance of having a multiple pregnancy is higher than with natural conception, most commonly twins. Multiple pregnancy may lead to complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of GONAL-f at the appropriate times. In assisted reproductive procedures, the risk of multiple pregnancy is related to age, quality, and number of fertilized eggs or embryos transferred.
Miscarriage
If you undergo assisted reproductive procedures or ovarian stimulation for egg production, the risk of miscarriage is higher than in other women.
Blood clotting disorders (thromboembolic events)
If you have had blood clots in the legs or lungs, a heart attack, or a stroke in the past or recently, or if these events have occurred in your family, your risk of developing or worsening these problems during treatment with GONAL-f may be increased.
Men with excessively high levels of FSH in the blood
If you are a man, excessively high levels of FSH in the blood may indicate testicular damage. In such cases, GONAL-f is generally ineffective.
If your doctor decides to attempt treatment with GONAL-f, they may ask you to provide sperm samples for follow-up testing 4–6 months after starting treatment.
Children and adolescents
The use of GONAL-f is not indicated in children and adolescents under 18 years of age.
Other medicines and GONAL-f
Inform your doctor if you are taking, have recently taken, or might take any other medicines.

• If you use GONAL-f together with other medicines that promote ovulation (such as hCG or clomiphene citrate), this may enhance the follicular response.
• If you use GONAL-f simultaneously with a gonadotropin-releasing hormone (GnRH) agonist or antagonist (these medicines reduce sex hormone levels and block ovulation), you may require a higher dose of GONAL-f to produce follicles.

Pregnancy and breastfeeding
Do not use GONAL-f during pregnancy or breastfeeding.
Driving and using machines
This medicine is not expected to affect your ability to drive or use machinery.
GONAL-f contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is essentially “sodium-free”.

3. How to use GONAL-f

Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.

How to use the medicine

• GONAL-f is administered as an injection just under the skin (subcutaneously). The pre-filled pen may be used for multiple injections.
• The first injection of GONAL-f must be given under the supervision of a doctor.
• Your doctor or nurse will show you how to use the GONAL-f pre-filled pen to inject the medicine.
• If you are self-administering GONAL-f, carefully read and follow the “Instructions for use”.

What dose to use
Your doctor will determine how much medicine you should use and how often. The doses listed below are expressed in International Units (IU).

Women

If you do not ovulate and have irregular or absent menstrual cycles

• GONAL-f is generally administered daily.
• If you have irregular menstrual cycles, start using GONAL-f within the first 7 days of your cycle. If you do not have menstrual cycles, you may start using the medicine on any day.
• The initial dose of GONAL-f is usually individualized and may be gradually adjusted.
• The daily dose of GONAL-f should not exceed 225 IU.
• When the desired response is achieved, you will receive a single injection of 250 micrograms of recombinant “hCG” (r-hCG, a laboratory-produced hCG using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last GONAL-f injection. The most suitable days for sexual intercourse are the day of the hCG injection and the following day.

If your doctor does not observe the desired response, continuation of that treatment cycle with GONAL-f should be evaluated and managed according to standard clinical practice.
If your body responds excessively, treatment will be stopped and you will not be given hCG (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). In the next cycle, your doctor will administer a lower dose of GONAL-f.

If you have been diagnosed with very low levels of FSH and LH hormones

• The usual initial dose of GONAL-f is between 75 and 150 IU together with 75 IU of lutropin alfa.
• You will need to use both medicines daily for up to five weeks.
• The dose of GONAL-f may be increased every 7 or 14 days by 37.5–75 IU until the desired response is achieved.
• When the desired response is achieved, you will receive a single injection of 250 micrograms of recombinant “hCG” (r-hCG, a laboratory-produced hCG using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last injection of GONAL-f and lutropin alfa. The most suitable days for sexual intercourse are the day of the hCG injection and the following day. Alternatively, intrauterine insemination or another assisted reproductive procedure may be performed, based on your doctor’s judgment.

If your doctor observes no response after 5 weeks, that treatment cycle with GONAL-f should be discontinued. In the next treatment cycle, your doctor may prescribe a higher initial dose of GONAL-f.
If your body responds excessively, treatment will be stopped and you will not be given hCG (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). In the next cycle, your doctor will administer a lower dose of GONAL-f.

If you need to stimulate the development of multiple eggs for assisted reproductive techniques

• The initial dose of GONAL-f is usually individualized and may be gradually adjusted up to a maximum of 450 IU per day.
• Treatment continues until the eggs have reached a certain stage of development. Your doctor will determine the appropriate time using blood tests and/or ultrasound.
• When the eggs have developed, you will receive a single injection of 250 micrograms of recombinant “hCG” (r-hCG, a laboratory-produced hCG using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last GONAL-f injection. This prepares the eggs for retrieval.

Men

• The usual dose of GONAL-f is 150 IU together with hCG.
• You will need to use both medicines three times a week for at least 4 months.
• If after 4 months you have not responded to treatment, your doctor may recommend continuing treatment with both medicines for up to 18 months.

If you use more GONAL-f than you should
No effects related to overdose with GONAL-f have been reported. However, you may develop Ovarian Hyperstimulation Syndrome (OHSS), as described in section 4. Nevertheless, OHSS can occur only if hCG has also been administered (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”).

If you forget to use GONAL-f
If you forget to use GONAL-f, 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 experiences them.

Serious side effects in women

• Pelvic pain in combination with nausea or vomiting may be symptoms of ovarian hyperstimulation syndrome (OHSS). This may indicate that the ovaries are overreacting to treatment and that large ovarian cysts have developed (see also section 2, "Ovarian hyperstimulation syndrome (OHSS)"). This side effect is common (may affect up to 1 in 10 people).
• OHSS may become severe, with markedly enlarged ovaries, reduced urine output, weight gain, breathing difficulties, and/or possible accumulation of fluid in the abdomen or chest. This side effect is not common (may affect up to 1 in 100 people).
• Rarely, complications of OHSS such as ovarian torsion or blood clotting may occur (may affect up to 1 in 1,000 people).
• Very rarely, serious blood clotting complications (thromboembolic events) may occur, sometimes independent of OHSS (may affect up to 1 in 10,000 people). These may cause chest pain, shortness of breath, stroke, or heart attack (see also section 2, "Blood clotting disorders").

Serious side effects in men and women

• Occasionally, allergic reactions such as rash, redness, hives, facial swelling with breathing difficulties, may be severe. This side effect is very rare (may affect up to 1 in 10,000 people).

If you notice any of the side effects described, contact your doctor immediately. Your doctor may
instruct you to stop using GONAL-f.

Other side effects in women
Very common (may affect more than 1 in 10 people):

• Fluid-filled sacs in the ovary (ovarian cysts)
• Headache
• Local reactions at the injection site such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Abdominal pain
• Nausea, vomiting, diarrhoea, abdominal cramps and bloating

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as rash, skin redness, hives, facial swelling with breathing difficulties may occur. These reactions may be severe.
• Asthma may worsen.

Other side effects in men
Very common (may affect more than 1 in 10 people):

• Local reactions at the injection site such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Swelling of the veins located above and behind the testicles (varicocele)
• Enlargement of the breast gland, acne or weight gain

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as rash, skin redness, hives, facial swelling with breathing difficulties may occur. These reactions may be severe.
• Asthma may worsen.

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 listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store GONAL-f

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cartridge label or on the
box after Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C-8 °C). Do not freeze.
Before first use and within the expiry period, the product may be stored outside the refrigerator at a maximum temperature of 25 °C for a single period of up to 3 months; it must be discarded if not used within these 3 months.
Keep the cap on the pen to protect the medicine from light.
Do not use GONAL-f if you notice visible signs of deterioration, if the liquid contains particles, or if it is not clear.
Once in use, the pen must be stored for a maximum of 28 days at a temperature between 2 °C and 25 °C. Do not use any remaining medicine in the pre-filled pen after 28 days.
At the end of treatment, any unused solution must be disposed of.
Do not dispose of medicines 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 GONAL-f contains

• The active substance is follitropin alfa.
• Each pre-filled multidose cartridge pen contains 450 IU (33 micrograms) of follitropin alfa in 0.72 mL of solution.
• The other components are poloxamer 188, sucrose, methionine, monobasic monohydrate sodium phosphate, dibasic dihydrate sodium phosphate, m-cresol, and phosphoric acid concentrate and sodium hydroxide used to adjust pH, as well as water for injections.

Description of the appearance of GONAL-f and contents of the pack

• GONAL-f is a clear, colourless injectable liquid in a pre-filled pen.
• It is supplied in packs of 1 pre-filled pen and 12 single-use needles.

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
Manufacturer
Merck Serono S.p.A., Via delle Magnolie 15, 70026 Modugno (Bari), Italy
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu .

Instructions for use

GONAL-f PREFILLED PEN 450 UI/0.72 mL

Injectable solution in a prefilled pen
Follitropin alfa
Important information about the GONAL-f prefilled pen

• Read the Instructions for Use and the Package Leaflet before using the prefilled pen

GONAL-f.

• Always follow all instructions provided in these Instructions for Use and those given by your healthcare provider, as they may differ from those used previously. These instructions will help you avoid treatment errors, infections from needlestick injuries, or injuries caused by broken glass.
• The GONAL-f pre-filled pen is intended for subcutaneous injection only.
• Use the GONAL-f pre-filled pen only if a healthcare professional has shown you how to use it correctly.
• Your healthcare provider will tell you how many GONAL-f pre-filled pens you need to complete your treatment.
• Administer the injection at the same time every day.
• The numbers shown in the dose control window indicate the dose of follitropin alfa in International Units (IU). Your healthcare provider will tell you how many IU of follitropin alfa you must inject each day.
• The numbers displayed in the dose control window will help you:

a. Set the prescribed dose (Figure 1).

b. Confirm that the injection has been completed (Figure 2).

c. Read the remaining dose to be injected with a second pen (Figure 3).

• Remove the needle from the pen immediately after each injection.

Do not reuse needles.
Do not share the pen and/or needles with other people.
Do not use the GONAL-f pre-filled pen if it has been dropped or if the pen is cracked or damaged, as you may get injured.

How to use the treatment diary with the GONAL-f pre-filled pen
A treatment diary is attached at the end of these Instructions for Use. Use the treatment diary to record the amounts injected.
Injecting incorrect amounts of medication may affect your treatment.

• Record the day of treatment (column 1), date (column 2), time of injection (column 3), and volume in the pen (column 4).
• Record the prescribed dose (column 5).
• Check that the dose is correctly set before injection (column 6).
• After injection, read the number shown in the dose control window.
• Confirm administration of a complete injection (column 7), or record the number shown in the dose control window if it is not “0” (column 8).
• If necessary, administer an injection with a second pen, setting the remaining dose recorded in the column “Amount to select for second injection” (column 8).
• Record this remaining dose in the next column “Amount to inject” (column 6).

By using the treatment diary to record your daily injection(s), you can verify each day that you have received the full prescribed dose.
Example of a treatment diary:

Become familiar with the GONAL-f pre-filled pen

Needle*:
Pre-filled pen:
Step 1 Prepare the necessary items

1.1 Allow the pre-filled pen to reach room temperature for at least 30 minutes before use, so that the medication reaches room temperature.
Do not use a microwave or other heating devices to warm the pen.
1.2 Prepare a clean, flat surface in a well-lit area, such as a table or countertop.

1.3 Additional required materials (not included in the package):

• Alcohol wipes and a sharps disposal container (Figure 4).
  1.4 Wash your hands thoroughly with soap and water, then dry them completely (Figure 5).
  1.5 Remove the GONAL-f pre-filled pen from the

package using one hand.
Do not use tools or other devices, as they may damage the pen.
1.6 Check that the name printed on the pre-filled pen is GONAL-f.
1.7 Check the expiration date printed on the pen label (Figure 6).
Do not use the GONAL-f pre-filled pen if the expiration date has passed or if the pen does not say GONAL-f.

Step 2 Prepare for injection

2.1 Remove the pen cap (Figure 7).
2.2 Make sure the medication appears clear, colorless, and free of particles.
Do not use the pre-filled pen if the medication is cloudy or has changed color, as this may cause infection.
2.3 Ensure that the dose control window displays “0” (Figure 8).

Choose an injection site:
2.4 A healthcare professional will instruct you on the appropriate injection sites on the abdominal area (Figure 9). To minimize skin irritation, choose a different injection site each day.
2.5 Clean the skin at the injection site with an alcohol wipe.
Do not touch or cover the cleaned skin.

Step 3 Attach the needle
Important: Always use a new needle for each injection. Using a previously used needle may cause infection.
3.1 Take a new needle. Use only the “single-use” needles supplied in the package.
3.2 Check that the outer needle cap is not damaged.
3.3 Hold the outer needle cap firmly.
3.4 Check that the pull-tab on the outer needle cap is not damaged or loose, and that the expiration date has not passed (Figure 10).
3.5 Remove the pull-tab (Figure 11).
Do not use the needle if it is damaged or expired, or if the outer needle cap or pull-tab is damaged or loose. Using an expired needle or one with a damaged pull-tab or cap may lead to infection. Dispose of it in a sharps container and take a new needle.
3.6 Screw the outer needle cap onto the threaded tip of the GONAL-f pre-filled pen until slight resistance is felt (Figure 12).
Do not overtighten the needle, as this may make it difficult to remove after injection.
3.7 Remove the outer needle cap by pulling gently (Figure 13).
3.8 Set it aside for later use (Figure 14).
Do not discard the outer needle cap, as it will be needed later to prevent needlestick injuries and infections when removing the needle from the pre-filled pen.
3.9 Hold the GONAL-f pre-filled pen with the needle pointing upward (Figure 15).
3.10 Carefully remove and discard the inner protective cap (Figure 16).

Do not replace the inner protective cap onto the needle. You may injure yourself and develop an infection.
3.11 Carefully observe the needle tip and check whether one or more small drops of liquid are present (Figure 17).

If one or more small drops of liquid are not observed at or near the needle tip the first time a new pen is used:

1. Gently rotate the dose selector knob forward until the dose display window shows “25” (Figure 18).
   • If you pass “25”, you may turn the dose knob back.

2. Hold the pen with the needle pointing upward.
3. Lightly tap the cartridge reservoir (Figure 19).
4. Press fully the dose selector knob. A small drop of liquid should appear at the needle tip (Figure 20).
5. Check that the dose display window shows “0” (Figure 21).
6. Proceed to Step 4 Set the dose.

If no drop of liquid appears, contact your healthcare provider.
Step 4 Set the dose
Note: The pen contains 450 IU of follitropin alfa. The maximum single dose that can be set with the 450 IU pen is 450 IU. The minimum single dose is 12.5 IU, and the dose can be increased in increments of 12.5 IU.
4.1 Turn the dose selector knob until the prescribed dose appears in the dose display window.

• Example: if the prescribed dose to be injected is “150” IU, ensure that the number “150” appears in the dose display window (Figure 22). Injecting incorrect amounts of medication may affect treatment.

4.2 Check that the dose display window shows the full prescribed dose before proceeding to the next step.
Step 5 Inject the dose
Important: inject the dose according to the instructions provided by your healthcare provider.
5.1 Slowly insert the entire needle into the skin (Figure 24).
5.2 Place your thumb in the center of the dose selector knob.
Slowly and fully press the dose knob and keep it pressed to complete the injection (Figure 25).
Note: the higher the dose, the longer it will take to inject.

5.3 Keep the dose knob pressed for at least 5 seconds before removing the needle from the skin (Figure 26).

• The number shown in the dose display window will return to “0”.

• After at least 5 seconds, while keeping the dose selector knob pressed, remove the needle from the skin (Figure 27).

• Once the needle has been removed from the skin, release the dose selector knob.

Do not release the dose knob until the needle has been removed from the skin.
Step 6 Remove the needle after each injection

6.1 Place the outer needle cap on a flat surface.
6.2 Hold the GONAL-f pre-filled pen firmly in one hand and place the needle into the outer cap.
6.3 Now press the needle, covered by its cap, against a hard surface until you hear a click (“click”) (Figure 29).
6.4 Grasp the outer needle cap and unscrew the needle by turning it in the opposite direction (Figure 30).

6.5 Dispose of the used needle safely in a sharps container (Figure 31). Handle the needle with care to avoid needlestick injury.
Do not reuse or share a used needle.
Step 7 After the injection

7.1 Check that you have completed a full injection:

• Check that the dose display window shows “0” (Figure 32). If the dose display window shows “0”, this means the full dose has been administered. If the dose display window shows a number higher than “0”, the GONAL-f pre-filled pen is empty. The full prescribed dose has not been administered, and you must perform step 7.2 below.

7.2 Complete a partial injection (only if necessary):

• The dose display window indicates the remaining amount to be injected using a new pen. In the example shown, the amount still to be administered is 50 IU (Figure 33).
• To complete the dose with a second pen, repeat steps 1 to 8.

Step 8 Store the GONAL-f pre-filled pen

8.1 Replace the cap on the pen to prevent infection (Figure 34).
8.2 Store the pen with the cap on in a safe place as indicated in the Package Leaflet.
8.3 When the pen is empty, ask your healthcare provider how to dispose of it properly.
Do not store the pen with the needle still attached, as this may cause infection.
Do not reuse the GONAL-f pre-filled pen if it has been dropped or if the pen is cracked or damaged, as this may cause injury.
If you have any questions, contact your healthcare provider.
Treatment diary for the GONAL-f pre-filled pen

These Instructions for Use were last updated on: {MM/YYYY}.

Patient Information Leaflet: Information for the user

GONAL-f 900 UI/1.44 mL solution for injection in a prefilled pen

follitropin alfa
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, consult 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 side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What GONAL-f is and what it is used for

What GONAL-f is
GONAL-f contains an active substance called "follitropin alfa". Follitropin alfa is a "follicle-stimulating hormone" (FSH), belonging to a family of hormones known as "gonadotropins". Gonadotropins are involved in reproduction and fertility.

What GONAL-f is used for
In adult women, GONAL-f is used

• to stimulate the release of an egg from the ovary (ovulation) in women who do not ovulate and who have not responded to treatment with a medicine called "clomiphene citrate".
• in combination with another medicine called "lutropin alfa" ("luteinizing hormone" or LH) to stimulate the release of an egg from the ovary (ovulation) in women whose bodies produce very low levels of gonadotropins (FSH and LH).
• to promote the development of multiple follicles (each containing an egg) in women undergoing assisted reproductive procedures (procedures that can help achieve pregnancy), such as "in vitro fertilization", "gamete intrafallopian transfer", or "zygote intrafallopian transfer".

In adult men, GONAL-f is used

• in combination with another medicine called "human chorionic gonadotropin" (hCG) to stimulate sperm production in infertile men due to low levels of certain hormones.

2. What you need to know before using GONAL-f

Before starting treatment, a doctor experienced in the management of fertility disorders should have thoroughly evaluated your couple's fertility.
Do not use GONAL-f

• if you are allergic to follicle-stimulating hormone or to any of the other ingredients of this medicine (listed in section 6).
• if you have a tumor of the hypothalamus or pituitary gland (both parts of the brain).
• if you are a woman
  • with enlarged ovaries or fluid-filled sacs in the ovary (ovarian cysts) of unknown origin
  • with vaginal bleeding of unknown origin
  • with cancer of the ovary, uterus, or breast
  • with a condition that usually makes normal pregnancy impossible, such as ovarian failure (premature menopause) or congenital malformations of the reproductive system.
• if you are a man
  • with irreversible testicular damage.

Do not use GONAL-f if you have any of these conditions. If you have any doubts, consult your doctor before using this medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using GONAL-f.
Porphyria
Inform your doctor before starting treatment if you or a family member has porphyria (an inability to break down porphyrins, which can be inherited from parents).
Immediately inform your doctor if:

• your skin becomes fragile and blisters easily, especially in areas frequently exposed to sunlight, and/or
• you have stomach, arm, or leg pain.

In such cases, your doctor may recommend that you stop treatment.
Ovarian hyperstimulation syndrome (OHSS)
If you are a woman, this medicine increases the risk of OHSS. In this condition, ovarian follicles develop excessively and turn into large ovarian cysts. Immediately inform your doctor if you experience lower abdominal pain, rapid weight gain, nausea or vomiting, or difficulty breathing; your doctor may ask you to stop taking the medicine (see section 4).
If you are an anovulatory patient and the recommended dosage and administration schedule are properly followed, the risk of OHSS is less likely.
Treatment with GONAL-f rarely causes severe OHSS if a medicine (containing human chorionic gonadotropin – hCG) is not administered to induce ovulation. If you are developing OHSS, your doctor may decide not to administer hCG in this treatment cycle and may advise you to avoid sexual intercourse or to use a barrier contraceptive method for at least four days.
Multiple pregnancy
When using GONAL-f, the risk of multiple pregnancy is higher than with natural conception, most commonly twins. Multiple pregnancy may lead to complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of GONAL-f at the appropriate time. In assisted reproductive procedures, the risk of multiple pregnancy is related to age, quality, and number of fertilized oocytes or embryos transferred.
Miscarriage
If you undergo assisted reproductive procedures or ovarian stimulation for oocyte production, the risk of miscarriage is higher than in other women.
Blood clotting disorders (thromboembolic events)
If you have previously or recently had blood clots in the legs or lungs, a heart attack, or a stroke, or if such events have occurred in your family, your risk of these problems occurring or worsening during treatment with GONAL-f may increase.
Men with excessively high FSH levels in blood
If you are a man, excessively high FSH levels in the blood may indicate testicular damage. In such cases, GONAL-f is generally ineffective.
If your doctor decides to attempt treatment with GONAL-f, they may ask you to provide sperm samples for follow-up testing 4–6 months after starting treatment.
Children and adolescents
The use of GONAL-f is not indicated in children and adolescents under 18 years of age.
Other medicines and GONAL-f
Inform your doctor if you are taking, have recently taken, or might take any other medicines.

• If you use GONAL-f together with other medicines that promote ovulation (such as hCG or clomiphene citrate), this may enhance the follicular response.
• If you use GONAL-f simultaneously with a gonadotropin-releasing hormone (GnRH) agonist or antagonist (medicines that reduce sex hormone levels and block ovulation), you may require a higher dose of GONAL-f to produce follicles.

Pregnancy and breastfeeding
Do not use GONAL-f during pregnancy or breastfeeding.
Driving and using machines
This medicine is not expected to affect your ability to drive vehicles or operate machinery.
GONAL-f contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is essentially "sodium-free".

3. How to use GONAL-f

Use this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor or pharmacist.

How to use the medicine

• GONAL-f is administered by subcutaneous injection (just under the skin). The pre-filled pen may be used for multiple injections.
• The first injection of GONAL-f must be given under the supervision of your doctor.
• Your doctor or nurse will show you how to use the GONAL-f pre-filled pen to inject the medicine.
• If you are self-administering GONAL-f, carefully read and follow the “Instructions for Use”.

What dose to use
Your doctor will decide how much medicine you should use and how often. The doses listed below are expressed in International Units (IU).

Women

If you do not ovulate and have irregular or absent menstrual cycles

• GONAL-f is usually given daily.
• If you have irregular menstrual cycles, start using GONAL-f within the first 7 days of your cycle. If you do not have menstrual cycles, you may start using the medicine on any day.
• The starting dose of GONAL-f is usually individualized and may be gradually adjusted.
• The daily dose of GONAL-f must not exceed 225 IU.
• When the desired response is achieved, you will receive a single injection of 250 micrograms of recombinant hCG (“r-hCG”, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last GONAL-f injection. The most suitable days for sexual intercourse are the day of the hCG injection and the following day.

If your doctor does not observe the desired response, continuation of that treatment cycle with GONAL-f should be evaluated and managed according to standard clinical practice.
If your body responds excessively, treatment will be stopped and you will not receive hCG (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). In the next cycle, your doctor will administer a lower dose of GONAL-f.

If you have been diagnosed with very low levels of FSH and LH hormones

• The usual starting dose of GONAL-f is between 75 and 150 IU, together with 75 IU of lutropin alfa.
• You will need to use these two medicines daily for up to five weeks.
• The dose of GONAL-f may be increased every 7 or 14 days by 37.5–75 IU until the desired response is achieved.
• When the desired response is achieved, you will receive a single injection of 250 micrograms of recombinant hCG (“r-hCG”, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last injection of GONAL-f and lutropin alfa. The most suitable days for sexual intercourse are the day of the hCG injection and the following day. Alternatively, intrauterine insemination or another assisted reproductive procedure may be performed, according to your doctor’s judgment.

If your doctor observes no response after 5 weeks, that treatment cycle with GONAL-f should be discontinued. In the next treatment cycle, your doctor will administer a higher starting dose of GONAL-f.
If your body responds excessively, treatment will be stopped and you will not receive hCG (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). In the next cycle, your doctor will administer a lower dose of GONAL-f.

If you need to stimulate the development of multiple oocytes for assisted reproductive techniques

• The starting dose of GONAL-f is usually individualized and may be gradually adjusted up to a maximum of 450 IU per day.
• Treatment continues until the oocytes have reached a certain stage of development. Your doctor will determine the appropriate timing using blood tests and/or ultrasound monitoring.
• When the oocytes have developed, you will receive a single injection of 250 micrograms of recombinant hCG (“r-hCG”, an hCG produced in the laboratory using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last GONAL-f injection. This prepares the oocytes for retrieval.

Men

• The usual dose of GONAL-f is 150 IU together with hCG.
• You must use these two medicines three times a week for at least 4 months.
• If, after 4 months, you have not responded to treatment, your doctor may recommend continuing treatment with both medicines for up to 18 months.

If you use more GONAL-f than you should
No adverse effects due to overdose of GONAL-f have been reported. However, you may develop ovarian hyperstimulation syndrome (OHSS) as described in section 4. Nevertheless, OHSS can occur only if hCG has also been administered (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”).

If you forget to use GONAL-f
If you forget to use GONAL-f, 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.

Serious side effects in women

• Pelvic pain in combination with nausea or vomiting may be symptoms of ovarian hyperstimulation syndrome (OHSS). This may indicate that the ovaries are over-responding to treatment and that large ovarian cysts have developed (see also section 2 under "Ovarian hyperstimulation syndrome (OHSS)"). This side effect is common (may affect up to 1 in 10 people).
• OHSS may become severe, with markedly enlarged ovaries, reduced urine production, weight gain, breathing difficulties and/or possible accumulation of fluid in the abdomen or chest. This side effect is not common (may affect up to 1 in 100 people).
• Rarely, complications of OHSS such as ovarian torsion or blood clotting (thromboembolism) may occur (may affect up to 1 in 1,000 people).
• Very rarely, serious blood clotting complications (thromboembolic events) may occur, sometimes independent of OHSS (may affect up to 1 in 10,000 people). These may cause chest pain, shortness of breath, stroke or heart attack (see also section 2 under "Blood clotting disorders").

Serious side effects in men and women

• Occasionally, allergic reactions such as rash, redness, urticaria (hives), or facial swelling with breathing difficulties may occur and can be serious. This side effect is very rare (may affect up to 1 in 10,000 people).

If you experience any of the side effects described, contact your doctor immediately, who may
ask you to stop using GONAL-f.

Other side effects in women
Very common (may affect more than 1 in 10 people):

• Fluid-filled sacs in the ovary (ovarian cysts)
• Headache
• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Abdominal pain
• Nausea, vomiting, diarrhoea, abdominal cramps and bloating

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as rash, skin redness, urticaria, facial swelling with breathing difficulties may occur. These reactions can be serious.
• Asthma may worsen.

Other side effects in men
Very common (may affect more than 1 in 10 people):

• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

Common (may affect up to 1 in 10 people):

• Swelling of the veins located above and behind the testicles (varicocele)
• Enlargement of the breast gland, acne or weight gain

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions such as rash, skin redness, urticaria, facial swelling with breathing difficulties may occur. These reactions can be serious.
• Asthma may worsen.

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 listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store GONAL-f

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cartridge label or on the box after "Exp". The expiry date refers to the last day of that month.
Store in the refrigerator (2 °C–8 °C). Do not freeze.
Before opening and within the shelf life, the product may be stored outside the refrigerator at a maximum temperature of 25 °C for a single period of up to 3 months and must be discarded if not used within these 3 months.
Keep the cap on the pen to protect the medicine from light.
Do not use GONAL-f if you notice any visible signs of deterioration, if the liquid contains particles, or if it is not clear.
After first use, the pen should be stored for a maximum of 28 days at a temperature between 2 °C and 25 °C. Do not use any remaining medicine in the pre-filled pen after 28 days.
At the end of treatment, any unused solution must be disposed of.
Do not dispose of medicines 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 GONAL-f contains

• The active substance is follitropin alfa.
• Each pre-filled multidose pen contains 900 IU (66 micrograms) of follitropin alfa in 1.44 mL of solution.
• The other components are poloxamer 188, sucrose, methionine, monobasic monohydrate sodium phosphate, dibasic dihydrate sodium phosphate, m-cresol, and phosphoric acid concentrated and sodium hydroxide used to adjust pH, and water for injections.

Description of the appearance of GONAL-f and contents of the pack

• GONAL-f is a clear, colourless injectable liquid in a pre-filled pen.
• It is supplied in packs containing 1 pre-filled pen and 16 disposable needles.

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
Manufacturer
Merck Serono S.p.A., Via delle Magnolie 15, 70026 Modugno (Bari), Italy
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu .

Instructions for use

GONAL-f FOLLITROPIN ALFA 900 UI/1.44 mL PREFILLED PEN

Injectable solution in a prefilled pen
Follitropin alfa
Important information about the GONAL-f prefilled pen

• Read the Instructions for Use and the Package Leaflet before using the prefilled pen

GONAL-f.

• Always follow all the instructions provided in these Instructions for Use and given by your healthcare provider, as they may differ from those used previously. These instructions will help you avoid treatment errors, infections from needlestick injuries, or injuries caused by broken glass.
• The GONAL-f pre-filled pen is intended for subcutaneous injection only.
• Use the GONAL-f pre-filled pen only if a healthcare professional has shown you how to use it correctly.
• Your healthcare provider will tell you how many GONAL-f pre-filled pens you need to complete your treatment.
• Administer the injection at the same time every day.
• The numbers shown in the dose control window indicate the dose of follitropin alfa in International Units (IU). Your healthcare provider will tell you how many IU of follitropin alfa you must inject each day.
• The numbers displayed in the dose control window will help you to:

a. Set the prescribed dose (Figure 1).

b. Confirm that the injection has been completed (Figure 2).

c. Read the remaining dose to be injected using a second pen (Figure 3).

• Immediately remove the needle from the pen after each injection.

Do not reuse needles.
Do not share the pen and/or needles with other people.
Do not use the GONAL-f pre-filled pen if it has been dropped or if the pen is cracked or damaged, as you may injure yourself.

How to use the GONAL-f pre-filled pen treatment diary
A treatment diary is attached at the end of these Instructions for Use. Use the treatment diary to record the amounts injected.
Injecting incorrect amounts of medication could affect your treatment.

• Record the treatment day (column 1), date (column 2), time of injection (column 3), and volume in the pen (column 4).
• Record the prescribed dose (column 5).
• Check correct dose setting before injection (column 6).
• After injection, read the number shown in the dose control window.
• Confirm administration of a complete injection (column 7), or record the number shown in the dose control window if it is not “0” (column 8).
• If necessary, administer an injection with a second pen, setting the remaining dose recorded in the column “Amount to select for second injection” (column 8).
• Record this remaining dose in the next column “Amount to inject” (column 6).

By using the treatment diary to record your daily injection(s), you can verify each day that you have received the full prescribed dose.
Example of a treatment diary:

Become familiar with the GONAL-f pre-filled pen

Needle*:
Pre-filled pen:
Step 1 Prepare the necessary items

1.1 Allow the pre-filled pen to reach room temperature for at least 30 minutes before use, so that the medication reaches room temperature.
Do not use a microwave or other heating devices to warm the pen.
1.2 Prepare a clean, flat surface in a well-lit area, such as a table or countertop.

1.3 Additional required materials (not included in the package):

• Alcohol wipes and a sharps disposal container (Figure 4).
  1.4 Wash your hands thoroughly with soap and water, then dry them completely (Figure 5).
  1.5 Remove the GONAL-f pre-filled pen from the

package using one hand.
Do not use tools or other devices, as they may damage the pen.
1.6 Check that the name printed on the pre-filled pen is GONAL-f.
1.7 Check the expiration date printed on the pen label (Figure 6).
Do not use the GONAL-f pre-filled pen if the expiration date has passed or if the pen does not say GONAL-f.

Step 2 Prepare for injection

2.1 Remove the pen cap (Figure 7).
2.2 Make sure the medication appears clear, colorless, and free of particles.
Do not use the pre-filled pen if the medication is cloudy or has changed color, as this may cause infection.
2.3 Ensure that the dose control window displays “0” (Figure 8).

Choose an injection site:
2.4 A healthcare professional will instruct you on the appropriate injection sites on the abdominal area (Figure 9). To minimize skin irritation, choose a different injection site each day.
2.5 Clean the skin at the injection site with an alcohol wipe.
Do not touch or cover the cleaned skin.

Step 3 Attach the needle
Important: Always use a new needle for each injection. Using a previously used needle may cause infection.
3.1 Take a new needle. Use only the “single-use” needles provided in the package.
3.2 Check that the outer needle cap is not damaged.
3.3 Hold the outer needle cap securely.
3.4 Check that the tear-off tab on the outer needle cap is not damaged or loose, and that the expiration date has not passed (Figure 10).
3.5 Remove the tab (Figure 11).
Do not use the needle if it is damaged or expired, or if the outer needle cap or tear-off tab is damaged or loose.
Using an expired needle or one with a damaged or loose tear-off tab or outer cap may lead to infection. Dispose of it in a sharps container and take a new needle.
3.6 Screw the outer needle cap onto the threaded tip of the GONAL-f pre-filled pen until you feel slight resistance (Figure 12).
Do not overtighten the needle, as this may make it difficult to remove after injection.
3.7 Remove the outer needle cap by gently pulling it off (Figure 13).
3.8 Set it aside for later use (Figure 14).
Do not discard the outer needle cap, as it will be needed later to prevent needlestick injuries and infections when removing the needle from the pre-filled pen.
3.9 Hold the GONAL-f pre-filled pen with the needle pointing upward (Figure 15).
3.10 Carefully remove and dispose of the inner protective cap (Figure 16).

Do not replace the inner protective cap onto the needle. You could injure yourself with the needle and develop an infection.
3.11 Carefully observe the needle tip and check for one or more small drops of liquid (Figure 17).

If you do not see one or more small drops of liquid at or near the needle tip the first time you use a new pen:

1. Gently turn the dose knob forward until the dose display window shows “25” (Figure 18).
   • If you go past “25”, you may turn the dose knob back.

2. Hold the pen with the needle pointing upward.
3. Gently tap the cartridge holder (Figure 19).
4. Press the dose knob fully in. A small drop of liquid will appear at the needle tip (Figure 20).
5. Check that the dose display window shows “0” (Figure 21).
6. Proceed to Step 4 Set the Dose.

If no drop of liquid appears, contact your healthcare provider.
Step 4 Set the Dose
Note: The pen contains 900 IU of follitropin alfa. The maximum single dose that can be set with the 900 IU pen is 450 IU. The minimum single dose is 12.5 IU, and the dose can be increased in increments of 12.5 IU.
4.1 Turn the dose knob until the prescribed dose appears in the dose display window.

• Example: if the prescribed dose to be injected is “150” IU, make sure the number “150” appears in the dose display window (Figure 22). Injecting incorrect amounts of medication may affect your treatment.

4.2 Check that the dose display window shows the full prescribed dose before proceeding to the next step.
Step 5 Inject the Dose
Important: Inject the dose according to the instructions provided by your healthcare provider.
5.1 Slowly push the entire needle into the skin (Figure 24).
5.2 Place your thumb in the center of the dose knob.
Slowly and fully press in the dose knob and keep it pressed to complete the injection (Figure 25).
Note: The higher the dose, the longer it will take to inject.

5.3 Keep the dose knob fully pressed for at least 5 seconds before removing the needle from the skin (Figure 26).

• The number in the dose display window will return to “0”.

• After at least 5 seconds, while keeping the dose knob fully pressed, remove the needle from the skin (Figure 27).

• Once the needle has been removed from the skin, release the dose knob.

Do not release the dose knob until the needle has been removed from the skin.
Step 6 Remove the Needle After Each Injection

6.1 Place the outer needle cap on a flat surface.
6.2 Hold the GONAL-f pre-filled pen firmly in one hand and insert the needle into the outer cap.
6.3 Now press the needle, covered by its cap, against a hard surface until you hear a “click” (Figure 29).
6.4 Grasp the outer needle cap and unscrew the needle by turning it in the opposite direction (Figure 30).

6.5 Dispose of the used needle safely in a sharps container (Figure 31). Handle the needle with care to avoid needlestick injury.
Do not reuse or share a used needle.
Step 7 After the Injection

7.1 Check that you have completed a full injection:

• Check that the dose display window shows “0” (Figure 32). If the dose display window shows “0”, this means the full dose has been administered. If the dose display window shows a number higher than “0”, the GONAL-f pre-filled pen is empty. The full prescribed dose has not been administered, and you must perform step 7.2 below.

7.2 Complete a partial injection (only if necessary):

• The dose display window indicates the remaining amount to be injected using a new pen. In the example shown, the amount still to be administered is “50” IU (Figure 33).
• To complete the dose with a second pen, repeat steps 1 to 8.

Step 8 Store the GONAL-f Pre-filled Pen

8.1 Replace the pen cap to prevent infection (Figure 34).
8.2 Store the pen with the cap on in a safe place as indicated in the Package Leaflet.
8.3 When the pen is empty, ask your healthcare provider how to dispose of it.
Do not store the pen with the needle still attached. This may cause infection.
Do not reuse the GONAL-f pre-filled pen if it has been dropped or if the pen is cracked or damaged, as you may be injured.
If you have any questions, contact your healthcare provider.
Treatment Diary for the GONAL-f Pre-filled Pen

These Instructions for Use were last updated on: {MM/YYYY}.