GONAL-F 300 IU/0.48 ML PRE-FILLED PEN INJECTION SOLUTION

Introduction

Package Leaflet: Information for the User

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

follicle stimulating hormone alfa

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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What GONAL-f is and what it is used for
2. What you need to know before you use GONAL-f
3. How to use GONAL-f
4. Possible side effects
5. Storing 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 a substance called ‘follicle stimulating hormone alfa’ (FSH). FSH is a type of ‘gonadotropin’ hormone that plays a key role in fertility and reproduction.

What GONAL-f is used for

In adult women,GONAL-f is used:

• to help release an egg from the ovary (ovulation) in women who do not ovulate and have not responded to treatment with a medicine called ‘clomiphene citrate’.
• in combination with another medicine called ‘lutropin alfa’ (‘luteinizing hormone’ or LH), to help release an egg from the ovary (ovulation) in women whose body produces very small amounts of gonadotropins (FSH and LH).
• to help develop multiple follicles (each containing an egg) in women undergoing assisted reproduction techniques (techniques that can help you get pregnant), such as ‘in vitro fertilization’, ‘intratubal gamete transfer’, or ‘intratubal embryo transfer’.

In adult men,GONAL-f is used:

• in combination with another medicine called ‘human chorionic gonadotropin’ (hCG), to help produce sperm in men who are infertile due to low levels of certain hormones.

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

Before starting treatment, your fertility and that of your partner should be assessed by a doctor experienced in the treatment of fertility disorders.

Do not use GONAL-f

• if you are allergic to follicle stimulating hormone or any of the other ingredients of this medicine (listed in section 6).
• if you have a tumor in the hypothalamus or pituitary gland (both are parts of the brain).
• if you are a woman:

• with enlarged ovaries or fluid-filled sacs in the ovaries (ovarian cysts) of unknown origin.
• with unexplained vaginal bleeding.
• with cancer of the ovaries, uterus, or breast.
• if you have a condition that normally makes pregnancy impossible, such as premature ovarian failure (early menopause) or a malformation of the reproductive organs.

• if you are a man:

• with damaged testes that cannot be cured.

Do not use GONAL-f if any of the above conditions apply to you. If you are not sure, consult your doctor before starting treatment with this medicine.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting treatment with GONAL-f.

Porphyria

Tell your doctor before starting treatment if you or a family member has porphyria (a disorder that can be inherited from parents to children).

Tell your doctor immediately if:

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

In these cases, your doctor may recommend that you interrupt treatment.

Ovarian Hyperstimulation Syndrome (OHSS)

If you are a woman, this medicine increases the risk of OHSS. This occurs when your follicles develop too much and become large cysts. If you have pelvic pain, rapid weight gain, nausea, vomiting, or difficulty breathing, consult your doctor immediately, who may interrupt treatment (see section 4).

In case you do not ovulate and you follow the recommended dose and dosing schedule, this syndrome is less likely to occur. Treatment with GONAL-f rarely causes a severe ovarian hyperstimulation syndrome, unless the medicine used for final follicular maturation (containing human chorionic gonadotropin, hCG) is administered. In case of OHSS, your doctor may not prescribe hCG in this treatment cycle and advise you to abstain from intercourse or use barrier contraceptives for at least 4 days.

Multiple Pregnancy

If you use GONAL-f, you have a higher risk of becoming pregnant with more than one baby at the same time (‘multiple pregnancy’, usually twins), than if you were to become pregnant naturally. Multiple pregnancy can cause medical complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of GONAL-f at the right times. If you undergo assisted reproduction techniques, the risk of multiple pregnancy is related to your age and the quality and number of eggs fertilized or embryos placed inside you.

Abortion

If you undergo assisted reproduction techniques or ovarian stimulation to produce eggs, the likelihood of having a miscarriage is higher than average.

Blood Clotting Problems (Thromboembolic Events)

If you or a family member have had blood clots in the leg or lung, heart attack, or stroke in the past or recently, you may have a higher risk of having these problems or of them getting worse with treatment with GONAL-f.

Men with High FSH Levels in the Blood

If you are a man, very high FSH levels in the blood can be a sign of testicular damage. GONAL-f is usually not effective in these cases.

If your doctor decides to try treatment with GONAL-f, to monitor treatment, your doctor may ask you to have a semen analysis 4 to 6 months after starting treatment.

Children and Adolescents

GONAL-f should not be used in children and adolescents under 18 years of age.

Other Medicines and GONAL-f

Tell your doctor if you are taking, have recently taken, or might take any other medicines.

• If you use GONAL-f with other medicines that help ovulation (e.g., hCG or clomiphene citrate), your follicles' response may be increased.
• If you use GONAL-f at the same time as a gonadotropin-releasing hormone (GnRH) agonist or antagonist (these medicines decrease sex hormone levels and stop ovulation), you may need a higher dose of GONAL-f to produce follicles.

Pregnancy and Breast-feeding

Do not use GONAL-f if you are pregnant or breast-feeding.

Driving and Using Machines

GONAL-f is not expected to affect your ability to drive or use machines.

GONAL-f contains Sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially ‘sodium-free’.

3. How to use GONAL-f

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are not sure, consult your doctor or pharmacist again.

Using this medicine

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

How much to use

Your doctor will decide how much medicine to administer and how often. The doses described below are expressed in International Units (IU).

Women

If you are not ovulating and have irregular periods or no periods.

• GONAL-f is usually administered every day.
• If you have irregular periods, start using GONAL-f on the first 7 days of your menstrual cycle. If you do not have periods, you can start using the medicine on any day that is convenient for you.
• The initial dose of GONAL-f is usually individualized and may be adjusted stepwise.
• The daily dose of GONAL-f should not exceed 225 IU.
• When the desired response is obtained, you will be given a single injection of 250 micrograms of ‘recombinant human chorionic gonadotropin’ (r-hCG), or 5,000 to 10,000 IU of hCG, 24 to 48 hours after the last injection of GONAL-f. The best time to have intercourse is on the day of the hCG injection and the day after.

If your doctor does not observe the desired response, the continuation of that treatment cycle with GONAL-f should be evaluated and managed according to usual clinical practice.

If an excessive response is obtained, treatment will be interrupted and hCG will not be administered (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). For the next cycle, your doctor will administer a lower dose of GONAL-f than in the previous cycle.

If you have very low levels of FSH and LH

• The usual initial dose of GONAL-f is 75 to 150 IU, together with 75 IU of lutropin alfa.
• You will use these two medicines every day for up to 5 weeks.
• The dose of GONAL-f may be increased every 7 or 14 days, in steps of 37.5 to 75 IU, until the desired response is obtained.
• When the desired response is obtained, you will be given a single injection of 250 micrograms of ‘recombinant human chorionic gonadotropin’ (r-hCG), or 5,000 to 10,000 IU of hCG, 24 to 48 hours after the last injection of GONAL-f and lutropin alfa. The best time to have intercourse is on the day of the hCG injection and the day after. Alternatively, intrauterine insemination or another assisted reproduction procedure may be performed at the discretion of your doctor.

If your doctor does not observe the desired response after 5 weeks, that treatment cycle with GONAL-f should be discontinued. For the next cycle, your doctor will administer a higher initial dose of GONAL-f than in the canceled cycle.

If an excessive response is obtained, treatment will be interrupted and hCG will not be administered (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). For the next cycle, your doctor will administer a lower dose of GONAL-f than in the previous cycle.

If you need to develop multiple eggs before any assisted reproduction technique

• The initial dose of GONAL-f is usually individualized and may be adjusted stepwise up to a maximum of 450 IU per day.
• Treatment continues until the eggs have developed to the desired stage. Your doctor will check this by blood tests and/or ultrasound scans.
• When the eggs are ready, you will be given a single injection of 250 micrograms of ‘recombinant human chorionic gonadotropin’ (r-hCG), or 5,000 IU of hCG, 24 to 48 hours after the last injection of GONAL-f. This makes your eggs ready for retrieval.

Men

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

If you use more GONAL-f than you should

The effects of using too much GONAL-f are not known. However, it can be expected that ovarian hyperstimulation syndrome (OHSS) may occur, which is described in section 4. However, this syndrome will only occur if hCG is also 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 forgotten doses. Consult your doctor as soon as you realize you have forgotten to take a dose.

If you have any further questions on the use of this medicine, ask 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, accompanied by nausea or vomiting, can be symptoms of ovarian hyperstimulation syndrome (OHSS). This can indicate that your ovaries have over-reacted to treatment and have developed large cysts (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). This side effect is common (affects up to 1 in 10 people).
• Ovarian hyperstimulation syndrome can worsen with clearly enlarged ovaries, reduced urine production, weight gain, difficulty breathing, and/or possible fluid accumulation in the abdomen or chest. This side effect is uncommon (affects up to 1 in 100 people).
• In rare cases, complications of ovarian hyperstimulation syndrome such as ovarian torsion or blood clotting can occur (affects up to 1 in 1,000 people).
• In very rare cases (affects up to 1 in 10,000 people), serious complications of blood clotting (thromboembolic events) can occur, sometimes independent of ovarian hyperstimulation syndrome. This could cause chest pain, shortness of breath, stroke, or heart attack (see also section 2, “Blood Clotting Problems”).

Serious Side Effects in Men and Women

• Allergic reactions, such as skin rash, redness of the skin, blisters, swelling of the face with difficulty breathing, can occur. This side effect is very rare (affects up to 1 in 10,000 people).

If you notice any of the above side effects, you should contact your doctor immediately, who may tell you to stop treatment with GONAL-f.

Other Side Effects in Women

Very common (affects more than 1 in 10 people):

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

Common (affects up to 1 in 10 people):

• Abdominal pain.
• Nausea, vomiting, diarrhea, abdominal cramps, and flatulence.

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

• Allergic reactions, such as skin rash, redness of the skin, blisters, swelling of the face with difficulty breathing, can occur. In some cases, these reactions can be serious.
• Asthma may worsen.

Other Side Effects in Men

Very common (affects more than 1 in 10 people):

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

Common (affects up to 1 in 10 people):

• Swelling of the veins above and behind the testicles (varicocele).
• Development of breast tissue, acne, or weight gain.

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

• Allergic reactions, such as skin rash, redness of the skin, blisters, swelling of the face with difficulty breathing, can occur. In some cases, these reactions can be serious.
• Asthma may worsen.

Reporting of Side Effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing GONAL-f

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the cartridge label or carton after EXP. The expiry date is the last day of the month stated.

Store in a refrigerator (2°C - 8°C). Do not freeze.

Before opening and within its validity period, the product can be stored out of the refrigerator at temperatures up to a maximum 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 it 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.

Once opened, the pen should be stored between 2°C and 25°C for a maximum of 28 days.

Do not use the medicine remaining in the pre-filled pen after 28 days.

At the end of the treatment, the unused solution should be discarded.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

GONAL-f Composition

• The active ingredient is folitropin alfa.
• Each pre-filled, multi-dose pen contains 300 IU (22 micrograms) of folitropin alfa in 0.48 ml of solution.
• The other components are poloxamer 188, sucrose, methionine, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate dihydrate, and m-cresol, as well as concentrated phosphoric acid and sodium hydroxide for pH adjustment and water for injectable preparations.

Product Appearance and Container Content

• GONAL-f is presented as a clear and colorless injectable liquid in a pre-filled pen.
• It is supplied in boxes with 1 pre-filled pen and 8 disposable needles.

Marketing Authorization Holder

Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, Netherlands

Manufacturer

Merck Serono S.p.A., Via delle Magnolie 15, 70026 Modugno (Bari), Italy

Date of Last Revision of this Leaflet: {MM/AAAA}.

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/.

Instructions for Use

GONAL-f PRE-FILLED PEN 300 IU/0.48 ml

Injectable solution in pre-filled pen

Folitropin alfa

Important Information about the GONAL-f Pre-filled Pen

• Read the instructions for use and the leaflet before using the GONAL-f pre-filled pen.
• Always follow all the instructions in these instructions for use and the training provided by the healthcare professional, as they may be different from those received previously. This information will help avoid errors in treatment or infections from needle pricks or glass breakage injuries.
• The GONAL-f pre-filled pen is for subcutaneous injection only.
• Only use the GONAL-f pre-filled pen if the healthcare professional has taught you how to use it correctly.
• The healthcare professional will tell you how many GONAL-f pre-filled pens you need to complete your treatment.
• Take the injection at the same time every day.
• The numbers on the dose information windowrepresent the number of international units (IU) and show the dose of folitropin alfa. The healthcare professional will tell you how many IU of folitropin alfa to inject each day.
• The numbers shown on the dose information windowhelp you:

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

Do notreuse needles.

Do notshare the pen or needles with anyone else.

Do notuse the GONAL-f pre-filled pen if it has been dropped or if the pen is cracked or damaged, as this may cause injury.

How to Use the GONAL-f Pre-filled Pen Treatment Diary

A treatment diary is included at the end of the instructions for use. Use the treatment diary to record the amount injected.

Injecting an incorrect amount of medication can affect treatment.

• Record the day of treatment (column 1), date (column 2), time of injection (column 3), and pen volume (column 4).
• Record the prescribed dose (column 5).
• Check that you have selected the correct dose before administering the injection (column 6).
• After the injection, read the number indicated on the dose information window.
• Confirm that you have received a complete injection (column 7) or record the number indicated on the dose information windowif it is different from "0" (column 8).
• When necessary, perform another injection with a second pen, selecting the remaining dose that appears in the "Amount to adjust for a second injection" section (column 8).
• Record this remaining dose in the "Adjusted amount for injection" section (column 6) on the next line.

The use of the treatment diary to record the daily injection(s) allows you to check that you have received the complete prescribed dose every day.

An example of a treatment diary:

Familiarize Yourself with the GONAL-f Pre-filled Pen

*For illustrative purposes only.

**The numbers on the dose information windowand the cartridge holder represent the number of international units (IU) of the medication.

Step 1 Gather Materials

Step 2 Prepare for Injection

Step 3 Attach the Needle

If you do not see any drop of liquid on the needle tip or its surroundings the first time you use a new pen:

1. Gently turn the dose adjustment button forward until it indicates "25"on the dose information window(Figure 18).

• You can turn the dose adjustment button backward if you have turned it past "25".

1. Hold the pen with the needle pointing upward.
2. Gently tap the cartridge holder (Figure 19).
3. Press the dose adjustment button completely. A drop of liquid will appear on the needle tip (Figure 20).
4. Check that the dose information windowindicates "0" (Figure 21).
5. Proceed with Step 4 Select the dose.

If a drop of liquid does not appear, contact the healthcare professional.

Step 4 Select the Dose

Note:The pen contains 300 IU of folitropin alfa. The maximum single dose that can be adjusted in a 300 IU pen is 300 IU. The minimum single dose is 12.5 IU, and the dose can be increased in increments of 12.5 IU.

4.1Turn the dose adjustment button until the desired dose appears in the dose information window

• Example: if the desired dose is "150" IU, confirm that the dose information window shows "150" (Figure 22). Injecting an incorrect amount of medication can affect treatment.

4.2Check that the dose information windowindicates the complete prescribed dosebefore proceeding to the next step.

Step 5 Inject the Dose

Step 6 Remove the Needle after Each Injection

Step 7 After Injection

Step 8 Storage of the GONAL-f Pre-filled Pen

a in the

prospectus.

8.3 When the pen is empty, ask the

healthcare professional how to dispose of it.

Donot keep the pen with the needle still attached, as this can cause an infection.

Donot reuse the GONAL-f preloaded pen if it has fallen, or if the pen is cracked or damaged, as this can cause injury.

Contact the healthcare professional if you have any questions.

GONAL-f Preloaded Pen Treatment Diary

Date of the last revision of these instructions for use: {MM/YYYY}.