Gonal-f 150 IU/0.24 ml solution for injection in pre-filled pen

Patient Information Leaflet

Introduction

Patient Information Leaflet

GONAL-f 150 IU/0.24ml solution for injection in a pre-filled pen

folitropin alfa

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet as 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 pass it on to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, talk to your doctor or pharmacist, even if the effects are not listed in this leaflet. See section 4.

Contents of the 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 a substance called "folitropin alfa". Folitropin alfa is a type of 'follicle-stimulating hormone' (FSH), which belongs to a family of hormones known as 'gonadotropins'. Gonadotropins play a role in reproduction and fertility.

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 are unable to ovulate and who have not responded to treatment with a substance called 'clomiphene citrate'.
• in combination with another substance called 'lutein alfa' ('luteinizing hormone' or LH), to help release an egg from the ovary (ovulation) in women whose bodies produce very low levels of gonadotropins (FSH and LH).
• to help develop several follicles (each containing an egg) in women undergoing assisted reproductive techniques (techniques that may help them become pregnant), such as in vitro fertilization, gamete intrafallopian transfer, or zygote intrafallopian transfer.

In adult men, GONAL-f is used:

• in combination with another substance called 'human chorionic gonadotropin' (hCG), to help produce sperm in infertile men due to low levels of certain hormones.

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

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

Do not use GONAL-f

• if you are allergic to follicle-stimulating hormone or to any of the other components 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 ovarian, uterine, or breast cancer.

• if you have a condition that normally makes pregnancy impossible, such as ovarian failure (premature menopause) or a malformation of the reproductive organs.

• if you are a man:

• with irreversibly damaged testicles.

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

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use GONAL-f.

Porphyria

Inform your doctor before starting treatment if you or a family member has porphyria (a disorder affecting the breakdown of porphyrins, which can be inherited).

Immediately inform your doctor if:

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

In such cases, your doctor may recommend that you discontinue treatment.

Ovarian hyperstimulation syndrome (OHSS)

If you are a woman, this medicine increases your risk of developing OHSS. This occurs when your follicles develop excessively and become large cysts. If you experience pelvic pain, rapid weight gain, nausea or vomiting, or difficulty breathing, contact your doctor immediately, as they may discontinue treatment (see section 4).

If you do not ovulate and the recommended dosage and treatment schedule are followed, this syndrome is less likely to occur. Treatment with GONAL-f rarely causes severe ovarian hyperstimulation syndrome unless the medication used to trigger final follicular maturation (containing human chorionic gonadotropin, hCG) is administered. If OHSS develops, your doctor may decide not to prescribe hCG in this treatment cycle and may advise you to abstain from sexual intercourse or to use barrier contraceptive methods for at least 4 days.

Multiple pregnancy

If you use GONAL-f, you have a higher chance of becoming pregnant with more than one baby at a time ("multiple pregnancy," usually twins) compared to natural conception. Multiple pregnancy may lead to 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 correct times. If you undergo assisted reproductive techniques, the risk of multiple pregnancy depends on your age and the quality and number of fertilized eggs or embryos transferred.

Miscarriage

If you undergo assisted reproductive techniques or ovarian stimulation to produce eggs, the risk of miscarriage is higher than in the general female population.

Blood clotting problems (thromboembolic events)

If you or a family member has had blood clots in the leg or lung, myocardial infarction, or stroke in the past or recently, you may have an increased risk of developing these problems or of them worsening during treatment with GONAL-f.

Men with high FSH levels in the blood

If you are a man, abnormally high levels of FSH in the blood may indicate testicular damage. In such cases, GONAL-f is generally not effective.

If your doctor decides to attempt treatment with GONAL-f, they may request a semen analysis 4 to 6 months after starting treatment to monitor the response.

Children and adolescents

GONAL-f must not be used 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 need to take any other medicines.

• If you use GONAL-f together with other medications that promote ovulation (e.g., hCG or clomiphene citrate), your follicular response may be increased.
• If you use GONAL-f simultaneously with a gonadotropin-releasing hormone (GnRH) agonist or antagonist (medications that reduce sex hormone levels and suppress ovulation), you may require a higher dose of GONAL-f to produce follicles.

Pregnancy and breastfeeding

Do not use GONAL-f if you are pregnant 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 of sodium (23 mg) per dose; hence, it is essentially "sodium-free."

3. How to use GONAL-f

Follow exactly the administration instructions for this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

Use of this medicine

• GONAL-f is designed to be administered by injection just under the skin (subcutaneously). The pre-filled pen can 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 teach you how to use the GONAL-f pre-filled pen to self-inject the medicine.
• If you are self-administering GONAL-f, read and carefully follow the “Instructions for Use”.

What dose 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 menstruation

• GONAL-f is usually administered every day.
• If you have irregular menstruation, start using GONAL-f within the first 7 days of the menstrual cycle. If you do not have menstruation, you may 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 in a stepwise manner.
• 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, a form of hCG produced in a laboratory using a special recombinant DNA technique), or 5,000 to 10,000 IU of hCG, 24 to 48 hours after the last GONAL-f injection. The best time for sexual intercourse is on the day of the hCG injection and the following day.

If your doctor does not observe the desired response after 4 weeks of treatment, that cycle of treatment with GONAL-f should be discontinued. For the next cycle, your doctor will administer a higher initial dose of GONAL-f than in the previous cycle.

If an excessive response occurs, your treatment will be stopped and you will not be given hCG (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 been diagnosed with very low levels of FSH and LH hormones

• 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 five weeks.
• The dose of GONAL-f may be increased every 7 or 14 days by 37.5 to 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 form of hCG produced in a laboratory using a special recombinant DNA technique), 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 for sexual intercourse is on the day of the hCG injection and the following day. Alternatively, intrauterine insemination or another medically assisted reproduction procedure may be performed, at your doctor’s discretion.

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

If an excessive response occurs, your treatment will be stopped and you will not be given hCG (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 for retrieval prior to any assisted reproductive 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 monitor this through blood tests and/or ultrasound scans.
• When the eggs are ready, you will be given a single injection of 250 micrograms of 'recombinant hCG' (r-hCG, a form of hCG produced in a laboratory using a special recombinant DNA technique), or 5,000 to 10,000 IU of hCG, 24 to 48 hours after the last GONAL-f injection. This causes your eggs to become 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 continuing with these two medicines for at least 18 months.

If you use more GONAL-f than you should

The effects of using an excessive amount of GONAL-f are unknown. However, ovarian hyperstimulation syndrome (OHSS), described in section 4, may be expected. 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 the missed dose. Consult your doctor as soon as you realize you have missed a dose.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Serious adverse effects in women

• Pelvic pain, accompanied by nausea or vomiting, may be symptoms of ovarian hyperstimulation syndrome (OHSS). This may indicate that the ovaries have over-responded to treatment and large ovarian cysts have developed (see section 2, “Ovarian hyperstimulation syndrome (OHSS)”). This adverse effect is common (may affect up to 1 in 10 people).
• Ovarian hyperstimulation syndrome may worsen with clearly enlarged ovaries, reduced urine output, weight gain, difficulty breathing, and/or possible accumulation of fluid in the abdomen or chest. This adverse effect is uncommon (may affect up to 1 in 100 people).
• In rare cases, complications of ovarian hyperstimulation syndrome may occur, such as ovarian torsion or blood clotting (may affect up to 1 in 1,000 people).
• In very rare cases (may affect up to 1 in 10,000 people), serious blood clotting complications (thromboembolic events) may occur, sometimes independent of ovarian hyperstimulation syndrome. This could cause chest pain, breathlessness, stroke, or myocardial infarction (see also section 2, “Blood clotting problems”).

Serious adverse effects in men and women

• Allergic reactions, such as skin rash, redness of the skin, blisters, swelling of the face with difficulty breathing, may sometimes be severe. This adverse effect is very rare (may affect up to 1 in 10,000 people).

If you experience any of the adverse effects listed above, you must consult your doctor immediately, who may instruct you to stop treatment with GONAL-f.

Other adverse effects in women

Very common (may affect 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 (may affect up to 1 in 10 people):

• Abdominal pain.
• Nausea, vomiting, diarrhoea, cramps, and flatulence.

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

• Allergic reactions may occur, such as skin rash, redness of the skin, blisters, swelling of the face with difficulty breathing. Occasionally, these reactions may be severe.
• Asthma may worsen.

Other adverse 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 above and behind the testicles (varicocele).
• Breast development, acne, or weight gain.

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

• Allergic reactions may occur, such as skin rash, redness of the skin, blisters, swelling of the face with difficulty breathing. Occasionally, these reactions may be severe.
• Asthma may worsen.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 label of the cartridge or the carton, following the letters CAD. The expiry date refers to the last day of the month indicated.

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

Before first use and within its validity period, the product may be stored outside the refrigerator at temperatures up to a maximum of 25°C for a single continuous 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 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.

After first use, the pen should be stored at between 2°C and 25°C for a maximum of 28 days.

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

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

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

6. Contents of the pack and other information

Composition of GONAL-f

• The active substance is follitropin alfa.
• There are 600 IU (44 micrograms) of follitropin alfa in each millilitre of liquid. Each pre-filled pen delivers 150 IU (11 micrograms) in 0.25 ml.
• The other components are poloxamer 188, sucrose, methionine, monosodium 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 injections.

Appearance of the product and contents of the pack

• GONAL-f is presented as an injectable, clear, colourless 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

Date of the most recent revision of this leaflet: {MM/YYYY}.

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

Instructions for use

GONAL-f PRE-FILLED PEN 150 IU/0.24 ml

Injectable solution in a pre-filled pen

Follitropin alfa

Important information about the GONAL-f pre-filled pen

• Read the instructions for use and the package leaflet before using the GONAL-f pre-filled pen.
• Always follow all instructions in these instructions for use and the training provided by your healthcare professional, as they may differ from previous instructions you have received. This information will help prevent treatment errors or needle-stick infections and injuries from broken glass.
• The GONAL-f pre-filled pen is 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 professional will tell you how many GONAL-f pre-filled pens you need to complete your treatment.
• Administer your injection at the same time each day.
• The numbers in the dose information window represent the number of International Units (IU) and indicate the dose of follitropin alfa. Your healthcare professional will tell you how many IU of follitropin alfa you must inject each day.
• The numbers shown in the dose information window help you to:

Select the prescribed dose (Figure 1).
Check that the injection has been completed (Figure 2).
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 or needles with anyone else.

Do not use the GONAL-f prefilled 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 prefilled 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 may affect your treatment.

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

Using the treatment diary to record your daily injection(s) allows you to verify that you have received the full prescribed dose each day.

An example of a treatment diary:

Familiarize yourself with the GONAL-f prefilled pen

Step 1 Gather the materials

1.1 Leave the pre-filled pen at room temperature for at least 30 minutes before use to allow the medication to reach room temperature. Do not use a microwave or any other heating device to warm the pen. 1.2 Prepare a clean, flat surface, such as a table or countertop, in a well-lit area. 1.3 You will also need (not included in the package): Alcohol wipes and a sharps container (Figure 4). 1.4 Wash your hands thoroughly with soap and water and dry them well (Figure 5). 1.5 Remove the GONAL-f pre-filled pen from the package by hand. Do not use any tools, as they may damage the pen. 1.6 Check that the label on the pre-filled pen reads GONAL-f. 1.7 Check the expiration date 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 is not labeled GONAL-f.

Step 2 Prepare for the injection

2.1 Remove the pen cap (Figure 7). 2.2 Check that the medicine is clear and colorless and contains no particles. Do not use the pre-filled pen if the medicine has changed color or is cloudy, as this may cause an infection. 2.3 Check that the dose information window is set to “0” (Figure 8).
Choose an injection site: 2.4 Your healthcare professional will instruct you on the injection sites to use around 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 skin you have just cleaned.

Step 3 Attach the needle

Important: always make sure to use a new needle for each injection. Reusing needles may cause infection. 3.1 Take a new needle. Use only the "single-use" needles supplied. 3.2 Check that the outer needle cap is not damaged. 3.3 Hold the outer needle cap firmly. 3.4 Check that the closure tab of the outer needle cap is not damaged or loose and that the expiration date has not passed (Figure 10). 3.5 Remove the closure tab (Figure 11). Do not use the needle if it is damaged or expired, or if the outer needle cap or closure tab is damaged or loose. Using expired needles or needles with damaged or loose closure tabs or outer caps may cause 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 when attaching it, as it may become difficult to remove after the 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 prevent needle-stick 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 green inner needle cap (Figure 16). Do not recap the needle with the green inner needle cap, as this may cause needle-stick injuries and infections. 3.11 Carefully examine the needle tip for one or more drops of liquid.
If	Then
Using a new pen	Check that there is a drop of liquid at the needle tip (Figure 17). If you see a drop of liquid, proceed to Step 4 Select the dose. If you do not see any drop at or near the needle tip, perform the steps described on the following page to remove air from the system.
Reusing a pen	It is not necessary to check for a drop of liquid. Proceed directly to Step 4 Select the dose.

If you do not see a small drop of liquid at the tip or near it the first time you use a new pen:

1. Carefully turn the dose adjustment knob forward until “25” appears in the dose information window (Figure 18).

• You may turn the dose adjustment knob backward if you have gone past “25”.

1. Hold the pen with the needle pointing upward.
2. Gently tap the cartridge holder (Figure 19).
3. Fully press the dose adjustment button. A drop of liquid should appear at the needle tip (Figure 20).
4. Check that the dose information window displays “0” (Figure 21).
5. Proceed to Step 4 Select the dose.

If no drop of liquid appears, contact your healthcare professional.

Step 4 Select the dose

Note: The pen contains 150 IU of follitropin alfa. The maximum single dose that can be set on a 150 IU pen is 150 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 adjustment knob 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 may affect your treatment.

Turn the dose selector knob forward to select the dose (Figure 22).	You can turn the dose selector knob backward if you turn past the desired dose (Figure 23).

4.2. Check that the dose information window displays the full prescribed dose before proceeding to the next step.

Step 5 Inject the dose

Important: inject the dose exactly as shown to you by your healthcare professional. 5.1 Slowly insert the entire needle into the skin (Figure 24). 5.2 Place your thumb on the center of the dose adjustment button. Firmly and slowly press the dose adjustment button completely and keep it pressed to fully administer the injection (Figure 25). Note: the larger the dose, the longer the injection will take.

5.3 Keep the dose adjustment button pressed for at least 5 seconds before removing the needle from the skin (Figure 26). The number in the dose information window will return to “0”. After at least 5 seconds, remove the needle from the skin while keeping the dose adjustment button pressed (Figure 27). Once the needle is out of the skin, release the dose adjustment button. Do not release the dose adjustment button 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 needle cap (Figure 28). 6.3 Continue pushing the capped needle against a firm surface until you hear a click (Figure 29). 6.4 Hold the outer needle cap and unscrew the needle by turning it in the opposite direction (Figure 30). 6.5 Safely dispose of the used needle in a sharps container (Figure 31). Handle the needle carefully to avoid injury. Do not reuse or share any used needles.

Step 7 After the injection

7.1 Check that a complete injection has been administered: Check that the dose information window displays “0” (Figure 32). If the dose information window displays “0”, the dose has been fully delivered. If the dose information window displays a number greater than “0”, the GONAL-f pre-filled pen is empty. You have not received the full prescribed dose and must perform step 7.2 described below.
7.2 Complete a partial injection (only when necessary): The dose information window will indicate the remaining amount to be injected using a new pen. In the example shown, the remaining amount is “50” IU (Figure 33). To complete the dose with a second pen, repeat Steps 1 to 8.

Step 8 Storage of the GONAL-f pre-filled pen

8.1 Replace the pen cap to prevent infections (Figure 34). 8.2 Store the pen with the cap on, in a safe place and as indicated in the package insert. 8.3 When the pen is empty, ask your healthcare professional how to dispose of it.

Do not store the pen with the needle still attached, as this may cause an infection.

Do not reuse the GONAL-f prefilled pen if it has been dropped, or if the pen is cracked or damaged, as this may cause injury.

Contact your healthcare professional if you have any questions.

GONAL-f prefilled pen treatment diary

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