GONAL-F 450 IU/0.72 mL PRE-FILLED PEN SOLUTION FOR INJECTION

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 (an inability to break down porphyrins that can be passed 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 pain, 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 dosage regimen, this syndrome is less likely to occur. Treatment with GONAL-f rarely causes severe OHSS, unless the medicine used for final follicular maturation (containing 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 child at a time (‘multiple pregnancy’, usually twins), than if you become pregnant through natural conception. 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 correct 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 in the average woman.

Blood Clotting Problems (Thromboembolic Events)

If you or a family member has suffered from blood clots in the leg or lung, heart attack, or stroke, you may have a higher risk of developing these problems or worsening them with GONAL-f treatment.

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 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 Breastfeeding

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

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; it is essentially ‘sodium-free’.

3. How to Use GONAL-f

Follow the instructions for administration of this medicine exactly as prescribed by your doctor. If you are unsure, 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 any day you find convenient.
• 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 hCG’ (r-hCG, a hCG made in a laboratory using a special DNA technique), 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, along with 75 IU of lutropin alpha.
• 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 37.5 to 75 IU increments, until the desired response is obtained.
• When the desired response is obtained, you will be given a single injection of 250 micrograms of ‘recombinant hCG’ (r-hCG, a hCG made in a laboratory using a special DNA technique), or 5,000 to 10,000 IU of hCG, 24 to 48 hours after the last injection of GONAL-f and lutropin alpha. 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 several 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 point. Your doctor will check 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 hCG made in a laboratory using a special DNA technique), or 5,000 to 10,000 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, along 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 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 a dose.

If you have any other questions about 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 OHSS. This can indicate that your ovaries have overreacted to treatment and developed large cysts (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). This side effect is common (may affect up to 1 in 10 people).
• OHSS can worsen with clearly enlarged ovaries, decreased urine production, weight gain, difficulty breathing, and/or possible fluid accumulation in the abdomen or chest. This side effect is uncommon (may affect up to 1 in 100 people).
• In rare cases, OHSS can also cause complications 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) can occur, sometimes independent of OHSS. 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, skin redness, blisters, facial swelling with difficulty breathing, can occur. This side effect is very rare (may affect up to 1 in 10,000 people).

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

Other Side 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, diarrhea, abdominal cramps, and flatulence.

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

• Allergic reactions, such as skin rash, skin redness, blisters, facial swelling with difficulty breathing, can occur. In some cases, these reactions can 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 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, such as skin rash, skin redness, blisters, facial swelling with difficulty breathing, can occur. In some cases, these reactions can be severe.
• 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 through 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 carton or label after EXP. The expiry date refers to the last day of the month shown.

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

Before opening and within its validity period, the product can be stored outside 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 more than 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 Contents and Additional Information

GONAL-f Composition

• The active ingredient is folitropin alfa.
• Each pre-filled pen with a multi-dose cartridge contains 450 IU (33 micrograms) of folitropin alfa in 0.72 ml of solution.
• The other components are poloxamer 188, sucrose, methionine, sodium dihydrogen phosphate monohydrate, disodium 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 Contents

• 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 12 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 450 IU/0.72 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 sticks 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.

Using 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 reservoir support 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:

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

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

2Hold the pen with the needle pointing upwards.

3Gently tap the reservoir support (Figure 19).

4Press the dose adjustment button completely. A drop of liquid will appear on the needle tip (Figure 20).

5Check that the dose information windowshows "0" (Figure 21).

6Proceed with Step 4 Choose the dose.

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

Step 4 Choose the Dose

Note:The pen contains 450 IU of folitropin alfa. The maximum single dose that can be adjusted in a 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.

4.1Turn the dose adjustment button until the desired dose appears on 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 the Injection

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

pecto.

8.3 When the pen is empty, ask the healthcare professional how to dispose of it.

Do notkeep the pen with the needle still attached, as this can cause an infection.

Do notreuse the GONAL-f pre-filled 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 Pre-filled Pen Treatment Diary

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