GONAL-F 75 IU POWDER AND SOLVENT FOR INJECTION

Introduction

Package Leaflet: Information for the User

GONAL-f 75 UI powder and solvent for solution for injection

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 symptoms 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

How to prepare and use the powder and solvent of GONAL-f

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’. Follicle-stimulating hormone alfa is a type of ‘follicle-stimulating hormone’ (FSH), which belongs to the family of hormones called ‘gonadotropins’. Gonadotropins are involved 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 cannot ovulate and who have not responded to treatment with a substance called ‘clomiphene citrate’.
• in combination with another substance 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 several 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 substance 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 to 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 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 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 average.

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 in the past or recently, 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 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 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 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.

Use of this Medicine

• GONAL-f is designed to be administered by injection just under the skin (subcutaneously).
• The first injection of GONAL-f should be administered under the supervision of your doctor.
• Your doctor or nurse will teach you how to inject GONAL-f before you can self-administer it.
• If you self-administer GONAL-f, read and follow carefully the instructions at the end of this leaflet, section “How to prepare and use the powder and solvent of GONAL-f”.

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 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 you have very low levels of FSH and LH

• The usual initial dose of GONAL-f is 75 to 150 IU, in combination 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 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 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. This makes your eggs ready for retrieval.

Men

• The usual dose of GONAL-f is 150 IU, in combination with hCG.
• You will use these two medicines 3 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 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).
• 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 (may affect up to 1 in 100 people).
• In rare cases, complications of ovarian hyperstimulation syndrome such as ovarian torsion or blood clotting can occur (may affect up to 1 in 1,000 people).
• In very rare cases (may affect 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, skin redness, blisters, facial swelling with difficulty breathing, can sometimes be severe. 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 immediately consult your doctor, 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. Sometimes 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. Sometimes 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 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 vial after EXP.

The expiry date is the last day of the month stated.

Do not store above 25°C.

Store in the original package to protect 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 should be administered immediately after preparation.

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.

GONAL-f should not be mixed with other medicines in the same injection, except with lutropin alfa. Certain studies have shown that these two medicines can be mixed and injected together without harming either product.

6. Container Contents and Additional Information

Composition of Gonal-f

• The active ingredient is folitropin alfa.
• Each vial contains 5.5 micrograms of folitropin alfa.
• After preparation of the final injectable solution, there are 75 IU (5.5 micrograms) of folitropin alfa in each milliliter of solution.
• The other components are sucrose, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate dihydrate, methionine, and polysorbate 20, as well as concentrated phosphoric acid and sodium hydroxide for pH adjustment.
• The solvent is water for injectable preparations.

Appearance of the Product and Container Contents

• GONAL-f is presented as a powder and solvent used to prepare an injectable solution.
• The powder is a white tablet in a glass vial.
• The solvent is a clear, colorless liquid in a pre-filled syringe containing 1 ml.
• GONAL-f is presented in boxes of 1, 5, or 10 powder vials along with the corresponding number of pre-filled solvent syringes. Only certain package sizes may be marketed.

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/YYYY}.

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

HOW TO PREPARE AND USE THE GONAL-f POWDER AND SOLVENT

• This section explains how to prepare and use the GONAL-f powder and solvent.
• Before starting preparation, read these instructions thoroughly.
• Administer the injection at the same time every day.

1. Wash Your Hands and Find a Clean Place

• It is essential that your hands and the materials you use are as clean as possible.
• A suitable place is a clean table or kitchen surface.

1. Gather and Lay Out Everything You Will Need:

• 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.

The following are not supplied with the container:

• 2 alcohol swabs.
• 1 container for sharp objects.

1. Preparation of the Solution

• Remove the protective caps from the powder vial and the pre-filled syringe.
• Place the preparation needle on the pre-filled syringe, insert it into the powder vial, and slowly inject all the solvent. Gently rotate, without removing the syringe. Do not shake.
• Check that the resulting solution is clear and does not contain particles.
• Hold the vial upside down and gently withdraw the solution with the syringe by pulling the plunger.
• Remove the syringe from the vial and carefully set it down. Do not touch the needle and do not let it touch any surface.

(If you have been prescribed more than one vial of GONAL-f, slowly reinject the solution into another powder vial until the prescribed amount of powder vials is dissolved. If you have been prescribed lutropin alfa in addition to GONAL-f, you can also mix the two medications as an alternative to injecting each product separately. After dissolving the lutropin alfa powder, load the solution into the syringe and reinject it into the vial containing GONAL-f. Once the powder is dissolved, withdraw the solution with the syringe. Check for particles as indicated above and do not use the solution if it is not clear. Up to 3 powder containers can be dissolved in 1 ml of solvent).

1. Preparation of the Syringe for Injection

• Now put on the fine needle.
• Eliminate any air bubbles. If you see any bubbles in the syringe, hold it with the needle facing upwards and tap the syringe until the air collects at the top. Push the plunger until the air bubbles disappear.

1. Injection of the Dose

• Inject the solution immediately: your doctor or nurse will have told you where to administer the injection (e.g., in the abdomen, in the front of the thigh). To minimize skin irritation, select a different site each day for injection.
• Clean the selected skin area with an alcohol swab, using a circular motion.
• Firmly pinch the skin and insert the needle at an angle of 45° to 90°, with a dart-like motion.
• Inject under the skin, slowly pushing the plunger, as instructed. Do not inject directly into a vein. Take all the time you need to inject the entire solution.
• Immediately remove the needle and clean the skin where you performed the injection with an alcohol swab, using a circular motion.

1. After the Injection

Discard all materials: once the injection is complete, immediately and safely discard all needles and empty glass containers, preferably in the container for sharp objects. Any unused portion of the solution should be discarded.