Bemfola 300 IU/0.50 ml solution for injection in pre-filled pen

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Bemfola 75 IU/0.125 ml solution for injection in a prefilled pen

Bemfola 150 IU/0.25 ml solution for injection in a prefilled pen

Bemfola 225 IU/0.375 ml solution for injection in a prefilled pen

Bemfola 300 IU/0.50 ml solution for injection in a prefilled pen

Bemfola 450 IU/0.75 ml solution for injection in a prefilled pen

Follitropin alfa

Read all of this leaflet carefully before you start using this medicine, because 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Bemfola is and what it is used for

What Bemfola is

This medicinal product contains the active substance follitropin alfa, which is almost identical to a natural hormone produced by your body called "follicle-stimulating hormone" (FSH). FSH is a gonadotropin, a type of hormone that plays an important role in human reproduction and fertility. In women, FSH is necessary for the growth and development of the sacs (follicles) in the ovaries that contain the eggs. In men, FSH is necessary for sperm production.

What Bemfola is used for

In adult women, Bemfola 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 "clomifene citrate"
• together 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 low levels of gonadotropins (FSH and LH)
• to help develop multiple 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, Bemfola is used:

• together 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 using Bemfola

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 Bemfola

• 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.

• with 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 Bemfola if you have any of these conditions. If you are unsure, consult your doctor before using this medicine.

Warnings and precautions

Talk to your doctor or pharmacist before using Bemfola.

Porphyria

Inform your doctor before starting treatment if you or any family member has porphyria (a disorder affecting the breakdown of porphyrins, which may 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 advise you to discontinue treatment.

Ovarian hyperstimulation syndrome (OHSS)

If you are a woman, this medicine increases the 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 regimen are followed, this syndrome is less likely to occur. Treatment with Bemfola 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 refrain from prescribing hCG in this treatment cycle and advise you to abstain from sexual intercourse or to use barrier contraceptive methods for at least 4 days.

Multiple pregnancy

If you use Bemfola, you have a higher risk of becoming pregnant with more than one baby at a time ("multiple pregnancy," usually twins) compared to natural conception. Multiple pregnancy may cause medical complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of Bemfola at the correct times. If you undergo

assisted reproductive techniques, the risk of multiple pregnancy depends on your age and on the quality and number of fertilized eggs or embryos transferred into your uterus.

Miscarriage

If you undergo assisted reproductive techniques or ovarian stimulation to produce eggs, you have a higher risk of miscarriage than the average woman.

Blood clotting disorders (thromboembolic events)

If you or any family member has had, in the past or recently, blood clots in the leg or lung, heart attack, or stroke, you may have an increased risk of developing these problems or of them worsening during treatment with Bemfola.

Men with high levels of FSH in the blood

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

If your doctor decides to attempt treatment with Bemfola, they may request a semen analysis 4 to 6 months after starting treatment.

Children and adolescents

Bemfola is not indicated for use in children and adolescents under 18 years of age.

Use of Bemfola with other medicines

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

• If you use Bemfola together with other ovulation-inducing medicines (e.g., hCG or clomiphene citrate), the response of your follicles may be enhanced.
• If you use Bemfola simultaneously with a gonadotropin-releasing hormone (GnRH) agonist or antagonist (these medicines reduce sex hormone concentrations and suppress ovulation), you may require a higher dose of Bemfola to produce follicles.

Pregnancy and breastfeeding

Do not use Bemfola if you are pregnant or during the breastfeeding period.

Driving and using machines

This medicine is not expected to affect your ability to drive or operate machinery.

Bemfola contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose, and is therefore considered essentially "sodium-free."

3. How to use Bemfola

Follow exactly the administration instructions for this medicine given by your doctor. Consult your doctor or pharmacist if you have any doubts.

Use of this medicine

• Bemfola is designed to be administered by injection just beneath the skin (subcutaneously). Use each pre-filled pen once only and then dispose of it safely. Do not administer the solution if it contains particles or is not clear.
• The first injection of Bemfola should be given under the supervision of your doctor.
• Your doctor or nurse will teach you how to use the Bemfola pre-filled pen so that you can inject the medicine yourself.
• If you self-administer Bemfola, read and carefully follow the “Instructions for use”. These instructions can be found at the end of the leaflet.

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) and millilitres (ml).

Women

If you are not ovulating and have irregular or no menstruation

• Bemfola is usually administered daily.
• If you have irregular menstruation, start using Bemfola 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 usual initial dose of Bemfola is 75 to 150 IU (0.12 to 0.25 ml) each day.
• Your Bemfola dose may be increased every 7 or 14 days by 37.5 to 75 IU until the desired response is achieved.
• The maximum daily dose of Bemfola is usually not more than 225 IU (0.375 ml).
• When the desired response is obtained, you will be given a single injection of

250 micrograms of “recombinant hCG” (hCG-r, a 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 Bemfola. 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 Bemfola should be discontinued. For the next cycle, your doctor will administer a higher initial dose of Bemfola 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 Bemfola than in the previous cycle.

If you have been diagnosed with FSH and LH hormone deficiency

• The usual initial dose of Bemfola is 75 to 150 IU (0.12 to 0.25 ml), together with 75 IU (0.12 ml) of lutropin alfa.
• You will use these two medicines daily for up to five weeks.
• The dose of Bemfola 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 obtained, you will be given a single injection of

250 micrograms of “recombinant hCG” (hCG-r, a 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 Bemfola and lutropin alfa. The best time for sexual intercourse is on the day of the hCG injection and the following day. Intrauterine insemination or another assisted reproductive technique may also be performed, according to your doctor’s recommendation.

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

If you need to develop several eggs for retrieval prior to any assisted reproductive technique

• The usual initial dose of Bemfola is 150 to 225 IU (0.25 to 0.37 ml) daily, starting on day 2 or 3 of your treatment cycle.
• The dose of Bemfola may be increased depending on your response. The maximum daily dose is 450 IU (0.75 ml).
• Treatment continues until the eggs have developed to the desired stage. This usually takes about 10 days, but may vary between 5 and 20 days. Your doctor will monitor this with blood tests and/or ultrasounds.
• When the eggs are ready, you will be given a single injection of 250 micrograms of “recombinant hCG” (hCG-r, a 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 Bemfola. This causes your eggs to mature and become ready for retrieval.

In other cases, your doctor may first suppress ovulation using a gonadotropin-releasing hormone (GnRH) agonist or antagonist. In such cases, Bemfola administration is started approximately 2 weeks after initiating treatment with the agonist, with both treatments continuing until adequate follicular development is achieved. For example, after two weeks of treatment with the GnRH agonist, 150 to 225 IU of Bemfola are administered for 7 days. The dose is then adjusted according to the ovarian response.

Men

• The usual dose of Bemfola is 150 IU (0.25 ml) 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 advise you to continue using these two medicines for at least 18 months.

If you use more Bemfola than you should

The effects of using an excessive amount of Bemfola are unknown. However, ovarian hyperstimulation syndrome, described in section 4, may be expected. This syndrome will occur only if hCG is also administered (see section 2, “Ovarian hyperstimulation syndrome (OHSS)”).

If you forget to use Bemfola

If you forget to use Bemfola, do not use 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 further 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 everyone will experience them.

Serious side 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 also section 2 “Ovarian hyperstimulation syndrome (OHSS)”). This side 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 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 (thromboembolism) may occur (may affect up to 1 in 1,000 people).
• In very rare cases, serious blood clotting complications (thromboembolic events) may occur, sometimes independent of ovarian hyperstimulation syndrome (may affect up to 1 in 10,000 people). This could cause chest pain, shortness of breath, stroke, or myocardial infarction (see also section 2 “Problems with blood clotting (thromboembolic events)”).

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, may 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-mentioned side effects, you must consult your doctor immediately, who may advise you to stop treatment with Bemfola.

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, 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 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 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 side effects

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

5. Storage of Bemfola

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

Do not use this medicine after the expiry date stated on the label or carton after EXP. 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. Keep in the original packaging to protect from light.

During its shelf life, the unopened medicine may be stored unrefrigerated at a temperature not exceeding 25 °C for up to 3 months; if not used within 3 months, it must be discarded.

Do not use this medicine if you notice any visible signs of deterioration, if the liquid contains particles, or if it is not clear.

Once opened, the medicine should be administered immediately.

Medicines must 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 Bemfola

• The active substance is follitropin alfa.

• Bemfola 75 IU/0.125 ml: each cartridge contains 75 IU (equivalent to 5.5 micrograms) of follitropin alfa in 0.125 ml of solution.

• Bemfola 150 IU/0.25 ml: each cartridge contains 150 IU (equivalent to 11 micrograms) of follitropin alfa in 0.25 ml of solution.

• Bemfola 225 IU/0.375 ml: each cartridge contains 225 IU (equivalent to 16.5 micrograms) of follitropin alfa in 0.375 ml of solution.

• Bemfola 300 IU/0.50 ml: each cartridge contains 300 IU (equivalent to 22 micrograms) of follitropin alfa in 0.50 ml of solution.

• Bemfola 450 IU/0.75 ml: each cartridge contains 450 IU (equivalent to 33 micrograms) of follitropin alfa in 0.75 ml of solution.

• Each ml of solution contains 600 IU (equivalent to 44 micrograms) of follitropin alfa.

• The other components are poloxamer 188, sucrose, methionine, disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, phosphoric acid, and water for injections.

Appearance of Bemfola and contents of the pack

• Bemfola is a clear, colourless injectable liquid supplied in a pre-filled pen.
• Bemfola is available in packs containing 1, 5 or 10 pre-filled pens, 1, 5 or 10 disposable needles and 1, 5 or 10 alcohol swabs. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Gedeon Richter Plc.

Gyömroi út 19-21.

1103 Budapest

Hungary

Date of the most recent revision of this leaflet

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

Bemfola 75 IU/0.125 ml pre-filled pen

Bemfola 150 IU/0.25 ml pre-filled pen

Bemfola 225 IU/0.375 ml pre-filled pen

Bemfola 300 IU/0.50 ml pre-filled pen

Bemfola 450 IU/0.75 ml pre-filled pen

Instructions for Use

CONTENTS

1. How to use the Bemfola pre-filled pen
2. Before you start using the pre-filled pen
3. Preparing the pre-filled pen for injection
4. Setting the dose prescribed by your doctor
5. Injecting the dose
6. After the injection

Warning: Read and follow these Instructions for Use of the Bemfola pre-filled pen. Do not follow instructions from sources other than these Instructions for Use or a healthcare professional, as this may compromise the proper use of the pre-filled pen and your treatment.

1. How to use the Bemfola pre-filled pen

• Before starting to use your pre-filled pens, read carefully the complete Instructions for Use and the package leaflet.
• Each pre-filled pen is for individual use only; do not allow anyone else to use it.
• The numbers shown on the dose indicator of the pre-filled pens are measured in International Units or IU. Your doctor will have instructed you how many IU to inject each day.
• Your doctor/pharmacist will tell you how many single-use Bemfola pre-filled pens you need to use for your complete treatment cycle.
• Administer your injection at approximately the same time each day.

1. Before starting to use the pre-filled pen

2. Remove the pen from the refrigerator

   • Remove the pen from the refrigerator 5 to 10 minutes before use.
   • Do not use the medication if it has been frozen.

3. Wash your hands

   • Wash your hands with warm water and soap, then dry them thoroughly.
   • It is important that your hands and any items used to prepare the pen are as clean as possible.

4. Choose a clean place

   • A suitable place is a clean table or surface.

5. Preparing the pre-filled pen for injection

The different parts of your pre-filled pen

1. Set the dose prescribed by your doctor

1. Injecting the dose

You are now ready to administer the injection immediately: your doctor or nurse will have instructed you where to inject (e.g., in the abdomen, or in the front of the thigh). To minimize skin irritation, select a different injection site each day.

1. After the injection