Product Information for the User

Bemfola 75 IU/0.125 ml pre-filled syringe

Bemfola 150 IU/0.25 ml pre-filled syringe

Bemfola 225 IU/0.375 ml pre-filled syringe

Bemfola 300 IU/0.50 ml pre-filled syringe

Bemfola 450 IU/0.75 ml pre-filled syringe

Folitropina alfa

Read this entire 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 must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

What is Bemfola

This medication contains the active ingredient 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 the production of sperm.

What is Bemfola used for

In adult women,Bemfola is used:

"intratubal embryo transfer".

In adult men,Bemfola is used:

• along with another medication called "human chorionic gonadotropin" (hCG), to help produce sperm in men who are infertile due to low concentrations of certain hormones.

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

Do not use Bemfola

• with large 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 premature ovarian insufficiency (early menopause) or a malformation of the reproductive organs.
• • if you area man:

• with damaged testicles that cannot be cured.

Do not use Bemfola if you have any of these conditions. If you are unsure, ask your doctor before using this medication.

Warnings and precautions

Consult your doctor or pharmacist before using Bemfola.

Porphyria

Inform your doctor before starting treatment if you or any family member suffers from porphyria (a disorder that cannot break down porphyrins that can be passed from parents to children).

Inform your doctor immediately if:

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

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

Hyperstimulation syndrome (HSS)

If you are a woman, this medication increases the risk of developing HSS. 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 stop treatment (see section 4).

In the case of not ovulating and respecting the recommended dose and treatment schedule, this syndrome is less likely to occur. Bemfola treatment rarely causes severe HSS, unless the medication used for final follicular maturation (containing human chorionic gonadotropin, hCG) is administered. If you develop HSS, your doctor may not prescribe hCG for this treatment cycle and advise you to abstain from intercourse or 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 child at a time («multiple pregnancy», usually twins), than if you 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 Bemfola 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, you are more likely to have an abortion than the average woman.

Blood clotting disorders (thromboembolic episodes)

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

Males with high FSH levels in the blood

If you are a man, high FSH levels in the blood may be a sign of testicular damage. Bemfola is usually not effective in these cases.

If your doctor decides to try Bemfola treatment to control treatment, your doctor may ask you to have a semen analysis, 4 to 6 months after starting treatment.

Children and adolescents

Bemfola is not indicated in children and adolescents under 18 years old.

Use of Bemfola and other medications

Inform your doctor if you are taking, have taken recently, or may need to take other medications.

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

Pregnancy and breastfeeding

Do not use Bemfola if you are pregnant or breastfeeding.

Driving and operating machinery

This medication is not expected to affect your ability to drive and operate machinery.

Bemfola contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per dose, making it essentially «sodium-free».

Follow exactly the administration instructions of this medication as indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

Use of this medication

• Bemfola is designed to be administered by injection just below the skin (subcutaneously). Use each preloaded pen only once and then dispose of it safely. Do not administer the solution if it contains particles or is not transparent.
• The first injection of Bemfola should be administered under the supervision of your doctor.
• Your doctor or nurse will teach you how to use the preloaded pen of Bemfola so that you can inject the medication yourself.
• If you self-administer Bemfola, read and follow the «Instructions for use» carefully. These instructions can be consulted at the end of the prospectus.

What quantity should be used

Your doctor will decide what amount of medication to administer and how often. The doses described below are expressed in International Units (UI) and milliliters (ml).

Women

If you are not ovulating and have irregular or no menstruation

• Bemfola is usually administered every day.
• If you have irregular menstruation, start using Bemfola on the first 7 days of your menstrual cycle. If you do not have menstruation, you can start using the medication on any day that is convenient for you.
• The usual initial dose of Bemfola is 75 to 150 UI (0.12 to 0.25 ml) per day.
• Your Bemfola dose may be increased every 7 or 14 days by 37.5 to 75 UI, until the desired response is obtained.
• The maximum daily dose of Bemfola is usually not more than 225 UI (0.375 ml).
• When the desired response is obtained, a single injection of

250 micrograms of «recombinant hCG» (hCG-r, a hCG manufactured in a laboratory using a special DNA technique), or 5,000 to 10,000 UI of hCG, 24 to 48 hours after the last injection of Bemfola. The best time for sexual intercourse is the same day as the hCG injection and the next day.

If your doctor does not observe the desired response after 4 weeks of treatment, that treatment cycle with Bemfola should be interrupted. For the next cycle, your doctor will administer a higher initial dose of Bemfola than the previous one.

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 Bemfola than the previous one.

If you have been diagnosed with an FSH and LH hormone deficiency

• The usual initial dose of Bemfola is 75 to 150 UI (0.12 to 0.25 ml), along with 75 UI (0.12 ml) of lutropin alfa.
• You will use these two medications every day, for a period of up to five weeks.
• Your Bemfola dose may be increased every 7 or 14 days by 37.5 to 75 UI, until the desired response is obtained.
• When the desired response is obtained, a single injection of

250 micrograms of «recombinant hCG» (hCG-r, a hCG manufactured in a laboratory using a special DNA technique), or 5,000 to 10,000 UI of hCG, 24 to 48 hours after the last injection of Bemfola and lutropin alfa. The best time for sexual intercourse is the same day as the hCG injection and the next day. You may also undergo intrauterine insemination or other assisted reproduction techniques as recommended by your doctor.

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

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 Bemfola than the previous one.

If you need to develop multiple eggs for extraction prior to any assisted reproduction technique

• The usual initial dose of Bemfola is 150 to 225 UI (0.25 to 0.37 ml) per day, starting from the 2nd or 3rd day of your treatment cycle.
• Your Bemfola dose may be increased, depending on your response. The maximum daily dose is 450 UI (0.75 ml).
• Treatment continues until the eggs have developed to the desired point. This usually takes around 10 days, but can vary between 5 and 20 days. Your doctor will check this through blood tests and/or ultrasound scans.
• Cuando los óvulos estén listos, se le administrará una inyección única de

250 micrograms of «recombinant hCG» (hCG-r, a hCG manufactured in a laboratory using a special DNA technique), or 5,000 to 10,000 UI of hCG, 24 to 48 hours after the last injection of Bemfola. This makes your eggs ready for extraction.

In other cases, your doctor may first interrupt ovulation using a GnRH agonist or antagonist. In such cases, Bemfola administration is initiated approximately 2 weeks after starting treatment with the agonist, continuing both treatments until an adequate follicular development is achieved. For example, after 2 weeks of treatment with the GnRH agonist, 150 to 225 UI of Bemfola are administered for 7 days. The dose is then adjusted according to the response of the ovaries

Men

If you use more Bemfola than you should

The effects of using an excessive amount of Bemfola are unknown. However, it is expected that an ovarian hyperstimulation syndrome will 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 Bemfola

If you forget to use Bemfola, do not use a double dose to compensate for the missed doses. Consult your doctor as soon as you realize that you have forgotten to administer a dose.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe 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 reacted excessively to treatment and have developed large ovarian cysts (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, decreased urine production, weight gain, difficulty breathing, and/or possible accumulation of fluid in the abdomen or chest. This side effect is rare (may affect up to 1 in 100 people).
• In rare cases, complications of ovarian hyperstimulation syndrome such as ovarian torsion or blood clotting may also occur (may affect up to 1 in 1,000 people).
• In very rare cases, severe blood clotting complications (thromboembolic episodes) may occur, sometimes independent of ovarian hyperstimulation syndrome (may affect up to 1 in 10,000 people). This could cause chest pain, feeling of lack of air, stroke, or myocardial infarction (see also section 2 “Blood clotting problems (thromboembolic episodes)”).

Severe side effects in men and women

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

If you observe any of the mentioned side effects, you should consult your doctor immediately, who may ask you to stop treatment with Bemfola.

Other severe 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, hematoma, 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. In some cases, 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, hematoma, swelling, and/or irritation.

Common (may affect up to 1 in 10 people):

• Varicocele (swelling of the veins above and below the testicles).
• Development of breasts, 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. In some cases, these reactions may be severe.
• Asthma may worsen

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label or the box after CAD. The expiration date is the last day of the month indicated.

Store in the refrigerator (between 2 °C and 8 °C). Do not freeze. Store in the original packaging to protect it from light.

During its validity period, the unopened medication can be stored at a temperature equal to or less than 25 °C for a maximum of 3 months without refrigeration and should be discarded if not used within 3 months.

Do not use this medication if you observe any visible sign of deterioration, if the liquid contains particles, or if it is not transparent.

Once opened, the medication will be administered immediately.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you do not need. In this way, you will help protect the environment.

Composition of Bemfola

• The active principle is recombinant human follicle-stimulating hormone (r-hFSH) alfa.

• Bemfola 75 UI/0.125 ml: each cartridge contains 75 UI (equivalent to 5.5 micrograms) of recombinant human follicle-stimulating hormone (r-hFSH) alfa in 0.125 ml of solution.
• Bemfola 150 UI/0.25 ml: each cartridge contains 150 UI (equivalent to 11 micrograms) of recombinant human follicle-stimulating hormone (r-hFSH) alfa in 0.25 ml of solution.
• Bemfola 225 UI/0.375 ml: each cartridge contains 225 UI (equivalent to 16.5 micrograms) of recombinant human follicle-stimulating hormone (r-hFSH) alfa in 0.375 ml of solution.
• Bemfola 300 UI/0.50 ml: each cartridge contains 300 UI (equivalent to 22 micrograms) of recombinant human follicle-stimulating hormone (r-hFSH) alfa in 0.50 ml of solution.
• Bemfola 450 UI/0.75 ml: each cartridge contains 450 UI (equivalent to 33 micrograms) of recombinant human follicle-stimulating hormone (r-hFSH) alfa in 0.75 ml of solution.
• Each ml of the solution contains 600 UI (equivalent to 44 micrograms) of recombinant human follicle-stimulating hormone (r-hFSH) alfa.
• The other components are poloxamer 188, sucrose, methionine, disodium dihydrogen phosphate, disodium dihydrogen phosphate, phosphoric acid, and water for injections.

Appearance of Bemfola and contents of the package

• Bemfola is presented as a clear, colorless injectable solution in a pre-filled syringe.
• Bemfola is supplied in packages of 1, 5, or 10 pre-filled syringes, 1, 5, or 10 disposable needles, and 1, 5, or 10 alcohol-soaked swabs. Only some package sizes may be commercially available.

Marketing authorization holder and manufacturer

Gedeon Richter Plc.

Gyömroi út 19-21.

1103 Budapest

Hungary

Last update of this leaflet

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

Bemfola 75 UI/0.125 ml pre-filled syringe

Bemfola 150 UI/0.25 ml pre-filled syringe

Bemfola 225 UI/0.375 ml pre-filled syringe

Bemfola 300 UI/0.50 ml pre-filled syringe

Bemfola 450 UI/0.75 ml pre-filled syringe

Instructions for Use

CONTENTS

1. How to use the pre-filled syringe of Bemfola
2. Before starting to use the pre-filled syringe
3. Preparing the pre-filled syringe for injection
4. Adjusting the dose prescribed by your doctor
5. Injecting the dose
6. After the injection

1. How to use the pre-filled syringe of Bemfola

1. Before starting to use the pre-filled syringe

1. Preparing the pre-filled syringe for injection

The different parts of your pre-filled syringe

1. Adjusting 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 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 injection site each day.

1. After the injection