BEMFOLA 75 IU/0.125 ml injectable solution in a pre-filled pen

Introduction

Package Leaflet: Information for the User

Bemfola 75 IU/0.125 ml solution for injection in pre-filled pen

Bemfola 150 IU/0.25 ml solution for injection in pre-filled pen

Bemfola 225 IU/0.375 ml solution for injection in pre-filled pen

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

Bemfola 450 IU/0.75 ml solution for injection in pre-filled pen

Follitropin alpha

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

1. What is Bemfola and what is it used for

What is Bemfola

This medicine contains the active substance follitropin alpha, 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 is Bemfola used for

In adult women,Bemfola is used:

• to help release an egg from the ovary (ovulation) in women who cannot ovulate and have not responded to treatment with a substance called ‘clomifene citrate’
• in combination with another substance called ‘lutropin alpha’ (‘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 become pregnant), such as ‘in vitro fertilization’, ‘gamete intrafallopian transfer’ or ‘zygote intrafallopian transfer’.

In adult men,Bemfola is used:

• in combination 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 you use Bemfola

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 Bemfola

• 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 ovarian, uterine or breast cancer.
• with 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 Bemfola if you have any of these conditions. If you are not sure, ask your doctor before using this medicine.

Warnings and precautions

Consult your doctor or pharmacist before using Bemfola.

Porphyria

Tell your doctor before starting treatment if you or any member of your family 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, arm or leg pain.

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

Ovarian Hyperstimulation Syndrome (OHSS)

If you are a woman, this medicine increases the risk of you developing OHSS. This happens 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).

If you do not ovulate and you follow the recommended dose and dosing schedule, this syndrome is less likely to occur. Treatment with Bemfola rarely causes a severe ovarian hyperstimulation syndrome, unless the medicine used for final follicular maturation (containing human chorionic gonadotropin, hCG) is also administered. If you develop 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 Bemfola, you have a higher risk of becoming pregnant with more than one baby at the same 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 Bemfola at the right 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 a miscarriage than the average woman.

Blood Clotting Problems (Thromboembolic Events)

If you or a family member have had blood clots in the leg or lung, heart attack or stroke in the past or recently, you may have a higher risk of having these problems or of them getting worse with Bemfola 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. Bemfola is usually not effective in these cases.

If your doctor decides to try treatment with Bemfola, 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 of age.

Using Bemfola with Other Medicines

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

• If you use Bemfola with other medicines that help ovulation (such as hCG or clomifene citrate), your follicles’ response may be increased.
• If you use Bemfola 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 Bemfola to produce follicles.

Pregnancy and Breast-feeding

Do not use Bemfola if you are pregnant or breast-feeding.

Driving and Using Machines

Bemfola is not expected to affect your ability to drive or use machines.

Bemfola Contains Sodium

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

3. How to Use Bemfola

Follow the instructions for administration of this medicine exactly as told by your doctor. Ask your doctor or pharmacist if you have any questions.

Using this Medicine

• Bemfola is designed to be administered by injection just under the skin (subcutaneously). Use each pre-filled pen only once and then discard it safely. Do not administer the solution if it contains particles or is not clear.
• 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 Bemfola pre-filled pen so that you can inject the medicine yourself.
• If you are self-administering Bemfola, read and follow the ‘Instructions for Use’ carefully. These instructions can be found at the end of the package leaflet.

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) and milliliters (ml).

Women

If you are not ovulating and have irregular periods or no periods

• Bemfola is usually administered every day.
• If you have irregular periods, start using Bemfola on the first 7 days of your menstrual cycle. If you do not have periods, you can start using the medicine on any day that is convenient for you.
• The usual starting dose of Bemfola is 75 to 150 IU (0.12 to 0.25 ml) each day.
• Your dose of Bemfola 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 achieved, you will be administered a single injection of 250 micrograms of ‘recombinant human chorionic gonadotropin’ (hCG-r, a hCG produced 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 Bemfola. The best time to have intercourse is on the day of the hCG injection and the day after.

If your doctor does not see the desired response after 4 weeks of treatment, that treatment cycle with Bemfola should be stopped. For the next cycle, your doctor will administer a higher starting dose of Bemfola than before.

If an excessive response is obtained, treatment will be stopped 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 in the previous cycle.

If you need to develop several eggs before any assisted reproduction technique

• The usual starting dose of Bemfola is 150 to 225 IU (0.25 to 0.37 ml) each day, from the 2nd or 3rd day 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 point. This usually takes about 10 days, but can vary between 5 and 20 days. Your doctor will check this with blood tests and/or ultrasound scans.
• When the eggs are ready, you will be administered a single injection of 250 micrograms of ‘recombinant human chorionic gonadotropin’ (hCG-r, a hCG produced 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 Bemfola. This makes your eggs ready for collection.

In other cases, your doctor may first stop ovulation using a gonadotropin-releasing hormone (GnRH) agonist or antagonist. In such cases, administration of Bemfola starts about 2 weeks after starting treatment with the GnRH agonist, and both treatments continue until adequate follicular development is achieved. For example, after 2 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 response of the ovaries.

Men

• The usual dose of Bemfola is 150 IU (0.25 ml) in combination 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 Bemfola than you should

The effects of using too much Bemfola are not known. However, it can be expected that ovarian hyperstimulation syndrome 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 Bemfola

If you forget to use Bemfola, do not use a double dose to make up for forgotten doses. Consult your doctor as soon as you realize you have forgotten to administer 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 may cause adverse effects, although not all people may experience them.

Severe Adverse Effects in Women

• Pelvic pain, accompanied by nausea or vomiting, can be symptoms of ovarian hyperstimulation syndrome (OHSS). This may indicate that the ovaries have overreacted to treatment and large ovarian cysts have developed (see also section 2 "Ovarian Hyperstimulation Syndrome (OHSS)"). This adverse effect is frequent (may affect up to 1 in 10 people).
• Ovarian hyperstimulation syndrome can worsen with clearly enlarged ovaries, decreased urine production, weight gain, difficulty breathing, and/or possible fluid accumulation 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 such as ovarian torsion or blood clotting may also occur (may affect up to 1 in 1,000 people).
• In very rare cases, severe complications of blood clotting (thromboembolic episodes) 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 "Blood Clotting Problems (Thromboembolic Episodes)").

Severe Adverse Effects in Men and Women

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

If you notice any of the above adverse effects, you should consult your doctor immediately, who may ask you to interrupt treatment with Bemfola.

Other Adverse Effects in Women

Very common (may affect more than 1 in 10 people):

• Fluid-filled bags 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, swelling of the face with difficulty breathing, can occur. Sometimes, these reactions can 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).
• Development of breast tissue, acne, or weight gain.

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

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

Reporting Adverse Effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse 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 expiration date stated on the label or carton after EXP. The expiration date is the last day of the month indicated.

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

During its validity period, the unopened medicine can be stored at a temperature of 25°C or below for a maximum of 3 months without refrigeration and must be discarded if not used within 3 months.

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

Once opened, the medicine should be injected immediately.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Bemfola Composition

• The active ingredient is folitropin alfa.

• Bemfola 75 IU/0.125 ml: each cartridge contains 75 IU (equivalent to 5.5 micrograms) of folitropin alfa in 0.125 ml of solution.
• Bemfola 150 IU/0.25 ml: each cartridge contains 150 IU (equivalent to 11 micrograms) of folitropin alfa in 0.25 ml of solution.
• Bemfola 225 IU/0.375 ml: each cartridge contains 225 IU (equivalent to 16.5 micrograms) of folitropin alfa in 0.375 ml of solution.
• Bemfola 300 IU/0.50 ml: each cartridge contains 300 IU (equivalent to 22 micrograms) of folitropin alfa in 0.50 ml of solution.
• Bemfola 450 IU/0.75 ml: each cartridge contains 450 IU (equivalent to 33 micrograms) of folitropin alfa in 0.75 ml of solution.
• Each ml of the solution contains 600 IU (equivalent to 44 micrograms) of folitropin alfa.
• The other ingredients are poloxamer 188, sucrose, methionine, disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, phosphoric acid, and water for injections.

Bemfola Appearance and Package Contents

• Bemfola is presented as a clear and colorless injectable liquid in a pre-filled pen.
• Bemfola is supplied in packs of 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 Authorization Holder and Manufacturer

Gedeon Richter Plc.

Gyömroi út 19-21.

1103 Budapest

Hungary

Date of Last 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 Starting to Use the Pre-filled Pen
3. Preparing the Pre-filled Pen for Injection
4. Adjusting the Prescribed Dose
5. Injecting the Dose
6. After the Injection

1. How to Use the Bemfola Pre-filled Pen

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

1. Before Starting to Use the Pre-filled Pen

1. Remove the Pen from the Refrigerator
   • Remove the pen from the refrigerator 5 to 10 minutes before using it.
   • If the medicine is frozen, do not use it.

1. Wash Your Hands
   • Wash your hands with warm water and soap, then dry them.
   • It is important that your hands and the objects you use to prepare the pen are as clean as possible.

1. Find a Clean Place
   • A suitable place is a clean table or surface.

1. Preparing the Pre-filled Pen for Injection

The Different Parts of Your Pre-filled Pen

1. Adjusting the Prescribed Dose

1. Injecting the Dose

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

1. After the Injection