Bemfola 150 IU/0.25 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 pre-filled pen

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

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

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

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

Follitropin alfa

Read the entire leaflet carefully before you start using this medicine, as 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 others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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 ovarian sacs (follicles) that contain 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 "clomiphene citrate"
• together with another substance called "lutropin alfa" ("luteinizing hormone" or LH), to help release an egg from the ovary (ovulation) in women whose bodies produce very low amounts of gonadotropins (FSH and LH)
• to help develop several 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 management of fertility disorders.

Do not use Bemfola

• 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 of the hypothalamus or pituitary gland (both 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 member of your family 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 recommend that you 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 treatment may need to be discontinued (see section 4).

If you do not ovulate and the recommended dose and dosing schedule are followed, the occurrence of this syndrome is less likely. Treatment with Bemfola rarely causes severe OHSS unless the medication used for final follicular maturation (containing human chorionic gonadotropin, hCG) is administered. If OHSS develops, your doctor may decide not to prescribe hCG in this treatment cycle and may 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 chance of becoming pregnant with more than one baby at a time ("multiple pregnancy," usually twins) than with 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 problems (thromboembolic events)

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 an increased risk of developing these conditions or of their worsening during treatment with Bemfola.

Men with high FSH levels in the blood

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

If your doctor decides to attempt treatment with Bemfola, they 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.

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 medicines that promote ovulation (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 (medicines that reduce sex hormone levels 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 use of 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 under 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 self-inject the medicine.
• 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 absent menstruation

• Bemfola is usually administered daily.
• If you have irregular menstruation, start using Bemfola within the first 7 days of your 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) daily.
• 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, 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 Bemfola injection. 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, this 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 receive 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, 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, as determined by your doctor.

If your doctor does not observe the desired response after five weeks, this 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 receive 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 multiple 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, 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 Bemfola injection. 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 is 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 medicines for at least 18 months.

If you use more Bemfola than you should

The effects of taking an excessive amount of Bemfola are unknown. However, ovarian hyperstimulation syndrome, described in section 4, may be expected. This syndrome will only occur, however, 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 doses. 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 adverse effects

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

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

Serious adverse 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 adverse effect is very rare (may affect up to 1 in 10,000 people).

If you experience any of the above-mentioned adverse effects, you must consult your doctor immediately, who may instruct you to discontinue treatment with Bemfola.

Other adverse 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, diarrhoea, 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 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).
• 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 adverse effects

If you experience any type of adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed 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 expiry date stated on the label or carton following 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 validity period, the unopened medicine may be stored unrefrigerated at a temperature not exceeding 25 °C for up to 3 months; if not used within this 3-month period, it must be discarded.

Do not use this medicine if you notice any visible signs of deterioration, if the solution 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 UI/0.125 ml: each cartridge contains 75 IU (equivalent to 5.5 micrograms) of follitropin alfa in 0.125 ml of solution.

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

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

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

• Bemfola 450 UI/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 about this medicine is available on the website of the European Medicines Agency: 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 those provided in these Instructions for Use or by 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, carefully read 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 medicine 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 the items you use 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

	Inject the medication at approximately the same time each day. Remove the pen from the refrigerator 5 to 10 minutes before use. Note: check that the medication is not frozen.
	Prepare the needle for injection. Take a new needle: use only the single-use needles provided in the medication package. Check that the seal on the outer needle cap is intact and not damaged or detached. Firmly hold the outer needle cap and remove the seal by pulling the tab. Caution: If the seal is damaged or detached, do not use the needle. Dispose of it in a sharps container. Use a new needle.
	Attach the needle. Hold the pen on both sides, aligning the needle, and press it firmly onto the end of the pen. Make sure the needle is straight and securely attached to the pen. Caution: Although there is a thread at the end of the pen, never attempt to screw the needle onto the pen, as this may cause incorrect assembly. Do not press the dosage button while attaching the needle.

	Remove the outer needle cap (G). Keep it, as you will need it later to dispose of the pen. Remove the inner needle cap (F). Make sure the needle is properly attached.

1. Adjustment of the dose prescribed by your doctor

	First, hold the pen with the needle pointing upward. To remove air bubbles, gently tap the side of the pen so that any air bubbles rise to the top.
	While keeping the pen in an upright position, press the dose adjustment button until the activation bar with the small arrow disappears. You should hear a click and a small amount of liquid may be expelled (this is normal). The pen is now ready for dose setting. Caution:If no liquid is expelled, or if leakage is observed at the point where the needle attaches to the pen, do not use the pen. Contact your doctor or pharmacist if you notice any problems.
	Gently rotate the dose adjustment button until the prescribed dose aligns with the center of the pen's slot. Note:For the pre-filled Bemfola 75 IU/0.125 ml pen, the dose adjustment button cannot be fully rotated, but it can be rotated backward. The pen is now ready for injection. Caution:Do not press the dose adjustment button further at this time.

1. Injection of the dose

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

	Clean the injection site with the alcohol wipe provided in the package, using a circular motion. Wait a few seconds until the alcohol has evaporated and the skin is dry before administering the injection.
	Double-check that the correct dose is displayed on the pen. Gently pinch the skin at the injection site. Hold the pen at approximately a right angle (90º angle) and insert the needle completely into the skin with a steady motion. Caution:Do not press the dose button while inserting the needle or change the direction of the needle.

Once the needle is fully inserted into the injection site, press the dose button slowly and continuously until it stops and the dose indicator bar has completely disappeared. Do not remove the needle immediately; wait at least 5 seconds before withdrawing it to ensure the full dose has been delivered. After removing the needle: clean the skin with an alcohol wipe, using a circular motion at the injection site. Caution: If leakage of liquid is observed at the junction between the needle and the pen during injection, inform your doctor or pharmacist.

1. After injection

Carefully replace the outer needle cap.

You may only use the pre-filled injection pen once and must discard it even if some liquid remains in the pen after the injection. Dispose of the packaging, inner needle cap, removable seal, alcohol swab, and instructions for use in household waste. Do not dispose of any medication via sinks, toilets, or household waste. The used pen must be discarded in a sharps container and returned to the pharmacy for proper disposal. Ask your pharmacist how to dispose of medications you no longer need.