Bemfola

Patient Information Leaflet: Information for the User

Bemfola 75 UI/0.125 ml solution for injection in pre-filled pen, 150 UI/0.25 ml solution for injection in pre-filled pen, 225 UI/0.375 ml solution for injection in pre-filled pen, 300 UI/0.50 ml solution for injection in pre-filled pen, 450 UI/0.75 ml solution for injection in pre-filled pen

follitropin alfa
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this 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
Bemfola contains an active substance called "follitropin alfa". Follitropin alfa is a "follicle-stimulating hormone" (FSH), belonging to a family of hormones known as "gonadotropins". Gonadotropins are involved in reproduction and fertility.

What Bemfola is used for

In adult women, Bemfola is used:

• to stimulate the release of an egg from the ovary (ovulation) in women who do not ovulate and who have not responded to treatment with a medicine called "clomiphene citrate";
• in combination with another medicine called "lutropin alfa" ("luteinizing hormone" or LH), to stimulate the release of an egg from the ovary (ovulation) in women whose bodies produce very low levels of gonadotropins (FSH and LH);
• to promote the development of multiple follicles (each containing an egg) in women undergoing assisted reproductive procedures (procedures that can help achieve pregnancy), 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 stimulate sperm production in infertile men due to low levels of certain hormones.

2. What you should know before using Bemfola

Before starting treatment, a doctor experienced in the treatment of fertility disorders should thoroughly evaluate your couple's fertility.
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 ovary (ovarian cysts) of unknown origin
  • with vaginal bleeding of unknown origin
  • with ovarian, uterine, or breast cancer
  • with a condition that usually makes normal pregnancy impossible, such as ovarian failure (premature menopause) or malformations of the reproductive system;
• if you are a man
  • with irreversible testicular damage.

Do not use Bemfola if you have any of these conditions. If you have any doubts, 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 a family member has porphyria (an inability to break down porphyrins, which can be inherited from parents to children).
Immediately inform your doctor if:

• your skin becomes fragile and easily develops blisters, especially in areas frequently exposed to sunlight, 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 OHSS. In this condition, ovarian follicles develop excessively and turn into large cysts. Immediately inform your doctor if you experience lower abdominal pain, rapid weight gain, nausea or vomiting, or difficulty breathing; your doctor may ask you to stop taking the medicine (see section 4).
If you are an anovulatory patient and follow the recommended dosage and administration schedule correctly, the risk of OHSS is less likely. Treatment with Bemfola rarely causes severe OHSS if a medicine (containing human chorionic gonadotropin – hCG) is not administered to induce ovulation. If you are developing OHSS, your doctor may decide not to administer hCG in this treatment cycle and may recommend that you avoid sexual intercourse or use a barrier contraceptive for at least four days.
Multiple pregnancy
When using Bemfola, you have a higher chance of multiple pregnancy—most commonly twins—compared to natural conception. Multiple pregnancy may lead to complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of Bemfola at the correct time. In assisted reproductive procedures, the risk of multiple pregnancy is related to age, quality, and number of fertilized eggs or embryos transferred.
Miscarriage
If you undergo assisted reproductive procedures or ovarian stimulation to produce eggs, you have a higher chance of miscarriage compared to other women.
Blood clotting disorders (thromboembolic events)
If you have had, or have recently had, blood clots in your legs or lungs, a heart attack, or a stroke, or if such events have occurred in your family, your risk of these problems occurring or worsening during treatment with Bemfola may increase.
Men with excessively high FSH levels in the blood
If you are a man, excessively high FSH levels in the blood may indicate testicular damage. In such cases, Bemfola is generally ineffective. If your doctor decides to try treatment with Bemfola, 4–6 months after starting treatment, you may be asked to provide sperm samples for follow-up testing.
Children and adolescents
The use of Bemfola is not indicated in children and adolescents under 18 years of age.
Other medicines and Bemfola
Inform your doctor if you are taking, have recently taken, or might take any other medicines.

• If you use Bemfola together with other medicines that promote ovulation (such as hCG or clomiphene citrate), this may enhance the follicular response.
• If you use Bemfola simultaneously with a gonadotropin-releasing hormone (GnRH) agonist or antagonist (these medicines reduce sex hormone levels and block ovulation), you may require a higher dose of Bemfola to produce follicles.

Pregnancy and breastfeeding
Do not use Bemfola during pregnancy or breastfeeding.
Driving and using machines
This medicine is not expected to affect your ability to drive or use machinery.
Bemfola contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.

3. How to use Bemfola

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
How to use the medicine

• Bemfola is administered by subcutaneous injection (just under the skin). Each pre-filled pen should be used only once and then safely disposed of. Do not administer the solution if it contains particles or is not clear.
• The first injection of Bemfola must be given under medical supervision.
• Your doctor or nurse will show you how to use the pre-filled Bemfola pen to self-inject the medicine.
• If you are self-administering Bemfola, carefully read and follow the “Instructions for Use” located at the end of this leaflet.

What dose to use
Your doctor will determine how much medicine you should take and how often. The doses listed below are expressed in International Units (IU) and millilitres (mL).
Women
If you do not ovulate and have irregular or absent menstrual cycles

• Bemfola is generally administered daily.
• If you have irregular menstrual cycles, start using Bemfola within the first 7 days of your cycle. If you do not have menstrual cycles, you may start using the medicine on any day.
• The initial dose of Bemfola is usually individualized and may be gradually adjusted.
• The daily dose of Bemfola must not exceed 225 IU (0.375 mL).
• When the desired response is achieved, you will receive a single injection of 250 micrograms of recombinant hCG (r-hCG, a laboratory-produced hCG using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last Bemfola injection. The most suitable days for sexual intercourse are the day of the hCG injection and the following day.

If your doctor does not observe the desired response, continuation of that treatment cycle with Bemfola should be evaluated and managed according to standard clinical practice.
If your body responds excessively, treatment will be stopped and hCG will not be administered (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). In the next treatment cycle, your doctor will administer a lower dose of Bemfola.
If you have been diagnosed with very low levels of FSH and LH hormones

• The usual initial dose of Bemfola is between 75 and 150 IU (0.12–0.25 mL), together with 75 IU (0.12 mL) of lutropin alfa.
• You will need to use both medicines daily for up to five weeks.
• The dose of Bemfola may be increased every 7 or 14 days by 37.5–75 IU until the desired response is achieved.
• When the desired response is achieved, you will receive a single injection of 250 micrograms of recombinant hCG (r-hCG, a laboratory-produced hCG using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last injection of Bemfola and lutropin alfa. The most suitable days for sexual intercourse are the day of the hCG injection and the following day. Alternatively, intrauterine insemination or another assisted reproductive procedure may be performed, as determined by your doctor.

If your doctor observes no response after 5 weeks, that treatment cycle with Bemfola should be discontinued. In the next treatment cycle, your doctor may prescribe a higher initial dose of Bemfola.
If your body responds excessively, treatment with Bemfola will be stopped and hCG will not be administered (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”). In the next cycle, your doctor will administer a lower dose of Bemfola.
If you need to stimulate the development of multiple oocytes for assisted reproductive techniques

• The initial dose of Bemfola is usually individualized and may be gradually adjusted up to a maximum of 450 IU per day (0.75 mL).
• Treatment continues until the oocytes have reached a certain stage of development. Your doctor will determine the appropriate timing using blood tests and/or ultrasound.
• When the oocytes have developed, you will receive a single injection of 250 micrograms of recombinant hCG (r-hCG, a laboratory-produced hCG using recombinant DNA technology) or 5,000–10,000 IU of hCG, 24–48 hours after the last Bemfola injection. This prepares the oocytes for retrieval.
  Men
• The usual dose of Bemfola is 150 IU (0.25 mL) together with hCG.
• You must use both medicines three times a week for at least 4 months.
• If you do not respond to treatment after 4 months, your doctor may recommend continuing treatment with both medicines for up to 18 months.

If you use more Bemfola than you should
No effects due to overdose of Bemfola have been reported. However, ovarian hyperstimulation syndrome (OHSS) may occur, as described in section 4. However, OHSS can only occur if hCG has also been administered (see section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”).
If you forget to use Bemfola
If you forget to use Bemfola, do not take a double dose to make up for the missed dose. Inform your doctor as soon as you realize you have missed a dose.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Serious side effects in women

• Pelvic pain in combination with nausea or vomiting may be symptoms of ovarian hyperstimulation syndrome (OHSS). This may indicate that the ovaries are overreacting to treatment and that 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).
• OHSS may become severe, with markedly enlarged ovaries, reduced urine production, weight gain, breathing difficulties and/or possible accumulation of fluid in the abdomen or chest. This side effect is uncommon (may affect up to 1 in 100 people).
• Rarely, complications of OHSS such as ovarian torsion or blood clotting may occur (may affect up to 1 in 1,000 people).
• Very rarely, serious complications related to blood clotting (thromboembolic events) may occur, sometimes independent of OHSS (may affect up to 1 in 10,000 people). These may cause chest pain, shortness of breath, stroke or heart attack (see also section 2, "Blood clotting disorders (thromboembolic events)").

Serious side effects in men and women

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

If you experience any of the side effects listed above, contact your doctor immediately. Your doctor may ask you to stop using Bemfola.

Other side effects in women
Very common (may affect more than 1 in 10 people):

• Fluid-filled sacs in the ovary (ovarian cysts)
• Headache
• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

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

• Abdominal pain
• Nausea, vomiting, diarrhoea, abdominal cramps and bloating

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

• Allergic reactions such as skin rash, redness, itching, facial swelling with breathing difficulties may occur. These reactions may be severe.
• Asthma may worsen.

Other side effects in men
Very common (may affect more than 1 in 10 people):

• Local injection site reactions such as pain, redness, bruising, swelling and/or irritation

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

• Swelling of the veins located above and behind the testicles (varicocele)
• Enlargement of breast gland, acne or weight gain

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

• Allergic reactions such as skin rash, redness, itching, facial swelling with breathing difficulties may occur. These reactions may be severe.
• Asthma may worsen.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bemfola

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pen label or on the box after "Exp". The expiry date refers to the last day of that month.
Store in the refrigerator (2°C–8°C). Do not freeze.
Keep in the original packaging to protect the medicine from light.
Within the shelf life, the intact pen may be stored at a temperature not exceeding 25°C for a maximum period of 3 months without the need for further refrigeration; 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 must be injected immediately.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Bemfola contains

• 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 of follitropin alfa (equivalent to 44 micrograms).
• The other components are poloxamer 188, sucrose, methionine, disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, phosphoric acid, and water for injections.

Description of the appearance of Bemfola and contents of the pack

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

Marketing Authorisation Holder and Manufacturer
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.
Bemfola pre-filled pen 75 IU /0.125 ml
Bemfola pre-filled pen 150 IU /0.25 ml
Bemfola pre-filled pen 225 IU /0.375 ml
Bemfola pre-filled pen 300 IU /0.50 ml
Bemfola pre-filled pen 450 IU /0.75 ml

Instructions for use

SUMMARY
1. How to use the Bemfola pre-filled pen
2. Before starting to use the pre-filled pen
3. How to prepare a pre-filled pen for injection
4. How to set the dose prescribed by your doctor
5. How to inject the dose
6. After the injection

Warning: Please read and follow these Instructions for use of the Bemfola pre-filled pens.
Do not follow instructions from sources other than those described in these Instructions for use or provided by healthcare professionals, as this may compromise the correct use of the pre-filled pen and your treatment.

1. How to use the Bemfola prefilled pen

• Before starting to use the prefilled pens, carefully read the entire Instructions for Use and the Package Leaflet.
• Each prefilled pen is for single use only – do not allow anyone else to use it.
• The numbers shown on the dose dial of the prefilled pens are expressed 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 single-use Bemfola prefilled pens you will need for the complete treatment cycle.
• Administer the injection at approximately the same time each day.

2. Before starting to use the pre-filled pen

2.1. Remove the pen from the refrigerator

• Remove one of the pens from the refrigerator 5 to 10 minutes before use.
• If the medicine has been frozen, do not use it.

2.2. Wash your hands

• Wash your hands with soap and lukewarm water and dry them thoroughly.
• It is important that your hands and the items you use to prepare the pen are as clean as possible.

2.3. Choose a clean work surface

• A clean table or surface is suitable.

3. How to prepare a pre-filled pen for injection

The different parts of your pre-filled pen

Inject the medicine at approximately the

same time each day. Remove the pen from the
refrigerator 5–10 minutes before use.
Note: Check that the medicine has not been
frozen.
Prepare the injection needle

Take a new needle – use only the single-use
needles supplied in the pack. Hold the outer
needle cap firmly. Always check that the
removable seal on the outer needle cap is
intact and not loose.
Remove the removable seal from the needle
before injection.
Caution: If the removable seal is damaged or
loose, do not use the needle. Discard it into a
sharps disposal container. Take a new needle.

Attach the needle.
Hold the pen by the sides, aligning the needle
with the pen; place the needle on. Screw the
needle clockwise onto the pen tip until it is
securely attached. Make sure the needle is
properly fixed in a straight position on the pen.
Caution: Do not overtighten the needle. Do not
press the dose button while attaching the
needle.
Remove the outer needle cap (G).
Keep it aside. You will need it later to
dispose of the pen after injection.
Remove the inner needle cap (F).
Make sure the needle is properly positioned.

Correct needle position Incorrect needle position

4. How to set the dose prescribed by the doctor

First, hold the pen so that

the needle is pointing upwards. To remove
air bubbles from the system, gently tap
the side of the pen to allow any air bubbles
to rise upwards.
While keeping the pen pointing upwards,
press the dose setting button until the activation bar,
marked with a small arrow, disappears from view.
You should hear a click and a small amount of liquid should come out (this is normal).
The pen is now ready to set the dose.
Warning: if no liquid comes out or if leakage is observed at the needle attachment site, the pen must not be used. Contact your doctor or pharmacist if you notice any problems.

Gently rotate the dose setting button until the prescribed dose mark aligns with the center of the mark on the pen.
Note: for the pre-filled pen Bemfola 75 IU/0.125 mL, the dose setting button cannot make a full rotation, but it can still be rotated backwards. The pen is now ready for injection.
Warning: at this point, do not press the dose setting button again.

5. How to inject the dose

You can now immediately proceed to administer the injection at the injection site (e.g.,
abdomen, front of the thigh) indicated by your doctor or nurse. To minimize skin irritation,
choose a different injection site each day.
Using a circular motion,

clean the injection site
with the alcohol swab
provided in the package.
Before administering the
injection, wait a few
seconds for the alcohol to
evaporate completely.
The skin must be dry.

Double-check that the
correct dose is displayed
on the pen.
With two fingers, gently
pinch the skin at the
injection site.
Hold the pen at approximately
a right angle (90° angle)
and insert the needle
completely into the skin
with one firm, swift motion.
Caution : during needle
insertion, do not press the
dose setting

dose and do not change the
direction of the needle.
Once the needle is
fully inserted into the
injection site, press
the dose button slowly
and steadily until it
stops and the dose bar
has completely
disappeared.
Do not remove the
needle immediately;
wait at least 5
seconds before removing
it to ensure the full
dose has been injected.
After removing the
needle: clean the skin
with an alcohol-soaked
cotton ball using a
circular motion at the
injection site.
Caution : if liquid leaks
from the needle or pen
connection during
injection, inform your
doctor or pharmacist.

6. After the injection

Carefully reattach the outer cap

onto the needle.
Use the pre-filled injection pen only once and discard the pen even if there is
liquid remaining in the pen after the injection. Dispose of the
carton, inner needle cap, tab,
alcohol swab, and instructions for use in the
normal household waste. Do not dispose of any medicine via
washbasin, toilet, or household waste. Used
pens must be placed in a sharps or sharp objects container
and taken to a pharmacy for proper
disposal. Ask your pharmacist how to dispose of medicines no longer in use.