Leaflet: information for the user

Ovaleap 300UI/0.5mlinjectable solution

Ovaleap 450UI/0.75mlinjectable solution

Ovaleap 900UI/1.5mlinjectable solution

Folitropina alfa

Read this leaflet carefully before starting to use 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, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribedonlyfor you, 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, pharmacist, or nurse,even if they are not listed in this leaflet.

1.What isOvaleapand what is it used for

2.What you need to knowbefore starting touseOvaleap

3.How to useOvaleap

4.Possible side effects

5.Storage ofOvaleap

6.Contents of the package andadditional information

What is Ovaleap

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

How is Ovaleap usedOvaleap

In adult women, Ovaleap is used:

• to help ovulation (release of a mature egg from the follicle) in women who cannot ovulate and who have not responded to treatment with a substance called "clomiphene citrate".
• to help the development of follicles in women undergoing assisted reproductive techniques (techniques that may help her become pregnant), such as "in vitro fertilization", "intratubal gamete transfer" or "intratubal embryo transfer".
• in combination with another substance called "lutropin alfa" (a version of another gonadotropin, luteinizing hormone or LH), to help ovulation in women whose body produces too little FSH and LH.

In adult men, Ovaleap is used:

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

Do not use Ovaleap:

• If you are allergic to follitropin alfa, the hormone follicle-stimulating hormone (FSH), or any of the other components of this medication (listed in section6).
• If you have a tumor in the hypothalamus or pituitary gland (parts of the brain).
• If you areawomanwith:

• Large ovaries or fluid-filled sacs in the ovaries (ovarian cysts) of unknown origin.
• Unexplained vaginal bleeding.
• Ovarian, uterine, or breast cancer.
• Any condition that normally makes pregnancy impossible, such as premature ovarian insufficiency (early menopause), uterine fibroids, or reproductive organ malformations.

• If you areamanwith:

• Untreatable testicular insufficiency.

Do not use this medication if any of the above conditions apply to you. If you are unsure, ask your doctor or pharmacist before using this medication.

Warnings and precautions

A doctor experienced in the treatment of fertility disorders should evaluate your fertility and that of your partner before starting treatment.

Consult your doctor, pharmacist, or nurse before starting to use Ovaleap.

Porphyria

Inform your doctor before starting treatment if you or any family member has porphyria. This is a condition that can be passed down from parents to children, characterized by an inability to break down porphyrins (organic compounds).

Inform your doctor immediately if:

• Your skin becomes fragile and blisters easily, especially in sun-exposed areas, and/or
• You have stomach, arm, or leg pain.

If you experience these symptoms, your doctor may recommend that you discontinue treatment.

Hyperstimulation syndrome (SHO)

If you are a woman, this medication increases the risk of developing SHO. This occurs when your follicles develop too much and become large cysts.

Inform your doctor immediately if:

• You experience lower abdominal pain (barriga),
• You gain weight rapidly,
• You experience nausea or vomiting,
• You experience difficulty breathing.

If you experience these symptoms, your doctor may recommend that you discontinue use of this medication (see also section4, under the heading“Severe adverse reactions in women").

If you do not ovulate and follow the recommended doses and administration times, this syndrome is less likely to occur. Ovaleap treatment rarely causes severe hyperstimulation syndrome, unless the medication used for final follicular maturation (containing human chorionic gonadotropin, hCG) is administered. In the event of developing SHO, your doctor may not prescribe hCG for this treatment cycle. You may be advised to abstain from intercourse or use barrier contraceptive methods for at least 4days.

Multiple pregnancy

If you use this medication, you have a higher risk of becoming pregnant with more than one child (i.e., "multiple pregnancy," usually twins). 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 this medication 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 or embryos placed inside you.

Abortion

If you undergo assisted reproduction techniques or ovarian stimulation to produce eggs, the likelihood of having an abortion is higher than the average for women.

Ectopic pregnancy

If you undergo assisted reproduction techniques and have fallopian tube damage, the likelihood of having an ectopic pregnancy (pregnancy outside the uterus) is higher than the average for women.

Congenital anomalies

A baby conceived through assisted reproduction techniques may have a slightly higher risk of congenital anomalies than if it had been conceived naturally. This may be associated with multiple pregnancies or characteristics of the parents, such as maternal age or sperm characteristics.

Blood clotting problems (thromboembolic episodes)

If you or any family member has ever had blood clots in the leg or lung, heart attack, or stroke, inform your doctor. You may have a higher risk of developing these problems or of them worsening with Ovaleap treatment.

Men with high FSH levels in the blood

If you are a man, high natural FSH levels in the blood may be a sign of testicular damage. This medication is usually not effective in these cases. If your doctor decides to try treatment with Ovaleap, your doctor may monitor you by asking you to have a semen analysis, 4 to 6 months after starting treatment.

Children and adolescents

This medication should not be used in children and adolescents under 18years of age.

Other medications and Ovaleap

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

• If you useOvaleapwith other medications that help ovulation, such as human chorionic gonadotropin (hCG) or clomiphene citrate, your follicle response may be increased.
• If you useOvaleapat the same time as a gonadotropin-releasing hormone (GnRH) agonist or antagonist (these medications reduce sex hormone levels and stop ovulation), you may need a higher dose ofOvaleapto produce follicles.

Pregnancy and breastfeeding

You should not use this medicationif you are pregnant or breastfeeding.

Driving and operating machinery

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

Ovaleap contains sodium, benzalkonium chloride, and benzyl alcohol

This medication contains less than 1mmol of sodium (23mg) per dose; it is essentially "sodium-free."

This medication also contains 0.02mg per ml of benzalkonium chloride and 10.0mg per ml of benzyl alcohol. Consult your doctor or pharmacist if you have liver or kidney disease and if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol can accumulate in the body and cause adverse effects (metabolic acidosis).

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again..

This medication is administered in the form of an injection into the tissue just below the skin (subcutaneous injection).Your doctor or nurse will instruct you on how to administer the medication. If you self-administer this medication, read and carefully follow the "Instructions for use" provided with the pen.

What is the recommended dose

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

Women

If you are not ovulating and have irregular or no menstruation

• This medication is usually administered every day.
• If you have irregular menstruation, start using this medication 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 this medication is 75 to 150 IU per day.
• Your dose of this medication may be increased every 7 or 14 days by 37.5 to 75 IU, until the desired response is obtained.
• The maximum daily dose of this medication is usually not more than 225 IU.
• When the desired response is obtained, you will be administered hCG or "recombinant hCG" (r-hCG, a hCG manufactured in a laboratory using a special DNA technique). The single injection will be 250 micrograms of r-hCG or 5,000 to 10,000 IU of hCG, 24 to 48 hours after the last injection of Ovaleap. The best time for sexual intercourse is the same day as the hCG injection and the next day.Alternatively, intrauterine insemination may be performed by introducing sperm into the uterine cavity.

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

If an excessive response is obtained, treatment will be interrupted and hCG will not be administered (see also section 2, under the heading "Hyperstimulation Syndrome (HSS)"). For the next cycle, your doctor will administer a lower dose of Ovaleap than the previous cycle.

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

• The usual initial dose of this medication is 150 to 225 IU per day, starting from the 2nd or 3rd day of your menstrual cycle.
• Your dose may be increased, depending on your response. The maximum daily dose is 450 IU.
• Treatment continues until the follicles have developed to the desired point. This usually takes about 10 days, but may vary between 5 and 20 days. Your doctor will check this by blood tests and/or ultrasound.
• When the follicles are ready, you will be administered hCG or r-hCG. The single injection will be 250 micrograms of r-hCG or 5,000 to 10,000 IU of hCG, 24 to 48 hours after the last injection of Ovaleap. This makes your follicles ready for extraction.

In other cases, your doctor may interrupt ovulation first, using a GnRH agonist or antagonist. In such cases, Ovaleap administration is started approximately 2 weeks after starting treatment with the agonist, continuing both treatments until an adequate follicular development is achieved.

If you have been diagnosed with very low levels of FSH and LH hormones

• The usual initial dose of Ovaleap is 75 to 150 IU, along with 75 IU of lutropin alfa.

• You will use these two medications every day for a maximum of 5 weeks.
• Your dose of Ovaleap may be increased every 7 or 14 days by 37.5 to 75 IU, until the desired response is obtained.
• When the desired response is obtained, you will be administered hCG or r-hCG. The single injection will be 250 micrograms of r-hCG or 5,000 to 10,000 IU of hCG, 24 to 48 hours after the last injections of Ovaleap and lutropin alfa. The best time for sexual intercourse is the same day as the hCG injection and the next day. Alternatively, intrauterine insemination or other medically assisted reproduction procedures may be performed, at the discretion of your doctor.

If your doctor does not observe a response after 5 weeks of treatment, that cycle of treatment must be interrupted. For the next cycle, your doctor will administer a higher initial dose of this medication than the previous one.

If an excessive response is obtained, treatment with Ovaleap will be interrupted and hCG will not be administered (see also section 2, under the heading "Hyperstimulation Syndrome (HSS)"). For the next cycle, your doctor will administer a lower dose of Ovaleap than the previous cycle.

Men

• The usual dose of this medication is 150 IU, along with hCG.
• You will use these two medications 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 medications for at least 18 months.

How are injections administered?

This medication is administeredin the form of an injection into the tissue just below the skin (subcutaneous injection)using the Ovaleap Pen.The Ovaleap Pen is a device (a "pen") used for the administration of injectionsinto the tissue just below the skin.

Your doctor may suggest that you learn to administer the medication yourself. Your doctor or nurse will give you instructions on how to do it, and you can also find them in the separate "Instructions for use" provided with the pen. Do not attempt to self-administer this medication if you have not received this training from your doctor or nurse. The first injection of this medication must always be administered in the presence of a doctor or nurse.

Ovaleap injectable solution in cartridges has been designed for use with the Ovaleap Pen. You must carefully follow the separate "Instructions for use" provided with the Ovaleap Pen. The instructions for use of the pen will be provided with the Ovaleap Pen. However, the proper treatment of your condition requires constant and close collaboration with your doctor.

Dispose of the used needles immediately after the injection.

If you use moreOvaleapthan you should

The effects of using an excessive amount of Ovaleap are unknown. However, it is expected that a hyperstimulation syndrome will occur, which is described in section 4 under the heading "Severe adverse effects in women". However, this syndrome will only occur if hCG is also administered (see also section 2, under the heading "Hyperstimulation Syndrome (HSS)").

If you forgot to useOvaleap

Do not use a double dose to compensate for the missed doses. Consult your doctor as soon as you realize you have missed a dose..

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

Like all medications,this medicationcan cause side effects, although not everyone will experience them.

Important side effects

Severe side effects in men and women

• Rare cases (may affect up to 1 in 10,000 people) ofallergic reactions such as skin rash, raised and itchy skin areas andsevere allergic reactionswith weakness, low blood pressure,difficulty breathingandswelling of the face. If you think you are experiencing this type of reaction, you must interrupt the Ovaleap injection and seek medical help immediately.

Severe side effects in women

• Abdominal 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 large ovarian cysts have developed (see also section2, in “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 fluid accumulation in the abdomen or chest. This side effect is infrequent (may affect up to 1 in 100 people).
• In rare cases (may affect up to 1 in 1,000 people), complications of ovarian hyperstimulation syndrome such as ovarian torsion or blood clotting may also occur.
• In very rare cases (may affect up to 1in 10,000people) severe complications of blood clotting (thromboembolic episodes) may occur, sometimes independent of ovarian hyperstimulation syndrome. This could cause chest pain, feeling of lack of air, stroke or myocardial infarction (see also section2, in “Blood Clotting Problems (Thromboembolic Episodes)”).

If you observe any of the mentioned side effects, you must consult your doctor immediately, who may ask you to interrupt the treatment with Ovaleap.

Other side effects in women

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
• Headache
• Cysts in the ovaries (ovarian cysts)

Common(may affect up to 1 in 10 people)

• Abdominal pain
• Abdominal flatulence
• Abdominal cramps
• Nausea
• Vomiting
• Diarrhea

Rare(may affect up to 1 in 10,000 people)

• 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
• Weight gain

Rare(may affect up to 1 in 10,000 people)

• Asthma may worsen.

Reporting side effects

If you experienceany type of side effect, consult your doctor, pharmacist or nurse, even if it is a possibleside effect that does not appear in this leaflet.You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.

By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keepthis medicationout of the sight and reach of children.

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

Store in the refrigerator (between2°Cand8°C).

Do not freeze.

Storethe cartridge intheouter packagingto protect it from light.

Before opening and within its validity period, you may remove this medication from the refrigerator, without refrigerating again, for a maximum of 3months. Do not store at a temperature above25°C. You must discard this medication if it has not been used in 3months.

Once opened, the cartridge in use within the pen may be stored for a maximum period of 28days.Do not storeat a temperature above25°C.Record the date of the first use in the patient's diary, which will be provided with the Ovaleap Pen.

Replace the pen cap on the Ovaleap Pen after each injection to protect the cartridge from light.

Do not use this medication if you observethat it is cloudy or contains particles.

Medicines should not be disposed of through the drains.Ask your pharmacist how to dispose ofthe packaging and medications that you no longerneed.By doing so, you will help protect the environment.

Composition ofOvaleap

• The active principle is follitropin alfa.
  Ovaleap 300UI/0.5ml: Each cartridge contains 300UI(equivalent to 22micrograms) offollitropin alfain 0.5mlof solution.
  Ovaleap 450UI/0.75ml: Each cartridge contains 450UI(equivalent to 33micrograms) offollitropin alfain 0.75mlof solution.
  Ovaleap 900UI/1.5ml: Each cartridge contains 900UI(equivalent to 66micrograms) offollitropin alfain 1.5mlof solution.

Each ml of the solution contains 600UI(equivalent to 44micrograms) offollitropin alfa.

• The other components aredihydrogen phosphate sodium dihydrate, sodium hydroxide (2 M) (for pH adjustment), mannitol, methionine, polisorbate 20, benzyl alcohol, benzalkonium chloride, andwater for injection.

All the aforementioned presentations contain the other components.

Appearance of the product and contents of the pack

Ovaleapis an injectable solution (injection).Ovaleapis a transparent and colourless solution.

Ovaleap 300UI/0.5ml is presentedin boxes containing1cartridge and 10injection needles.
Ovaleap 450UI/0.75ml is presentedin boxes containing1cartridge and 10injection needles.
Ovaleap 900UI/1.5ml is presentedin boxes containing1cartridge and 20injection needles.

Only some sizes of packaging may be commercially available.

Marketing authorisation holder

Theramex Ireland Limited

3rdFloor, Kilmore House,

Park Lane, Spencer Dock,

Dublin 1

D01 YE64

Ireland

Manufacturer responsible

Merckle GmbH

Graf-Arco-Straße 3

89079 Ulm,

Germany

Rechon Life Science AB

Soldattorpsvägen 5

216 13 Limhamn

Sweden