Ovaleap 450 IU/0.75 ml solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Ovaleap 300UI/0.5ml solution for injection

Ovaleap 450UI/0.75ml solution for injection

Ovaleap 900UI/1.5ml solution for injection

Follitropin alfa

Read all of this 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, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if such effects are not listed in this leaflet.

Contents of the leaflet

1. What Ovaleap is and what it is used for
2. What you need to know before using Ovaleap
3. How to use Ovaleap
4. Possible adverse effects
5. How to store Ovaleap
6. Contents of the pack and other information

1. What Ovaleap is and what it is used for

What Ovaleap is

This medicinal product contains the active substance 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 the ovarian follicles that contain the eggs. In men, FSH is necessary for sperm production.

What Ovaleap is used for

In adult women, Ovaleap is used:

• to help ovulation (release of a mature egg from the follicle) in women who are unable to ovulate and who have not responded to treatment with a substance called "clomiphene citrate".
• to help follicle development 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 combination with another substance called "lutropin alfa" (a version of another gonadotropin, "luteinizing hormone" or LH), to help ovulation in women whose bodies produce too little FSH and LH.

In adult men, Ovaleap is used:

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

2. What you need to know before using Ovaleap

Do not use Ovaleap:

• if you are allergic to follitropin alfa, follicle-stimulating hormone (FSH), or any of the other components of this medicine (listed in section 6).

• if you have a tumor in the hypothalamus or pituitary gland (parts of the brain).

• if you are a woman with:

• enlarged ovaries or fluid-filled sacs in the ovaries (ovarian cysts) of unknown origin.

• unexplained vaginal bleeding.

• ovarian, uterine, or breast cancer.

• a condition that normally makes pregnancy impossible, such as ovarian failure (premature menopause), uterine fibroids, or a malformation of the reproductive organs.

• if you are a man with:

• untreated testicular failure.

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

Warnings and precautions

Fertility in both you and your partner should be evaluated by a physician experienced in the treatment of fertility disorders before starting treatment.

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

Porphyria

Inform your doctor before starting treatment if you or a family member has porphyria. This is an inherited condition characterized by the inability to break down porphyrins (organic compounds).

Inform your doctor immediately if:

• your skin becomes fragile and blisters easily, especially in areas frequently exposed to sunlight, and/or
• you experience stomach, arm, or leg pain.

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

Ovarian hyperstimulation syndrome (OHSS)

If you are a woman, this medicine increases your risk of developing OHSS. This occurs when your follicles develop excessively and become large cysts.

Inform your doctor immediately if:

• you have pain in the lower abdomen (stomach),
• you gain weight rapidly,
• you experience nausea or vomiting,
• you have difficulty breathing.

If you experience these symptoms, your doctor may instruct you to stop using this medicine (see also section 4, under the heading “Serious side effects in women”).

If ovulation does not occur and the recommended dose and administration schedule are followed, the risk of this syndrome is reduced. Treatment with Ovaleap rarely causes severe ovarian hyperstimulation syndrome unless the medication used to trigger final follicular maturation (containing human chorionic gonadotropin, hCG) is administered. If OHSS develops, your doctor may not prescribe hCG in this treatment cycle. You may be advised to abstain from sexual intercourse or to use barrier contraceptive methods for at least 4 days.

Multiple pregnancy

When using this medicine, you have a higher chance of becoming pregnant with more than one baby (i.e., "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 this medicine at the correct times. If you undergo assisted reproductive techniques, the risk of multiple pregnancy depends on your age and the quality and number of fertilized eggs or embryos transferred.

Miscarriage

If you undergo assisted reproductive techniques or ovarian stimulation to produce eggs, your risk of miscarriage is higher than in the average woman.

Ectopic pregnancy

If you undergo assisted reproductive techniques and have damage to your fallopian tubes, your risk of ectopic pregnancy (pregnancy outside the uterus) is higher than in the average woman.

Congenital abnormalities

A baby conceived using assisted reproductive techniques may have a slightly increased risk of congenital abnormalities compared to a naturally conceived baby. This may be related to multiple pregnancies or parental characteristics such as maternal age or sperm quality.

Blood clotting problems (thromboembolic events)

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

Men with high levels of FSH in the blood

If you are a man, very high levels of natural FSH in the blood may indicate testicular damage. This medicine is generally not effective in such cases. If your doctor decides to try treatment with Ovaleap, they may monitor you by requesting a semen analysis 4 to 6 months after starting treatment.

Children and adolescents

This medicine must not be used in children and adolescents under 18 years of age.

Other medicines and Ovaleap

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

• If you use Ovaleap together with other medicines that promote ovulation, such as human chorionic gonadotropin (hCG) or clomiphene citrate, your follicular response may be increased.
• If you use Ovaleap at the same time as a "gonadotropin-releasing hormone" (GnRH) agonist or antagonist (medicines that reduce sex hormone levels and suppress ovulation), you may require a higher dose of Ovaleap to produce follicles.

Pregnancy and breastfeeding

You must not use this medicine if you are pregnant or during the breastfeeding period.

Driving and use of machines

This medicine does not affect your ability to drive or operate machinery.

Ovaleap contains sodium, benzalkonium chloride, and benzyl alcohol

This medicine contains less than 1 mmol of sodium (23 mg) per dose, which is essentially "sodium-free."

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

3. How to use Ovaleap

Follow exactly the administration instructions for this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

This medicine is administered as an injection into the tissue just beneath the skin (subcutaneous injection). Your doctor or nurse will instruct you on how to inject the medicine. If you are self-administering this medicine, carefully read and follow the "Instructions for Use" provided with the pen.

What is the recommended dose

Your doctor will decide how much medicine you should receive 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 medicine is usually administered daily.
• If you have irregular menstruation, start using this medicine within the first 7 days of your menstrual cycle. If you do not have menstruation, you may begin treatment on any convenient day.
• The initial dose of this medicine is usually individualized and may be adjusted in a stepwise manner.
• The daily dose of this medicine must not exceed 225 IU.
• When the desired response is achieved, you will be given hCG or "recombinant hCG" (r-hCG, laboratory-made hCG produced using a special DNA technique). A single injection of 250 micrograms of r-hCG or 5,000 to 10,000 IU of hCG will be administered 24 to 48 hours after the last Ovaleap injection. The best time for sexual intercourse is on the day of the hCG injection and the following day. Alternatively, intrauterine insemination may be performed by introducing sperm into the uterine cavity.

If your doctor does not observe the desired response, continuation of that Ovaleap treatment cycle should be evaluated and managed according to standard clinical practice.

If an excessive response occurs, your treatment will be stopped and you will not receive hCG (see also section 2, under the heading "Ovarian Hyperstimulation Syndrome (OHSS)"). For the next cycle, your doctor will administer a lower dose of Ovaleap than in the previous cycle.

If you need to develop several eggs for retrieval prior to any assisted reproductive technique

• The initial dose of this medicine is usually individualized and may be adjusted stepwise up to a maximum of 450 IU per day.
• Treatment continues until the eggs have developed to the desired stage. Your doctor will monitor this through blood tests and/or ultrasound examinations.
• When the eggs are mature, you will be given hCG or r-hCG. A single injection of 250 micrograms of r-hCG or 5,000 to 10,000 IU of hCG will be administered 24 to 48 hours after the last Ovaleap injection. This triggers final maturation of the eggs, making them ready for retrieval.

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 together with 75 IU of lutropin alfa.
• You will use both medicines daily for up to 5 weeks.
• The dose of Ovaleap 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 achieved, you will be given hCG or r-hCG. A single injection of 250 micrograms of r-hCG or 5,000 to 10,000 IU of hCG will be administered 24 to 48 hours after the last injections of Ovaleap and lutropin alfa. The best time for sexual intercourse is on the day of the hCG injection and the following day. Alternatively, intrauterine insemination or another medically assisted reproductive procedure may be performed, as determined by your doctor.

If your doctor does not observe a response after 5 weeks of treatment, that treatment cycle should be discontinued. For the next cycle, your doctor will administer a higher initial dose of this medicine than in the previous cycle.

If an excessive response occurs, your treatment with Ovaleap will be stopped and you will not receive hCG (see also section 2, under the heading "Ovarian Hyperstimulation Syndrome (OHSS)"). For the next cycle, your doctor will administer a lower dose of Ovaleap than in the previous cycle.

Men

• The usual dose of this medicine is 150 IU together with hCG.
• You will use both medicines three times per week for at least 4 months.
• If you have not responded to treatment after 4 months, your doctor may advise continuing treatment with both medicines for up to 18 months.

How are the injections administered?

This medicine is administered as a subcutaneous injection (into the tissue just beneath the skin) using the Ovaleap Pen. The Ovaleap Pen is a device (a "pen") used for administering injections into the subcutaneous tissue.

Your doctor may suggest that you learn to self-inject this medicine. Your doctor or nurse will provide instructions on how to do this, which are also available in the separate Instructions for Use provided with the pen. Do not attempt to self-administer this medicine unless you have been trained by your doctor or nurse. The first injection of this medicine must always be given under the supervision of a doctor or nurse.

Ovaleap injectable solution in cartridges is designed for use with the Ovaleap Pen. You must carefully follow the separate Instructions for Use provided with the Ovaleap Pen. These pen instructions will be supplied together with the Ovaleap Pen. However, proper management of your condition requires continuous and close collaboration with your doctor.

Dispose of used needles immediately after injection.

If you use more Ovaleap than you should

The effects of an overdose of Ovaleap are unknown. However, ovarian hyperstimulation syndrome may be expected, as described in section 4 under the heading "Serious adverse reactions in women". However, this syndrome will only occur if hCG is also administered (see also section 2, under the heading "Ovarian Hyperstimulation Syndrome (OHSS)").

If you forget to use Ovaleap

Do not use a double dose to make up for a missed dose. 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, pharmacist, or nurse.

4. Possible adverse effects

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

Important adverse effects

Serious adverse effects in men and women

• Very rare cases (may affect up to 1 in 10,000 people) of allergic reactions such as skin rash, raised itchy skin areas, and severe allergic reactions with weakness, low blood pressure, breathing difficulties, and/or facial swelling have been reported. If you think you are experiencing such a reaction, you must stop the Ovaleap injection and seek immediate medical help.

Serious adverse 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 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 fluid accumulation in the abdomen or chest. This adverse effect is uncommon (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 1 in 10,000 people), serious blood clotting complications (thromboembolic events) may sometimes occur, sometimes independent of ovarian hyperstimulation syndrome. This could cause chest pain, shortness of breath, stroke, or myocardial infarction (see also section 2, “Blood clotting problems (thromboembolic events)”).

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

Other adverse effects in women

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
• Headache
• Fluid-filled sacs in the ovaries (ovarian cysts)

Common (may affect up to 1 in 10 people)

• Abdominal pain
• Abdominal bloating
• Abdominal cramps
• Nausea
• Vomiting
• Diarrhea

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

• 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 veins above and behind the testicles (varicocele)
• Breast development
• Acne
• Weight gain

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

• Asthma may worsen.

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect 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 Ovaleap

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

Do not use this medicine after the expiry date stated on the label and outer packaging 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 the cartridge in the outer packaging to protect it from light.

Before opening and within its shelf life, this medicine may be removed from the refrigerator and stored unrefrigerated for up to 3 months. Do not store above 25°C. This medicine must be discarded if not used within 3 months.

Once opened, the cartridge in use within the pen may be stored for a maximum of 28 days. Do not store above 25°C. Record the date of first use in the patient 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 medicine if it appears cloudy or contains particles.

Medicines must not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Ovaleap

• The active substance is follitropin alfa.
  Ovaleap 300 UI/0.5 ml: Each cartridge contains 300 IU (equivalent to 22 micrograms) of follitropin alfa in 0.5 ml of solution.
  Ovaleap 450 UI/0.75 ml: Each cartridge contains 450 IU (equivalent to 33 micrograms) of follitropin alfa in 0.75 ml of solution.
  Ovaleap 900 UI/1.5 ml: Each cartridge contains 900 IU (equivalent to 66 micrograms) of follitropin alfa in 1.5 ml of solution.
  Each ml of solution contains 600 IU (equivalent to 44 micrograms) of follitropin alfa.

• The other components are sodium dihydrogen phosphate dihydrate, sodium hydroxide (2 M) (for pH adjustment), mannitol, methionine, polysorbate 20, benzyl alcohol, benzalkonium chloride, and water for injections.

All of the presentations mentioned above contain the same excipients.

Nature and contents of the container

Ovaleap is an injectable solution (injection). Ovaleap is a clear, colourless solution.

Ovaleap 300 IU/0.5 ml is supplied in packs containing 1 cartridge and 10 injection needles.
Ovaleap 450 IU/0.75 ml is supplied in packs containing 1 cartridge and 10 injection needles.
Ovaleap 900 IU/1.5 ml is supplied in packs containing 1 cartridge and 20 injection needles.

Only some pack sizes may be marketed.

Marketing Authorisation Holder

Theramex Ireland Limited
3rd Floor, Kilmore House,
Park Lane, Spencer Dock,
Dublin 1
D01 YE64
Ireland

Manufacturer

Merckle GmbH
Graf-Arco-Straße 3
89079 Ulm,
Germany

Rechon Life Science AB
Soldattorpsvägen 5
216 13 Limhamn
Sweden

Date of the latest revision of this leaflet: {month YYYY}.

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.