Ovaleap

Package leaflet: Information for the user

Ovaleap 300 UI/0.5 mL solution for injection, 450 UI/0.75 mL solution for injection, 900 UI/1.5 mL solution for injection

follitropin alfa
Please read all of this leaflet carefully before 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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse.

Contents of this 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 side 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 ovarian follicles, which contain the egg cells. In men, FSH is necessary for sperm production.

What Ovaleap is used for
In adult women, Ovaleap is used

• to stimulate ovulation (the release of a mature egg cell from the follicle) in women who do not ovulate and who have not responded to treatment with a medicine called clomifene citrate.
• to stimulate follicular development in women undergoing assisted reproductive procedures (procedures that may help achieve pregnancy), such as in vitro fertilization, gamete intrafallopian transfer, or zygote intrafallopian transfer.
• in combination with a medicine called lutropin alfa (a form of another gonadotropin, "luteinizing hormone" or LH) to stimulate ovulation in women whose bodies produce insufficient amounts of FSH and LH gonadotropins.

In adult men, Ovaleap is used

• in combination with a medicine called human chorionic gonadotropin (hCG) to stimulate sperm production in infertile men 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 ingredients of this medicine (listed in section 6).
• if you have a tumor of the hypothalamus or pituitary gland (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 cancer of the ovary, uterus, or breast.
  • with any condition that usually makes normal pregnancy impossible, such as ovarian failure (premature menopause), uterine fibroids, or malformations of the reproductive system.
• if you are a man
  • with testicular failure that cannot be treated.

Do not use this medicine if you have any of these conditions. If you are in doubt, consult your doctor or pharmacist before using this medicine.

Warnings and precautions

Before starting treatment, your fertility should be properly evaluated by a doctor experienced in treating fertility disorders.

Talk to your doctor, pharmacist, or nurse before using Ovaleap.

Porphyria

Tell your doctor before starting treatment if you or a family member has porphyria. This is a condition that can be inherited from parents to children and results in the inability to break down porphyrins (organic compounds).

Immediately inform your doctor if:

• your skin becomes fragile and easily develops blisters, especially in areas frequently exposed to sunlight, and/or
• you have pain in your stomach, arms, or legs. If you experience the above symptoms, your doctor may advise you to 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.

Contact your doctor immediately if you:

• feel pain in the lower abdomen (belly),
• gain weight rapidly,
• experience nausea or vomiting,
• have difficulty breathing. If you experience the above symptoms, your doctor may ask you to stop taking the medicine (see also section 4, “Serious side effects in women”).

If you do not ovulate and if the recommended dosage and timing are properly followed, the risk of OHSS is less likely. Treatment with Ovaleap 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 not administer hCG during this treatment cycle. You may be advised to avoid sexual intercourse or to use a barrier contraceptive method for at least 4 days.

Multiple pregnancy

When using this medicine, you have a higher chance of multiple pregnancy (usually twins) compared to 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 time. In assisted reproductive procedures, the risk of multiple pregnancy is related to age, quality, and number of fertilized eggs or embryos transferred to you.

Miscarriage

If you undergo assisted reproductive procedures or ovarian stimulation for egg production, your risk of miscarriage is higher than in other women.

Ectopic pregnancy

If you undergo assisted reproductive procedures and have damaged fallopian tubes, your risk of pregnancy outside the uterus (ectopic pregnancy) is higher than in other women.

Birth defects

Children conceived through assisted reproductive techniques may have a slightly increased risk of birth defects compared to those conceived naturally. This may be related to multiple pregnancies or parental characteristics, such as maternal age and sperm properties.

Blood clotting disorders (thromboembolic events)

If you have previously had blood clots in your legs or lungs, a heart attack, or a stroke, or if these events have occurred in your family, inform your doctor. The risk of these problems occurring or worsening during treatment with Ovaleap may be increased.

Men with high levels of FSH in the blood

If you are a man, high levels of natural FSH in the blood may indicate testicular damage. In such cases, this medicine is generally ineffective. If your doctor decides to try treatment with Ovaleap, they may ask you to provide sperm samples 4–6 months after starting treatment to monitor therapy.

Children and adolescents

This medicine is not indicated for use in children and adolescents under 18 years of age.

Other medicines and Ovaleap

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

• If you use Ovaleap together with other medicines that promote ovulation, such as human chorionic gonadotropin (hCG) or clomiphene citrate, this may enhance the follicular response.
• If you use Ovaleap 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 Ovaleap to produce follicles.

Pregnancy and breastfeeding

You must not use this medicine during pregnancy or breastfeeding.

Driving and using machines

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

Ovaleap contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., it 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.

3. How to use Ovaleap

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
This medicine is administered as an injection into the tissue directly beneath the skin
(subcutaneous injection). Your doctor or nurse will show you how to inject the medicine. If you are
self-injecting, read and carefully follow the “Instructions for Use” of the pen.
What is the recommended dose?
Your doctor will decide how much medicine you should use and how often. The doses listed below
are expressed in International Units (IU).
Women
If you do not ovulate and have irregular or absent menstrual cycles

• This medicine is usually administered daily.
• If you have irregular menstrual cycles, start using this medicine 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 this medicine is usually individualized and may be gradually adjusted.
• 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, an hCG produced in the laboratory using a specific DNA technique). A single injection of 250 micrograms of r-hCG or 5,000–10,000 IU of hCG will be administered 24–48 hours after the last injection of Ovaleap. The most suitable days for sexual intercourse are the day of the hCG injection and the following day. Alternatively, intrauterine insemination may be performed, depositing sperm into the uterine cavity.

If your doctor does not observe the desired response, continuation of that treatment cycle with
Ovaleap 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 also section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”]. In the next cycle, your doctor will administer a lower dose of Ovaleap.
If you need multiple oocytes to be developed for assisted reproductive techniques

• The usual initial dose of this medicine is individualized and may be gradually increased up to a maximum of 450 IU per day.
• 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 be given hCG or r-hCG. A single injection of 250 micrograms of r-hCG or 5,000–10,000 IU of hCG will be administered 24–48 hours after the last injection of Ovaleap. This prepares the oocytes for retrieval.

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

• The usual initial dose of Ovaleap is between 75 and 150 IU together with 75 IU of lutropin alfa.

• You will need to use these two medicines daily for up to 5 weeks.

• The dose of Ovaleap 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 be given hCG or r-hCG. A single injection of 250 micrograms of r-hCG or 5,000–10,000 IU of hCG will be administered 24–48 hours after the last injection of Ovaleap 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 medically assisted reproductive procedure may be performed,
  based on your doctor’s judgment.
  If your doctor does not observe the desired response after 5 weeks, that treatment cycle should be
  discontinued. In the next treatment cycle, your doctor may administer a higher initial dose of this medicine.
  If an excessive response occurs, treatment with Ovaleap must be stopped and administration of hCG should be withheld [see also section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”]. In the next cycle, treatment should be restarted with a lower dose of Ovaleap.
  Men

• The usual dose of this medicine is 150 IU together with hCG.

• You will need to use these two medicines three times a week for at least 4 months.

• If, after 4 months, you have not responded to treatment, your doctor may recommend continuing the use of both medicines for at least 18 months.

How are the injections given?
This medicine is administered by injection into the tissue directly beneath the skin (subcutaneous injection) using the Ovaleap Pen. The Ovaleap Pen is a device (a “pen”) used to administer injections into the tissue directly beneath the skin.
Your doctor may suggest that you learn to self-inject the medicine. Your doctor or nurse will provide instructions on how to do this, and additional information can be found in the separate instructions for use of the pen. Do not attempt to self-administer this medicine without proper training from your doctor or nurse. The first injection of this medicine must be given only under the supervision of a doctor or nurse.
The injectable solution in Ovaleap cartridges is designed for use with the Ovaleap Pen. You must carefully follow the separate instructions for using the Ovaleap Pen. The pen’s instructions for use are provided with the Ovaleap Pen. However, appropriate management of your condition requires close and continuous cooperation with your doctor.
Dispose of used needles immediately after injection.
If you use more Ovaleap than you should
No effects due to overdose of Ovaleap have been reported; however, Ovarian Hyperstimulation Syndrome (OHSS) may occur, as described in section 4, “Serious side effects in women”. However, OHSS can occur only if hCG has also been administered [see also section 2, “Ovarian Hyperstimulation Syndrome (OHSS)”].
If you forget to use Ovaleap
Do not use a double dose to make up for a forgotten dose. Inform your doctor as soon as you realize you have missed a dose.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or
nurse.

4. Possible side effects

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

Important side effects

Severe side effects in both men and women

• Very rarely (may affect up to 1 in 10,000 people), allergic reactions have been reported, such as rash, raised itchy areas of skin, and severe allergic reactions with weakness, drop in blood pressure, breathing difficulties, and swelling of the face. If you think you are experiencing such a reaction, stop your Ovaleap injections and contact your doctor immediately.

Severe side effects in women

• Lower abdominal pain in combination with nausea or vomiting may be symptoms of ovarian hyperstimulation syndrome (OHSS). This may indicate that the ovaries are over-responding 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 output, 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 (may affect up to 1 in 1,000 people), complications of OHSS may occur, such as ovarian torsion or blood clotting.
• Very rarely (may affect up to 1 in 10,000 people), serious blood clotting complications (thromboembolic events), sometimes independent of OHSS, may occur. These may cause chest pain, shortness of breath, stroke, or heart attack [see also section 2 “Blood clotting disorders (thromboembolic events)”]. If you experience any of the side effects described, contact your doctor immediately; your doctor may instruct you to stop using 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, bruising, swelling and/or irritation
• Headache
• Fluid-filled sacs in the ovary (ovarian cysts)

Common (may affect up to 1 in 10 people)

• Abdominal pain
• Bloating
• Abdominal cramps
• Nausea
• Vomiting
• Diarrhoea

Very 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, 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 the breast gland
• Acne
• Weight gain

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

• Asthma may worsen

Reporting of side effects

If you get any side effects, including any not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 that month.
Store in a refrigerator (2 °C–8 °C).
Do not freeze.
Keep the cartridge in the outer packaging to protect the medicine from light.
Before opening and within the shelf-life period, the medicine may be removed from refrigeration and stored unrefrigerated for up to 3 months. Do not store above 25 °C.
Discard the medicine if not used within 3 months.
Once opened, the cartridge contained in 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 together with the Ovaleap Pen.
Replace the 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.
Do not dispose of medicines via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Ovaleap contains

• 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 disodium dihydrogen phosphate dihydrate, sodium hydroxide (2 M) (for pH adjustment), mannitol, methionine, polysorbate 20, benzyl alcohol, benzalkonium chloride, and water for injections. All the dosage forms listed above contain these excipients.

Description of the appearance of Ovaleap and contents of the pack
Ovaleap is an injectable solution (injection preparation). Ovaleap is a clear and colourless solution.
Ovaleap 300 UI/0.5 mL is available in packs containing 1 cartridge and 10 injection needles.
Ovaleap 450 UI/0.75 mL is available in packs containing 1 cartridge and 10 injection needles.
Ovaleap 900 UI/1.5 mL is available in packs containing 1 cartridge and 20 injection needles.
Not all 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

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/.