Pergoveris

Package leaflet: Information for the user

Pergoveris 150 UI/75 UI powder and solvent for injectable solution

follitropin alfa/lutropin alfa
Please read 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 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, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Pergoveris is and what it is used for

What Pergoveris is
Pergoveris contains two different active substances called "follitropin alfa" and "lutropin alfa". Both belong to a family of hormones known as "gonadotropins", which are involved in reproduction and fertility.

What Pergoveris is used for
This medicine is used to stimulate the development of follicles (each of which contains an egg) in the ovaries. This helps you become pregnant. It is intended for use in adult women (aged 18 years and older) who have low levels (severe deficiency) of "follicle-stimulating hormone" (follicle stimulating hormone, FSH) and "luteinising hormone" (luteinising hormone, LH). These women are generally infertile.

How Pergoveris works
The active substances in Pergoveris are copies of the natural hormones FSH and LH. In the body:

• FSH stimulates egg production
• LH triggers egg release

By replacing the missing hormones, Pergoveris enables women with low levels of FSH and LH to develop a follicle. This follicle will then release an egg following an injection of the hormone "human chorionic gonadotropin" (human Chorionic Gonadotropin, hCG). This process helps women become pregnant.

2. What you need to know before using Pergoveris

Before starting treatment, a doctor experienced in the treatment of fertility disorders should adequately assess the fertility status of both partners.
Do not use Pergoveris

• if you are allergic to follicle-stimulating hormone (FSH), luteinizing hormone (LH), or any of the other ingredients of this medicine (listed in section 6)
• if you have a brain tumor (of the hypothalamus or pituitary gland)
• if you have ovarian enlargement or fluid-filled sacs in the ovary (ovarian cysts) of unknown origin
• if you have vaginal bleeding of unknown origin
• if you have cancer of the ovary, uterus, or breast
• if you have a condition that would make a normal pregnancy impossible, such as premature menopause, reproductive tract malformations, or benign uterine tumors.

Do not use this medicine if you have any of these conditions. If you have any doubts, consult your doctor, pharmacist, or nurse before using this medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Pergoveris.
Porphyria
Talk to your doctor before starting treatment if you or a family member has porphyria (a condition involving inability to break down porphyrins, which may be inherited).
Contact your doctor immediately if:

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

In such cases, your doctor may recommend that you stop treatment.
Ovarian hyperstimulation syndrome (OHSS)
This medicine stimulates the ovary. This increases the risk of developing ovarian hyperstimulation syndrome (OHSS). In this condition, ovarian follicles develop excessively and turn into large cysts. Inform your doctor immediately 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 “More serious side effects”).
If you are anovulatory and follow the recommended dose and administration schedule correctly, the risk of severe OHSS is less likely. Treatment with Pergoveris rarely causes severe OHSS. The risk is higher if a medicine (containing human chorionic gonadotropin – hCG) is administered to induce ovulation (see section 3 “What dose to use” for further details). If you are developing OHSS, your doctor may decide not to administer hCG during this treatment cycle and may advise you to avoid sexual intercourse or to use a barrier contraceptive method for at least four days.
Your doctor will schedule careful monitoring of ovarian response using ultrasound and blood tests (estradiol measurements) before and during treatment.
Multiple pregnancy
When using Pergoveris, there is a higher chance of multiple pregnancy compared to natural conception, most commonly twins. 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 Pergoveris at the appropriate times.
To minimize the risk of multiple pregnancy, ultrasound scans and blood tests are recommended.
Miscarriage
If you undergo assisted reproductive procedures or ovarian stimulation for egg production, your risk of miscarriage is higher than in women who conceive naturally.
Ectopic pregnancy
Women who have blocked or damaged fallopian tubes (tubal disorders) are at risk of ectopic pregnancy (pregnancy with embryo implanted outside the uterus), whether pregnancy occurs spontaneously or through infertility treatments.
Blood clotting disorders (thromboembolic events)
Talk to your doctor before using Pergoveris if you have had blood clots in your legs or lungs, a heart attack, or a stroke, or if these events have occurred in your family. You may be at increased risk of blood clots, or existing clots may worsen during treatment with Pergoveris.
Sex organ tumors
Cases of benign and malignant tumors of the ovaries or other sex organs have been reported in women undergoing repeated infertility treatments.
Allergic reactions
Isolated cases of non-severe allergic reactions to Pergoveris have been observed. If you have ever had such a reaction to similar medicines, inform your doctor before using Pergoveris.
Children and adolescents
Pergoveris is not indicated for use in children and adolescents under 18 years of age.
Other medicines and Pergoveris
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pergoveris must not be used with other medicines in the same injection, except follitropin alfa, if prescribed by your doctor.
Pregnancy and breastfeeding
Do not use Pergoveris during pregnancy or breastfeeding.
Driving and using machines
This medicine is not expected to affect your ability to drive or use machinery.
Pergoveris contains sodium
Pergoveris contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially “sodium-free”.

3. How to use Pergoveris

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

• Pergoveris must be administered by subcutaneous injection (under the skin). To minimize skin irritation, choose a different injection site each day.
• It is supplied as a powder and solvent, which you must mix together and use immediately.
• Your doctor or nurse will show you how to prepare and inject this medicine. They will supervise your first injection.
• If they are confident that you can safely administer Pergoveris, you may prepare and inject the medicine at home. In doing so, carefully read and follow the instructions below entitled “How to prepare and use the powder and solution of Pergoveris”.

Which dose to use
The usual starting dose of Pergoveris is one vial per day.

• Depending on your response, your doctor may decide to add a daily dose of a licensed preparation of follitropin alfa to the Pergoveris injection. In this case, the dose of follitropin alfa is generally increased every 7 or 14 days from 37.5 to 75 IU.
• Treatment continues until the desired response is achieved, that is, when you have developed an adequate follicle, as assessed by ultrasound and blood tests.
• This may take up to 5 weeks.

When the desired response is achieved, you will receive a single injection of human chorionic gonadotropin (hCG) 24–48 hours after the last Pergoveris injection. 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, according to your doctor’s judgment.
If your body responds excessively, treatment will be stopped and you will not receive hCG (see section 2 “Ovarian hyperstimulation syndrome (OHSS)”). In this case, your doctor will prescribe a lower dose of follitropin alfa in the next cycle.
How to prepare and use the powder and solvent of Pergoveris
Before starting preparation, read these instructions in full:
Perform the self-injection at the same time each day.

1. Wash your hands and find a clean surface

• It is important to make sure that your hands and equipment are clean.
• Suitable places are a clean table or clean kitchen countertop.

2. Prepare and lay out on a surface all the necessary items:

• 1 vial containing Pergoveris powder
• 1 vial containing water for injectable solutions (solvent)

Not supplied in the package:

• 2 alcohol-impregnated cotton swabs
• 1 empty syringe for injection
• 1 needle for preparation
• 1 fine needle for subcutaneous injections
• a special container for the disposal of glass and needles

3. Prepare the solution

• Remove the protective closure cap from the vial filled with
  water (solvent vial).

• Attach the preparation needle to the empty injection syringe.

• Draw a small amount of air into the syringe by pulling the plunger to the mark indicating approximately 1 mL.

• Insert the needle into the solvent vial, then push the plunger to expel the air.

• Invert the vial and slowly withdraw all the water (solvent) into the syringe.

• Remove the syringe from the vial and place it gently aside. Do not touch the needle and avoid contact with any surface.

Remove the protective closure cap from the vial containing the
Pergoveris powder.

• Take the syringe and slowly inject its contents into the vial of powder.
• Gently rotate the vial without removing the syringe. Do not shake.
• After the powder has dissolved (which should occur immediately), check that the resulting solution is clear and free from particles.
• Invert the vial and slowly re-aspirate the solution back into the syringe. Check again for particles as before; if the solution is not clear, do not use it.

4. Prepare the syringe for injection

• Replace the needle with the thin needle for injection.
• Remove any air bubbles: if you see air bubbles in the syringe, hold it with the needle pointing upwards, and gently tap the syringe until all the air collects at the top. Gently push the plunger of the syringe until all air bubbles have been expelled.

5. Inject the dose

• Inject the solution immediately: your doctor or nurse should have already informed you of the injection site (e.g., abdomen, front of the thigh). To minimize skin irritation, choose a different injection site each day.
• Clean the injection area with alcohol using a circular motion.
• Firmly pinch the skin at the injection site and insert the needle at an angle between 45° and 90° with a quick, dart-like motion.
• Inject the solution subcutaneously, as you have been taught. Do not inject directly into a vein.
• Inject the solution by slowly depressing the syringe plunger. Make sure to inject the entire solution.
• Then, remove the needle and clean the skin with a new alcohol swab using a circular motion.

6. After injection

Disposal of used materials: Immediately after completing the injection, dispose of all needles and empty vials in a sharps disposal container. Any unused solution must also be discarded.
If you use more Pergoveris than you should
The effects of an overdose of Pergoveris are unknown; however, ovarian hyperstimulation syndrome (OHSS) may occur. This, however, can happen only if hCG is also administered (see section 2, "Ovarian hyperstimulation syndrome (OHSS)").
If you forget to use Pergoveris
Do not use a double dose to make up for a forgotten dose. Contact your doctor.
If you have any doubts 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.
More serious side effects
Contact your doctor immediately if you experience any of the side effects listed below. Your
doctor may ask you to stop using Pergoveris.
Allergic reactions
Sometimes, allergic reactions such as skin rash, redness, itching, swelling of the face with breathing difficulties can be severe. This side effect is very rare.
Ovarian Hyperstimulation Syndrome (OHSS)

• Pelvic pain in combination with nausea or vomiting may be symptoms of Ovarian Hyperstimulation Syndrome (OHSS). The ovaries may over-respond to treatment and develop large fluid-filled sacs or cysts (see section 2 “Ovarian hyperstimulation syndrome (Ovarian hyperstimulation syndrome, OHSS)”). This side effect is common. In such cases, your doctor should examine you as soon as possible.
• OHSS can 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 not common (may affect up to 1 in 100 people).
• Rarely, complications of OHSS may occur, such as ovarian torsion or blood clotting (may affect up to 1 in 1,000 people).
• Very rarely, severe blood clotting complications (thromboembolic events) may occur, usually associated with severe OHSS. This may cause chest pain, shortness of breath, stroke or heart attack. In rare cases, this may also occur independently of OHSS (see section 2 “Disturbances of blood clotting (thromboembolic events)”).

Other side effects include
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, itching, bruising, swelling or irritation.

Common (may affect up to 1 in 10 people)

• diarrhoea
• breast pain
• nausea or vomiting
• abdominal or pelvic pain
• abdominal cramps or bloating

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

• Asthma may worsen.

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

5. How to store Pergoveris

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vials and the outer carton after
Exp. The expiry date refers to the last day of that month.
Do not store above 25°C. Store in the original packaging to protect the medicine from light.
The medicine should be administered immediately after reconstitution.
Do not use Pergoveris if you notice any visible signs of deterioration.
The reconstituted solution must not be administered if it contains particles or is not clear.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Pergoveris contains
The active substances are follitropin alfa and lutropin alfa.

• One vial contains 150 IU (equivalent to 11 micrograms) of follitropin alfa and 75 IU (equivalent to 3 micrograms) of lutropin alfa.
• After reconstitution, each mL of solution contains 150 IU of follitropin alfa and 75 IU of lutropin alfa per millilitre.

The other components are

• Sucrose, disodium phosphate dihydrate, sodium dihydrogen phosphate monohydrate, methionine, polysorbate 20, as well as concentrated phosphoric acid and sodium hydroxide for pH adjustment.

Description of the appearance of Pergoveris and contents of the pack

• Pergoveris is presented as a powder and solvent for injectable solution.
• The powder is a white or almost white lyophilised granule in a glass vial with a bromobutyl rubber stopper, containing 150 IU (equivalent to 11 micrograms) of follitropin alfa and 75 IU (equivalent to 3 micrograms) of lutropin alfa.
• The solvent is a clear, colourless liquid in a glass vial containing 1 mL of water for injections.
• Pergoveris is supplied in pack sizes of 1, 3 and 10 vials of powder with the corresponding number of solvent vials (1, 3 and 10 vials). Not all pack sizes may be marketed.

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, Netherlands
Manufacturer
Merck Serono S.p.A, Via delle Magnolie 15 (Zona industriale), 70026 Modugno (Bari), Italy
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu/ .

Package leaflet: information for the user

Pergoveris (300 IU + 150 IU)/0.48 mL solution for injection in pre-filled pen

follitropin alfa/lutropin alfa
Please read 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, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Pergoveris is and what it is used for

What Pergoveris is
Pergoveris contains two different active substances called "follitropin alfa" and "lutropin alfa". Both belong to a family of hormones known as "gonadotropins", which are involved in reproduction and fertility.
What Pergoveris is used for
This medicine is used to stimulate the development of follicles (each containing an egg) in the ovaries, in order to help you become pregnant. It is intended for use in adult women (aged 18 years and older) who have low levels (severe deficiency) of "follicle-stimulating hormone" (FSH) and "luteinising hormone" (LH). These women are usually infertile.
How Pergoveris works
The active substances in Pergoveris are copies of the natural hormones FSH and LH. In the body:

• FSH stimulates the production of eggs
• LH stimulates the release of eggs.

By replacing the missing hormones, Pergoveris enables women with low levels of FSH and LH to develop a follicle. This follicle will then release an egg following an injection of the hormone "human Chorionic Gonadotropin (hCG)". This process helps women to become pregnant.

2. What you should know before using Pergoveris

Before starting treatment, a physician experienced in the management of fertility disorders should have adequately assessed the couple's fertility.
Do not use Pergoveris

• if you are allergic to follicle-stimulating hormone (FSH), luteinizing hormone (LH), or any of the other ingredients of this medicine (listed in section 6)
• if you have a brain tumor (of the hypothalamus or pituitary gland)
• if you have ovarian enlargement or fluid-filled sacs in the ovary (ovarian cysts) of unknown origin
• if you have vaginal bleeding of unknown origin
• if you have cancer of the ovary, uterus, or breast
• if you have a condition that would make a normal pregnancy impossible, such as premature menopause, reproductive tract malformations, or benign uterine tumors.

Do not use this medicine if you suffer from any of these conditions. If you have any doubts, consult your doctor, pharmacist, or nurse before using this medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Pergoveris.
Porphyria
Talk to your doctor before starting treatment if you or a family member has porphyria (an inability to break down porphyrins, which may be inherited from parents).
Immediately inform your doctor if:

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

In such cases, your doctor may recommend that you stop treatment.
Ovarian hyperstimulation syndrome (OHSS)
This medicine stimulates the ovary. This increases the risk of developing ovarian hyperstimulation syndrome (OHSS). In this condition, 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 “More serious side effects”).
If you are anovulatory patients and if the recommended dose and administration schedule are properly followed, the risk of severe OHSS is less likely. Treatment with Pergoveris rarely causes severe OHSS. This is more likely if a medicine (containing human chorionic gonadotropin – hCG) is administered to induce ovulation (see section 3 “What dose to use” for further details). If you are developing OHSS, your doctor may decide not to administer hCG in this treatment cycle and may advise you to avoid sexual intercourse or to use a barrier contraceptive for at least four days.
Your doctor will schedule careful monitoring of ovarian response through ultrasound and blood tests (estradiol measurements), both before and during treatment.
Multiple pregnancy
When using Pergoveris, you have a higher risk of multiple pregnancy than with natural conception, most commonly twins. 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 Pergoveris at the appropriate time.
To minimize the risk of multiple pregnancy, ultrasound scans and blood tests are recommended.
Miscarriage
If you undergo assisted reproductive procedures or ovarian stimulation for egg production, the risk of miscarriage is higher than in other women.
Ectopic pregnancy
Women who have blocked or damaged fallopian tubes (tubal disorders) are at risk of pregnancies where the embryo implants outside the uterus (ectopic pregnancy), whether the pregnancy occurs spontaneously or through infertility treatments.
Blood clotting disorders (thromboembolic events)
Talk to your doctor before using Pergoveris if you have had blood clots in your legs or lungs, a heart attack, or a stroke, or if such events have occurred in your family. You may be at increased risk of blood clots, or existing clots may worsen during treatment with Pergoveris.
Sex organ tumors
Cases of benign and malignant tumors of the ovaries or other sex organs have been reported in women undergoing repeated regimens for infertility treatment.
Allergic reactions
Isolated cases of non-severe allergic reactions to Pergoveris have been observed. If you have ever had this type of reaction to similar medicines, inform your doctor before using Pergoveris.
Children and adolescents
The use of Pergoveris is not indicated in children and adolescents under 18 years of age.
Other medicines and Pergoveris
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pergoveris must not be mixed with other medicines in the same injection. Pergoveris may be used with an authorized preparation of follitropin alfa as separate injections, if prescribed by your doctor.
Pregnancy and breastfeeding
Do not use Pergoveris during pregnancy or breastfeeding.
Driving and using machines
This medicine is not expected to affect your ability to drive or operate machinery.
Pergoveris contains sodium
Pergoveris contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.

3. How to use Pergoveris

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

• Pergoveris must be administered by subcutaneous injection (injected under the skin). To minimize skin irritation, choose a different injection site each day.
• Your doctor or nurse will show you how to use the Pergoveris pre-filled pen to inject the medicine.
• Once you and your doctor are confident that you can safely administer Pergoveris, you may prepare and inject the medicine at home.
• If you self-administer Pergoveris, read and carefully follow the instructions provided in the “Instructions for use”.

What dose to use
Treatment starts with the recommended dose of Pergoveris, which is 150 International Units (IU) of follitropin alfa and 75 IU of lutropin alfa, administered daily.

• Depending on your response, your doctor may decide to add daily injections of an authorized preparation of follitropin alfa to the Pergoveris injection. In this case, the dose of follitropin alfa is generally increased every 7 or 14 days by 37.5 to 75 IU.
• Treatment continues until the desired response is achieved—namely, when you have developed a suitable follicle, as assessed by ultrasound and blood tests.
• This may take up to 5 weeks.

When the desired response is achieved, you will receive a single injection of human chorionic gonadotropin (hCG) 24–48 hours after the last Pergoveris injection. 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, according to your doctor’s judgment.
If your body responds excessively, treatment will be stopped and you will not receive hCG (see section 2 “Ovarian hyperstimulation syndrome (OHSS)”). In this case, your doctor will administer a lower dose of follitropin alfa in the next cycle.
If you use more Pergoveris than you should
The effects of an overdose of Pergoveris are not known, but OHSS may occur. However, this can happen only if hCG is also administered (see section 2 “Ovarian hyperstimulation syndrome (OHSS)”).
If you forget to use Pergoveris
Do not use a double dose to make up for a forgotten dose. Contact your doctor.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

More serious side effects

Contact your doctor immediately if you notice any of the following side effects. Your doctor may ask you to stop using Pergoveris.

Allergic reactions
Allergic reactions such as skin rash, redness, itching, or swelling of the face with breathing difficulties may occasionally occur and can be severe. This side effect is very rare.

Ovarian Hyperstimulation Syndrome (OHSS)

• Pelvic pain in combination with nausea or vomiting may be symptoms of Ovarian Hyperstimulation Syndrome (OHSS). The ovaries may over-respond to treatment and develop large fluid-filled sacs or cysts (see section 2 “Ovarian hyperstimulation syndrome (Ovarian hyperstimulation syndrome, OHSS)”). This side effect is common. In such cases, your doctor should examine you as soon as possible.
• OHSS can 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, complications of OHSS may occur, such as ovarian torsion or blood clotting (may affect up to 1 in 1,000 people).
• Very rarely, serious blood clotting complications (thromboembolic events) may occur, usually in association with severe OHSS. These may cause chest pain, shortness of breath, stroke, or heart attack. In rare cases, this may also occur independently of OHSS (see section 2 “Blood clotting disorders (thromboembolic events)”).

Other side effects include

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, itching, bruising, swelling, or irritation.

Common (may affect up to 1 in 10 people)

• diarrhoea
• breast pain
• nausea or vomiting
• abdominal or pelvic pain
• abdominal cramps or bloating

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

• Asthma may worsen.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through 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 Pergoveris

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and on the carton 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.
After opening, the pre-filled pen may be stored for up to 28 days outside the refrigerator (at 25 °C). Do not use any medicine remaining in the pre-filled pen after 28 days.
Do not use Pergoveris if you notice any visible signs of deterioration, if the liquid contains particles or if it is not clear.
After injection, dispose of the used needle safely.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Pergoveris contains
The active substances are follitropin alfa and lutropin alfa.

• Each pre-filled pen of Pergoveris (300 IU + 150 IU)/0.48 mL contains 300 IU (International Units) of follitropin alfa and 150 IU of lutropin alfa in 0.48 mL and can deliver two doses of Pergoveris 150 IU/75 IU.

The other components are

• Sucrose, monohydrochloride arginine, poloxamer 188, methionine, phenol, disodium phosphate dihydrate, monosodium phosphate monohydrate and water for injections. Small amounts of concentrated phosphoric acid and sodium hydroxide are added to maintain normal acidity levels (pH levels).

Description of the appearance of Pergoveris and contents of the pack
Pergoveris is a clear, colourless to slightly yellowish, injectable solution in a multidose pre-filled pen:

• Pergoveris (300 IU + 150 IU)/0.48 mL is supplied in packs containing 1 multidose pre-filled pen and 5 single-use injection needles.

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
Manufacturer
Merck Serono S.p.A, Via delle Magnolie 15 (Zona industriale), 70026 Modugno (Bari), Italy
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/ .

Instructions for use

Pergoveris

(300 UI + 150 UI)/0.48 mL (450 UI + 225 UI)/0.72 mL (900 UI + 450 UI)/1.44 mL
Prefilled pen injection solution
Follitropin alfa/Lutropin alfa

Contents
Important information about the Pergoveris prefilled pen
How to use the treatment diary for the Pergoveris prefilled pen
Getting to know the Pergoveris prefilled pen
Step 1 Prepare what you need
Step 2 Prepare for injection
Step 3 Attach the needle
Step 4 Set the dose
Step 5 Inject the dose
Step 6 Remove the needle after each injection
Step 7 After the injection
Step 8 Store the Pergoveris prefilled pen
Treatment diary for the Pergoveris prefilled pen

Important information about the Pergoveris prefilled pen

• Read the Instructions for Use and the Package Leaflet before using the prefilled pen

Pergoveris.

• Always follow all instructions provided in these Instructions for Use and those given by your healthcare provider, as they may differ from those used previously. These instructions will help you avoid treatment errors, infections from needle sticks, or injuries caused by broken glass.
• The pre-filled pen Pergoveris is intended for subcutaneous injection only.
• Use the pre-filled Pergoveris pen only if a healthcare professional has shown you how to use it correctly.
• Your healthcare provider will tell you how many pre-filled Pergoveris pens you need to complete your treatment.
• Administer the injection at the same time every day.
• The pen is supplied in three different multi-dose formulations:

(300 UI + 150 UI)/0.48 mL • Contains 0.48 mL of Pergoveris solution
• Contains 300 UI of follitropin alfa and 150 UI of lutropin alfa.
(450 UI + 225 UI)/0.72 mL • Contains 0.72 mL of Pergoveris solution
• Contains 450 UI of follitropin alfa and 225 UI of lutropin alfa.
(900 UI + 450 UI)/1.44 mL • Contains 1.44 mL of Pergoveris solution
• Contains 900 UI of follitropin alfa and 450 UI of lutropin alfa.
Note: The maximum dose that can be set is 300 UI for the (300 UI + 150 UI)/0.48 mL formulation. The maximum dose that can be set is 450 UI for both the (450 UI + 225 UI)/0.72 mL and (900 UI + 450 UI)/1.44 mL formulations. The dose-setting knob rotates in increments of 12.5 UI to reach the desired dose.

Refer to the Package Leaflet for further information on the recommended dosing regimen and always follow the dose prescribed by your healthcare provider.

• The dose control window displays numbers in International Units (IU), corresponding to the dose of follitropin alfa. Your healthcare provider will tell you how many IU of follitropin alfa you should inject each day.
• The numbers displayed in the dose control window will help you to:

a. Set the prescribed dose (Figure 1).

b. Confirm that the injection has been

completed (Figure 2).
c. Read the remaining dose to be injected

using a second pen (Figure 3).

• Remove the needle from the pen immediately after each injection.

Do not reuse needles.
Do not share the pen and/or needles with other people.
Do not use the pre-filled Pergoveris pen if it has been dropped or if the pen is cracked or damaged, as you may injure yourself.

How to use the treatment diary with the pre-filled Pergoveris pen
A treatment diary is attached at the last page. Use the treatment diary to record the amounts injected.
Injecting incorrect amounts of medication could affect your treatment.

• Record the treatment day (column 1), date (column 2), time of injection (column 3), and volume contained in the pen (column 4).
• Record the prescribed dose (column 5).
• Check correct dose setting before injection (column 6).
• After the injection, read the number shown in the dose control window.
• Confirm administration of a complete injection (column 7), or record the number shown in the dose control window if different from “0” (column 8).
• If necessary, administer an injection with a second pen, setting the remaining dose that was recorded in the column “Amount to select for second injection” (column 8).
• Record this remaining dose in the “Amount to inject” section on the following line (column 6).

By using the treatment diary to record your daily injection(s), you can verify each day that you have received the full prescribed dose.
Example of a treatment diary using a pen of (450 UI + 225 UI)/0.72 mL:

Become familiar with the pre-filled Pergoveris pen

Needle*:
Pre-filled pen:
*For illustrative purposes only.
**The numbers in the dose control window and on the cartridge label indicate the number of International Units (IU) of medication.

Step 1 Prepare the necessary items
1.1 Allow the pre-filled pen to reach room temperature by leaving it at room temperature for at least 30 minutes before use.
Do not use a microwave or other heating devices to warm the pen.
1.2 Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.

1.3 Additional required materials (not included in the package):

• Alcohol wipes and a sharps disposal container (Figure 4).
  1.4 Wash your hands thoroughly with soap and water, then dry them

completely (Figure 5).
1.5 Remove the pre-filled Pergoveris pen from its packaging with one hand.
Do not use tools or other devices, as they may damage the pen.
1.6 Check that the name printed on the pen is Pergoveris.
1.7 Check the expiration date printed on the pen label

(Figure 6).
Do not use the pre-filled Pergoveris pen if the expiration date has passed or if the pen does not display the name Pergoveris.

Step 2 Prepare for injection
2.1 Remove the pen cap (Figure 7).

2.2 Ensure that the medication appears clear, colorless, and free of particles.
Do not use the pre-filled pen if the medication is cloudy or has changed color, as this may cause infection.
2.3 Ensure that the dose control window displays “0” (Figure 8).
Choose an injection site:

2.4 A healthcare professional will show you the recommended injection sites on the abdominal area (Figure 9). To minimize skin irritation, select a different injection site each day.
2.5 Clean the skin at the injection site with an alcohol wipe.
Do not touch or cover the cleaned skin.

Step 3 Attach the needle
Important: Always use a new needle for each injection.
Using a previously used needle may cause infection.

3.1 Take a new needle. Use only the “single-use” needles supplied in the package.
3.2 Check that the outer needle cap is not damaged.
3.3 Hold the outer needle cap securely.
3.4 Check that the tear-off tab on the outer needle cap is intact and not loose, and that the expiration date has not passed (Figure 10).
3.5 Remove the tab (Figure 11).
Do not use the needle if it is damaged or expired, or if the outer needle cap or tear-off tab is damaged or loose. Using an expired needle or one with a damaged cap or tab may lead to infection. Dispose of it in a sharps container and take a new needle.
3.6 Screw the outer needle cap onto the threaded tip of the pre-filled Pergoveris pen until you feel slight resistance (Figure 12).
Do not overtighten the needle, as it may become difficult to remove after injection.
3.7 Remove the outer needle cap by pulling gently (Figure 13).
3.8 Set it aside for later use (Figure 14).
Do not discard the outer needle cap, as it will be needed later to prevent needle-stick injuries and infections when removing the needle from the pre-filled pen.
3.9 Hold the pre-filled Pergoveris pen with the needle pointing upward (Figure 15).
3.10 Carefully remove and discard the green inner protective cap (Figure 16).
Do not reattach the green inner protective cap to the needle. You may injure yourself with the needle and develop an infection.
3.11 Carefully examine the needle tip and check for one or more small drops of liquid.

If you do not see one or more small drops of liquid at or near the needle tip
the first time you use a new pen:

1. Gently turn the dose selector knob forward until the dose control window shows “25” (Figure 18).
   • If you go past “25”, you may turn the dose knob back.

2. Hold the pen with the needle pointing upward.
3. Lightly tap the reservoir container (Figure 19).
4. Press the dose selector knob fully down. A small drop of liquid should appear at the needle tip (Figure 20).
5. Check that the dose control window shows “0” (Figure 21).
6. Proceed to Step 4 Set the Dose. If no drop of liquid appears, contact your healthcare provider.

Step 4 Set the Dose
4.1. Rotate the dose selector knob until the prescribed dose appears in the dose control window.

• Example: if the prescribed dose to be injected is “150” IU, ensure that the number “150” appears in the dose control window (Figure 22). Injecting an incorrect amount of medicine may affect your treatment.

4.2. Check that the dose control window displays the full prescribed dose before proceeding to the next step.
Step 5 Inject the Dose

Important: inject the dose according to the instructions provided by your healthcare provider.
5.1 Slowly insert the entire needle into the skin (Figure 24).
5.2 Place your thumb in the center of the dose selector knob. Press the dose knob slowly and completely down and keep it pressed to complete the injection (Figure 25).
Note: the higher the dose, the longer it will take to inject.
5.3 Keep the dose knob pressed for at least

5 seconds before removing the needle from the skin (Figure 26).

• The number in the dose control window will return to “0”.

• After at least 5 seconds, while keeping the dose selector knob fully pressed, remove the needle from the skin (Figure 27).

• Once the needle has been removed from the skin, release the dose selector knob.

Do not release the dose knob until the needle has been removed from the skin.
Step 6 Remove the needle after each injection
6.1 Place the outer needle cap on a flat surface.
6.2 Hold the pre-filled pen Pergoveris firmly in one hand and place the needle into the outer cap.
6.3 Press the needle, covered by its cap, against a hard surface until you hear a click (Figure 29).
6.4 Grasp the outer needle cap and unscrew the needle by turning it in the opposite direction

(Figure 30).
6.5 Dispose of the used needle safely into a sharps container

(Figure 31). Handle the needle with care to avoid needle-stick injuries.
Do not reuse or share a used needle.
Step 7 After Injection
7.1 Check that you have completed a full injection:

• Check that the dose control window shows “0” (Figure 32).

If the dose control window shows “0”, this means the full dose has been administered.
If the dose control window shows a number higher than “0”, the pre-filled pen Pergoveris is empty.
The full prescribed dose has not been administered, and you must perform step 7.2 below.
7.2 Complete a partial injection (only if necessary):

• The dose control window shows the remaining amount that needs to be injected using a new pen. In the example shown, the amount still to be administered is “50” IU (Figure 33).
• To complete the dose with a second pen, repeat steps 1 through 8.

Step 8 Storing the pre-filled pen Pergoveris

8.1 Replace the cap on the pen to prevent infection (Figure 34).
8.2 Store the pen in its original packaging in a safe place as indicated in the Package Leaflet.
8.3 When the pen is empty, ask your healthcare provider how to dispose of it properly.
Do not store the pen with the needle still attached, as this may lead to infection.
Do not reuse the pre-filled pen Pergoveris if it has been dropped or if the pen is cracked or damaged, as this may cause injury.
If you have any questions, contact your healthcare provider.
Treatment diary for the pre-filled pen Pergoveris

These Instructions for Use were last updated on:

Package leaflet: Information for the user

Pergoveris (450 IU + 225 IU)/0.72 mL solution for injection in pre-filled pen

folitropin alfa/lutropin alfa
Please read this entire 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, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Pergoveris is and what it is used for

What Pergoveris is
Pergoveris contains two different active substances called "follitropin alfa" and "lutropin alfa". Both belong to a family of hormones known as "gonadotropins", which are involved in reproduction and fertility.

What Pergoveris is used for
This medicine is used to stimulate the development of follicles (each containing an egg) in the ovaries. This helps you to become pregnant. It is intended for use in adult women (aged 18 years and older) who have low levels (severe deficiency) of "follicle-stimulating hormone" (follicle stimulating hormone, FSH) and "luteinising hormone" (luteinising hormone, LH). These women are generally infertile.

How Pergoveris works
The active substances in Pergoveris are copies of the natural hormones FSH and LH. In the body:

• FSH stimulates the production of eggs
• LH stimulates the release of eggs.

By replacing the missing hormones, Pergoveris enables women with low levels of FSH and LH to develop a follicle. This will then release an egg following an injection of the hormone "human chorionic gonadotropin" (human Chorionic Gonadotropin, hCG). This process helps women to become pregnant.

2. What you need to know before using Pergoveris

Before starting treatment, a doctor experienced in the management of fertility disorders must adequately assess the fertility status of both partners.

Do not use Pergoveris

• if you are allergic to follicle-stimulating hormone (FSH), luteinizing hormone (LH), or any of the other ingredients of this medicine (listed in section 6)
• if you have a brain tumor (of the hypothalamus or pituitary gland)
• if you have ovarian enlargement or fluid-filled sacs in the ovary (ovarian cysts) of unknown origin
• if you have vaginal bleeding of unknown origin
• if you have cancer of the ovary, uterus, or breast
• if you have a condition that would make a normal pregnancy impossible, such as premature menopause, reproductive tract malformations, or benign uterine tumors.

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

Warnings and precautions

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

Porphyria
Talk to your doctor before starting treatment if you or a family member has porphyria (a disorder in the breakdown of porphyrins, which may be inherited from parents to children).

Contact your doctor immediately if:

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

In such cases, your doctor may advise you to stop treatment.

Ovarian hyperstimulation syndrome (OHSS)
This medicine stimulates the ovary, increasing the risk of developing ovarian hyperstimulation syndrome (OHSS). In this condition, ovarian follicles develop excessively and turn into large cysts. Contact your doctor immediately 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 “More serious side effects”).

If you are an anovulatory patient and follow the recommended dose and administration schedule, the risk of severe OHSS is less likely. Treatment with Pergoveris rarely causes severe OHSS. The risk is higher when a medicine containing human chorionic gonadotropin (hCG) is administered to induce ovulation (see section 3 “Which dose to use” for further details). If you are developing OHSS, your doctor may decide not to administer hCG in this treatment cycle and may advise you to avoid sexual intercourse or to use a barrier contraceptive method for at least four days.

Your doctor will schedule careful monitoring of ovarian response using ultrasound and blood tests (estradiol measurements) before and during treatment.

Multiple pregnancy
When using Pergoveris, 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 Pergoveris at the appropriate times.

To minimize the risk of multiple pregnancy, ultrasound scans and blood tests are recommended.

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

Ectopic pregnancy
Women who have blocked or damaged fallopian tubes (tubal disorders) are at risk of ectopic pregnancy—where the embryo implants outside the uterus—whether pregnancy occurs spontaneously or through infertility treatments.

Blood clotting disorders (thromboembolic events)
Talk to your doctor before using Pergoveris if you have had blood clots in your legs or lungs, a heart attack, or a stroke, or if such events have occurred in your family. You may be at increased risk of blood clots, or existing clots may worsen during treatment with Pergoveris.

Sex organ tumors
Cases of benign and malignant tumors of the ovaries or other sex organs have been reported in women undergoing repeated infertility treatments.

Allergic reactions
Isolated cases of non-severe allergic reactions to Pergoveris have been reported. If you have ever had this type of reaction to similar medicines, inform your doctor before using Pergoveris.

Children and adolescents
Pergoveris is not indicated for use in children and adolescents under 18 years of age.

Other medicines and Pergoveris
Inform your doctor or pharmacist if you are currently using, have recently used, or might use any other medicines.

Pergoveris must not be mixed with other medicines in the same injection. Pergoveris may be used together with an authorized preparation of follitropin alfa as separate injections, if prescribed by your doctor.

Pregnancy and breastfeeding
Do not use Pergoveris during pregnancy or breastfeeding.

Driving and using machines
Pergoveris is not expected to affect your ability to drive or operate machinery.

Pergoveris contains sodium
Pergoveris contains less than 1 mmol (23 mg) of sodium per dose and is therefore essentially "sodium-free".

3. How to use Pergoveris

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

• Pergoveris must be administered by subcutaneous injection (under the skin). To minimize skin irritation, choose a different injection site each day.
• Your doctor or nurse will show you how to use the Pergoveris pre-filled pen to inject the medicine.
• If you and your doctor are confident that you can safely administer Pergoveris, you may prepare and inject the medicine at home.
• If Pergoveris is self-administered, read and carefully follow the instructions provided in the “Instructions for use”.

Which dose to use
Treatment begins with the recommended dose of Pergoveris, consisting of 150 International Units (IU) of follitropin alfa and 75 IU of lutropin alfa, administered daily.

• Depending on your response, your doctor may decide to add a daily dose of an authorized preparation of follitropin alfa to the Pergoveris injection. In this case, the dose of follitropin alfa is generally increased every 7 or 14 days by 37.5 to 75 IU.
• Treatment continues until the desired response is achieved, that is, until you have developed a suitable follicle, as assessed by ultrasound and blood tests.
• This may take up to 5 weeks.

When the desired response is achieved, you will receive a single injection of human chorionic gonadotropin (hCG) 24–48 hours after the last Pergoveris injection. 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, according to your doctor’s judgment.
If your body responds excessively, treatment will be stopped and you will not receive hCG (see section 2 “Ovarian hyperstimulation syndrome (OHSS)”). In this case, your doctor will administer a lower dose of follitropin alfa in the next cycle.
If you use more Pergoveris than you should
The effects of an overdose of Pergoveris are unknown; however, ovarian hyperstimulation syndrome (OHSS) may occur. This, however, can occur only if hCG is also administered (see section 2 “Ovarian hyperstimulation syndrome (OHSS)”).
If you forget to use Pergoveris
Do not use a double dose to make up for the missed dose. Contact your doctor.
If you have any doubts about how to use 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.

More serious side effects
Contact your doctor immediately if you experience any of the side effects listed below. Your doctor
may ask you to stop using Pergoveris.

Allergic reactions
Sometimes, allergic reactions such as skin rash, redness, itching, or facial swelling with breathing difficulties can be severe. This side effect is very rare.

Ovarian Hyperstimulation Syndrome (OHSS)

• Pelvic pain in combination with nausea or vomiting may be symptoms of Ovarian Hyperstimulation Syndrome (OHSS). The ovaries may over-respond to treatment and develop large fluid-filled sacs or cysts (see section 2 “Ovarian Hyperstimulation Syndrome (Ovarian hyperstimulation syndrome, OHSS)”). This side effect is common. In such cases, your doctor should examine you as soon as possible.
• OHSS can 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, OHSS may lead to complications such as ovarian torsion or blood clotting (may affect up to 1 in 1,000 people).
• Very rarely, severe blood clotting complications (thromboembolic events) may occur, usually in association with severe OHSS. This may cause chest pain, shortness of breath, stroke, or heart attack. In rare cases, this may also occur independently of OHSS (see section 2 “Disturbances of blood clotting (thromboembolic events)”).

Other side effects include
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, itching, bruising, swelling, or irritation.

Common (may affect up to 1 in 10 people)

• diarrhoea
• breast pain
• nausea or vomiting
• abdominal or pelvic pain
• abdominal cramps or bloating

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

• Asthma may worsen.

Reporting of side effects
If you experience any side effect, including those 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. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Pergoveris

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and the carton after
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep in the original packaging to protect the medicine from light.
Once opened, the pre-filled pen may be stored for up to 28 days outside the refrigerator (at 25 °C). Do not use any medicine remaining in the pre-filled pen after 28 days.
Do not use Pergoveris if you notice any visible signs of deterioration, if the liquid contains particles or if it is not clear.
After injection, dispose of the used needle safely.
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 Pergoveris contains
The active substances are follitropin alfa and lutropin alfa.

• Each Pergoveris pre-filled pen (450 IU + 225 IU)/0.72 mL contains 450 IU (International Units) of follitropin alfa and 225 IU of lutropin alfa in 0.72 mL and can deliver three doses of Pergoveris 150 IU/75 IU.

The other components are

• Sucrose, arginine hydrochloride, poloxamer 188, methionine, phenol, disodium phosphate dihydrate, sodium dihydrogen phosphate monohydrate and water for injections. Small amounts of concentrated phosphoric acid and sodium hydroxide are added to maintain normal acidity levels (pH levels).

Description of the appearance of Pergoveris and contents of the pack
Pergoveris is a clear, colourless to slightly yellow, injectable solution in a multidose pre-filled pen:

• Pergoveris (450 IU + 225 IU)/0.72 mL is supplied in packs containing 1 multidose pre-filled pen and 7 single-use injection needles.

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, Netherlands
Manufacturer
Merck Serono S.p.A, Via delle Magnolie 15 (Zona industriale), 70026 Modugno (Bari), Italy
Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/ .

Instructions for use

Pergoveris

(300 UI + 150 UI)/0.48 mL (450 UI + 225 UI)/0.72 mL (900 UI + 450 UI)/1.44 mL
Prefilled pen injection solution
Follitropin alfa / Lutropin alfa

Contents
Important information about the Pergoveris prefilled pen
How to use the Pergoveris prefilled pen treatment diary
Become familiar with the Pergoveris prefilled pen
Step 1 Prepare the necessary items
Step 2 Prepare for injection
Step 3 Attach the needle
Step 4 Set the dose
Step 5 Administer the dose
Step 6 Remove the needle after each injection
Step 7 After the injection
Step 8 Store the Pergoveris prefilled pen
Pergoveris prefilled pen treatment diary

Important information about the Pergoveris prefilled pen

• Read the Instructions for Use and the Package Leaflet before using the prefilled pen

Pergoveris.

• Always follow all instructions provided in this User Manual and by your healthcare provider, as they may differ from those previously used. These instructions will help you avoid treatment errors, infections from needlestick injuries, or cuts from broken glass.
• The pre-filled pen Pergoveris is intended for subcutaneous injection only.
• Use the pre-filled pen Pergoveris only if a healthcare professional has shown you how to use it correctly.
• Your healthcare provider will tell you how many pre-filled pens Pergoveris you need to complete your treatment.
• Administer the injection at the same time every day.
• The pen is supplied in 3 different multi-dose formulations:

(300 IU + 150 IU)/0.48 mL • Contains 0.48 mL of Pergoveris solution

• Contains 300 IU of follitropin alfa and 150 IU of lutropin alfa.
  (450 IU + 225 IU)/0.72 mL • Contains 0.72 mL of Pergoveris solution
• Contains 450 IU of follitropin alfa and 225 IU of lutropin alfa.
  (900 IU + 450 IU)/1.44 mL • Contains 1.44 mL of Pergoveris solution
• Contains 900 IU of follitropin alfa and 450 IU of lutropin alfa.
  Note: The maximum dose that can be set is 300 IU for the (300 IU + 150 IU)/0.48 mL formulation. The maximum dose that can be set is 450 IU for both the (450 IU + 225 IU)/0.72 mL and the (900 IU + 450 IU)/1.44 mL formulations. The dose-setting dial rotates in increments of 12.5 IU to reach the desired dose.

Refer to the Package Leaflet for more information on the recommended dosing regimen and always follow the dose prescribed by your healthcare provider.

• The dose control window displays numbers in International Units (IU), corresponding to the dose of follitropin alfa. Your healthcare provider will tell you how many IU of follitropin alfa you should inject each day.
• The numbers displayed in the dose control window will help you:

a. Set the prescribed dose (Figure 1).

b. Confirm that the injection has been

completed (Figure 2).
c. Read the remaining dose to be administered

using a second pen (Figure 3).

• Remove the needle from the pen immediately after each injection.

Do not reuse needles.
Do not share the pen and/or needles with other people.
Do not use the pre-filled pen Pergoveris if it has been dropped or if the pen is cracked or damaged, as you may injure yourself.

How to use the treatment diary with the pre-filled pen Pergoveris
A treatment diary is attached on the last page. Use the treatment diary to record the amounts injected.
Injecting incorrect amounts of medication may affect your treatment.

• Record the treatment day (column 1), date (column 2), time of injection (column 3), and volume in the pen (column 4).
• Record the prescribed dose (column 5).
• Check the correct dose setting before injection (column 6).
• After injection, read the number shown in the dose control window.
• Confirm administration of a complete injection (column 7) or record the number shown in the dose control window if different from “0” (column 8).
• If necessary, administer an injection using a second pen, setting the remaining dose recorded in the “Amount to select for second injection” column (column 8).
• Record this remaining dose in the “Amount to inject” section on the next line (column 6).

By using the treatment diary to record daily injection(s), you can verify each day that you have received the full prescribed dose.
Example of a treatment diary using a pen with (450 IU + 225 IU)/0.72 mL:

Become familiar with the pre-filled pen Pergoveris

Needle*:
Pre-filled pen:
*For illustration purposes only.
**The numbers in the dose control window and on the cartridge container indicate the number of International Units (IU) of medication.

Step 1 Prepare the necessary items
1.1 Allow the pre-filled pen to reach room temperature for at least 30 minutes before use, so that the medication reaches room temperature.
Do not use a microwave or other heating devices to warm the pen.
1.2 Prepare a clean, flat surface in a well-lit area, such as a table or countertop.

1.3 Additional required materials (not included in the package):

• Alcohol wipes and a sharps disposal container (Figure 4).
  1.4 Wash your hands thoroughly with soap and water, then dry them

completely (Figure 5).
1.5 Remove the pre-filled pen Pergoveris from its packaging with one hand.
Do not use tools, as they may damage the pen.
1.6 Check that the name printed on the pen is Pergoveris.
1.7 Check the expiration date on the pen label

(Figure 6).
Do not use the pre-filled pen Pergoveris if the expiration date has passed or if the pen does not display the name Pergoveris.

Step 2 Prepare for injection
2.1 Remove the pen cap (Figure 7).

2.2 Ensure the medication appears clear, colourless, and free of particles.
Do not use the pre-filled pen if the solution is cloudy or discoloured, as this may cause infection.
2.3 Ensure the dose control window displays “0” (Figure 8).
Choose an injection site:

2.4 A healthcare professional will advise you on suitable injection sites on the abdominal area (Figure 9). To minimize skin irritation, select a different injection site each day.
2.5 Clean the skin at the injection site with an alcohol wipe.
Do not touch or cover the cleaned skin.

Step 3 Attach the needle
Important: Always use a new needle for each injection.
Using a previously used needle may cause infection.

3.1 Take a new needle. Use only the “single-use” needles supplied in the package.
3.2 Ensure the outer needle cap is not damaged.
3.3 Hold the outer needle cap firmly.
3.4 Check that the tear-off tab on the outer needle cap is intact and not loose, and that the expiration date has not passed (Figure 10).
3.5 Remove the tab (Figure 11).
Do not use the needle if it is damaged or expired, or if the outer needle cap or tear-off tab is damaged or loose. Using an expired needle or one with a damaged cap or tab may lead to infection. Dispose of it in a sharps container and take a new needle.
3.6 Screw the outer needle cap onto the threaded tip

of the pre-filled pen Pergoveris until you feel slight resistance (Figure 12).
Do not overtighten the needle, as it may become difficult to remove after injection.
3.7 Remove the outer needle cap by pulling gently (Figure 13).
3.8 Set it aside for later use (Figure 14).
Do not discard the outer needle cap, as it will be needed later to prevent needlestick injuries and infections when removing the needle from the pre-filled pen.
3.9 Hold the pre-filled pen Pergoveris with the needle pointing upward (Figure 15).
3.10 Carefully remove and dispose of the green inner needle shield (Figure 16).
Do not replace the green inner needle shield onto the needle. You may injure yourself with the needle and develop an infection.
3.11 Carefully examine the needle tip and check for one or more small drops of liquid.

If you do not see one or more small drops of liquid at or near the needle tip
the first time you use a new pen:

1. Gently turn the dose selector knob forward until the dose control window shows “25” (Figure 18).
   • If you go past “25”, you may turn the dose knob back.

2. Hold the pen with the needle pointing upward.
3. Lightly tap the reservoir holder (Figure 19).
4. Press the dose selector knob fully in. A small drop of liquid should appear at the needle tip (Figure 20).
5. Check that the dose control window shows “0” (Figure 21).
6. Proceed to Step 4 Set the Dose. If no drop of liquid appears, contact your healthcare provider.

Step 4 Set the Dose
4.1. Turn the dose selector knob until the prescribed dose appears in the dose control window.

• Example: If the prescribed dose to be injected is “150” IU, ensure that the number “150” appears in the dose control window (Figure 22). Injecting the wrong amount of medication may affect your treatment.

4.2. Check that the dose control window displays the full prescribed dose before proceeding to the next step.
Step 5 Inject the Dose

Important: Inject the dose following the instructions provided by your healthcare provider.
5.1 Slowly insert the entire needle into the skin (Figure 24).
5.2 Place your thumb on the center of the dose selector knob. Press slowly and fully in the dose knob and keep it pressed to complete the injection (Figure 25).
Note: The higher the dose, the longer it will take to inject.
5.3 Keep the dose knob pressed for at least

5 seconds before removing the needle from the skin (Figure 26).

• The number in the dose control window will return to “0”.

• After at least 5 seconds, while keeping the dose selector knob fully pressed, remove the needle from the skin (Figure 27).

• Once the needle has been removed from the skin, release the dose selector knob.

Do not release the dose knob until the needle has been removed from the skin.
Step 6 Remove the Needle After Each Injection
6.1 Place the outer needle cap on a flat surface.
6.2 Hold the pre-filled pen Pergoveris firmly in one hand and place the needle into the outer cap (Figure 28).
6.3 Now press the needle, covered by its cap, against a hard surface until you hear a click (Figure 29).
6.4 Hold the outer needle cap and unscrew the needle by turning it in the opposite direction

(Figure 30).
6.5 Dispose of the used needle safely in a sharps container

(Figure 31). Handle the needle with care to avoid needle-stick injury.
Do not reuse or share a used needle.
Step 7 After Injection
7.1 Check that you have completed the full injection:

• Check that the dose control window shows “0” (Figure 32).

If the dose control window shows “0”, this means the full dose has been administered.
If the dose control window shows a number higher than “0”, the pre-filled pen Pergoveris is empty.
The full prescribed dose has not been administered and you must perform step 7.2 below.
7.2 Complete a partial injection (only if necessary):

• The dose control window indicates the remaining amount to be injected using a new pen. In the example shown, the amount still to be administered is “50” IU (Figure 33).
• To complete the dose with a second pen, repeat steps 1 to 8.

Step 8 Store the Pre-filled Pen Pergoveris

8.1 Replace the cap on the pen to prevent infection (Figure 34).
8.2 Store the pen in its original packaging in a safe place as indicated in the Package Leaflet.
8.3 When the pen is empty, ask your healthcare provider how to dispose of it properly.
Do not store the pen with the needle still attached, as this may cause infection.
Do not reuse the pre-filled pen Pergoveris if it has been dropped or if the pen is cracked or damaged, as you may be injured.
If you have any questions, contact your healthcare provider.
Treatment Diary for the Pre-filled Pen Pergoveris

These Instructions for Use were last updated on:

Package leaflet: information for the user

Pergoveris (900 IU + 450 IU)/1.44 mL solution for injection in a pre-filled pen

follitropin alfa/lutropin alfa
Please read 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 could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

1. What Pergoveris is and what it is used for
2. What you need to know before using Pergoveris
3. How to use Pergoveris
4. Possible side effects
5. How to store Pergoveris
6. Package contents and other information

1. What Pergoveris is and what it is used for

What Pergoveris is
Pergoveris contains two different active substances called "follitropin alfa" and "lutropin alfa". Both belong to a family of hormones known as "gonadotropins", which are involved in reproduction and fertility.

What Pergoveris is used for
This medicine is used to stimulate the development of follicles (each containing an egg) in the ovaries. This helps you become pregnant. It is intended for use in adult women (aged 18 years and older) who have low levels (severe deficiency) of "follicle-stimulating hormone" (follicle stimulating hormone, FSH) and "luteinising hormone" (luteinising hormone, LH). These women are generally infertile.

How Pergoveris works
The active substances in Pergoveris are copies of the natural hormones FSH and LH. In the body:

• FSH stimulates the production of eggs
• LH stimulates the release of eggs.

By replacing the missing hormones, Pergoveris enables women with low levels of FSH and LH to develop a follicle. This follicle will then release an egg following an injection of the hormone "human Chorionic Gonadotropin" (human Chorionic Gonadotropin, hCG). This process helps women to become pregnant.

2. What you need to know before using Pergoveris

Before starting treatment, a doctor experienced in the management of fertility disorders must adequately assess the fertility status of both partners.
Do not use Pergoveris

• if you are allergic to follicle-stimulating hormone (FSH), luteinizing hormone (LH), or any of the other ingredients of this medicine (listed in section 6)
• if you have a brain tumour (of the hypothalamus or pituitary gland)
• if you have ovarian enlargement or fluid-filled sacs in the ovary (ovarian cysts) of unknown origin
• if you have vaginal bleeding of unknown origin
• if you have cancer of the ovary, uterus, or breast
• if you have a condition that would make a normal pregnancy impossible, such as premature menopause, reproductive tract malformations, or benign uterine tumours.

Do not use this medicine if you have any of these conditions. If you are in doubt, consult your doctor, pharmacist, or nurse before using this medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Pergoveris.
Porphyria
Talk to your doctor before starting treatment if you or a family member have porphyria (an inability to break down porphyrins, which may be inherited from parent to child).
Immediately inform your doctor if:

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

In such cases, your doctor may recommend that you stop treatment.
Ovarian hyperstimulation syndrome (OHSS)
This medicine stimulates the ovary. This increases the risk of developing ovarian hyperstimulation syndrome (OHSS). In this condition, 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 “More serious side effects”).
If you are anovulatory and if the recommended dose and administration schedule are properly followed, the risk of severe OHSS is less likely. Treatment with Pergoveris rarely causes severe OHSS. The risk is higher if a medicine containing human chorionic gonadotropin (hCG) is administered to induce ovulation (see section 3 “What dose to use” for further details). If you are developing OHSS, your doctor may decide not to administer hCG in this treatment cycle and may advise you to avoid sexual intercourse or to use a barrier contraceptive for at least four days.
Your doctor will schedule careful monitoring of ovarian response using ultrasound and blood tests (estradiol measurements), both before and during treatment.
Multiple pregnancy
When using Pergoveris, you have a higher chance of multiple pregnancy—most commonly twins—than with 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 Pergoveris at the correct time.
To minimize the risk of multiple pregnancy, ultrasound scans and blood tests are recommended.
Miscarriage
If you undergo assisted reproductive procedures or ovarian stimulation for egg production, the risk of miscarriage is higher than in other women.
Ectopic pregnancy
Women who have blocked or damaged fallopian tubes (tubal disorders) are at risk of ectopic pregnancy (pregnancy with embryo implanted outside the uterus), whether pregnancy occurs spontaneously or with infertility treatments.
Blood clotting disorders (thromboembolic events)
Talk to your doctor before using Pergoveris if you have had blood clots in the legs or lungs, heart attack, or stroke, or if such events have occurred in your family. You may be at increased risk of blood clots, or existing clots may worsen during treatment with Pergoveris.
Sex organ tumours
Cases of benign and malignant tumours of the ovaries or other sex organs have been reported in women undergoing repeated infertility treatments.
Allergic reactions
Isolated cases of non-serious allergic reactions to Pergoveris have been observed. If you have ever had such a reaction to similar medicines, inform your doctor before using Pergoveris.
Children and adolescents
Pergoveris is not indicated for use in children and adolescents under 18 years of age.
Other medicines and Pergoveris
Inform your doctor or pharmacist if you are currently using, have recently used, or might use any other medicines.
Pergoveris must not be mixed with other medicines in the same injection. Pergoveris may be used together with an authorized preparation of follitropin alfa as separate injections, if prescribed by your doctor.
Pregnancy and breastfeeding
Do not use Pergoveris during pregnancy or breastfeeding.
Driving and using machines
Pergoveris is not expected to affect your ability to drive or operate machinery.
Pergoveris contains sodium
Pergoveris contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially “sodium-free”.

3. How to use Pergoveris

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

• Pergoveris must be administered by subcutaneous injection (injected under the skin). To minimize skin irritation, select a different injection site each day.
• Your doctor or nurse will show you how to use the Pergoveris pre-filled pen to inject the medicine.
• If you and your doctor are confident that you can safely self-administer Pergoveris, you may prepare and inject the medicine at home.
• If you self-administer Pergoveris, carefully read and follow the instructions provided in the “Instructions for use”.

What dose to use
Treatment begins with the recommended dose of Pergoveris, which is 150 International Units (IU) of follitropin alfa and 75 IU of lutropin alfa, administered daily.

• Depending on your response, your doctor may decide to add daily injections of a licensed preparation of follitropin alfa to your Pergoveris injection. In this case, the dose of follitropin alfa is generally increased every 7 or 14 days by 37.5 to 75 IU.
• Treatment continues until the desired response is achieved—namely, until you have developed a suitable follicle, as assessed by ultrasound and blood tests.
• This may take up to 5 weeks.

When the desired response is achieved, you will receive a single injection of human chorionic gonadotropin (hCG) 24–48 hours after the last Pergoveris injection. 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, according to your doctor’s judgment.
If your body responds excessively, treatment will be stopped and you will not receive hCG (see section 2 “Ovarian hyperstimulation syndrome (OHSS)”). In this case, your doctor will prescribe a lower dose of follitropin alfa in the next cycle.
If you use more Pergoveris than you should
The effects of a Pergoveris overdose are unknown; however, ovarian hyperstimulation syndrome (OHSS) may occur. However, this can occur only if hCG is also administered (see section 2 “Ovarian hyperstimulation syndrome (OHSS)”).
If you forget to use Pergoveris
Do not use a double dose to make up for a forgotten dose. Contact your doctor.
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.
More serious side effects
Contact your doctor immediately if you notice any of the side effects listed below. Your
doctor may ask you to stop using Pergoveris.
Allergic reactions
Sometimes, allergic reactions such as skin rash, redness, itching, or swelling of the face with breathing difficulties can be severe. This side effect is very rare.
Ovarian Hyperstimulation Syndrome (OHSS)

• Pelvic pain in combination with nausea or vomiting may be symptoms of Ovarian Hyperstimulation Syndrome (OHSS). The ovaries may over-respond to treatment and develop large fluid-filled sacs or cysts (see section 2 “Ovarian hyperstimulation syndrome (Ovarian hyperstimulation syndrome, OHSS)”). This side effect is common. In such cases, your doctor should examine you as soon as possible.
• OHSS can 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 not common (may affect up to 1 in 100 people).
• Rarely, complications of OHSS may occur, such as ovarian torsion or blood clotting (may affect up to 1 in 1,000 people).
• Very rarely, serious blood clotting complications (thromboembolic events) may occur, usually associated with severe OHSS. This may cause chest pain, shortness of breath, stroke or heart attack. In rare cases, this may occur even independently of OHSS (see section 2 “Blood clotting disorders (thromboembolic events)”).

Other side effects include
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, itching, bruising, swelling or irritation.

Common (may affect up to 1 in 10 people)

• diarrhoea
• breast pain
• nausea or vomiting
• abdominal or pelvic pain
• abdominal cramps or bloating

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

• Asthma may worsen.

Reporting of side effects
If you experience any side effect, including those 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 Pergoveris

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and on the carton 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.
Once opened, the pre-filled pen may be stored for up to 28 days outside the refrigerator (at 25 °C). Do not use any medicine remaining in the pre-filled pen after 28 days.
Do not use Pergoveris if you notice any visible signs of deterioration, if the solution contains particles or if it is not clear.
After injection, dispose of the used needle safely.
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. Contents of the pack and other information

What Pergoveris contains
The active substances are follitropin alfa and lutropin alfa.

• Each pre-filled pen of Pergoveris (900 UI + 450 UI)/1.44 mL contains 900 UI (International Units) of follitropin alfa and 450 UI of lutropin alfa in 1.44 mL and can deliver six doses of Pergoveris 150 UI/75 UI.

The other components are

• Sucrose, monochloride arginine hydrochloride, poloxamer 188, methionine, phenol, disodium phosphate dihydrate, sodium dihydrogen phosphate monohydrate and water for injections. Small amounts of concentrated phosphoric acid and sodium hydroxide are added to maintain normal acidity levels (pH levels).

Description of the appearance of Pergoveris and contents of the pack
Pergoveris is a clear, colourless to slightly yellow, injectable solution in a multi-dose pre-filled pen:

• Pergoveris (900 UI + 450 UI)/1.44 mL is supplied in packs containing 1 multi-dose pre-filled pen and 14 single-use injection needles.

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, Netherlands
Manufacturer
Merck Serono S.p.A, Via delle Magnolie 15 (Industrial Zone), 70026 Modugno (Bari), Italy
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/ .

Instructions for use

Pergoveris

(300 UI + 150 UI)/0.48 mL (450 UI + 225 UI)/0.72 mL (900 UI + 450 UI)/1.44 mL
Prefilled pen injection solution
Follitropin alfa/Lutropin alfa
Contents
Important information about the Pergoveris prefilled pen
How to use the Pergoveris prefilled pen treatment diary
Become familiar with the Pergoveris prefilled pen
Step 1 Prepare the necessary items
Step 2 Prepare for injection
Step 3 Attach the needle
Step 4 Set the dose
Step 5 Inject the dose
Step 6 Remove the needle after each injection
Step 7 After the injection
Step 8 Store the Pergoveris prefilled pen
Pergoveris prefilled pen treatment diary
Important information about the Pergoveris prefilled pen

• Read the Instructions for Use and the Package Leaflet before using the prefilled pen

Pergoveris.

• Always follow all instructions provided in this User Manual and those given by your healthcare provider, as they may differ from those previously used. These instructions will help you avoid treatment errors, infections from needle sticks, or injuries caused by broken glass.
• The pre-filled Pergoveris pen is intended for subcutaneous injection only.
• Use the pre-filled Pergoveris pen only if a healthcare professional has shown you how to use it correctly.
• Your healthcare provider will tell you how many pre-filled Pergoveris pens you need to complete your treatment.
• Administer the injection at the same time each day.
• The pen is supplied in 3 different multi-dose formulations:

(300 UI + 150 UI)/0.48 mL • Contains 0.48 mL of Pergoveris solution

• Contains 300 UI of follitropin alfa and 150 UI of lutropin alfa.
  (450 UI + 225 UI)/0.72 mL • Contains 0.72 mL of Pergoveris solution
• Contains 450 UI of follitropin alfa and 225 UI of lutropin alfa.
  (900 UI + 450 UI)/1.44 mL • Contains 1.44 mL of Pergoveris solution
• Contains 900 UI of follitropin alfa and 450 UI of lutropin alfa.

Note: The maximum dose that can be set is 300 UI for the (300 UI + 150 UI)/0.48 mL formulation. The maximum dose that can be set is 450 UI for both the (450 UI + 225 UI)/0.72 mL and the (900 UI + 450 UI)/1.44 mL formulations. The dose-setting knob rotates in increments of 12.5 UI to reach the desired dose.

Refer to the Package Leaflet for more information on the recommended dosing regimen and always follow the dose prescribed by your healthcare provider.

• The dose control window displays numbers in International Units (IU), corresponding to the dose of follitropin alfa. Your healthcare provider will tell you how many IU of follitropin alfa you should inject each day.
• The numbers displayed in the dose control window will help you:

a. Set the prescribed dose (Figure 1).

b. Verify that the injection has been

completed (Figure 2).
c. Read the remaining dose to be injected

using a second pen (Figure 3).

• Remove the needle from the pen immediately after each injection.

Do not reuse needles.
Do not share the pen and/or needles with other people.
Do not use the pre-filled Pergoveris pen if it has been dropped or if the pen is cracked or damaged, as
you may injure yourself.

How to use the treatment diary with the pre-filled Pergoveris pen
A treatment diary is attached at the end of this manual. Use the treatment diary to record the amounts injected.
Injecting incorrect amounts of medication may affect your treatment.

• Record the treatment day (column 1), date (column 2), time of injection (column 3), and volume in the pen (column 4).
• Record the prescribed dose (column 5).
• Check that the dose is correctly set before injection (column 6).
• After injection, read the number shown in the dose control window.
• Confirm administration of a complete injection (column 7) or record the number shown in the dose control window if it is not “0” (column 8).
• If necessary, administer an injection with a second pen, setting the remaining dose recorded in the “Amount to select for second injection” column (column 8).
• Record this remaining dose in the “Amount to inject” section on the following line (column 6).

By using the treatment diary to record your daily injection(s), you can verify each day that you have received the full prescribed dose.
Example of a treatment diary using a (450 UI + 225 UI)/0.72 mL pen:

Become familiar with the pre-filled Pergoveris pen

Needle*:
Pre-filled pen:
*For illustration purposes only.
**The numbers in the dose control window and on the cartridge container indicate the number of International Units (IU) of medication.

Step 1 Prepare the necessary items
1.1 Allow the pre-filled pen to reach room temperature by leaving it at room temperature for at least 30 minutes before use.
Do not use a microwave or other heating devices to warm the pen.
1.2 Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.

1.3 Additional required materials (not included in the package):

• Alcohol wipes and a sharps disposal container (Figure 4).
  1.4 Wash your hands thoroughly with soap and water, then dry them

completely (Figure 5).
1.5 Remove the pre-filled Pergoveris pen from its packaging using one hand.
Do not use tools or other devices, as they may damage the pen.
1.6 Check that the name printed on the pre-filled pen is Pergoveris.
1.7 Check the expiration date printed on the pen label

(Figure 6).
Do not use the pre-filled Pergoveris pen if the expiration date has passed or if the pen does not display the name Pergoveris.

Step 2 Prepare for injection
2.1 Remove the pen cap (Figure 7).

2.2 Ensure the medication appears clear, colorless, and free of particles.
Do not use the pre-filled pen if the medication is cloudy or discolored, as this may cause infection.
2.3 Ensure the dose control window displays “0” (Figure 8).
Select an injection site:

2.4 A healthcare professional will show you the recommended injection sites on the abdomen (Figure 9). To minimize skin irritation, select a different injection site each day.
2.5 Clean the skin at the injection site with an alcohol wipe.
Do not touch or cover the cleaned skin.

Step 3 Attach the needle
Important: Always use a new needle for each injection.
Using a previously used needle may cause infection.

3.1 Take a new needle. Use only the “single-use” needles supplied in the package.
3.2 Ensure the outer needle cap is not damaged.
3.3 Hold the outer needle cap firmly.
3.4 Check that the tear-off tab on the outer needle cap is intact and not loose, and that the expiration date has not passed (Figure 10).
3.5 Remove the tear-off tab (Figure 11).
Do not use the needle if it is damaged or expired, or if the outer needle cap or tear-off tab is damaged or loose. Using an expired needle or one with a damaged cap or tab may lead to infection. Discard it in a sharps container and take a new needle.
3.6 Screw the outer needle cap onto the threaded tip of the pre-filled Pergoveris pen until slight resistance is felt (Figure 12).
Do not overtighten the needle, as this may make it difficult to remove after injection.
3.7 Remove the outer needle cap by gently pulling it off (Figure 13).
3.8 Set it aside for later use (Figure 14).
Do not discard the outer needle cap, as it will be needed later to prevent needle-stick injuries and infections when removing the needle from the pre-filled pen.
3.9 Hold the pre-filled Pergoveris pen with the needle pointing upward (Figure 15).
3.10 Carefully remove and discard the green inner protective cap (Figure 16).
Do not reattach the green inner protective cap to the needle. You may injure yourself and develop an infection.
3.11 Carefully examine the needle tip and check for one or more small drops of liquid.

If you do not see one or more small drops of liquid at or near the tip of the needle
the first time you use a new pen:

1. Gently turn the dose selector knob forward until the dose control window shows “25” (Figure 18).
   • If you go past “25”, you may turn the dose knob back.

2. Hold the pen with the needle pointing upwards.
3. Gently tap the cartridge reservoir (Figure 19).
4. Press the dose selector knob fully in. A small drop of liquid should appear at the tip of the needle (Figure 20).
5. Check that the dose control window shows “0” (Figure 21).
6. Proceed to Step 4 Set the Dose. If no drop of liquid appears, contact your healthcare provider.

Step 4 Set the Dose
4.1. Turn the dose selector knob until the prescribed dose appears in the
dose control window.

• Example: if the prescribed dose to be injected is “150” IU, ensure that the number “150” appears in the dose control window (Figure 22). Injecting incorrect amounts of medicine may affect your treatment.

4.2. Check that the dose control window shows the full prescribed dose before
proceeding to the next step.
Step 5 Inject the Dose

Important: inject the dose following the instructions
provided by your healthcare provider.
5.1 Slowly insert the entire needle into the skin (Figure 24).
5.2 Place your thumb in the center of the dose selector knob. Press the dose knob slowly and fully in and keep it pressed to complete the injection (Figure 25).
Note: the higher the dose, the longer the injection will take.
5.3 Keep the dose knob pressed for at least

5 seconds before removing the needle from the skin (Figure 26).

• The number in the dose control window will return to “0”.

• After at least 5 seconds, while keeping the dose selector knob fully pressed , remove the needle from the skin (Figure 27).

• Once the needle has been removed from the skin, release the dose selector knob.

Do not release the dose knob until the needle has been
removed from the skin.
Step 6 Remove the needle after each injection
6.1 Place the outer needle cap on a flat surface.
6.2 Hold the pre-filled pen Pergoveris firmly with one hand and insert the needle into the outer cap (Figure 28).
6.3 Now press the needle, covered by its cap, against a hard surface until you hear a click (Figure 29).
6.4 Grasp the outer needle cap and unscrew the needle by turning it in the opposite direction (Figure 30).
6.5 Dispose of the used needle safely in a sharps container (Figure 31).
Handle the needle with care to avoid needle-stick injury.
Do not reuse or share a used needle.
Step 7 After Injection
7.1 Check that you have completed a full injection:

• Check that the dose control window shows “0” (Figure 32).

If the dose control window shows “0”, this means the full dose has been administered.
If the dose control window shows a number higher than “0”, the pre-filled pen Pergoveris is empty.
The full prescribed dose has not been administered and you must perform step 7.2 below.
7.2 Complete a partial injection (only if necessary):

• The dose control window shows the remaining amount that needs to be injected using a new pen. In the example shown, the amount still to be administered is “50” IU (Figure 33).
• To complete the dose with a second pen, repeat steps 1 to 8.

Step 8 Store the pre-filled pen Pergoveris

8.1 Replace the cap on the pen to prevent infection (Figure 34).
8.2 Store the pen in its original packaging in a safe place as indicated in the Package Leaflet.
8.3 When the pen is empty, ask your healthcare provider how to dispose of it properly.
Do not store the pen with the needle still attached, as this may cause infection.
Do not reuse the pre-filled pen Pergoveris if it has been dropped or if the pen is cracked or damaged, as you may be injured.
If you have any questions, contact your healthcare provider.
Treatment Diary for the pre-filled pen Pergoveris

These Instructions for Use were last updated on: