Package Insert: Information for the User

Pergoveris 150 UI/75 UI Powder and Diluent for Injectable Solution

Follitropin Alfa/Lutropina Alfa

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others who have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

What is Pergoveris

Pergoveris contains two different active principles called “folitropin alfa” and “lutropin alfa”. Both belong to the family of hormones called “gonadotropins”, which are involved in reproduction and fertility.

What is Pergoveris used for

This medication is used to stimulate the development of follicles (each containing an egg) in the ovaries in order to help a woman become pregnant. It is intended for use in adult women (18 years of age or older) with low (severe deficiency) levels of “follicle-stimulating hormone” (FSH) and “luteinizing hormone” (LH). Normally, these women are infertile.

How Pergoveris works

The active principles of 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 substituting the missing hormones, Pergoveris allows women with low levels of FSH and LH to develop a follicle, from which an egg will be released, after an injection of the hormone “human chorionic gonadotropin (hCG)”. This helps women to become pregnant.

Before starting treatment, your fertility and that of your partner should be evaluated by an experienced doctor in the treatment of fertility disorders.

Do not use Pergoveris:

• if you are allergic to the follicle-stimulating hormone (FSH), luteinizing hormone (LH), or any of the other components of this medication (listed in section 6).
• if you have a brain tumor (in the hypothalamus or pituitary gland).
• if you have large ovaries or fluid-filled sacs in the ovaries (ovarian cysts) of unknown origin.
• if you have unexplained vaginal bleeding.
• if you have ovarian, uterine, or breast cancer.
• if you have a condition that would prevent a normal pregnancy, such as premature menopause, genital malformations, or benign tumors in the uterus.

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

Warnings and precautions

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

Porphyria

Consult your doctor before starting treatment if you or any family member has porphyria (a condition that prevents the breakdown of porphyrins that can be passed down from parents to children).

Inform your doctor immediately if:

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

Your doctor may recommend stopping treatment in these cases.

Ovarian Hyperstimulation Syndrome (OHSS)

This medication stimulates your ovaries, increasing the risk of experiencing ovarian hyperstimulation syndrome (OHSS). This occurs when your follicles develop too much and become large cysts. If you have pelvic pain, rapid weight gain, nausea, vomiting, or difficulty breathing, consult your doctor immediately, who may order you to stop treatment (see section 4, "Serious side effects").

OHSS is less likely to occur if you do not ovulate and if the recommended dose and treatment schedule are followed. Pergoveris treatment rarely causes severe OHSS. This is more likely to occur if the medication used for final follicular maturation (containing human chorionic gonadotropin, hCG) is administered (see details in section 3, "How much to use"). If you develop OHSS, your doctor may not prescribe hCG for this treatment cycle and advise you to avoid intercourse or use a barrier method of contraception for at least 4 days.

Your doctor will ensure careful monitoring of your ovarian response, using ultrasound and blood tests (estradiol determinations), before and during treatment.

Multiple Pregnancy

If you use Pergoveris, you have a higher risk of becoming pregnant with more than one baby at a time ("multiple pregnancy," usually twins) than if you become pregnant naturally. Multiple pregnancy can cause medical complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of Pergoveris at the right times.

To minimize the risk of multiple pregnancy, it is recommended to perform ultrasound and blood tests.

Abortion

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

Ectopic Pregnancy

Women who have had a blockage or damage to the fallopian tubes (tubal disease) have a higher risk of pregnancy with implantation of the embryo outside the uterus (ectopic pregnancy). This is the case whether the pregnancy is spontaneous or achieved through fertility treatments.

Blood Clotting Disorders (Thromboembolic Episodes)

Consult your doctor before starting to use Pergoveris if you or any family member has ever had blood clots in the leg or lung, heart attack, or stroke. You may have a higher risk of developing severe blood clots or worsening existing clots with Pergoveris treatment.

Sex Organ Tumors

Cases of tumors in the ovaries and other sex organs, both benign and malignant, have been reported in women who have undergone multiple treatments for infertility.

Allergic Reactions

Isolated cases of non-severe allergic reactions to Pergoveris have been reported. If you have ever had this type of reaction with a similar medication, consult your doctor before starting to use Pergoveris.

Children and Adolescents

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

Other Medications and Pergoveris

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

Do not use Pergoveris with other medications in the same injection, except with recombinant follicle-stimulating hormone (rFSH), if prescribed by your doctor.

Pregnancy and Breastfeeding

Do not use Pergoveris if you are pregnant or breastfeeding.

Driving and Operating Machines

No impairment of your ability to drive or operate machines is expected from this medication.

Pergoveris contains sodium

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

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Use of this medication

• Pergoveris is designed to be injected just below the skin (subcutaneously). To minimize skin irritation, select a different injection site each day.
• It is presented in the form of powder and liquid, which must be mixed and used immediately.
• Your doctor or nurse will teach you how to prepare and inject this medication. They will supervise your first injection.
• If you are satisfied that you can administer Pergoveris safely, you will be able to prepare and inject the medication yourself at home. When you do, read and follow carefully the instructions described below in the section “How to prepare and use the powder and solvent of Pergoveris”.

How much to use

The usual initial dose is 1 vial of Pergoveris per day.

• Depending on the response, your doctor may decide to add daily a dose of a recombinant follicle-stimulating hormone (rFSH) authorized for injection to the Pergoveris injection. In this case, the rFSH dose is usually increased every 7 or 14 days by 37.5-75 IU.
• Treatment continues until the desired response is obtained. This occurs when you have developed an adequate follicle, evaluated by ultrasound and blood tests.
• It may take up to five weeks.

When the desired response is obtained, you will be given a single injection of human chorionic gonadotropin (hCG) 24 to 48 hours after your last Pergoveris injection. The best time for sexual intercourse is the same day of the hCG injection and the next day. Alternatively, intrauterine insemination or other medically assisted reproduction procedures may be performed at your doctor's discretion.

If an excessive response is obtained, treatment will be interrupted and hCG will not be administered (see section 2, in “Ovarian Hyperstimulation Syndrome (OHSS”). In this case, your doctor will prescribe a lower dose of rFSH in the next cycle.

How to prepare and use the powder and solvent of Pergoveris

Before starting preparation, read these instructions carefully:

Administer the injection at the same time every day.

1. Wash your hands and find a clean place

• It is essential that your hands and the materials you use are as clean as possible.
• A suitable place is a clean table or a kitchen surface.

1. Gather and arrange everything you will need

• 1 vial containing the Pergoveris powder
• 1 vial containing the water for injection (solvent)

The following items are not supplied in the packaging:

• 2 alcohol-soaked swabs
• 1 empty syringe for injection
• 1 needle for preparation
• 1 fine needle for subcutaneous injection
• A container for sharp objects to dispose of the glass vials and needles safely

1. Preparation of the solution

1. Preparation of the syringe for injection

1. Injection of the dose

1. After the injection

Dispose of all materials: Once the injection is complete, dispose of the needles and empty vials immediately in the container for sharp objects. Any unused portion of the solution must be disposed of safely.

If you use more Pergoveris than you should

The effects of an overdose of Pergoveris are unknown; however, it is expected that OHSS will occur. However, this will only occur if hCG is administered (see section 2, in “Ovarian Hyperstimulation Syndrome (OHSS”).

If you forget to use Pergoveris

Do not use a double dose to compensate for the missed doses. Contact your doctor.

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

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

More serious side effects

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

Allergic reactions

Allergic reactions, such as skin rash, skin redness, blisters, facial swelling with difficulty breathing, can sometimes be severe. This side effect is very rare.

Ovarian Hyperstimulation Syndrome (OHSS)

• Lower abdominal pain, accompanied by nausea or vomiting. These symptoms may be signs of Ovarian Hyperstimulation Syndrome (OHSS). It is possible that your ovaries have reacted excessively to treatment and have developed ovarian cysts or large fluid-filled sacs (see section 2 in “Ovarian Hyperstimulation Syndrome (OHSS)”). This side effect is common. If this happens, your doctor will have to examine you as soon as possible.
• OHSS can worsen with clearly enlarged ovaries, decreased urine production, weight gain, difficulty breathing, and/or possible fluid accumulation in the abdomen or chest. This side effect is uncommon (may affect up to 1 in 100 people).
• OHSS complications such as ovarian torsion or blood clotting occur rarely (may affect up to 1 in 1,000 people).
• Severe blood clotting problems (thromboembolic episodes), usually with severe OHSS, occur very rarely. This could cause chest pain, shortness of breath, stroke, or myocardial infarction. In rare cases, this can also occur independently of OHSS (see section 2 in “Blood clotting problems (thromboembolic episodes)”).

Other side effects

Very common(may affect more than 1 in 10 people)

• fluid-filled sacs inside the ovaries (ovarian cysts)
• headache
• local reactions at the injection site such as pain, itching, bruising, swelling, or irritation.

Common(may affect up to 1 in 10 people)

• diarrhea
• chest pain
• nausea or vomiting
• abdominal or pelvic pain
• cramping or abdominal distension

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

• asthma may worsen.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is possible side effects that do not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

Do not store at a temperature above 25 °C. Store in the original packaging to protect it from light.

The medication must be administered immediately after reconstitution.

Do not use Pergoveris if you observe visible signs of deterioration.

The reconstituted solution should not be administered if it contains particles or is not clear.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Pergoveris

The active principles are follitropin alfa and lutropin alfa.

• One vial contains 150 UI of follitropin alfa (equivalent to 11 micrograms) and 75 UI of lutropin alfa (equivalent to 3 micrograms).
• After reconstitution, each ml of the solution contains 150 UI of follitropin alfa and 75 UI of lutropin alfa per milliliter.

The other components are:

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

Appearance of the product and contents of the packaging

• Pergoveris is presented as a powder and solvent for injectable solution.
• The powder is a lyophilized tablet of white to off-white color in a glass vial with a bromobutyl rubber stopper containing 150 UI (equivalent to 11 micrograms) of follitropin alfa and 75 UI (equivalent to 3 micrograms) of lutropin alfa.
• The solvent is a clear and colorless liquid in a glass vial containing 1 ml of water for injection preparations.
• Pergoveris is presented in packaging that contains 1, 3 and 10 vials of powder along with the same number of vials of solvent (1, 3 and 10 vials). Some packaging sizes may only be marketed.

Marketing Authorization Holder

Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, Netherlands

Responsible for manufacturing

Merck Serono S.p.A, Via delle Magnolie 15 (Industrial Area), 70026 Modugno (Bari), Italy

Date of the last review of this leaflet: {MM/AAAA}.

Other sources of information

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