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

Patient Information Leaflet

Introduction

Patient Information Leaflet

Pergoveris (300 IU + 150 IU)/0.48 ml solution for injection in a prefilled pen

folitropin alfa/lutropin alfa

Please read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. 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 "folitropin alfa" and "lutropin alfa". Both belong to the 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 (18 years of age or older) who have low levels (severe deficiency) of "follicle-stimulating hormone" (FSH) and "luteinizing hormone" (LH). Typically, these women are 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, from which an egg will be released following an injection of the hormone "human chorionic gonadotropin (hCG)". This helps women become pregnant.

2. What you need to know before using Pergoveris

Before starting treatment, your fertility and that of your partner should be assessed by a physician experienced in the management of fertility disorders.

Do not use Pergoveris:

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

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

Warnings and precautions

Talk to 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 disorder impairing the breakdown of porphyrins, which may be inherited).

Inform 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 discontinue treatment.

Ovarian hyperstimulation syndrome (OHSS)

This medicine stimulates your ovaries, increasing the risk of developing ovarian hyperstimulation syndrome (OHSS). This occurs when your follicles develop excessively and become large cysts. If you experience pelvic pain, rapid weight gain, nausea or vomiting, or difficulty breathing, contact your doctor immediately, as they may instruct you to stop treatment (see section 4, “More serious side effects”).

If you do not ovulate and the recommended dosage and administration schedule are followed, the occurrence of severe OHSS is less likely. Treatment with Pergoveris rarely causes severe OHSS. The risk increases if the medication used to trigger final follicular maturation (containing human chorionic gonadotropin, hCG) is administered (see details in section 3, “What dose should be used”). If OHSS develops, your doctor may decide not to administer hCG in this treatment cycle and advise you to abstain from sexual intercourse or use a barrier contraceptive method for at least 4 days.

Your doctor will carefully monitor your ovarian response using ultrasound scans and blood tests (estradiol measurements) before and during treatment.

Multiple pregnancy

When using Pergoveris, you have a higher chance of becoming pregnant with more than one baby at a time (“multiple pregnancy,” usually twins) compared to natural conception. Multiple pregnancy may lead to medical complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of Pergoveris at the correct times.

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

Miscarriage

If you undergo ovarian stimulation to produce eggs, the likelihood of miscarriage is higher than in the general female population.

Ectopic pregnancy

Women who have previously had blocked or damaged fallopian tubes (tubal disease) are at risk of ectopic pregnancy (embryo implantation outside the uterus), whether conception occurs spontaneously or through fertility treatments.

Blood clotting problems (thromboembolic events)

Consult your doctor before starting Pergoveris if you or any family member has ever had blood clots in the leg or lung, myocardial infarction, or stroke. You may have an increased risk of developing serious blood clots or worsening of existing clots during treatment with Pergoveris.

Tumors of the reproductive organs

Benign and malignant tumors of the ovaries and other reproductive organs have been reported in women who have undergone multiple courses of infertility treatment.

Allergic reactions

Isolated cases of non-serious allergic reactions to Pergoveris have been reported. If you have ever experienced such a reaction to a similar medicine, consult your doctor before starting Pergoveris.

Children and adolescents

Pergoveris must not be used 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 need to take any other medicines.

Do not mix Pergoveris with other medicines in the same injection. You may use Pergoveris together with a licensed preparation of follitropin alfa in separate injections, if prescribed by your doctor.

Pregnancy and breastfeeding

Do not use Pergoveris if you are pregnant 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 of sodium (23 mg) per dose, i.e., essentially “sodium-free”.

3. How to use Pergoveris

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

Use of this medicine

• Pergoveris is designed to be injected just under the skin (subcutaneously). To minimize skin irritation, select a different injection site each day.
• Your doctor or nurse will teach you how to use the Pergoveris pre-filled pen to self-inject the medicine.
• If they are satisfied that you can safely administer Pergoveris yourself, you may then prepare and inject the medicine at home.
• If you self-administer Pergoveris, read and carefully follow the “Instructions for Use”.

What dose to use

A treatment regimen starts with the recommended dose of Pergoveris containing 150 international units (IU) of follitropin alfa and 75 IU of lutropin alfa, given daily.

• Depending on your response, your doctor may decide to add daily a dose of an authorized follitropin alfa preparation to the Pergoveris injection. In this case, the follitropin alfa dose is usually increased every 7 or 14 days by 37.5–75 IU.

• Treatment continues until the desired response is achieved. This occurs when you have developed a suitable follicle, assessed by ultrasound and blood tests.

• Up to five weeks may be needed.

When the desired response is achieved, you will receive a single injection of human chorionic gonadotropin (hCG) 24 to 48 hours after your last Pergoveris injection. The best time for sexual intercourse is on the day of the hCG injection and the following day. Alternatively, intrauterine insemination or another medically assisted reproductive procedure may be performed, at your doctor’s discretion.

If an excessive response occurs, your 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 be expected. However, this will only occur if hCG is 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 missed dose. Contact your doctor.

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

4. Possible adverse effects

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

Serious adverse effects

Contact your doctor immediately if you notice any of the adverse effects listed below. Your doctor may tell you to stop using Pergoveris.

Allergic reactions

Allergic reactions, such as skin rash, redness of the skin, blisters, swelling of the face with difficulty breathing, can sometimes be severe. This adverse effect is very rare.

Ovarian hyperstimulation syndrome (OHSS)

• Pelvic pain, accompanied by nausea or vomiting. These may be symptoms of ovarian hyperstimulation syndrome (OHSS). Your ovaries may have over-responded to treatment, resulting in the development of ovarian cysts or large fluid-filled sacs (see section 2 under “Ovarian hyperstimulation syndrome (OHSS)”). This adverse effect is common. If this occurs, your doctor will need to examine you as soon as possible.

• OHSS may worsen with clearly enlarged ovaries, decreased urine production, weight gain, difficulty breathing, and/or possible accumulation of fluid in the abdomen or chest. This adverse effect is uncommon (may affect up to 1 in 100 people).

• Complications of OHSS, such as ovarian torsion or blood clotting, occur rarely (may affect up to 1 in 1,000 people).

• Serious blood clotting problems (thromboembolic events), usually associated with severe OHSS, occur very rarely. This could cause chest pain, shortness of breath, stroke, or myocardial infarction. In rare cases, this could also occur independently of OHSS (see section 2 under “Blood clotting problems (thromboembolic events)”).

Other adverse effects

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

• fluid-filled sacs within 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
• abdominal cramps or bloating

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

• asthma may worsen.

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Pergoveris

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

Do not use this medicine after the expiry date stated on the label and the carton after EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze.

Keep in the original packaging to protect from light.

After first opening, the pre-filled pen may be stored for up to 28 days outside the refrigerator (at 25 °C). Do not use any remaining medicine in the pre-filled pen after 28 days.

Do not use Pergoveris if you notice visible signs of deterioration, if the liquid contains particles or is not clear.

After injection, dispose of the used needle safely.

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

6. Contents of the pack and other information

Composition of Pergoveris

The active substances are follitropin alfa and lutropin alfa.

• Each Pergoveris pre-filled pen (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, arginine monohydrochloride, poloxamer 188, methionine, phenol, disodium hydrogen 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).

Appearance of the product and contents of the pack

Pergoveris is presented as a clear, colourless to slightly yellowish injectable solution in a multidose pre-filled pen:

• Pergoveris (300 IU + 150 IU)/0.48 ml is available in packs containing 1 multidose pre-filled pen and 5 disposable 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

Date of the most recent revision of this leaflet: (MM/YYYY)

Other sources of information

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

Instructions for use

Pergoveris

(300 IU + 150 IU)/0.48 ml (450 IU + 225 IU)/0.72 ml (900 IU + 450 IU)/1.44 ml

Injectable solution in a pre-filled pen

Follitropin alfa / Lutropin alfa

Important information about the Pergoveris pre-filled pen

• Read the instructions for use and the package leaflet before using the Pergoveris pre-filled pen.

• Always follow all instructions in these instructions for use and the training provided by your healthcare professional, as they may differ from previous instructions you have received. This information will help you avoid treatment errors or needle-stick infections and injuries from broken glass.

• The Pergoveris pre-filled pen is for subcutaneous injection only.

• Only use the Pergoveris pre-filled pen after your healthcare professional has shown you how to use it correctly.

• Your healthcare professional will tell you how many Pergoveris pre-filled pens you need to complete your treatment.

• Administer your injection at the same time each day.

• The pen is available in three different multidose presentations:

(300 UI + 150 UI)/0.48 ml	Contains 0.48 ml of Pergoveris solution. Contains 300 IU of follitropin alfa and 150 IU of lutropin alfa.
(450 UI + 225 UI)/0.72 ml	Contains 0.72 ml of Pergoveris solution. Contains 450 IU of follitropin alfa and 225 IU of lutropin alfa.
(900 UI + 450 UI)/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 you can select is 300 IU for the (300 IU + 150 IU)/0.48 ml presentation.

• The maximum dose you can select is 450 IU for the (450 IU + 225 IU)/0.72 ml and (900 IU + 450 IU)/1.44 ml presentations.

• The dose adjustment button rotates in increments of 12.5 IU until the desired dose is reached.

Refer to the package leaflet for more information on the recommended dosing regimen and always follow the dose prescribed by your healthcare professional.

• The numbers in the dose information window represent the number of International Units (IU) and indicate the dose of follitropin alfa. Your healthcare professional will tell you how many IU of follitropin alfa you should inject each day.
• The numbers displayed in the dose information window help you to:

Select the prescribed dose (Figure 1).
Check that the injection has been completed (Figure 2).
Read the remaining dose to be injected with a second pen (Figure 3).

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

Do not reuse needles.

Do not share the pen or needles with anyone else.

Do not use the Pergoveris pre-filled pen if it has been dropped, or if the pen is cracked or damaged, as this may cause injury.

How to use the Pergoveris pre-filled pen treatment diary

A treatment diary is included at the end of the instructions for use. Use the treatment diary to record the amount injected.

Injecting an incorrect amount of medication may affect your treatment.

• Record the treatment day number (column 1), date (column 2), time of injection (column 3), and pen volume (column 4).
• Record the dose prescribed to you (column 5).
• Check that you have selected the correct dose before administering the injection (column 6).
• After the injection, read the number shown in the dose information window.
• Confirm that you have received a complete injection (column 7), or record the number shown in the dose information window if it is not “0” (column 8).
• When necessary, perform another injection using a second pen, selecting the remaining dose indicated in the section "Amount to be set for a second injection" (column 8).
• Record this remaining dose in the section "Amount set for injection" on the next row (column 6).

Using the treatment diary to record your daily injection(s) allows you to verify that you have received the full prescribed dose each day.

Example of a treatment diary using a pen of (450 UI + 225 UI)/0.72 ml:

Familiarize yourself with the Pergoveris pre-filled pen

• For illustrative purposes only. Supplied needles may look slightly different.

** The numbers in the dose information window and on the cartridge holder represent the number of International Units (IU) of the medication.

Step 1 Gather the materials

Leave the prefilled pen at room temperature for at least 30 minutes before use to allow the medication to reach room temperature. Do not use a microwave or any other heating device to warm the pen.
Prepare a clean, flat surface, such as a table or countertop, in a well-lit area. You will also need (not included in the package): Alcohol wipes and a sharps disposal container (Figure 4). Wash your hands with soap and water and dry them thoroughly (Figure 5).
Remove the Pergoveris prefilled pen from the package by hand. Do not use any tools, as they may damage the pen.
Check that the label on the prefilled pen reads Pergoveris.
Check the expiration date on the pen label (Figure 6). Do not use the Pergoveris prefilled pen if the expiration date has passed or if the pen is not labeled Pergoveris.

Step 2 Prepare for the injection

Remove the cap from the pen (Figure 7).
Check that the medicine is clear and colorless and contains no particles. Do not use the pre-filled pen if the medicine has changed color or is cloudy, as this may cause an infection. Check that the dose information window is set to “0” (Figure 8).
Choose an injection site:
Your healthcare professional will advise you on the injection sites to use around the abdominal area (Figure 9). To minimize skin irritation, select a different injection site each day. Clean the skin at the injection site with an alcohol wipe. Do not touch or cover the skin you have just cleaned.

Step 3 Attach the needle

Important: always make sure to use a new needle for each injection. Reusing needles may cause infection.
Take a new needle. Only use the “single-use” needles supplied
Check that the outer needle cap is not damaged.
Firmly hold the outer needle cap.
Check that the sealing tab on the outer needle cap is not damaged or loose and that the expiration date has not passed (Figure 10).
Remove the sealing tab (Figure 11).
Do not use the needle if it is damaged or expired, or if the outer needle cap or sealing tab is damaged or loose. Using expired needles or needles with damaged sealing tabs or outer caps may cause infection. Dispose of it in a sharps container and take a new needle.
Screw the outer needle cap onto the threaded tip of the Pergoveris pre-filled pen until you feel slight resistance (Figure 12). Do not overtighten the needle when attaching it, as this may make it difficult to remove after the injection.
Remove the outer needle cap by gently pulling it off (Figure 13). Set it aside for later use (Figure 14). Do not discard the outer needle cap, as it will prevent needle-stick injuries and infections when removing the needle from the pre-filled pen.
Hold the Pergoveris pre-filled pen with the needle pointing upward (Figure 15). Carefully remove and discard the inner needle cap (Figure 16). Do not recap the needle with the inner needle cap, as this may cause needle-stick injuries and infections.
Thoroughly examine the tip of the needle for one or more drops of liquid (Figure 17).

If	Then
Use a new pen	Check that there is a drop of liquid at the needle tip. If you see a drop of liquid, proceed to Step 4 Select the dose. If you do not see a drop at the needle tip or nearby, you must perform the steps described in the next section to remove air from the system.
Reuse a pen	It is NOT necessary to check for a drop of liquid. Proceed directly to Step 4 Select the dose.

If you do not see a small drop of liquid at the tip or in the surrounding area the first time you use a new pen:

1. Carefully turn the dose knob forward until “25” appears in the dose information window (Figure 18).

• You may turn the dose knob backward if you have gone past “25”.

1. Hold the pen with the needle pointing upward.
2. Gently tap the reservoir holder (Figure 19).
3. Press the dose knob completely. A drop of liquid should appear at the needle tip (Figure 20).
4. Check that the dose information window shows “0” (Figure 21).
5. Proceed to Step 4 Select the dose.

If no drop of liquid appears, contact your healthcare professional.

Step 4 Select the dose

1. Turn the dose knob until the desired dose appears in the dose information window.

• Example: if the desired dose is “150” IU, confirm that the dose information window shows “150” (Figure 22). Injecting an incorrect amount of medicine may affect your treatment.

Turn the dose adjustment button forward to select the dose (Figure 22).	You can turn the dose adjustment button backward if you turn past the desired dose (Figure 23).

1. Check that the dose information window shows the full prescribed dose before proceeding to the next step.

Step 5 Inject the dose

Important: inject the dose as shown to you by your healthcare professional.
Slowly insert the entire needle into the skin (Figure 24)
Place your thumb on the center of the dose button. Press the dose button slowly and completely, and keep it pressed to fully administer the injection (Figure 25).
Note: the higher the dose, the longer the injection will take.
Keep the dose button pressed for at least 5 seconds before removing the needle from the skin (Figure 26). The dose number in the dose information window will return to “0”. After at least 5 seconds, remove the needle from the skin while keeping the dose button pressed (Figure 27). When the needle is completely out of the skin, release the dose button.
Do not release the dose button until the needle has been removed from the skin.

Step 6 Remove the needle after each injection

Place the outer needle cap on a flat surface.
Hold the Pergoveris prefilled pen firmly in one hand and insert the needle into the outer needle cap (Figure 28).
Continue pushing the capped needle against a firm surface until you hear a click (“click”) (Figure 29).
Holding the outer needle cap, unscrew the needle by turning it in the opposite direction (Figure 30).
Dispose of the used needle safely in a sharps container (Figure 31). Handle the needle carefully to avoid injury.
Do not reuse or share any used needle.

Step 7 After the injection

Check that a complete injection has been administered: Check that the dose information window displays “0” (Figure 32). If the dose information window displays “0”, the dose has been fully administered. If the dose information window displays a number greater than “0”, the Pergoveris prefilled pen is empty. You have not received the full prescribed dose and must perform step 7.2 described below.
Complete a partial injection (only when necessary): The dose information window will indicate the remaining amount to be injected using a new pen. In the example shown, the remaining amount is “50” IU (Figure 33). To complete the dose with a second pen, repeat Steps 1 to 8.

Step 8 Storage of the Pergoveris pre-filled pen

Replace the pen cap back onto the pen to prevent infection (Figure 34).
Store the pen in its original packaging in a safe place and as indicated in the package leaflet.
When the pen is empty, ask your healthcare professional how to dispose of it.
Do not store the pen with the needle still attached, as this may cause infection.
Do not reuse the Pergoveris pre-filled pen if it has been dropped, or if the pen is cracked or damaged, as this may cause injury.
Contact your healthcare professional if you have any questions.

Treatment diary for the Pergoveris pre-filled pen

Date of last review of these instructions for use: