Meropur

Package leaflet: Information for the patient

MEROPUR 75 IU powder and solvent for injectable solution

Menotropin
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 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, contact your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What MEROPUR is and what it is used for

MEROPUR is a lyophilized powder to be dissolved with a liquid (solvent) before use. It is administered as a subcutaneous or intramuscular injection.
The active substance contained in MEROPUR is highly purified and known as menotropin. Menotropin is extracted from the urine of postmenopausal women and contains three hormones: follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), and luteinizing hormone (LH).
hCG, extracted from the urine of pregnant women, may be added to contribute to the total biological activity of LH.
FSH, hCG, and LH are natural hormones produced by women. They help the reproductive organs to function properly.
MEROPUR is indicated for the treatment of female infertility in the following two clinical situations:

• Women who are unable to become pregnant due to the ovaries’ inability to produce eggs (including polycystic ovary syndrome). MEROPUR is used in women who have already been treated without success for infertility with a medication called clomiphene citrate.
• Women undergoing assisted reproductive technology (ART) programs, including in vitro fertilization/embryo transfer (IVF-ET), gamete intrafallopian transfer (GIFT), and intracytoplasmic sperm injection (ICSI). MEROPUR helps the ovaries produce multiple follicles (egg sacs) in which eggs can develop (multiple follicular development).

2. What you should know before using MEROPUR

Before starting treatment with MEROPUR, both you and your partner must undergo a medical evaluation to determine the causes of infertility. In particular, the following conditions should have been assessed to consider alternative treatments:

• Hypofunction of the thyroid gland or adrenal glands
• High levels of a hormone called prolactin (hyperprolactinemia)
• Tumors of the pituitary gland (a gland located at the base of the brain)
• Tumors of the hypothalamus (an area below the part of the brain known as the thalamus)

If you know you have any of the conditions listed above, inform your doctor before starting treatment with MEROPUR.
Do not use MEROPUR in the following cases:

• You are allergic (hypersensitive) to menotropin or to any of the other ingredients of MEROPUR (listed in section 6).
• You have tumors of the uterus, ovaries, breasts, or of parts of the brain such as the pituitary or hypothalamus.
• You have fluid-filled sacs (ovarian cysts) in the ovaries or enlarged ovaries (not due to polycystic ovary syndrome).
• You have physical abnormalities of the uterus or other reproductive organs.
• You have vaginal bleeding of unknown origin.
• You have fibroids (benign tumors) of the uterus.
• You are pregnant or breastfeeding.
• You are in premature menopause.

Warnings and precautions
Contact your doctor if you experience:

• Abdominal pain
• Abdominal bloating
• Nausea
• Vomiting
• Diarrhea
• Weight gain
• Difficulty breathing
• Reduced urine output

Report any of the above symptoms to your doctor immediately, even if they occur several days after the last injection. These may be signs of excessive ovarian activity, which can become severe.
If symptoms become severe, infertility treatment must be stopped and you should go to the hospital.
Strict adherence to the recommended doses of MEROPUR and careful monitoring of treatment reduce the likelihood of these symptoms occurring.
You may continue to experience these symptoms even after discontinuation of treatment with MEROPUR. Contact your doctor immediately if any of the described symptoms occur.
During treatment with this medicine, your doctor will perform ultrasound scans and, sometimes, blood tests to monitor your response to treatment.

Treatment with hormones such as MEROPUR may increase the risk of:

• Ectopic pregnancy (pregnancy outside the uterus), especially if you have had previous problems with the Fallopian tubes
• Spontaneous abortion (miscarriage)
• Multiple pregnancy (twins, triplets, etc.)
• Congenital malformations (physical defects in the newborn present at birth)

Some women who have received infertility treatment with multiple drugs have developed ovarian tumors and tumors of other reproductive organs. It is not yet known whether hormone treatments such as MEROPUR cause these problems.
The formation of blood clots within blood vessels (veins or arteries) is more likely in pregnant women. Infertility treatments may increase this risk, especially if you are overweight, suffer from clotting disorders (thrombophilia), or if you or a close family member (blood relative) has had episodes of blood clot formation. Inform your doctor if any of these apply to you.

Children
There is no relevant use of MEROPUR in children.

Other medicines and MEROPUR
Inform your doctor if you are taking, have recently taken, or might take any other medicines, including those without a prescription.

Clomiphene citrate is another medicine used to treat infertility. If MEROPUR and clomiphene citrate are used together, the effect on the ovaries is increased.

Pregnancy and breastfeeding
MEROPUR must not be used during pregnancy or while breastfeeding.

Driving and using machines
It is unlikely that MEROPUR will affect your ability to drive or operate machinery.

For athletes
Using this medicine without therapeutic need constitutes doping and may lead to a positive anti-doping test.

Important information about some excipients in MEROPUR
MEROPUR contains less than 1 mmol of sodium (23 mg) per dose, therefore it is essentially "sodium-free".

3. How to use MEROPUR

Always use MEROPUR exactly as instructed by your doctor. If you have any doubts, consult your doctor.
Women who do not ovulate (do not produce eggs):
Treatment should begin within the first 7 days of the menstrual cycle (day 1 is the first day of the cycle).
Treatment is daily for at least 7 days.
The usual starting dose is 75–150 IU per day (1–2 vials of powder), but may be adjusted based on your individual response (up to a maximum of 225 IU per day – 3 vials of powder per day).
Each dosage should be maintained for at least 7 days before being modified by your doctor. A dose increase of 37.5 IU (half a vial of powder) is recommended for adjustment (and never more than 75 IU). If there is no adequate response after 4 weeks of treatment, that cycle should be discontinued.
Once the optimal response has been achieved, a single injection of 5,000 IU to 10,000 IU of another hormone called Human Chorionic Gonadotropin (hCG) should be administered one day after the last MEROPUR injection. Sexual intercourse is recommended on the same day and the day after the hCG injection. Alternatively, intrauterine insemination (injection of sperm directly into the uterus) may be performed. You will be closely monitored for at least 2 weeks after hCG administration.
Your doctor will monitor the effects of treatment with MEROPUR. Depending on your progress, the doctor may decide to stop treatment with MEROPUR and not administer hCG. In this case, you will be instructed to use barrier contraceptive methods (e.g. condom) or to abstain from sexual intercourse until the start of your first menstrual cycle.

Women undergoing assisted reproductive programs:
If you are simultaneously receiving a GnRH agonist (a medicine that helps the function of a hormone called Gonadotropin-Releasing Hormone (GnRH)), treatment with MEROPUR should start approximately 2 weeks after beginning treatment with the agonist.
If you have also received treatment with a GnRH antagonist, treatment with MEROPUR should start on day 2 or 3 of the menstrual cycle (day 1 is the first day of the cycle).
MEROPUR must be administered daily for at least 5 days. The usual starting dose of MEROPUR is 150–225 IU/day (2 or 3 vials of powder). Subsequent doses may be increased up to a maximum daily dose not exceeding 450 IU/day (6 vials of powder). The dose may be increased by up to 150 IU per single adjustment. Treatment usually should not last longer than 20 days.
If a sufficient number of follicles of adequate size are obtained, you will be given up to 10,000 IU of a medicine called human chorionic gonadotropin (hCG) in a single injection to induce ovulation (release of an egg).
Your doctor will monitor your clinical status for at least 2 weeks after the hCG injection.
Your doctor will monitor the effects of treatment with MEROPUR. Depending on your progress, the doctor may decide to stop treatment with MEROPUR and not administer hCG. In this case, you will be instructed to use barrier contraceptive methods (e.g. condom) or to abstain from sexual intercourse until the start of your first menstrual cycle.

INSTRUCTIONS FOR USE
If you have been instructed to self-administer MEROPUR, you must carefully follow all instructions provided to you.
The first injection of MEROPUR must be performed under the supervision of a doctor.

RECONSTITUTION OF MEROPUR
MEROPUR is supplied as a powder and must be dissolved before use.
The solvent (liquid) to be used for dissolution is supplied together with the powder. Mix thoroughly before use. Follow these steps:

• Firmly attach a long, thick needle (needle for aspiration/reconstitution) to the syringe.
• Break open the vial of liquid (solvent) by holding the break point towards you.

• Insert the needle into the solvent vial.
• Draw up the entire contents of the solvent vial into the syringe.
• Insert the needle through the rubber stopper of the vial containing the powder and slowly inject all the solvent into the vial, directing the stream against the side of the vial to avoid foaming.
• The powder should dissolve quickly (within 2 minutes) to form a clear solution. Normally, dissolution begins immediately after adding a few drops of solvent.

• To facilitate dissolution, gently tap the vial. Do not shake, to avoid bubble formation. If the solution is not clear or contains particles, do not use it.

• Draw the solution back into the syringe for use.

If you have been prescribed more than one vial of MEROPUR powder for a single injection, you may draw the solution (the first reconstitution of MEROPUR) into the syringe and inject it into a second vial of powder. You may repeat this step up to a maximum of three vials of powder in total – but only if prescribed by your doctor.

INJECTION OF MEROPUR

Once you have drawn into the syringe a sufficient amount from the vials to reach the prescribed dose, replace the needle with a short, fine one (injection needle).

• Turn the syringe with the needle pointing upwards and gently tap it to dislodge any air bubbles. Gently press the plunger until the first drop of liquid appears.
• Your doctor or nurse will tell you where to administer the injection (e.g. front of thigh, abdomen, etc.).
• Disinfect the injection site.

For the injection, pinch the skin to form a fold and insert the needle quickly at a 90-degree angle to the body. Push the plunger of the syringe to inject the solution, then remove the needle.

• After removing the syringe, apply pressure to the injection site to stop any bleeding. Gently massage the injection site to help disperse the solution under the skin.
• Do not dispose of the syringe and used materials with household waste; dispose of them properly.

If you use more MEROPUR than you should
Inform your nurse or doctor immediately.
If you forget to use MEROPUR
Do not take a double dose to make up for the missed dose. Inform your nurse or doctor.

4. Possible side effects

Like all medicines, MEROPUR can cause side effects, although not everyone experiences them.
Treatment with MEROPUR may lead to high levels of ovarian activity causing a condition called ovarian hyperstimulation syndrome (OHSS), especially in women with polycystic ovaries. Symptoms include: abdominal pain, abdominal swelling, nausea, vomiting, diarrhoea, and weight gain. In severe cases of OHSS, rare complications such as accumulation of fluid in the abdomen, pelvic and/or thoracic cavity, breathing difficulties, reduced urination, formation of blood clots in blood vessels (thromboembolism), and twisting of the ovaries (ovarian torsion) have been reported. If you notice any of these symptoms, contact your doctor immediately, even if they occur several days after the last injection.
With the use of this medicine, allergic reactions (hypersensitivity) may also occur. Symptoms of these reactions may include: redness, itching, swelling of the throat, and breathing difficulties. If you notice any of these symptoms, contact your doctor immediately.

The following are common side effects occurring in 1 to 10 out of 100 treated patients:

• Abdominal pain
• Headache
• Nausea
• Abdominal swelling
• Pelvic pain
• Ovarian hyperstimulation leading to high levels of activity (ovarian hyperstimulation syndrome)
• Local reactions at the injection site (such as pain, redness, bruising, swelling and/or itching).

The following are uncommon side effects occurring in 1 to 10 out of 1,000 treated patients:

• Vomiting
• Abdominal discomfort
• Diarrhoea
• Fatigue
• Dizziness
• Fluid-filled sacs within the ovaries (ovarian cysts)
• Breast disorders (including breast pain, breast tenderness to touch, breast discomfort, nipple pain, and breast swelling)
• Hot flushes.

The following are rare side effects occurring in 1 to 10 out of 10,000 treated patients:

• Acne
• Skin rash.

In addition to the above, the following side effects have been reported after the marketing of MEROPUR, and their frequency is unknown:

• Visual disturbances
• Fever
• Feeling unwell
• Allergic reactions
• Weight gain
• Muscle and joint pain (e.g. back pain, neck pain, pain in arms and legs)
• Ovarian torsion as a complication of increased ovarian activity due to hyperstimulation
• Itching
• Hives
• Blood clots as a complication of increased ovarian activity due to hyperstimulation.

If you experience any side effect, including those not listed in this leaflet, consult your doctor or nurse.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the website: “www.aifa.gov.it/content/segnalazioni-reazioni-avverse”.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MEROPUR

Do not store above 25°C. Do not freeze.
Keep in the original packaging to protect from light.
For single use and immediate use after reconstitution.
Keep this medicine out of the sight and reach of children.
Do not use MEROPUR after the expiry date stated on the packaging. The expiry date refers to the last day of the month indicated.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What MEROPUR contains:
The active substance is highly purified menotropin (menopausal human gonadotropin, hMG),
corresponding to 75 IU of follicle-stimulating hormone (FSH) biological activity and 75 IU of luteinizing hormone (LH) biological activity.
The excipients of the powder are:

• Monohydrate lactose
• Polysorbate 20
• Sodium hydroxide
• Hydrochloric acid.

The excipients of the solvent are:

• Water
• Hydrochloric acid
• Sodium chloride
• Sodium hydroxide.

Description of the appearance of MEROPUR and contents of the pack
MEROPUR is a powder and solvent for injectable solution.
The pack contains 5 or 10 clear glass vials containing a white to off-white powder.
The pack also contains an equal number of clear glass ampoules containing a clear solvent.
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Ferring S.p.A.
Via C. Imbonati, 18 - 20159 MILAN, ITALY

Manufacturer
Ferring GmbH
Wittland 11, D-24109 Kiel (Germany)

Trade names:
Belgium, Ireland, Luxembourg, Slovakia: Menotrophin Ferring
Czech Republic: Menotrophin Ferring-Léčiva
Bulgaria, Croatia, Cyprus, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Latvia,
Lithuania, Malta, Norway, Portugal, Romania, Slovenia, Spain, Sweden: Menopur
Italy: Meropur

Package leaflet: Information for the patient

MEROPUR 600 IU powder and solvent for injectable solution

Menotropin
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 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 could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What MEROPUR is and what it is used for

MEROPUR is a lyophilized powder to be dissolved with a liquid (solvent) before use. It is administered as a subcutaneous injection.
The active substance contained in MEROPUR is highly purified and known as menotropin. Menotropin is extracted from the urine of post-menopausal women and contains three hormones: follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), and luteinizing hormone (LH).
hCG, extracted from the urine of pregnant women, may be added to contribute to the total biological activity of LH.
FSH, hCG, and LH are natural hormones produced by women. They help the reproductive organs function properly.
MEROPUR is indicated for the treatment of female infertility in the following two clinical situations:

• Women who are unable to become pregnant due to the ovaries' inability to produce eggs (including polycystic ovary syndrome). MEROPUR is used in women who have already been treated without success for infertility with a medication called clomiphene citrate.
• Women undergoing assisted reproductive technology (ART) programs, including in vitro fertilization/embryo transfer (IVF-ET), gamete intrafallopian transfer (GIFT), and intracytoplasmic sperm injection (ICSI). MEROPUR helps the ovaries produce multiple follicles (fluid-filled sacs for eggs) in which eggs can develop (multiple follicular development).

2. What you need to know before using MEROPUR

Before starting treatment with MEROPUR, both you and your partner must undergo a medical evaluation to determine the causes of infertility. In particular, the following conditions must have been assessed to ensure appropriate treatment:

• Hypofunction of the thyroid gland or adrenal glands
• Elevated levels of the hormone called prolactin (hyperprolactinemia)
• Tumors of the pituitary gland (a gland located at the base of the brain)
• Tumors of the hypothalamus (an area below the part of the brain called the thalamus).

If you know you have any of the conditions listed above, inform your doctor before starting treatment with
MEROPUR.
Do not use MEROPUR in the following cases:

• You are allergic (hypersensitive) to menotropin or to any of the other components of MEROPUR (listed in section 6).
• You have tumors of the uterus, ovaries, breasts, or of brain areas such as the pituitary or hypothalamus.
• You have fluid-filled sacs known as ovarian cysts (ovarian cysts) or enlarged ovaries (not due to polycystic ovary syndrome).
• You have physical defects of the uterus or other reproductive organs.
• You have vaginal bleeding of unknown origin.
• You have fibroids (benign tumors) of the uterus.
• You are pregnant or breastfeeding.
• You are experiencing premature menopause.

Warnings and precautions
Contact your doctor if you experience:

• Abdominal pain
• Abdominal swelling
• Nausea
• Vomiting
• Diarrhea
• Weight gain
• Difficulty breathing
• Reduced urine output.

Report any of the above symptoms to your doctor immediately, even if they appear several days after the last injection. These may be signs of excessive ovarian activity, which can become severe.
If symptoms become severe, infertility treatment must be stopped and you should go to the hospital immediately.
Strict adherence to the recommended doses of MEROPUR and careful monitoring of treatment reduce the likelihood of these symptoms occurring.
You may continue to experience these symptoms even after stopping treatment with MEROPUR.
Contact your doctor immediately if any of the described symptoms occur.
During treatment with this medicine, your doctor will perform ultrasound examinations and, sometimes, blood tests to monitor your response to treatment.
Treatment with hormones such as MEROPUR may increase the risk of:

• Ectopic pregnancy (pregnancy outside the uterus) in case of previous fallopian tube problems
• Spontaneous abortion
• Multiple pregnancy (twins, triplets, etc.)
• Congenital malformations (physical defects in the newborn present at birth).

Some women who have received fertility treatment with multiple drugs have developed ovarian tumors and tumors of other reproductive organs. It is not yet known whether hormone treatments such as MEROPUR cause these problems.
The formation of a blood clot within blood vessels (veins or arteries) is more likely in pregnant women. Fertility treatments may increase this risk, especially if you are overweight, suffer from coagulation disorders (thrombophilia), or if you or a close family member (blood relative) have had episodes of blood clot formation. Inform your doctor if any of these apply to you.
Children
There is no relevant use of MEROPUR in children.
Other medicines and MEROPUR
Inform your doctor if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
Clomiphene citrate is another medicine used to treat infertility. If MEROPUR and clomiphene citrate are used together, the effect on the ovaries is increased.
Pregnancy and breastfeeding
MEROPUR must not be used during pregnancy or while breastfeeding.
Effects on ability to drive and use machines
It is unlikely that MEROPUR will affect the ability to drive or operate machinery.
For athletes
Using the drug without therapeutic need constitutes doping and may lead to a positive anti-doping test.
Important information about certain excipients in MEROPUR
MEROPUR contains less than 1 mmol of sodium (23 mg) per dose and is therefore essentially "sodium-free".

3. How to use MEROPUR

Always use MEROPUR exactly as instructed by your doctor. If you have any doubts, consult your doctor.
i. Women who do not ovulate (do not produce eggs):
Treatment should begin within the first 7 days of the menstrual cycle (day 1 is the first day of the cycle).
Treatment is daily for at least 7 days.
The usual starting dose is 75–150 IU per day. This dose may be increased based on your individual response, up to a maximum of 225 IU per day. A given dose should be administered for at least 7 days before being adjusted by your doctor. A dose increase of 37.5 IU per adjustment is recommended (and not more than 75 IU). If there is no adequate response after 4 weeks, the treatment cycle should be discontinued.
Once the optimal response has been achieved, a single injection of 5,000 IU to 10,000 IU of another hormone called human chorionic gonadotropin (hCG) should be administered one day after the last MEROPUR injection. Sexual intercourse is recommended on the same day and the day after the hCG injection. Alternatively, intrauterine insemination (direct injection of sperm into the uterus) may be performed. You will be closely monitored for at least 2 weeks after hCG administration.
Your doctor will monitor the effects of MEROPUR treatment. Depending on your progress, your doctor may decide to stop MEROPUR treatment and not administer hCG. In this case, you will be advised to use barrier contraceptive methods (e.g., condom) or abstain from sexual intercourse until the onset of the first menstrual cycle.
ii. Women undergoing assisted reproductive technology programs:
If you are simultaneously receiving a GnRH agonist (a medicine that helps regulate a hormone called gonadotropin-releasing hormone (GnRH)), MEROPUR treatment should begin approximately 2 weeks after starting the GnRH agonist.
If you have also received treatment with a GnRH antagonist, MEROPUR treatment should begin on day 2 or 3 of the menstrual cycle (day 1 is the first day of the cycle).
MEROPUR must be administered daily for at least 5 days. The usual starting dose of MEROPUR is 150–225 IU/day. Subsequent doses may be increased up to a maximum of 450 IU/day. The dose may be increased by up to 150 IU per single adjustment. Typically, treatment should not last longer than 20 days.
If a sufficient number of follicles of adequate size are obtained, you will be given up to 10,000 IU of a medicine called human chorionic gonadotropin (hCG) as a single injection to induce ovulation (release of an egg).
Your doctor will monitor your clinical condition for at least 2 weeks after the hCG injection.
Your doctor will monitor the effects of MEROPUR treatment. Depending on your progress, your doctor may decide to stop MEROPUR treatment and not administer hCG. In this case, you will be advised to use barrier contraceptive methods (e.g., condom) or abstain from sexual intercourse until the onset of the first menstrual cycle.
Instructions for use
If you have been instructed to self-administer MEROPUR, carefully follow all instructions provided to you.
The first injection of MEROPUR must be given under the supervision of a doctor or nurse.
MEROPUR is supplied in a vial as a powder that must be dissolved using a syringe containing the solvent before injection. The solvent to be used for dissolving MEROPUR is provided in a pre-filled syringe included in the package together with the powder.
MEROPUR 600 UI must be dissolved with a pre-filled syringe of solvent before use.
After dissolving the powder with the solvent, the vial contains medication sufficient for several days of treatment, so you must ensure that you withdraw only the amount of medication prescribed for you.
Your doctor has prescribed your dose of MEROPUR in IU (international units). To obtain the correct dose, you must use one of the 9 administration syringes, graduated in FSH/LH IU (units), provided in the package.

To do this:

1

2

3 4

1. Remove the protective cap from the powder vial and the rubber cap from the pre-filled solvent syringe (Figure 1).
2. Firmly attach the large needle (reconstitution needle) to the pre-filled solvent syringe and remove the protective cap from the needle (Figure 2).
3. Insert the needle vertically through the center of the rubber stopper of the powder vial and slowly inject all of the solvent to avoid formation of bubbles (Figure 3).
4. When the solvent is added, a slight overpressure is created inside the vial. Therefore, leave the syringe plunger for about 10 seconds to allow it to rise back on its own. This will remove the overpressure in the vial (Figure 4).

Remove the syringe and the reconstitution needle.

5	6	7	8

5. The powder should dissolve quickly (within 2 minutes) to form a clear solution. Although this usually occurs shortly after adding just a few drops of solvent, the entire amount of solvent must be added. To facilitate dissolution of the powder, gently rotate the solution (figure 5). Do NOT shake, to avoid formation of bubbles.

If the solution is not clear or contains particles, it must not be used.
The powder contained in the vial is now dissolved with the solvent from the syringe, and the medicine is
ready for use.

6. Take the administration syringe with pre-attached needle and insert the needle vertically into the center of the vial. The administration syringe already contains a small amount of air, which must be injected into the vial above the liquid. Invert the vial and withdraw the prescribed dose of MEROPUR into the injection syringe (figure 6).

REMEMBER: since the powder vial contains medication for several days of treatment,
you must ensure that you withdraw only the amount of medicine prescribed by your doctor.

7. Remove the syringe from the vial and draw a small amount of air into the syringe (figure 7).
8. Gently tap the administration syringe to collect all air bubbles to the tip (figure 8). Carefully push out all the air and continue pushing until the first drop of liquid appears at the needle tip.

Your doctor or nurse will tell you where to administer the injection (e.g., front of the thigh, abdomen, etc.).
Before injection, disinfect the injection site.

9. To perform the injection, pinch the skin to form a skin fold and insert the needle quickly at a 90-degree angle to the body. Gently push the syringe plunger to inject the solution (figure 9), then remove the used administration syringe.

After removing the administration syringe, apply pressure to the injection site to stop any possible bleeding.
Gently massage the injection site to help disperse the solution under the skin.
Do not dispose of the syringe and used materials in regular household waste; dispose of them properly.

10. For the next injection with the already-dissolved MEROPUR solution, repeat steps 6 to 9.

If you use more MEROPUR than you should
Inform your nurse or doctor.
If you forget to use MEROPUR
Do not use a double dose to make up for the missed dose. Inform your doctor or nurse.

4. Possible side effects

Like all medicines, MEROPUR can cause side effects, although not everybody experiences them.
The hormone used in infertility treatment such as MEROPUR may cause high levels of ovarian activity leading to a condition called ovarian hyperstimulation syndrome (OHSS), especially in women with polycystic ovaries. Symptoms include abdominal pain, abdominal swelling, nausea, vomiting, diarrhoea and weight gain. In severe cases of OHSS, rare complications have been reported, including fluid accumulation in the abdomen, pelvic and/or chest cavity, breathing difficulties, reduced urination, blood clot formation in blood vessels (thromboembolism), and ovarian twisting (ovarian torsion). If you experience any of these symptoms, contact your doctor immediately, even if they occur several days after the last injection.

With the use of this medicine, allergic reactions (hypersensitivity) may occur. Symptoms of these reactions may include redness, itching, swelling of the throat and difficulty breathing. If you notice any of these symptoms, contact your doctor immediately.

The following common side effects occur in between 1 and 10 out of 100 treated patients:

• Abdominal pain
• Headache
• Nausea
• Abdominal swelling
• Pelvic pain
• Ovarian hyperstimulation leading to increased ovarian activity (ovarian hyperstimulation syndrome)
• Local reactions at the injection site (such as pain, redness, bruising, swelling and/or itching)

The following uncommon side effects occur in between 1 and 10 out of 1,000 treated patients:

• Vomiting
• Abdominal discomfort
• Diarrhoea
• Fatigue
• Dizziness
• Fluid-filled sacs within the ovaries (ovarian cysts)
• Breast disorders (including breast pain, breast tenderness to touch, breast discomfort, nipple pain and breast swelling)
• Hot flushes

The following rare side effects occur in between 1 and 10 out of 10,000 treated patients:

• Acne
• Rash

In addition to the above, the following side effects have been reported after the marketing of MEROPUR, and their frequency is unknown:

• Visual disturbances
• Fever
• Feeling unwell
• Allergic reactions
• Weight gain
• Muscle and joint pain (e.g. back pain, neck pain, pain in arms and legs)
• Ovarian twisting (ovarian torsion) as a complication of increased ovarian activity due to hyperstimulation
• Itching
• Hives (urticaria)
• Blood clots as a complication of increased ovarian activity due to hyperstimulation

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MEROPUR

Keep this medicine out of the sight and reach of children.
Before reconstitution, store in the refrigerator (2°C–8°C). Do not freeze.
After reconstitution, the solution can be stored for up to 28 days at temperatures not exceeding 25°C.
The reconstituted solution must not be administered if it contains particles or is not clear.
Do not use MEROPUR after the expiry date stated on the packaging. The expiry date refers to the last day of the month indicated.
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 MEROPUR contains
The active substance is highly purified menotropin (menopausal human gonadotropin, hMG),
corresponding to 600 IU of follicle-stimulating hormone (FSH) biological activity and 600 IU of luteinizing hormone (LH)
biological activity. After reconstitution, 1 ml of reconstituted solution contains 600 IU of highly purified menotropin.
The other ingredients of the powder are:
Monohydrate lactose
Polysorbate 20
Disodium phosphate heptahydrate (as buffer and for pH adjustment)
Phosphoric acid (for pH adjustment).
The ingredients of the solvent are:
Water for injections
Metacresol.

Description of the appearance of MEROPUR and package contents
MEROPUR is a powder and solvent for injectable solution.
The product is available in a pack containing 1 vial of powder, 1 pre-filled syringe of solvent for reconstitution, 1 needle for reconstitution, and 9 disposable syringes for administration, graduated in FSH/LH units, with a pre-attached injection needle.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Ferring S.p.A.
Via C. Imbonati, 18 - 20159 MILAN, Italy
Manufacturer
Ferring GmbH
Wittland 11, D-24109 Kiel (Germany)

This medicinal product is authorized in the European Community Member States under the following
names:
Denmark, Finland, Greece, Norway, Portugal, Sweden: MENOPUR
Italy: MEROPUR

Patient information leaflet

MEROPUR 1200 IU powder and solvent for injectable solution

Menotropin
Please read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor 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 could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What MEROPUR is and what it is used for

MEROPUR is a lyophilized powder to be dissolved with a liquid (solvent) before use.
It is administered as a subcutaneous injection.
The active substance contained in MEROPUR is highly purified and known as menotropin.
Menotropin is extracted from the urine of post-menopausal women and contains three hormones: follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), and luteinizing hormone (LH).
The hCG, extracted from the urine of pregnant women, may be added to contribute to the total biological activity of LH.
FSH, hCG, and LH are natural hormones produced by women. They help the reproductive organs function properly.
MEROPUR is indicated for the treatment of female infertility in the following two clinical situations:

• Women who are unable to become pregnant due to the ovaries' inability to produce eggs (including polycystic ovary syndrome). MEROPUR is used in women who have already been treated without success for infertility with a medication called clomiphene citrate.
• Women undergoing assisted reproductive technology (ART) programs, including in vitro fertilization/embryo transfer (IVF-ET), gamete intrafallopian transfer (GIFT), and intracytoplasmic sperm injection (ICSI). MEROPUR helps the ovaries produce multiple follicles (fluid-filled sacs for eggs) in which eggs can develop (multiple follicular development).

2. What you need to know before using MEROPUR

Before starting treatment with MEROPUR, both you and your partner must undergo a medical evaluation to determine the causes of infertility. In particular, the following conditions must have been assessed to ensure appropriate treatment:

• Hypofunction of the thyroid or adrenal glands
• Elevated levels of the hormone called prolactin (hyperprolactinemia)
• Tumors of the pituitary gland (a gland located at the base of the brain)
• Tumors of the hypothalamus (an area below the part of the brain called thalamus).

If you know you have any of the conditions listed above, inform your doctor before starting treatment with
MEROPUR.
Do not use MEROPUR in the following cases:

• If you are allergic (hypersensitive) to menotropin or to any of the other components of MEROPUR (listed in section 6).
• If you have tumors of the uterus, ovaries, breasts, or of parts of the brain such as the pituitary gland or hypothalamus.
• If you have fluid-filled sacs known as ovarian cysts (ovarian cysts) or enlarged ovaries (not due to polycystic ovary syndrome).
• If you have physical abnormalities of the uterus or other reproductive organs.
• If you have vaginal bleeding of unknown origin.
• If you have fibroids (benign tumors) of the uterus.
• If you are pregnant or breastfeeding.
• If you are in premature menopause.

Warnings and precautions
Contact your doctor if you experience:

• Abdominal pain
• Abdominal swelling
• Nausea
• Vomiting
• Diarrhea
• Weight gain
• Difficulty breathing
• Reduced urine production.

Report these symptoms to your doctor immediately, even if they occur several days after the last injection. These may be signs of excessive ovarian activity, which can become severe.
If symptoms become severe, infertility treatment must be stopped and you should go to the hospital.
Strict adherence to the recommended doses of MEROPUR and careful monitoring of treatment reduce the likelihood of these symptoms occurring.
You may continue to experience these symptoms even after stopping treatment with MEROPUR.
Contact your doctor immediately if any of the symptoms described occur.
During treatment with this medicine, your doctor will perform ultrasound scans and, sometimes, blood tests to monitor your response to treatment.
Treatment with hormones such as MEROPUR may increase the risk of:

• Ectopic pregnancy (pregnancy outside the uterus), especially if you have previously had fallopian tube problems
• Spontaneous abortion
• Multiple pregnancy (twins, triplets, etc.)
• Congenital malformations (birth defects present at birth).

Some women who have received infertility treatment with multiple medications have developed ovarian and other reproductive organ tumors. It is not yet known whether hormone treatments such as MEROPUR cause these problems.
The formation of a blood clot within blood vessels (veins or arteries) is more likely in pregnant women. Infertility treatments may increase this risk, particularly if you are overweight, have a clotting disorder (thrombophilia), or if you or a close family member (blood relative) has had episodes of blood clot formation.
Tell your doctor if any of these apply to you.

Children
There is no relevant use of MEROPUR in children.

Other medicines and MEROPUR
Inform your doctor if you are taking, have recently taken, or might take any other medicines, including those without a prescription.

Clomiphene citrate is another medicine used to treat infertility. If MEROPUR and clomiphene citrate are used together, the effect on the ovaries is increased.

Pregnancy and breastfeeding
MEROPUR must not be used during pregnancy or while breastfeeding.

Effects on ability to drive and use machines
It is unlikely that MEROPUR will affect your ability to drive or operate machinery.

For those engaged in sports
Using this medicine without a medical need constitutes doping and may result in a positive anti-doping test.

Important information about certain excipients in MEROPUR
MEROPUR contains less than 1 mmol of sodium (23 mg) per dose, therefore it is essentially "sodium-free".

3. How to use MEROPUR

Always use MEROPUR exactly as your doctor has instructed. If you have any doubts, consult your doctor.
i. Women who do not ovulate (do not produce eggs):
Treatment should begin within the first 7 days of the menstrual cycle (day 1 is the first day of the cycle).
Treatment is daily for at least 7 days.
The initial dose is usually 75–150 IU per day. This dose may be increased based on your individual response, up to a maximum of 225 IU per day. A given dose should be administered for at least 7 days before being adjusted by your doctor. A dose increase of 37.5 IU per adjustment is recommended (and should not exceed 75 IU). If there is no adequate response after 4 weeks, the treatment cycle should be discontinued.
Once the optimal response is achieved, a single injection of 5,000 IU to 10,000 IU of another hormone called Human Chorionic Gonadotropin (hCG) should be administered one day after the last MEROPUR injection. It is recommended to have sexual intercourse on the same day and the day following the hCG injection. Alternatively, intrauterine insemination (injection of sperm directly into the uterus) may be performed. You will be closely monitored for at least 2 weeks after hCG administration.
Your doctor will monitor the effects of MEROPUR treatment. Depending on your progress, your doctor may decide to stop treatment with MEROPUR and not administer hCG. In this case, you will be instructed to use barrier contraceptive methods (e.g., condom) or to abstain from sexual intercourse until the onset of the first menstrual cycle.

ii. Women undergoing assisted reproductive technology programs:
If you are simultaneously receiving a GnRH agonist (a medicine that helps regulate a hormone called gonadotropin-releasing hormone (GnRH)), MEROPUR treatment should begin approximately 2 weeks after starting the GnRH agonist.
If you have also received treatment with a GnRH antagonist, MEROPUR treatment should begin on day 2 or 3 of the menstrual cycle (day 1 is the first day of the cycle).
MEROPUR must be administered daily for at least 5 days. The initial dose of MEROPUR is typically 150–225 IU/day. Subsequent doses may be increased up to a maximum dose not exceeding 450 IU/day. The dose may be increased by up to 150 IU per single adjustment. Typically, treatment should not last longer than 20 days.
When a sufficient number of follicles of adequate size have developed, you will receive a single injection of up to 10,000 IU of a medicine called human chorionic gonadotropin (hCG) to induce ovulation (release of an egg).
Your doctor will monitor your clinical condition for at least 2 weeks after the hCG injection.
Your doctor will monitor the effects of MEROPUR treatment. Depending on your progress, your doctor may decide to stop treatment with MEROPUR and not administer hCG. In this case, you will be instructed to use barrier contraceptive methods (e.g., condom) or to abstain from sexual intercourse until the onset of the first menstrual cycle.

Instructions for use
If you have been instructed to self-administer MEROPUR, carefully follow all instructions provided to you.
The first injection of MEROPUR should be given under the supervision of a doctor or nurse.
MEROPUR is supplied in a vial as a powder that must be dissolved using two pre-filled syringes containing solvent before injection. The solvent to be used for dissolving MEROPUR is provided in pre-filled syringes included in the package with the powder.
MEROPUR 1200 IU must be dissolved with two pre-filled syringes of solvent before use.
After dissolving the powder with the solvent, the vial contains medication sufficient for several days of treatment, so you must ensure that you withdraw only the amount of medication prescribed for you.
Your doctor has prescribed your MEROPUR dose in IU (units). To obtain the correct dose, you must use one of the 18 administration syringes provided in the package, graduated in FSH/LH IU (units).

To do this:

1. Remove the protective cap from the powder vial and the rubber cap from one of the pre-filled solvent syringes (Figure 1).
2. Firmly attach the large needle (reconstitution needle) to the pre-filled solvent syringe and remove the protective cap from the needle (Figure 2).

3

4

5

6

3. Insert the needle vertically through the center of the rubber stopper of the vial containing the powder and slowly inject the entire solvent to avoid bubble formation (Figure 3).
4. When adding the solvent, slight overpressure builds up inside the vial. Therefore, leave the syringe plunger for about 10 seconds so that it rises back on its own. This will remove the overpressure in the vial (Figure 4).
5. Carefully remove the syringe from the reconstitution needle by rotating it, leaving the needle in the vial.

Remove the rubber cap from the second pre-filled solvent syringe and firmly attach the syringe to the needle inserted in the vial. Slowly inject the entire solvent to avoid bubble formation (Figure 5).

6. When adding the solvent, slight overpressure builds up inside the vial. Therefore, leave the syringe plunger for about 10 seconds so that it rises back on its own. This will remove the overpressure in the vial (Figure 6).

Remove the syringe and the reconstitution needle.

7

8

9

10

7. The powder should dissolve quickly (within 2 minutes) to form a clear solution. Although this usually occurs already after adding just a few drops of solvent, the entire amount of solvent must be added. To facilitate dissolution of the powder, gently rotate the vial (Figure 7). Do not shake, to avoid formation of bubbles.

If the solution is not clear or contains particles, it must not be used.
The powder contained in the vial is now dissolved with the solvent from two syringes, and the medicine is
ready for use.

8. Take the administration syringe with pre-attached needle and insert the needle vertically into the center of the vial. The administration syringe already contains a small amount of air, which should be injected into the vial above the liquid. Invert the vial and withdraw the prescribed dose of MEROPUR into the injection syringe (Figure 8).

REMEMBER: since the powder vial contains medication for several days of treatment,
you must be sure to withdraw only the amount of medicine prescribed by your doctor.

9. Remove the syringe from the vial and draw a small amount of air into the syringe (Figure 9).
10. Gently tap the administration syringe to collect all air bubbles at the tip (Figure 10). Carefully expel all air and continue pushing until the first drop of liquid appears at the needle tip.

Your doctor or nurse will tell you where to administer the injection (e.g., front of thigh, abdomen, etc.).
Before injection, disinfect the injection site.

11. To perform the injection, pinch the skin to form a fold and insert the needle quickly at a 90-degree angle to the body. Gently push the syringe plunger to inject the solution (Figure 11), then remove the used administration syringe.

After removing the administration syringe, apply pressure to the injection site to stop any possible bleeding. Gently massage the injection site to help disperse the solution under the skin.
Do not dispose of the syringe and used materials in household waste; dispose of them properly.

12. For the next injection with the already-dissolved MEROPUR solution, repeat steps 8 to 11.

If you use more MEROPUR than you should
Inform your nurse or doctor.
If you forget to use MEROPUR
Do not use a double dose to make up for the missed dose. Inform your nurse or doctor.

4. Possible side effects

Like all medicines, MEROPUR can cause side effects, although not everyone experiences them.
The hormone used in infertility treatment such as MEROPUR may cause high levels of ovarian activity leading to a condition called ovarian hyperstimulation syndrome (OHSS), especially in women with polycystic ovaries. Symptoms include abdominal pain, abdominal swelling, nausea, vomiting, diarrhoea and weight gain. In severe cases of OHSS, rare complications have been reported including fluid accumulation in the abdomen, pelvic and/or thoracic cavity, breathing difficulties, reduced urination, blood clot formation in blood vessels (thromboembolism) and ovarian twisting (ovarian torsion). If you experience any of these symptoms, contact your doctor immediately, even if they appear several days after the last injection.
With the use of this medicine, allergic reactions (hypersensitivity) may occur. Symptoms of these reactions may include redness, itching, throat swelling and breathing difficulties. If you notice any of these symptoms, contact your doctor immediately.

The following common side effects occur in between 1 and 10 out of 100 treated patients:

• Abdominal pain
• Headache
• Nausea
• Abdominal swelling
• Pelvic pain
• Ovarian hyperstimulation leading to high levels of activity (ovarian hyperstimulation syndrome)
• Local reactions at the injection site (such as pain, redness, bruising, swelling and/or itching)

The following uncommon side effects occur in between 1 and 10 out of 1,000 treated patients:

• Vomiting
• Abdominal discomfort
• Diarrhoea
• Fatigue
• Dizziness
• Fluid-filled sacs within the ovaries (ovarian cysts)
• Breast disorders (including breast pain, breast tenderness to touch, breast discomfort, nipple pain and breast swelling)
• Hot flushes

The following rare side effects occur in between 1 and 10 out of 10,000 treated patients:

• Acne
• Skin rash

In addition to the above, the following side effects have been reported after marketing of MEROPUR, and their frequency is unknown:

• Visual disturbances
• Fever
• Feeling unwell
• Allergic reactions
• Weight gain
• Muscle and joint pain (e.g. back pain, neck pain, arm and leg pain)
• Ovarian twisting (ovarian torsion) as a complication of increased ovarian activity due to hyperstimulation
• Itching
• Urticaria
• Blood clots as a complication of increased ovarian activity due to hyperstimulation

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MEROPUR

Keep this medicine out of the sight and reach of children.
Before reconstitution, store in the refrigerator (2°C-8°C). Do not freeze.
After reconstitution, the solution can be stored for up to 28 days at temperatures not exceeding 25°C.
The reconstituted solution must not be administered if it contains particles or is not clear.
Do not use MEROPUR after the expiry date stated on the container. The expiry date refers to the last day of the month indicated.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What MEROPUR contains:
The active substance is highly purified menotropin (menopausal human gonadotropin, hMG),
corresponding to 1200 IU of follicle-stimulating hormone (FSH) biological activity and 1200 IU of luteinizing hormone (LH) biological activity.
After reconstitution, 1 ml of reconstituted solution contains 600 IU of highly purified menotropin.
The other ingredients of the powder are:
Monohydrate lactose
Polysorbate 20
Disodium phosphate heptahydrate (as buffer and for pH adjustment)
Phosphoric acid (for pH adjustment).
The ingredients of the solvent are:
Water for injections
Metacresol.

Description of the appearance of Meropur and contents of the pack
MEROPUR is a powder and solvent for injectable solution.
The product is available in packs containing 1 vial of powder, 2 pre-filled syringes of solvent for reconstitution, 1 needle for reconstitution and 18 single-use syringes for administration, graduated in FSH/LH units, with prefitted injection needle.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Ferring S.p.A.
Via C. Imbonati 18 - 20159 MILAN, ITALY

Manufacturer:
Ferring GmbH
Wittland 11, D-24109 Kiel, Germany

This medicinal product is authorized in the European Community Member States under the following names:
Denmark, Finland, Greece, Norway, Portugal, Sweden: MENOPUR
Italy: MEROPUR

Patient information leaflet

MEROPUR 600 IU injectable solution in pre-filled pen, 1200 IU injectable solution in pre-filled pen

menotropin
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 or pharmacist.
• 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 side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What MEROPUR is and what it is used for

MEROPUR is presented as an injectable solution in a pre-filled pen. The injection is administered under the skin (subcutaneous injection), usually in the abdomen.
The active substance contained in MEROPUR is highly purified and known as menotropin. Menotropin is extracted from the urine of postmenopausal women and contains three hormones: follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), and luteinizing hormone (LH).
hCG, extracted from the urine of pregnant women, may be added to contribute to the total biological activity of LH.
FSH, hCG, and LH are natural hormones produced by women. They help the reproductive organs function properly.

What MEROPUR is used for
MEROPUR is indicated for the treatment of female infertility in the following two clinical situations:

• Women who are unable to become pregnant due to the ovaries' inability to produce eggs (including polycystic ovary syndrome). MEROPUR is used in women who have already been treated without success for infertility with a medication called clomiphene citrate.
• Women undergoing assisted reproductive technology (ART) programs, including in*vitro* fertilization/embryo transfer (IVF*ET), gamete intrafallopian transfer (GIFT), and intracytoplasmic sperm injection (ICSI).

How MEROPUR works
MEROPUR helps the ovaries develop multiple follicles (fluid-filled sacs containing eggs), in which oocytes may mature (multiple follicular development).

2. What you should know before using MEROPUR

Checks to be carried out before treatment with MEROPUR
Before starting treatment with MEROPUR, both you and your partner must undergo a medical evaluation to determine the causes of infertility. In particular, the following conditions should have been assessed, as they may require a more appropriate treatment:

• Hypofunction of the thyroid gland or adrenal glands
• Elevated levels of the hormone called prolactin (hyperprolactinemia)
• Tumors of the pituitary gland (a gland located at the base of the brain)
• Tumors of the hypothalamus (an area below the part of the brain called the thalamus).

If you know you have any of the conditions listed above, inform your doctor before starting treatment with
MEROPUR.
Do not use MEROPUR in the following cases:

• You are allergic to menotropin or to any of the other components of MEROPUR (listed in section 6).
• You have tumors of the uterus, ovaries, breasts, or of parts of the brain such as the pituitary gland or hypothalamus.
• You have fluid-filled sacs in the ovaries (ovarian cysts) or ovarian enlargement (not due to polycystic ovary syndrome).
• You have physical abnormalities of the uterus or other reproductive organs.
• You have vaginal bleeding of unknown origin.
• You have fibroids (benign uterine tumors).
• You are pregnant or breastfeeding.

Warnings and precautions
Ovarian hyperstimulation syndrome (OHSS)
A serious side effect of this medicine, especially in women with polycystic ovaries, is "ovarian hyperstimulation" or "OHSS" (see section 4).
Speak to your doctor immediately if symptoms of OHSS occur, even if:

• Several days have passed since the last injection
• You have stopped treatment with MEROPUR

These may be symptoms of excessive ovarian activity, which can become severe. If this happens, your doctor will instruct you to stop treatment with MEROPUR and may refer you for hospital treatment.

Adhering to the recommended dose and careful monitoring of treatment will reduce the likelihood of such symptoms occurring.
Diagnostic tests and examinations
During treatment with this medicine, your doctor will usually perform ultrasound scans and, sometimes, blood tests to monitor your response to treatment.
Risks associated with pregnancy
Treatment with hormones such as MEROPUR may increase the risk of:

• Ectopic pregnancy (pregnancy outside the uterus) in case of previous fallopian tube disease
• Spontaneous abortion
• Multiple pregnancy (e.g. twins, triplets, etc.)
• Congenital malformations (physical defects in the newborn present at birth).

Some women who have received infertility treatment with multiple drugs have developed ovarian tumors and tumors of other reproductive organs. It is not yet known whether hormone treatment such as with MEROPUR causes these problems.
Blood clots
The formation of blood clots within blood vessels is more likely in pregnant women. This risk is higher if you have undergone infertility treatments and if you:

• are overweight
• have blood clotting disorders (thrombophilia)
• you or a close family member have had episodes of blood clot formation. Inform your doctor if any of these apply to you.

Children
MEROPUR is not used in children.
Other medicines and MEROPUR
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Clomiphene citrate is another medicine used to treat infertility. When MEROPUR is used simultaneously with clomiphene citrate, the effect on the ovaries may be increased.
Pregnancy and breastfeeding
MEROPUR must not be used during pregnancy or while breastfeeding.
Effects on ability to drive and use machines
It is unlikely that MEROPUR will affect the ability to drive or operate machinery.
For those engaged in sports
Using the medicine without therapeutic need constitutes doping and may lead to a positive result in anti-doping tests.
Important information about certain excipients in MEROPUR
MEROPUR contains less than 1 mmol of sodium (23 mg) per dose and is therefore essentially "sodium-free".

3. How to use MEROPUR

Always use MEROPUR exactly as instructed by your doctor. If you have any doubts, consult your doctor.
Women who do not ovulate (do not produce eggs):
Treatment should begin within the first 7 days of the menstrual cycle:

• Day 1 is the first day of the cycle.
• You will receive the injection daily for at least 7 days.

How much Meropur should you take?
The usual starting dose is between 75 and 150 UI per day.

• This dose may be increased based on your individual response, up to a maximum of 225 UI.
• You will receive the prescribed dose for at least 7 days before it is adjusted by your doctor.
• The dose is normally increased by 37.5 UI at a time, and not by more than 75 UI at any single adjustment. Your doctor will monitor the effects of treatment with MEROPUR. If there is no adequate response after 4 weeks, the treatment cycle should be discontinued.

If you respond positively to treatment with MEROPUR
You will be given a single injection of a hormone called human chorionic gonadotropin (hCG):

• The dose will be between 5,000 UI and 10,000 UI.
• The hCG injection will be administered one day after the last MEROPUR injection. It is recommended to have sexual intercourse on the same day and the day following the hCG injection. Alternatively, sperm may be injected directly into the uterus, known as “artificial insemination.”
• Your doctor will closely monitor you for at least 2 weeks. If you do not respond to treatment with MEROPUR:
• Your doctor will monitor the effects of treatment with MEROPUR.
• Depending on your progress, your doctor will decide whether to discontinue treatment with MEROPUR and not administer hCG.

Women undergoing assisted reproductive technology (ART) programmes:
If you are undergoing an assisted reproductive technology programme, you are simultaneously receiving a medicine that affects a hormone called “gonadotropin-releasing hormone” (GnRH). This medicine is called a “GnRH agonist.” Treatment with MEROPUR should begin approximately 2 weeks after starting treatment with the GnRH agonist.
You may also receive treatment with a medicine called a “GnRH antagonist.”
Treatment with MEROPUR should begin on day 2 or 3 of the menstrual cycle (day 1 is the first day of the cycle).
How much Meropur should you take?
MEROPUR must be administered daily for at least 5 days.

• The usual starting dose of MEROPUR is 150–225 UI.
• This dose may be increased, based on your response to treatment, up to a maximum dose of 450 UI/day.
• The dose may be increased by up to 150 UI per single adjustment. Normally, treatment should not last longer than 20 days.

If a sufficient number of follicles develop, you will be given an injection of up to 10,000 UI of hCG to induce ovulation (release of an egg).
Your doctor will closely monitor your clinical condition for at least 2 weeks after the hCG injection.
Your doctor will monitor the effects of treatment with MEROPUR.

• Depending on your progress, your doctor will decide whether to discontinue treatment with MEROPUR and not administer hCG.
• In this case, you will be advised to use barrier contraceptive methods (e.g. condom) or to abstain from sexual intercourse until the start of the next menstrual cycle.

Instructions for use of MEROPUR
Carefully follow all the “instructions for use” provided in the pre-filled pen package.
The first injection of MEROPUR must be administered under the supervision of a doctor or nurse.
Your doctor will decide whether you can self-administer subsequent injections at home, after you have received adequate training.
MEROPUR must be administered by subcutaneous injection (under the skin), usually in the abdominal area. The pre-filled pen may be used for multiple injections.
If you take more MEROPUR than you should
Inform your doctor.
If you forget to take MEROPUR
Do not take a double dose to make up for the missed dose. Inform your doctor.

4. Possible side effects

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

Serious side effects

Ovarian Hyperstimulation Syndrome (OHSS)

Contact your doctor immediately if you notice any of the following symptoms, which may be signs of OHSS:

• abdominal pain or swelling
• feeling unwell
• diarrhoea
• weight gain
• breathing difficulties
• reduced urine output

If you notice any of these symptoms, contact your doctor straight away, even if they appear several days after the last injection or after you have stopped using MEROPUR. You may require urgent medical treatment. These side effects may indicate that your ovaries have been overstimulated, a condition known as Ovarian Hyperstimulation Syndrome (OHSS). In cases of severe OHSS, rare complications have been reported, including accumulation of fluid in the abdomen, pelvic or chest cavity, breathing difficulties, reduced urine output, formation of blood clots in blood vessels (thromboembolism), and twisting of the ovaries (ovarian torsion).

Allergic reactions
Contact your doctor immediately if you notice any of the following symptoms:

• redness
• itching
• swelling of the throat and breathing difficulties

If you notice any of these symptoms, contact your doctor immediately.

Other side effects

Common side effects (may affect up to 1 in 10 people):

• Headache
• Feeling unwell (nausea)
• Abdominal pain or swelling
• Pelvic pain
• Pain, redness, swelling, itching or bruising at the injection site

Uncommon side effects (may affect up to 1 in 100 people):

• Feeling unwell (vomiting)
• Abdominal pain
• Diarrhoea
• Fatigue
• Dizziness
• Fluid-filled sacs in the ovaries (ovarian cysts)
• Breast disorders such as pain, breast tenderness, discomfort, swelling or nipple pain
• Hot flushes

Very rare side effects (may affect up to 1 in 1000 people):

• Acne

Other side effects (frequency not known):

• Visual disturbances
• Fever
• Feeling unwell
• Weight gain
• Muscle and joint pain
• Ovarian torsion as a consequence of ovarian hyperstimulation
• Hives (urticaria)
• Blood clots due to ovarian hyperstimulation

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MEROPUR

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pre-filled pen label and
on the packaging, after "EXP". The expiry date refers to the last day of the month indicated.
Before use:
Store in a refrigerator (2°C–8°C).
Do not freeze.
After opening:
Use each pre-filled pen within 28 days of opening. After opening, store at a temperature
below 25°C.
Always keep the pen in its cap to protect it from light.
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 MEROPUR contains
The active substance is highly purified menotropin (human menopausal gonadotropin, HMG).
MEROPUR 600 UI injectable solution in pre-filled pen:
One multi-dose pre-filled pen delivers menotropin equivalent to 600 IU of follicle-stimulating hormone (FSH) biological activity and 600 IU of luteinizing hormone (LH) biological activity.
MEROPUR 1200 UI injectable solution in pre-filled pen:
One multi-dose pre-filled pen delivers menotropin equivalent to 1200 IU of follicle-stimulating hormone (FSH) biological activity and 1200 IU of luteinizing hormone (LH) biological activity.

The other ingredients are:
Phenol
Methionine
Arginine hydrochloride
Polysorbate 20
Sodium hydroxide
Hydrochloric acid
Water for injections

Description of the appearance of MEROPUR and contents of the pack
MEROPUR is a clear, colourless injectable solution in a pre-filled pen.
MEROPUR 600 UI injectable solution in pre-filled pen is available in packs of 1 pen and 12 injection needles.
MEROPUR 1200 UI injectable solution in pre-filled pen is available in packs of 1 pen and 21 injection needles.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Ferring S.p.A.
Via C. Imbonati, 18 - 20159 MILAN, Italy

Manufacturer
Ferring GmbH
Wittland 11, D-24109 Kiel (Germany)

< This medicinal product is authorised in the European Economic Area Member States under the following names:
Belgium, Ireland, Luxembourg, Slovakia: Menotrophin Ferring
Czech Republic: Menotrophin Ferring-Léčiva
Bulgaria, Croatia, Cyprus, Denmark, Estonia, Finland, Greece, Hungary, Iceland, Latvia, Lithuania, Malta, Norway, Poland, Portugal, Romania, Slovenia, Spain, Sweden: Menopur
Germany: Menogon HP
Italy: Meropur>

Instructions for Use

MEROPUR Pre-filled Pen

Menotropin solution for injection

A healthcare professional (doctor, nurse, or pharmacist) must show you how to correctly prepare and inject MEROPUR before your first injection.
Read this entire leaflet carefully before using the MEROPUR pre-filled pen and each time you receive a new pen. There may be new information. Follow the instructions carefully, even if you have previously used a similar pen for injection. Incorrect use of the pen may result in administering an incorrect dose of the medication. Contact your healthcare provider if you have any doubts about how to perform your MEROPUR injection.
The MEROPUR pre-filled pen is a disposable dose pen that can be used to administer more than one dose of MEROPUR. The numbers you see in the dose display window represent the number of International Units (IU) of MEROPUR. The pen is available in two different strengths:

• 600 IU
• 1200 IU

Instructions for Use – MEROPUR Pre-filled Pen
Important Information

• The Meropur pre-filled pen and needles are designed for single-person use only and must not be shared with others.
• Use the pen only for the medical condition it was prescribed for and as directed by your healthcare provider.
• If you are blind or visually impaired, do not use this pen without assistance. Ask someone with no visual difficulties who has been trained to use the pen to help you.

Information about the MEROPUR pre-filled pen
The pen can be set to deliver doses of MEROPUR ranging from 6.25 IU to 450 IU in fixed increments of 6.25 IU.

• The pen’s dose scale is numbered from 0 to 450 IU.
• Moving from one labeled dose increment to the next unlabeled increment will increase or decrease the dose by 6.25 IU, depending on whether you are increasing or decreasing the dose. See "Examples of how to select a dose" on pages 20–21.
• When rotating the dose selector, you will feel a click and resistance at each increment to help you set the correct dose.

Cleaning

• If necessary, the exterior of the pen may be cleaned with a cloth dampened with water.
• Do not immerse the pen in water or any other liquid.

Storage

• Do not freeze.
• Before first use, store the pen in the refrigerator at 2°C to 8°C.
• After first use, use the pen within 28 days and store it at temperatures below 25°C.
• Always store the pen with the cap on and without the needle attached.
• Do not use the pen after the expiry date (EXP) printed on the label. The expiry date refers to the last day of the month indicated.
• Do not store the pen at extreme temperatures, in direct sunlight, or in very cold conditions, such as in a car or freezer.
• Keep the pen out of sight and reach of children.

Before Use – (Step 1)
1.

• Wash your hands.
• Make sure you have the correct pen with the right strength.
• Check the expiry date on the pen label.

Attaching the Needle – (Steps 2 to 6)
Important:

• Always use a new needle for each injection.
• Use only the single-use “click-on” needles supplied with the pen.

2.

• Remove the pen cap.
• Check that the pen is not damaged.
• Check that the medication is clear and free from particles.
• Do not use the pen if it is damaged, or if the medicine in the cartridge contains particles or is not clear.

3.

• Remove the protective tab from the needle.

4.

• Attach the needle to the pen.
• You will hear or feel a click when the needle is correctly attached.

5.

• Remove the outer needle cap.
• Do not discard the outer needle cap. You will need it to safely dispose of the needle after injecting the medicine.

6.

• Remove and discard the inner needle cap.

Priming – (Steps 7 to 9)

• Before using the pen for the first time, air bubbles must be removed from the cartridge (priming) to ensure you receive the correct dose of medication.
• Prime the pen only the first time it is used.
• Perform steps 7 to 9 even if you do not see air bubbles.
• If the pen has already been used, proceed directly to step 10.

7.

• Rotate the dose selector clockwise until a droplet symbol aligns with the dose indicator.
• If you select the wrong injection dose, you can correct the dose—either increasing or decreasing it—without wasting medication by rotating the dose selector in either direction until the droplet symbol aligns with the dose indicator.

8.

• Hold the pen with the needle pointing upward.
• Gently tap the cartridge holder to allow air bubbles to rise to the top of the cartridge.

9.

• With the needle still pointing upward (away from your face), press the injection button fully until you see the number '0' aligned with the dose indicator.

• Check that a drop of liquid appears at the needle tip.
• If no drop appears, repeat steps 7 to 9 (priming) until a small droplet is visible.
• If no droplet appears after five attempts, remove the needle (see Step 13), attach a new needle (see Steps 3 to 6), and repeat priming (see Steps 7 to 9).
• If no drop appears even after using a new needle, replace the pen.

Setting the Dose – (Step 10)
10.

• Rotate the dose selector clockwise until the prescribed dose aligns with the dose indicator in the dose display window.
• The dose can be corrected—either increased or decreased—without wasting medication by rotating the dose selector in either direction until the correct dose aligns with the dose indicator.
• Do not press the injection button while selecting the dose to avoid wasting medication. See "Examples of how to select a dose" on pages 20–21.

Split Dosing:

• You may need to use more than one pen to complete the prescribed dose.
• If you are unable to set the full dose, this means there is not enough medication left in the pen. You will need to administer an injection with a split dose or discard the current pen and use a new pen to administer the full prescribed dose in a single injection.

See "Administering a split dose of MEROPUR" on pages 22–23 for examples of how to calculate and record a split dose.
Injecting the Dose – (Steps 11 to 12)
Important:

• Read Steps 11 and 12 on pages 14 and 15 before administering your injection.
• This medicine must be administered by subcutaneous injection (under the skin) in the abdominal area (stomach).
• Use a new injection site for each injection to reduce the risk of skin reactions such as redness and irritation.
• Do not inject into areas that are tender, bruised, red, hard, injured, or have stretch marks.

11.

• Hold the pen so that the dose window is visible during injection.
• Pinch the skin and insert the needle perpendicularly into the skin as shown by your healthcare provider. Do not press the injection button yet (see Fig. 11).
• After inserting the needle, place your thumb on the injection button.
• Press and hold the injection button fully.
• Continue holding the injection button down until you see the number '0' aligned with the dose indicator, then wait 8 seconds (count slowly to 8) (see Fig. 12). This ensures the full dose is delivered.

12.

• After holding the injection button for 8 seconds, release the injection button. Then slowly remove the needle from the injection site by pulling it perpendicularly away from the skin.
• If blood appears at the injection site, gently press a gauze pad or cotton ball against the site.

Notes:

• Do not tilt the pen during injection or removal from the skin.
• Tilting the pen may cause the needle to bend or break.
• If a broken needle remains in the body or under the skin, seek immediate medical assistance.

Disposing of the Needle – (Step 13)
13.

• Carefully re-cap the needle by firmly pressing the outer needle cap back on (Fig. 13 A).
• Unscrew the needle counterclockwise to remove it from the pen (Fig. 13 B and 13 C).
• Dispose of the used needle carefully (Fig. 13 D).
• See "Disposal" on page 18.

Note:

• Always remove the needle after each use. Needles are for single use only.
• Do not store the pen with the needle attached.

Replacing the Pen Cap – (Step 14)
14.

• Firmly replace the pen cap to protect it between injections.

Note:

• The pen cap does not fit over the needle.
• Keep the pen cap on the pen when not in use.

Disposal
Needles:
Place used needles immediately into a puncture-resistant container, such as a sharps disposal container.
If you do not have a sharps disposal container, you may use a household container that:

• is made of strong plastic,
• has a tightly sealed, puncture-resistant lid that prevents needles from escaping,
• remains upright and stable during use,
• is leak-proof, and
• is clearly labeled to indicate the presence of hazardous waste inside.

Dispose of the sharps container when it is nearly full. Ask your doctor, nurse, or pharmacist for proper disposal methods. Do not dispose of used sharps containers in household waste unless permitted by local regulations.
MEROPUR pre-filled pens:

• Ask your pharmacist how to dispose of unused or expired medicines.

The following pages contain additional information on the following topics:

• Examples of how to select a dose – pages 20–21
• Administering a split dose of MEROPUR – page 22
• Split dose diary – page 23

As well as:

• Frequently Asked Questions (FAQ) – page 24
• Warnings – page 25
• Contacts – page 25

Examples of How to Select a Dose
Examples of setting a dose using the MEROPUR pre-filled pen.
The chart shows on the right examples of prescribed doses, how to select the prescribed dose examples, and how the dose display window appears for the prescribed doses.

Administering a Split Dose of MEROPUR
If you are unable to set the full prescribed dose on the pen, this means there is not enough medication in the pen to deliver the complete dose. You will need to administer part of the prescribed dose with the pen you are currently using and the remainder using a new pen (split-dose injection), or you may discard the current pen and use a new pen to administer the full prescribed dose in a single injection. If you choose to administer a split-dose injection, follow these instructions and record how much medication you administered in the split-dose diary on page 23.

• Column A shows an example of a prescribed dose. Write your prescribed dose in column A.
• Column B shows an example of the dose remaining in the pen (corresponding to what you are able to set).
• Write the remaining dose in the pen in column B. Administer the injection using the remaining medication in the pen.
• Prepare and prime a new pen (Steps 1 to 9).
• Calculate and record the remaining dose to be injected in column C by subtracting the number in column B from the number in column A. Use a calculator if needed to verify the result.
• See "Examples of how to select a dose" on pages 20–21 if needed.
• Contact your healthcare provider if you have any doubts about calculating a split dose.
• Inject the remaining dose of medication (number in column C) using the new pen to complete the prescribed dose.

Split Dose Diary
Frequently Asked Questions (FAQ)

1. Is the loading step required before each injection?

• No. Loading must only be performed at the time of the first injection with a new pen.

2. How can I tell that the injection is complete?

• You have fully pressed down the injection button.
• The number '0' has aligned with the dose indicator in the dose display window.
• You have slowly counted to 8 while keeping the injection button pressed and the needle still in the skin.

3. Why do I need to count to 8 while pressing the injection button?

• Pressing the injection button for 8 seconds ensures the full dose is delivered and absorbed through the skin.

4. What should I do if the dose selector cannot be turned to the required dose?

• The cartridge in the pen may not contain enough medication to deliver the prescribed dose.
• The pen does not allow you to set a dose higher than the amount remaining in the cartridge.
• You may inject the remaining medication in the pen and complete the prescribed dose using a new pen (fractional dosing), or use a new pen to administer the full prescribed dose.

5. What should I do if I do not have enough needles?

• If you need additional needles, contact your healthcare provider. Only use needles supplied with the MEROPUR pre-filled pen or prescribed by your healthcare provider.

Warnings

• Do not use a pen if it has been dropped or has hit a hard surface.
• If the injection button is difficult to press, do not force it. Change the needle. If the injection button remains difficult to press after changing the needle, use a new pen.
• Do not attempt to repair a damaged pen. If the pen is damaged, contact your healthcare provider or the marketing authorization holder.

Contacts
If you have any questions or problems regarding the use of the pen, contact your healthcare provider or the
local representative of the marketing authorization holder.
Marketed by:
Ferring S.p.A.
Via C. Imbonati 18
20159 - Milan, Italy
Date of revision: