Menopur

Package leaflet: Information for the user

MENOPUR, 75 IU, powder and solvent for solution for injection
Menotropinum
Read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of the leaflet:

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

1. What Menopur is and what it is used for

Menopur is a powder that must be dissolved in a liquid (solvent) before use. The medicine is administered as a subcutaneous or intramuscular injection.
The active substance in MENOPUR is highly purified menotropin. Menotropin is obtained from the urine of postmenopausal women and contains three hormones: follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), and luteinizing hormone (LH).
To achieve full biological LH activity, hCG obtained from the urine of pregnant women may be added.
FSH, hCG, and LH are natural hormones produced in women's bodies. They support the proper functioning of the reproductive organs.
Menopur is used in the treatment of infertility in women in the following two situations:
i. in women who are unable to become pregnant because their ovaries do not produce oocytes (including cases of polycystic ovarian syndrome). Menopur is used in women who have already been treated with clomiphene citrate for infertility, but the treatment was ineffective;
ii. in women undergoing assisted reproductive technologies such as in vitro fertilization (IVF) and embryo transfer, gamete intrafallopian transfer (GIFT), and intracytoplasmic sperm injection (ICSI). Menopur supports the development of multiple ovarian follicles in the ovaries, in which oocytes can mature (multifollicular development).

2. Important information before using Menopur

Before starting treatment with Menopur, your doctor should carefully evaluate the causes of infertility in both partners. In particular, the following conditions should be ruled out, as they require different, specific treatments:
hypothyroidism and adrenal insufficiency;
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 located below the thalamus in the brain).
If you have any of the above conditions, you must inform your doctor before starting treatment with Menopur.

When not to use Menopur
if you are allergic (hypersensitive) to menotropin or any of the other ingredients of Menopur (listed in section 6);
if you have tumors of the uterus, ovaries, breast, or areas of the brain such as the pituitary gland or hypothalamus;
if you have ovarian cysts or enlarged ovaries (not caused by polycystic ovary syndrome);
if you have congenital malformations of the uterus or genital organs;
if you have vaginal bleeding of unknown cause;
if you have uterine fibroids (benign tumors);
if you are pregnant or breastfeeding;
if you have premature menopause.

Warnings and precautions
Use caution if you experience:
abdominal pain;
abdominal distension;
nausea;
vomiting;
diarrhea;
weight gain;
difficulty breathing;
decreased frequency or amount of urination.

You should immediately inform your doctor about the above symptoms, even if they occur several days after the last dose of the medication. These may be signs of ovarian hyperstimulation, which can be severe.
If symptoms worsen, infertility treatment should be discontinued and appropriate treatment initiated in a hospital.
Following the recommended dose and careful monitoring during treatment reduces the likelihood of these symptoms occurring.
These symptoms may also occur after stopping Menopur. If any of these symptoms appear, contact your doctor immediately.

During treatment with this medicine, your doctor will usually arrange for you to have ultrasound scans (USG) and sometimes blood tests to monitor your response to treatment.

Treatment with hormones such as Menopur may increase the risk of:
ectopic pregnancy (tubal pregnancy) in women with previously diagnosed fallopian tube disease;
miscarriage;
multiple pregnancy (twins, triplets, etc.);
congenital malformations (physical birth defects present at birth).

In some women undergoing infertility treatment with multiple medications, tumors of the ovaries or other reproductive organs have developed. It is not yet known whether this was caused by treatment with hormones such as Menopur.

The risk of blood clots in blood vessels (veins or arteries) is higher in women who are pregnant. Infertility treatment may increase the risk of blood clots, especially if you are overweight or if you or a family member (relative) has had blood clots (thrombophilia) in the past. You should inform your doctor if you think this applies to you.

Children and adolescents
Menopur should not be used in children and adolescents.

Menopur with other medicines
Tell your doctor about all medicines you are currently taking or have recently taken, including medicines obtained without a prescription.
Clomiphene citrate is another medicine used to treat infertility. If Menopur is used at the same time as clomiphene citrate, the effect on the ovaries may be enhanced.

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

Driving and operating machinery
It is unlikely that Menopur will affect the ability to drive or operate machinery.

Important information about some ingredients of Menopur
Menopur contains less than 1 mmol of sodium chloride (23 mg) per dose and is therefore considered "sodium-free".

3. How to use Menopur

This medicine should always be used exactly as prescribed by your doctor. If in doubt, 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 being the first day of menstrual bleeding). The medicine should be administered daily for at least 7 days.
The initial dose is usually between 75 IU (international units) and 150 IU (i.e. 1 to 2 vials of powder) per day, but may be adjusted depending on the patient's response (up to a maximum of 225 IU – i.e. 3 vials of powder per day). The selected dose should be maintained for at least 7 days before any dose adjustment by the doctor. Dose increases should be made in increments of 37.5 IU (i.e. half a vial of powder) at each adjustment (but not more than 75 IU at a time). The treatment cycle should be discontinued if no response is observed after 4 weeks.
When a satisfactory response has been achieved, the next day after the last Menopur injection, another hormone called human chorionic gonadotropin (hCG) should be administered as a single injection at a dose of 5,000 IU to 10,000 IU. Sexual intercourse is recommended on the day of hCG administration and the following day. Alternatively, insemination (direct placement of semen into the uterus) may be performed. The patient should remain under close medical supervision for at least 2 weeks after hCG administration.
Your doctor will monitor the response to Menopur treatment. Depending on treatment progress, the doctor may decide to discontinue Menopur administration and withhold hCG. In such a case, the patient will be advised to use a mechanical contraceptive method (e.g. condom) or abstain from sexual intercourse until the next menstrual period occurs.

ii. Women undergoing assisted reproductive technology programs:
If the patient has also been treated with a GnRH agonist (a medicine that enhances the action of gonadotropin-releasing hormone, GnRH), Menopur administration should begin approximately 2 weeks after starting the GnRH agonist treatment.
If the patient has also been treated with a GnRH antagonist, Menopur administration should begin on day 2 or 3 of the menstrual cycle (day 1 being the first day of menstrual bleeding).
The medicine should be administered daily for at least 5 days. The initial dose of Menopur is usually between 150 IU and 225 IU (i.e. 2 to 3 vials of powder) per day. Depending on the patient's response, this dose may be increased up to a maximum of 450 IU (i.e. 6 vials of powder) per day. Dose increases should not exceed 150 IU at any one time. Treatment usually should not last longer than 20 days.
Once a sufficient number of ovarian follicles of appropriate size have developed, the patient will receive a single injection of human chorionic gonadotropin (hCG) at a dose of up to 10,000 IU to trigger ovulation (release of the egg).
The patient should remain under close medical supervision for at least 2 weeks after hCG injection.
Your doctor will monitor the response to Menopur treatment. Depending on treatment progress, the doctor may decide to discontinue Menopur administration and withhold hCG. In such a case, the patient will be advised to use a mechanical contraceptive method (e.g. condom) or abstain from sexual intercourse until the next menstrual period occurs.

INSTRUCTIONS FOR USE
If your doctor has instructed you to self-inject Menopur, you must strictly follow all instructions provided.
The first Menopur injection should be performed under the supervision of a doctor.

RECONSTITUTION OF MENOPUR:
Menopur is a powder that must be dissolved before injection. The solvent (liquid) to be used for reconstitution is supplied with the powder. Menopur should be reconstituted immediately before use. To do this:

• Attach a thick, long needle firmly to the syringe (reconstitution needle).
• Snap off the top of the ampoule containing the solvent at the point indicated by the dot.
• Insert the needle into the ampoule.

• Draw all the liquid from the ampoule into the syringe.
• Insert the needle through the rubber stopper of the vial containing the powder and slowly inject all the liquid. Aim at the vial wall to avoid foaming.
• The powder should dissolve quickly (within 2 minutes), forming a clear solution. This usually occurs as soon as only a few drops of solvent are added.
• To facilitate reconstitution, gently swirl the vial. Do not shake, as this may cause air bubbles to form. If the solution is not clear or contains particles, do not use it.

• Draw the solution back into the syringe.

If your doctor has prescribed more than one vial of Menopur powder per injection, the solution (first reconstituted Menopur) may be drawn back into the syringe and injected into a second vial of powder. This procedure may be repeated with up to a total of three vials of powder, but only if specifically instructed by your doctor.

ADMINISTRATION OF MENOPUR:

• After drawing the prescribed dose into the syringe, change the needle

to a short, thin needle (injection needle).

• Hold the syringe with the needle pointing upwards and gently tap the syringe to allow air bubbles to rise to the top. Carefully press the plunger until the first drop of liquid appears at the tip of the needle.
• The patient should be informed by the doctor or nurse where to administer the injection (e.g. front of the thigh, abdomen, etc.).
• Disinfect the skin at the injection site.

• To administer the injection, pinch a skin fold between the fingers and insert the needle quickly at a 90-degree angle (perpendicular). Inject the solution by pressing the plunger, then withdraw the needle.
• After removing the needle, press gently on the injection site to prevent bleeding. Gentle massage at the injection site helps the solution disperse under the skin.
• Used materials must not be disposed of in household waste containers but must be discarded appropriately.

Overdose of Menopur
If more Menopur than prescribed has been administered, inform your nurse or doctor immediately.

Missed dose of Menopur
Do not administer a double dose to make up for a missed dose. If a dose of Menopur has been missed, inform your nurse or doctor.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
Treatment with Menopur may cause excessive ovarian activity, leading to a condition known as Ovarian Hyperstimulation Syndrome (OHSS), especially in women with polycystic ovary syndrome. Symptoms include: abdominal pain, abdominal bloating, nausea, vomiting, diarrhoea, and weight gain. In severe cases of OHSS, complications such as accumulation of fluid in the abdominal cavity, pelvic cavity, and/or pleural cavity, breathing difficulties, reduced frequency or amount of urine, blood clot formation in blood vessels (thromboembolic disorders), and ovarian torsion have rarely occurred. If any of these symptoms occur, contact your doctor immediately, even if symptoms appear several days after the last injection of the medicine.

Allergic (hypersensitivity) reactions may occur during treatment. Symptoms of such reactions may include: rash, itching, throat swelling, and breathing difficulties. If any of these symptoms occur, contact your doctor immediately.

The following adverse reactions occur frequently, i.e. in 1 to 10 out of every 100 treated patients:

• abdominal pain;
• headache;
• nausea;
• abdominal distension;
• pelvic pain;
• excessive ovarian stimulation leading to high ovarian activity (ovarian hyperstimulation syndrome);
• reactions at the injection site (such as pain, redness, bruising, swelling, and/or itching).

The following adverse reactions occur less frequently, i.e. in 1 to 10 out of every 1,000 treated patients:

• vomiting;
• gastrointestinal discomfort;
• diarrhoea;
• feeling of fatigue;
• dizziness;
• fluid-filled sacs in the ovaries (ovarian cysts);
• breast discomfort (including breast pain, breast tenderness, discomfort, nipple pain, and breast swelling);
• hot flushes.

The following adverse reactions occur rarely, i.e. in 1 to 10 out of every 10,000 treated patients:

• acne;
• rash.

In addition to the above, the following adverse reactions have been observed after Menopur was placed on the market, with frequency not known:

• visual disturbances;
• fever;
• malaise;
• allergic (hypersensitivity) 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 caused by excessive stimulation;
• itching;
• urticaria;
• blood clots, as a complication of increased ovarian activity caused by excessive stimulation.

If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or nurse. This also applies to any adverse reactions not mentioned in this leaflet.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Aleje Jerozolimskie 181C, 02-222 Warsaw, Tel: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Menopur

Do not store above 25°C. Do not freeze.
Keep in the original packaging to protect from light.
After reconstitution: for immediate and single use only.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Menopur contains

• The active substance is highly purified menotropin (human menopausal gonadotrophin, hMG) in an amount corresponding to a follicle-stimulating hormone (FSH) biological activity of 75 IU and a luteinizing hormone (LH) biological activity of 75 IU.
• Other ingredients of the powder: monohydrate lactose, polysorbate 20, sodium hydroxide, hydrochloric acid.
• Ingredients of the solvent: water, hydrochloric acid, sodium chloride, sodium hydroxide.

What Menopur looks like and contents of the pack
Menopur is a powder and solvent for solution for injection.
The carton box contains five or ten vials made of colourless glass containing a white or almost white powder. The carton box also contains the same number of ampoules made of colourless glass containing a colourless solvent.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:
Ferring GmbH
Wittland 11
D-24109 Kiel
Germany

Local representative of the Marketing Authorisation Holder:
Ferring Pharmaceutical Poland Sp. z o.o.
Szamocka 8 Street
01-748 Warsaw
Poland
Tel.: + 48 22 246 06 80