Menopur

Patient Information Leaflet

MENOPUR, 600 IU FSH + 600 IU LH, powder and solvent for solution for injection
Menotropinum
Please read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet for future reference.
• If you have any further questions, please ask your doctor.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor. See section 4.

Leaflet Contents:

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 (in this case, a solid, compacted mass) which 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 derived from the urine of pregnant women may be added.
FSH, hCG, and LH are natural hormones produced in the female body. They support the normal functioning of the reproductive organs.
Menopur is used in the treatment of infertility in the following situations:
i. in women who are unable to become pregnant because their ovaries do not produce oocytes (including cases of polycystic ovary syndrome). Menopur is used in women who have already been treated with clomifene citrate for infertility, but the treatment was ineffective;
ii. in women undergoing assisted reproductive technologies such as in vitro fertilization and embryo transfer, gamete intrafallopian transfer, and intracytoplasmic sperm injection. Menopur supports the development of multiple ovarian follicles in the ovaries, in which oocytes can mature (multiple follicular development);
iii. in men whose testes produce an insufficient number of spermatozoa due to gonadotropin deficiency (hormones produced by the pituitary gland that affect the testes).

2. Important information before using Menopur

Before starting treatment with Menopur, your doctor must evaluate the causes of infertility in both partners. In particular, the following conditions should be ruled out, as they require specific alternative treatment:

• Hypothyroidism and adrenal insufficiency;
• High levels of a hormone called prolactin (hyperprolactinemia);
• Pituitary tumors (gland located at the base of the brain);
• Hypothalamic tumors (area located below a part of the brain called the thalamus).

If you have any of the above conditions, inform your doctor before starting treatment with Menopur.

When not to use Menopur

In women and men:

• If you are allergic to menotropin or any of the other ingredients of this medicine (listed in section 6);
• If pituitary or hypothalamic tumors have been diagnosed.

In women:

• If you are pregnant or breastfeeding;
• If ovarian cysts or enlarged ovaries not caused by polycystic ovary syndrome have been diagnosed;
• If you have vaginal bleeding of unknown cause;
• If you have tumors of the uterus, ovaries, or breast;
• If you have congenital abnormalities of the reproductive organs that prevent pregnancy;
• If you have uterine fibroids that prevent pregnancy;
• If you have premature menopause.

In men:

• If prostate cancer has been diagnosed;
• If testicular tumors have been diagnosed.

Warnings and precautions

Use caution if you experience any of the following symptoms:

• Abdominal pain;
• Abdominal distension;
• Nausea;
• Vomiting;
• Diarrhea;
• Weight gain;
• Difficulty breathing;
• Decreased frequency or amount of urine.

Inform your doctor immediately about these symptoms, even if they occur several days after the last dose of the medicine. These may be signs of ovarian hyperstimulation, which can be severe.

If these symptoms worsen, stop infertility treatment and seek immediate hospital care. Adhering to the prescribed dose and careful monitoring of treatment reduces the likelihood of these symptoms occurring.

These symptoms may also occur after stopping treatment with Menopur. If any of these symptoms develop, contact your doctor immediately.

During treatment with Menopur, your doctor will usually arrange for ultrasound scans (ultrasound imaging) and sometimes blood tests to monitor your response to treatment.

Hormonal treatment 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 abnormalities present at birth).

In some women treated for infertility, tumors of the ovaries or other reproductive organs have developed. It is not currently known whether this is caused by hormonal treatment such as Menopur.

The risk of venous or arterial blood clots 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 have had blood clots in the past. Inform your doctor if you think this applies to you.

Menopur, in combination with a hormone called human chorionic gonadotropin (hCG), may be used in the treatment of male infertility.

Children and adolescents

Menopur should not be used in children and adolescents.

Other medicines and Menopur

Tell your doctor about all medicines you are currently taking, have recently taken, or plan to take.

Clomiphene citrate is another medicine used in infertility treatment. If Menopur is used at the same time as clomiphene citrate, the effect on the ovaries may be enhanced.

Menopur may be used simultaneously with Bravelle. See section 3.

Pregnancy and breastfeeding

Menopur must not be used during pregnancy or breastfeeding.

Driving and operating machinery

It is unlikely that Menopur will affect your ability to drive or operate machinery.

Menopur contains sodium chloride

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 directed by your doctor. If you are unsure, you should 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 menstruation). The medicine should be administered daily for at least 7 days.
The usual starting dose is from 75 IU (international units) FSH + 75 IU LH to 150 IU FSH + 150 IU LH per day. Depending on the patient's response, the dose may be increased up to a maximum of 225 IU FSH + 225 IU LH. The selected dose should be maintained for at least 7 days before any dose adjustment is made. It is recommended to increase the dose by increments of 37.5 IU FSH + 37.5 IU LH, but not more than 75 IU FSH + 75 IU LH at a time. Treatment should be discontinued if there is no response after 4 weeks.

When a satisfactory response is achieved, another hormone, hCG, should be administered as a single injection of 5000 IU to 10,000 IU the day after the last Menopur injection. Sexual intercourse is recommended on the day of hCG administration and the following day. Alternatively, insemination (direct placement of sperm 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 treatment with Menopur. Depending on treatment progress, your doctor may decide to discontinue Menopur and withhold hCG. In such a case, the patient will be advised to use a mechanical method of contraception (e.g. condom) or to abstain from sexual intercourse until the next menstrual period occurs.

Women undergoing assisted reproductive technology (ART) programs
If the patient has also been treated with a GnRH agonist (a medicine that enhances the action of gonadotropin-releasing hormone, GnRH), Menopur should be started approximately 2 weeks after beginning GnRH agonist treatment.

If the patient has been treated with a GnRH antagonist, Menopur should be started on day 2 or 3 of the menstrual cycle (day 1 of menstruation being day 1 of the cycle).
The medicine should be administered daily for at least 5 days. The usual starting dose of Menopur is from 150 IU FSH + 150 IU LH to 225 IU FSH + 225 IU LH per day. Depending on the patient's response, this dose may be increased up to a maximum of 450 IU FSH + 450 IU LH per day. The dose should not be increased by more than 150 IU FSH + 150 IU LH at any one time. Treatment usually should not last longer than 20 days.

Once a sufficient number of ovarian follicles of appropriate size are observed, the patient receives a single injection of hCG 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 administration.

Your doctor will monitor the response to treatment with Menopur. Depending on treatment progress, your doctor may decide to discontinue Menopur and withhold hCG. In such a case, the patient will be advised to use a mechanical method of contraception (e.g. condom) or to abstain from sexual intercourse until the next menstrual period occurs.

Men:
Treatment begins with hCG administered 3 times per week at a dose of 1000 IU to 3000 IU until normal serum testosterone levels are achieved. Then Menopur is administered intramuscularly at a dose of 75 IU FSH + 75 IU LH to 150 IU FSH + 150 IU LH, 3 times per week for several months.

INSTRUCTIONS FOR USE

If your doctor has instructed you to self-inject Menopur, you must follow all instructions provided.

The first Menopur injection should be performed under the supervision of a doctor.

Menopur is supplied as a powder in a vial and must be reconstituted (dissolved) before injection. The diluent to be used for dissolving Menopur is contained in a pre-filled syringe supplied with the vial of powder.

Menopur 600 IU FSH + 600 IU LH must be dissolved before use with the diluent provided in one pre-filled syringe.

After reconstitution, the solution from one vial is used over several days; therefore, ensure that only the dose prescribed by your doctor is withdrawn each time.

Your doctor will prescribe the Menopur dose in international units (IU). One of the 9 supplied syringes, graduated in FSH/LH international units, should be used for administration.

To do this:

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2

3

4

1. Remove the protective cap from the powder vial and the rubber cap from the syringe cartridge containing the solvent (Figure 1).
2. Firmly attach the needle (reconstitution needle) to the syringe cartridge with solvent and remove the protective needle cap (Figure 2).
3. Insert the needle vertically through the center of the rubber stopper of the powder vial and slowly inject the entire fluid into the vial to avoid formation of bubbles (Figure 3).
4. During solvent injection, slight overpressure may develop in the vial. Therefore, after injecting the solvent, release pressure on the plunger for about 10 seconds and allow the plunger to retract upward by itself. This will eliminate overpressure in the vial (Figure 4).

Remove the syringe cartridge and the reconstitution needle.

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6

7

8

5. The powder should dissolve quickly (within 2 minutes), forming a clear solution. Although this normally occurs shortly after injecting a few drops of solvent, the entire solvent volume must be injected. To facilitate dissolution of the powder, gently swirl the vial (Figure 5). Do not shake the vial, as this may cause air bubbles to form.

If the solution is not clear or contains particles, do not use it.
The solution obtained after dissolving the powder with solvent from one prefilled syringe is now ready for use.

6. Remove the injection syringe with attached needle from its packaging and insert the needle vertically through the center of the vial’s rubber stopper. The injection syringe contains a small amount of air, which should be injected into the vial above the solution. Turn the vial upside down and withdraw the prescribed dose of Menopur into the syringe (Figure 6).

NOTE: Since the vial contains medication intended for use over several days, ensure that only the dose prescribed by the physician is withdrawn.
If the physician has prescribed Bravelle together with Menopur, both medications may be mixed.
To do this, after dissolving Menopur, inject the prescribed dose of Menopur into the vial containing the reconstituted Bravelle solution. Then withdraw the mixed solution containing both medications into the syringe and administer it subcutaneously. This procedure avoids the need to inject each medication separately.

7. Disconnect the syringe from the vial and draw a small amount of air into the syringe (Figure 7).
8. Hold the syringe with the needle pointing upward and gently tap the syringe to bring all air bubbles to the top (Figure 8). Expel the air by carefully pressing the plunger until the first drop of liquid appears at the needle tip.

The patient will be informed by the physician or nurse about the appropriate injection site (e.g., front of the thigh, abdomen, etc.).
Before injection, disinfect (cleanse) the skin at the injection site.

9. To perform the injection, pinch a fold of skin between the fingers and insert the needle quickly at a 90-degree angle (perpendicularly). Inject the solution by gently pressing the syringe plunger (Figure 9), then withdraw the syringe with the needle.

After removing the syringe and needle, press gently on the injection site to prevent possible bleeding. Light massage at the injection site helps disperse the solution under the skin.
Used materials must not be disposed of in household waste containers; they must be discarded appropriately.

10. Subsequent injections of the reconstituted Menopur solution are administered by repeating the steps described in points 6 to 9.

Use of a higher than recommended dose of Menopur
If a higher than recommended dose of Menopur is administered, inform the physician immediately.
Missed dose of Menopur
Do not administer a double dose to make up for a missed dose. If a dose of Menopur is missed, inform the physician.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everybody will experience them.
Hormones used in infertility treatment, such as Menopur, may cause excessive ovarian activity, leading to a condition called ovarian hyperstimulation syndrome (OHSS), particularly in women with polycystic ovary syndrome. Symptoms include abdominal pain, abdominal distension, nausea, vomiting, diarrhoea and weight gain.
In severe cases of OHSS, complications have rarely occurred, such as accumulation of fluid in the abdominal cavity, pelvic cavity and (or) pleural cavity, breathing difficulties, reduced frequency or volume of urine, formation of blood clots in blood vessels (thromboembolic disorders), and ovarian torsion.
If any of these symptoms occur, contact your doctor immediately, even if symptoms appear several days after the last dose 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 effects occur frequently, i.e. in 1 to 10 out of 100 treated patients:

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

The following adverse effects occur uncommonly, i.e. in 1 to 10 out of 1,000 treated patients:

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

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

• acne;
• rash.

In addition to the above, the following adverse effects have been observed after Menopur was placed on the market, and their frequency is unknown:

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

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor. Adverse effects 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
e-mail: [email protected]
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Menopur

Keep this medicine out of the sight and reach of children.
Before reconstitution, store in a refrigerator (2°C - 8°C). Do not freeze. Store in the original packaging to protect from light.
After reconstitution, the solution can be stored for 28 days at a temperature below 25°C.
Do not freeze.
Do not administer the solution if it contains solid particles or is not clear.
Do not use this medicine after the expiry date stated on the packaging after the EXP label. The expiry date refers to the last day of the specified month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Menopur contains

• The active substance is highly purified menotropin (Menotropinum) (human menopausal gonadotrophin, hMG), corresponding to a biological activity of follicle-stimulating hormone (FSH) 600 IU and luteinizing hormone (LH) biological activity 600 IU.
• Other ingredients are:
  Powder: monohydrate lactose, polysorbate 20, disodium phosphate heptahydrate, phosphoric acid (concentrated)
  Solvent: water for injections, m-cresol (preservative)

What Menopur looks like and contents of the pack
Menopur is a powder and solvent for solution for injection.
The pack contains:
1 vial with powder;
1 ampoule-syringe with solvent for reconstitution;
1 needle for reconstitution;
9 single-use injection syringes graduated in FSH/LH units
with attached needles.

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

For further information about this medicinal product, please contact the representative of the Marketing Authorisation Holder:
Ferring Pharmaceuticals Poland Sp. z o.o.
Szamocka Street 8, 01-748 Warsaw, Poland
Tel.: +48 22 246 06 80, Fax: +48 22 246 06 81