Prospect: information for the user

MENOPUR 600 International Units powder and solvent for injectable solution

Purified menotropin

Read the prospect carefully before starting to take the medication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed only to you and should not be given to other people even if they present the same symptoms of disease as you, as it may harm them.
• If you experience adverse effects,consult your doctor, or pharmacist,even if it is an adverse effect that does not appear in this prospect(see section 4).

1. What is Menopur and for what it is used

2. What you need to know beforeusing Menopur

3. How to use Menopur

4. Possible adverse effects

5. Conservation of Menopur

6. Contents of the package and additional information

Menopur contains menotropin (also known as human menopausal gonadotropin or hMG-HP). It is a highly purified extract of urine from postmenopausal women, and contains two hormones called follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH are present in both men and women, and help the reproductive organs to function normally.

Menopur is indicated for the treatment of infertility in the following situations:

* Women who cannot become pregnant because their ovaries do not produce eggs (including polycystic ovary syndrome). Menopur is used in women who have been treated with a medication called clomiphene citrate to treat their infertility, but this medication has not been effective.

*Women in assisted reproduction programs (including in vitro fertilization/embryo transfer [IVF/ET], gamete intrafallopian transfer [GIFT], and intracytoplasmic sperm injection [ICSI]). Menopur helps the ovaries to develop many sacs of eggs (follicles) where an egg can develop (multiple follicular development).

* Male infertility with hypogonadotropic or normogonadotropic hypogonadism: in combination with human chorionic gonadotropin to stimulate spermatogenesis.

Menopur is used with human chorionic gonadotropin to stimulate spermatogenesis.

Before starting treatment with Menopur, you and your partner must be evaluated by a doctor to see the causes of the fertility problem. In particular, the following diseases should be controlled so that the most suitable treatment can be administered:

- Thyroid gland dysfunction and adrenal cortex dysfunction

- High levels of a hormone called prolactin (hyperprolactinemia)

- Tumors in the pituitary gland (a gland located at the base of the brain)

- Tumors in the hypothalamus (an area located under the part of the brain called the thalamus).

If you know you have any of the diseases listed above, please inform your doctor before starting treatment with Menopur.Please inform your doctor before starting treatment with Menopur.

Do not use Menopur if:

- You are allergic (hypersensitive) to menotropin or any of the other components of Menopur, including those listed in section 6.

In women:

- If you have a tumor in the uterus, ovaries, breasts, or some parts of the brain such as the hypothalamus-pituitary

- If you have an increase in the ovaries or non-induced cysts not caused by polycystic ovary syndrome

- If you have malformations in the reproductive organs or uterus (womb)

- 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.

In men:

• If you have prostate cancer
• If you have a tumor in the testicles.

Warnings and precautions

If you have:

• Abdominal pain

• Abdominal swelling

• Nausea

• Vomiting

• Diarrhea

• Weight gain

• Difficulty breathing

• Decreased urine output.

Consult your doctor directly, even if the symptoms develop a few days after the last injection. These may be signs of high ovarian activity that can become serious.

If these symptoms become severe, the fertility treatment must be discontinued and you must receive treatment in a hospital.

Maintaining the recommended dose and careful monitoring of the treatment will reduce the likelihood of experiencing these symptoms.

If you stop usingMenopur, you may still experience these symptoms. Please contact your doctor immediately if you experience any of these symptoms.

While you are being treated with this medication, your doctor will usually send youultrasoundand sometimesblood teststo monitor your response to treatment.

When treated with hormones like Menopur, there may be an increased risk of:

- Ectopic pregnancy (pregnancy outside the uterus) if you have a history of fallopian tube disease

- Miscarriage

- Multiple pregnancy (twins, triplets, etc.)

- Congenital malformations (physical defects present at birth).

Some women who have been treated with several medications for infertility have developed tumors in the ovaries and other reproductive organs. It is not yet known if treatment with hormones like this medication causes these problems.

It is more likely that blood clots will form within blood vessels (veins or arteries) in pregnant women. Fertility treatment may increase the likelihood of this occurring, especially if you are overweight or have known blood clotting disease (thrombophilia) or if you or a family member (consanguineous) have had coagulation problems. Inform your doctor if you think this applies to you.

Use in children

Menopur has no suitable indications for use in children.

Use of Menopur with other medications

Inform your doctor or pharmacist if you are using, have used recentlyor may need to use any othermedication.

No studies have been conducted on the interaction of other medications with Menopur in humans.

When treating infertile men, menotropin and human chorionic gonadotropin can be administered at the same time.

Clomiphene citrate is another medication used in fertility treatment. If Menopur is used at the same time as clomiphene citrate, the effect on the ovaries may be increased.

Menopur can be used at the same time as Bravelle (another medication used for fertility treatment). Please see section 3 “How to use Menopur”.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Menopur is not indicated in any case for treating pregnant women or breastfeeding women.

Driving and operating machinery

It is very rare for Menopur to affect the ability to drive and operate machinery.

Important information about one of the components of Menopur:

Menopur contains less than 1 mmol of sodium chloride (23 mg) per dose, so it is essentially sodium-free.

Follow exactly the administration instructions for Menopur as indicated by your doctor.

In case of doubt, consult your doctor or pharmacist again.

i. Women who do not ovulate (do not produce eggs):

The treatment will begin within the first 7 days of the menstrual cycle (day 1 is the first day of the period). The treatment must be administered daily for at least 7 days.

The initial dose is usually 75-150 IU per day. This dose may be increased according to your response to treatment up to a maximum of 225 IU per day. An individual dose should be administered at least 7 days before adjusting the dose by your doctor. The recommended dose increase is 37.5 IU per adjustment (and not more than 75 IU). The treatment cycle should be discontinued if it does not respond adequately after 4 weeks.

When an optimal response is obtained, a single injection of another hormone called human chorionic gonadotropin (hCG) will be administered, at a dose of 5,000 to 10,000 IU, 1 day after the last dose of Menopur. It is recommended to have intercourse on the same day as the administration of hCG and the following day. Alternatively, intrauterine insemination (injection of sperm directly into the uterus) may be performed. Your doctor should closely monitor your progress for at least 2 weeks after the administration of hCG.

Your doctor will follow the effect of Menopur treatment. Depending on the progress, your doctor will decide to interrupt the treatment with Menopur and not administer the hCG injection. In this case, you should use a contraceptive method (condom) or not have sex until the next period begins.

ii. Women in assisted reproduction programs:

If you are also receiving treatment with GnRH agonists (a medication that helps the hormone called Gonadotropin-Releasing Hormone (GnRH) to function), the treatment with Menopur should begin approximately 2 weeks after starting the GnRH agonist treatment.

If you are also receiving treatment with GnRH antagonists, the treatment with Menopur should begin on day 2 or 3 of the menstrual cycle (day 1 is the first day of the period).

Menopur will be administered daily for at least 5 days. The recommended initial dose of Menopur is 150-225 IU. This dose may be increased according to your response to treatment up to a maximum of 450 IU per day. The dose should not be increased more than 150 IU per adjustment. Normally, treatment is not recommended for more than 20 days.

If there are enough egg sacs, a single injection of a medication called human chorionic gonadotropin (hCG) at a dose of up to 10,000 IU will be administered to induce ovulation (release of an egg).

Your doctor should closely monitor your progress for at least 2 weeks after the administration of hCG.

Your doctor will follow the effect of Menopur treatment. Depending on the progress, your doctor will decide to interrupt the treatment with Menopur and not administer the hCG injection. In this case, you should use a contraceptive method (condom) or not have sex until the next period begins.

Male infertility:

Initially, 1,000 to 3,000 IU of human chorionic gonadotropin will be administered 3 times a week until a normal serum testosterone level is reached.

Then, a dose of Menopur of 75-150 IU (1-2 vials) will be administered 3 times a week, intramuscularly (IM), for several months.

Use in children:

Menopur has no adequate indications for use in children.

USAGE INSTRUCTIONS:

If your doctor tells you to inject Menopur yourself, you should follow any instructions they provide.

The first injection of this medication should be administered under the supervision of a doctor or nurse.

Menopur is provided as a powder in a vial and should be dissolved with a syringe with a solvent before injection. The liquid to be used to dissolve Menopur is provided in a pre-loaded syringe.

Menopur 600 IU should be reconstituted with a pre-loaded syringe with the solvent before use.

After dissolving the powder with the solvent, the vialcontains medication for several days of treatment, so you should be sure that you only extract the amount of medication prescribed by your doctor.

Your doctor has prescribed a dose of Menopur in IU (units). You should use one of the 9 administration syringes graduated in IU (units) FSH/LH provided.

Follow these steps:

1.Remove the protective cap from the vial of powder and the rubber stopper from the pre-loaded syringe with the solvent (image 1).

2. Tighten the long and thin needle (reconstitution needle) firmly to the pre-loaded syringe with the solvent and remove the protective cap (image 2).

3. Insert the needle vertically through the center of the rubber stopper of the vial of powder andinject slowly allthe solvent to avoid the formation of bubbles (image 3).

4When the solvent is added, aslight overpressureis created in the vial.Therefore,push the plunger of the syringe to allow theexcess pressure in the vial to be released (image 4).

Remove the syringe and the reconstitution needle.

5.The powder will dissolve quickly (in 2 minutes) forming a transparent solution. Although this usually happens when only a few drops of solvent have been added, you should add the total amount of solvent. To help dissolve the powder, gently move the vial (image 5).Do not shake, as this may cause the formation of air bubbles.

Do not use the reconstituted solution if it contains particles or is not transparent.

The vial of powder is now dissolved with a syringe of solvent and ready to use.

6. Take the administration syringe with the pre-loaded needle and insert the needle vertically into the center of the vial. The administration syringe already contains a small amount of air that should be injected into the vial above the liquid. Place the vial upside down and remove the prescribed dose of Menopur from the administration syringe for injection (image 6).

REMEMBER: since the vial contains medication for several days of treatment, you should be sure that you only remove the amount of medication prescribed by your doctor.

If you have been prescribed Bravelle at the same time as Menopur, you can mix the two medications by reconstituting Menopur and inject the prescribed dose of Menopur into the reconstituted solution of Bravelle. Extract the mixed solution, so you can inject the two medications together and not separately.

7.Remove the syringefrom the vialand extracta small amount ofair from the syringe (image 7).

8. Gently tap the administration syringe so that all the air bubbles remain at the top (image 8). Push all the air carefully until the first drop of liquid from the solution comes out of the needle.

Your doctor or nurse will tell you where to inject (for example, the front of the thigh, abdomen, etc.).

Before injection, clean the skin at the injection site with an alcohol swab.

9. To inject, pinch the skin to create a fold, and insert the needle quickly at a 90-degree angle to the body. Press the plunger to inject the solution (image 9), and then remove the syringe.

After removing the syringe, apply pressure to the injection site to stop any bleeding. A gentle massage at the injection site will help to disperse the solution under the skin.

Do not throw the used material in the trash, it should be disposed of properly.

10. For subsequent injections with the reconstituted solution of Menopur, repeat steps 6 to 9.

If you use more Menopur than you should.In case of overdose or if you accidentally swallow the solution, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount used.

If you forgot to use Menopur,do not use a double dose to compensate for the missed doses. Please tell your doctor or pharmacist.

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

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

Treatment with Menopur may causehigh levels of activity in the ovariesthat may lead to a condition called Ovarian Hyperstimulation Syndrome (OHSS), especially in women with polycystic ovaries.The symptoms include:abdominal distension and discomfort, nausea, vomiting, diarrhea, weight gain.In severe cases of OHSS, rare complications have been reported, includingfluid accumulation in the abdomen, pelvis, and/or pleural cavity, difficulty breathing, and decreased urine output.

blood clots in the blood vessels (thromboembolism) and ovarian torsion. If you experience any of these symptoms, contact your doctor immediately, even if they develop several days after the last injection.

Reactionsallergic (hypersensitivity)may occur when using this medication. The symptoms of these reactions may include:skin rash, itching, throat swelling, and difficulty breathing.If you experience any of these symptoms, contact your doctor immediately.

Thefollowing frequent side effectsaffect between 1 and 10 of every 100 patients treated:

- Abdominal pain

- Headache

- Nausea

- Abdominal bloating

- Pelvic pain

- Ovarian hyperstimulation that results in high levels of activity (Ovarian Hyperstimulation Syndrome)

- Local reactions at the injection site (such as pain, redness, bruising, swelling, and/or irritation).

The following side effects are infrequentand affect between 1 and 10 of every 1,000 patients treated:

The following side effects are rareand affect between 1 and 10 of every 10,000 patients treated:

In addition to the side effects listed above, the following side effects have been reported after the marketing of Menopurand with an unknown frequency:

- Vision changes

- Fever

- Feeling unwell

- Allergic reactions

- Weight gain

- Muscle and joint pain (e.g., back pain, neck pain, arm pain, and leg pain)

- Ovarian torsion as a complication of increased ovarian activity due to hyperstimulation.

- Pruritus

- Urticaria

- Blood clots as a complication of increased ovarian activity due to hyperstimulation.

Reporting of side effects.

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use https://www.notificaRAM.es. By reporting side effects, you can contribute to providing more information about the safety of this medication.

Keep out of sight and reach of children.

Before reconstitution, store in refrigerator (2°C – 8°C). Do not freeze. Store in original packaging to protect from light.

After reconstitution, the solution can be stored for a maximum of 28 days at no more than 25°C.

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

Do not use Menopur after the expiration date that appears on the packaging after “CAD”. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Deposit empty packaging and unused medicines at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medicines. By doing so, you will help protect the environment.

Composition of Menopur

The active principle is highly purified menotropin (human menopausal gonadotropin, hMG-HP) corresponding to 600 IU of FSH with follicle-stimulating hormone activity and 600 IU of LH with luteinizing hormone activity.

After reconstitution, 1 ml of the reconstituted solution contains 600 IU of highly purified menotropin.

The other components of the powder are: lactose monohydrate, polisorbate 20, sodium phosphate heptahydrate (as a buffering agent and pH adjuster), and phosphoric acid (for pH adjustment).

The components of the solvent are: metacresol and water for injection.

Appearance of the product and contents of the packaging.

MENOPUR is a lyophilized powder and solvent for injectable solution.

Menopur is a white to grayish lyophilized powder presented in a glass vial along with a preloaded syringe with a transparent, colorless reconstitution solution, 1 reconstitution needle, and 9 disposable syringes graduated in units of FSH/LH with prefixed needles for administration.

Holder of the marketing authorization and responsible for manufacturing:

Holder of the marketing authorization

Ferring, S.A.U

C/ del Arquitecto Sánchez Arcas nº3, 1º

28040 Madrid

- Spain.

Responsible for manufacturing:

FERRING GmbH

Wittland 11,

D-24109 Kiel

GERMANY

This leaflet was approved inSeptember 2015

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/