Label: information for the user

Puregon 150UI/0.18ml injectable solution

Puregon 300UI/0.36ml injectable solution

Puregon 600UI/0.72ml injectable solution

Puregon 900UI/1.08ml injectable solution

folitropina beta

Read this label carefully before starting to use the medication,because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribedonlyto you, and you should not give it to others, even if they have the same symptomsas you, as it may harm them.
• Ifyou experienceadverse effects, consult your doctor or pharmacist,even if they do not appear in this label. See section4.

Puregon injectable solution contains follitropin beta, a hormone known as follicle-stimulating hormone (FSH).

FSH belongs to the group of gonadotropins, which play an important role in human fertility and reproduction. In women, FSH is necessary for the growth and development of follicles in the ovaries. Follicles are small rounded vesicles that contain oocytes. In men, FSH is necessary for sperm production.

Puregon is used to treat infertility in any of the following situations:

Women

In women who do not ovulate and who do not respond to treatment with clomiphene citrate, Puregon may be used to induce ovulation.

In women undergoing assisted reproductive techniques, such as in vitro fertilization (IVF) and other methods, Puregon may produce the development of multiple follicles.

Men

In infertile men due to low hormone levels, Puregon may be used to produce sperm.

No use Puregon

Si:

• is allergic to follitropin beta or to any of the other components of Puregon (see section 6)
• has a tumour in the ovary, breast, uterus, testicles or brain (pituitary gland or hypothalamus)
• has heavy or irregular vaginal bleeding of unknown cause
• has ovaries that do not function due to a disease called primary ovarian insufficiency
• has ovarian cysts or an increase in the size of the ovaries, not due to polycystic ovary syndrome (PCOS)
• has malformations of the sexual organs that make a normal pregnancy impossible
• has uterine fibroids that make a normal pregnancy impossible
• is a man, infertile due to a disease called primary testicular insufficiency

Advertencias y precauciones

Consult your doctor before starting to use Puregon if:

• you have had an allergic reaction to certain antibiotics (neomycin and/or streptomycin)
• you do not have controlled pituitary gland or have hypotalamic problems
• your thyroid gland is not active enough (hypothyroidism)
• your adrenal glands do not function properly (adrenal insufficiency)
• you have high levels of prolactin in your blood (hyperprolactinemia)
• you have any other disease (for example, diabetes, heart disease, or any other long-term disease)

Si es usted mujer:

Síndrome de hiperestimulación ovárica (SHO)

Your doctor will check regularly the effects of treatment to be able to choose the right dose of Puregon at each time. Regular ultrasound scans of the ovaries will be performed.Your doctor may also check the hormone levels in your blood.This is very important, because an excessive dose of FSH can lead to rare but serious complications, in which the ovaries are overstimulated and the growing follicles become too large. This disease is serious and is called ovarian hyperstimulation syndrome (OHSS).OHSS can be potentially fatal in rare cases. OHSS causes sudden accumulation of fluid in your stomach and in areas of your chest, which can cause blood clots to form.Contact your doctor immediately if you feel intense swelling of your abdomen, stomach pain, discomfort (nausea), vomiting, sudden weight gain due to fluid accumulation, diarrhoea, decreased urine volume or difficulty breathing.

The regular monitoring of the response to FSH treatment helps to prevent ovarian overstimulation. Contact your doctor immediately if you feel stomach pain, and also if symptoms occur a few days after the last injection.

Embarazo múltiple o defectos de nacimiento

After treatment with gonadotropins, there is a higher risk of having multiple pregnancies, even when only one embryo is transferred to the uterus. Multiple pregnancies increase the risk for the mother and the children in the days before and after birth. In addition, multiple pregnancies and the characteristics of patients undergoing fertility treatment (e.g. age of the woman, characteristics of the semen, genetic background of both parents) may be associated with a higher risk of birth defects.

Complicaciones en el embarazo

The risk of an ectopic pregnancy is slightly higher.Therefore, your doctor should perform an ultrasound scan at the beginning to exclude the possibility of an ectopic pregnancy.

In women undergoing fertility treatment, there is a slightly higher risk of miscarriage.

Coágulos de sangre (Trombosis)

Treatment with Puregon, like pregnancy itself, may increase the risk of blood clots (thrombosis). Thrombosis is the formation of a clot in a blood vessel.

Blood clots can cause serious diseases, such as:

• obstruction in your lungs (pulmonary embolism)
• stroke
• heart attack
• problems with blood vessels (thrombophlebitis)
• lack of blood flow (deep vein thrombosis), which can cause loss of your arm or leg

Discuss this topic with your doctor before starting treatment, especially in the following cases:

• if you already know that you have a higher risk of thrombosis
• if you or any of your direct relatives have ever had thrombosis
• if you have significant overweight

Torsión ovárica

Torsion can occur after treatment with gonadotropins, including Puregon.Torsion is the twisting of an ovary. The twisting of the ovary could cause the blood flow to the ovary to be cut off.

Before starting to use this medicine, inform your doctor if:

• you have ever had ovarian hyperstimulation syndrome (OHSS)
• you are pregnant or think you might be
• you have ever had abdominal surgery
• you have ever had a torsion of an ovary
• you have or have had ovarian cysts

Tumores de ovario y otros tumores del sistema reproductor

Cases of ovarian tumours and other reproductive system tumours have been reported in women who have undergone fertility treatment. It is not known whether treatment with fertility medications increases the risk of these tumours in infertile women.

Otras enfermedades

Before starting to use this medicine, inform your doctor if:

• your doctor has told you that a pregnancy could be dangerous for you

Si es usted varón:

Varones con exceso de FSH en su sangre

The increase in FSH levels in the blood is a sign of damage to the testicles. In such cases, Puregon is usually not effective. To control the effects of treatment, your doctor may ask you to provide a semen sample for analysis, four to six months after starting treatment.

Niños y adolescentes

Puregon is not intended for use in children and adolescents.

Uso de Puregon con otros medicamentos

Inform your doctor or pharmacist if you are using, have used recently or may need to use any other medicine.

If Puregon is administered together with clomifene citrate, the effect of Puregon may increase. If an agonist of GnRH (medication to prevent early ovulation) has been administered, higher doses of Puregon may be needed.

Embarazo y lactancia

Consult your doctor or pharmacist before using any medicine. Do not use Puregon if you are already pregnant, or think you might be.

Puregon may affect milk production. It is unlikely that Puregon will pass into breast milk.Inform your doctor before using Puregon if you are breastfeeding.

Conducción y uso de máquinas

Puregon is unlikely to affect your ability to drive or use machines.

Puregoncontains alcohol bencílico

This medicine contains 10mg of benzyl alcohol per ml.

Benzyl alcohol can cause allergic reactions.

Consult your doctor or pharmacist if you have liver or kidney disease. This is because large amounts of benzyl alcohol can accumulate in the body and cause adverse effects (metabolic acidosis).

Consult your doctor or pharmacist if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol can accumulate in your body and cause adverse effects (metabolic acidosis).

Puregoncontiene sodio

This medicine contains less than 1mmol of sodium (23mg) per injection; that is, it is essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor.This medicationindicated by your doctor.In case of doubt, consult your doctor or pharmacist again.

Dosage in women

Your doctor will decide on the initial dose. This dose may be adjusted as your treatment progresses. The following details are provided on the dosing schedule.

There are great variations in the response of the ovaries to FSH among women, making it impossible to establish an appropriate dosing schedule for all patients. To find the correct dosage, your doctor will monitor the growth of the follicle with ultrasound and measure the amount of estradiol (female sex hormone) in the blood.

• Women who do not ovulate
  Your doctor sets an initial dose that is maintained for at least seven days. If no ovarian response is detected, the daily dose is gradually increased until the growth of the follicle and/or plasma estradiol levels indicate an appropriate response, and this daily dose is maintained until a follicle of the appropriate size is detected. Normally, 7 to 14days of treatment are sufficient. Treatment with Puregon is then interrupted, and ovulation is induced by providing human chorionic gonadotropin (hCG).
• Assisted reproduction programs, such as in vitro fertilization
  Your doctor sets an initial dose that is maintained for the first four days, at a minimum. Your dose may then be adjusted based on your ovarian response. When a sufficient number of follicles of the appropriate size are detected, the final phase of follicular maturation is induced by providing hCG. Oocyte (egg) recovery is performed 34‑35hours later.

Dosage in men

Normally, Puregon is prescribed at a dose of 450UI per week, almost always in three injections of 150UI, along with another hormone (hCG), for at least 3 to 4months. The treatment period is equal to the time needed for sperm development and the period in which an improvement is expected. If your sperm production has not started after this period, your treatment may continue for at least 18months.

How to administer the injection

Puregon injectable solution in cartridges has been developed for use with the Puregon Pen type syringe. You must carefully follow the instructions for using the syringe, which are provided separately. Do not use the cartridge if the solution contains particles or is not transparent.

With the syringe type pen, subcutaneous injections (e.g., in the lower abdomen) can be administered by yourself or your partner. Your doctor will tell you when and how to do it. If you inject Puregon yourself, carefully follow the instructions for administering Puregon correctly and with minimal discomfort.

The first injection of Puregon should only be administered in the presence of a doctor or nurse.

It is possible that a small amount of the medication will remain in the cartridge after completing treatment with Puregon, even when all doses have been administered correctly. Do not attempt to use the remaining medication. After the administration of the last dose, the cartridge should be disposed of properly.

If you use more Puregon than you should

Inform your doctor immediately.

A too high dose of Puregon may cause excessive ovarian stimulation (OOS), which may manifest as abdominal pain. If you experience abdominal discomfort, inform your doctor immediately. See also section4 on possible side effects.

If you forgot to use Puregon

If you forgot a dose, do not apply a double dose to compensate for the missed doses.

?Contact your doctor.

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

Like all medicines,this medicinecan cause side effects, although not everyone will experience them.

Inform your doctor if you notice:

Signs of a severe allergic reaction (anaphylactic reaction), such as swelling of the face, lips, throat, or tongue that causes difficulty swallowing or breathing, shortness of breath, sensation of loss of consciousness.

Severe side effects in women

A complication of FSH is ovarian hyperstimulation.Ovarian overstimulation can trigger a condition calledovarian hyperstimulation syndrome (OHSS), which can be a serious clinical problem.The risk of this can be reduced by carefully controlling the development of follicles during treatment. Your doctorwill perform ultrasound scans of your ovaries to carefully monitor the number of mature follicles.Your doctor may also check hormone levels in your blood. The first symptoms are abdominal pain, discomfort, or diarrhea. In more severe cases, you may experience an increase in the size of your ovaries, accumulation of fluid in the abdomen and/or chest,(which can causerapid weight gain due to fluid accumulation) or the appearance of blood clotsin the circulatory system. Seesection 2 Warnings and precautions.

?Contact your doctor immediately if you experience abdominal pain or any of these symptoms of ovarian hyperstimulation, even if they occur a few days after the last injection.

If you are a woman:

Side effectsfrequent (may affect up to1in 10 people):

• Headache
• Reactions at the injection site (such asredness, pain, swelling, and itching)

and itching)

• Ovarian hyperstimulation syndrome (OHSS)
• Lower abdominal pain
• Abdominal pain and/or distension

Side effectsinfrequent (may affect up to1 in 100 people):

• Mastalgia (including pain when touched).
• Diarhea, constipation, and abdominal discomfort
• Uterine enlargement
• Nausea
• Hypersensitivity reactions (such as skin rash, redness, urticaria, and itching)
• Ovarian cysts or ovarian enlargement
• Ovarian torsion (twisting of the ovaries)
• Vaginal bleeding

Side effectsrare (may affect up to1 in 1,000 people):

• Thrombosis (this can also occur independently of any unwanted ovarian overstimulation, see section 2,Warnings and precautionss)

Unknown frequency (cannot be estimated from available data):

• Allergic reactions

• Swelling of the face, lips, throat, or tongue that causes difficulty swallowing or breathing, shortness of breath
• Pale skin, weak and rapid pulse, or sensation of loss of consciousness

Also, ectopic pregnancies, spontaneous abortions, and multiple pregnancies have been reported. These side effects are not considered related to the use of Puregon, but to Assisted Reproductive Techniques (ART) or a subsequent pregnancy.

If you are a man:

Side effectsfrequent (may affect up to1in 10 people):

• Acne
• Reactions at the injection site (such ashardening and pain)
• Headache
• Skin rash
• Development of breasts
• Testicular cysts

Unknown frequency (cannot be estimated from available data):

• Allergic reactions

• Swelling of the face, lips, throat, or tongue that causes difficulty swallowing or breathing, shortness of breath
• Pale skin, weak and rapid pulse, or sensation of loss of consciousness

Reporting of side effects

If you experienceany type of side effect, consult your doctor or pharmacist, even if it is apossibleside effect that does not appear in this leaflet.You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medication out of the sight and reach of children.

Storage by the pharmacist

Store between 2°C - 8°C (in the refrigerator).Do not freeze.

Storage by the patient

You have two options:

1.Store between 2°C - 8°C (in the refrigerator). Do not freeze.

2.Store below or at 25°C for a maximum period of 3months.

Note the day you start storing the product outside the refrigerator.

Store the cartridge in the outer packaging.

Once the rubber membrane of the cartridge has been pierced with a needle, the product can be stored for a maximum of 28days.

Please note the first day of use of the cartridge in the control table, as shown in the Puregon Pen User Manual.

Do not use this medication after the expiration date that appears on the packaging after ‘CAD’. The expiration date is the last day of the month indicated.

Dispose of used needles immediately after injection.

Do not mix any other medication in the cartridges. Do not refill empty cartridges.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications thatyouno longer need. This will help protect the environment.

Composition of Puregon

• Each cartridge contains the active principle follitropin beta, a hormone known as follicle-stimulating hormone (FSH) at a dose of 833 UI/ml of aqueous solution.
• The other components are sucrose, sodium citrate, L-methionine, polysorbate 20 and benzyl alcohol in water for injection. The pH may have been adjusted with sodium hydroxide and hydrochloric acid.

Appearance of the product and contents of the pack

Puregon injectable solution (injectable) is a transparent and colourless liquid, whichis presented in a glass cartridge. It is available in packs of 1cartridge.

Marketing authorisation holder and manufacturer responsible

N.V. Organon

Kloosterstraat 6

5349 AB Oss

Netherlands

For more information about this medicine, please contact the local representative of the marketing authorisation holder:

Last update of this leaflet:month YYYY

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agencyhttps://www.ema.europa.eu.