PUREGON 900 IU/1.08 mL INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Puregon 150UI/0.18ml solution for injection

Puregon 300UI/0.36ml solution for injection

Puregon 600UI/0.72ml solution for injection

Puregon 900UI/1.08ml solution for injection

Follitropin beta

Read all of this leaflet carefully before you start 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 pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Puregon and what is it used for

Puregon solution for injection 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. The follicles are small, rounded sacs that contain the eggs. In men, FSH is necessary for sperm production.

Puregon is used to treat infertility in the following situations:

Women

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

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

Men

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

2. What you need to know before you use Puregon

Do not use Puregon

If:

• you are allergic to follitropin beta or any of the other ingredients of Puregon (listed in section 6)
• you have a tumor in the ovary, breast, uterus, testicle, or brain (pituitary gland or hypothalamus)
• you have heavy or irregular vaginal bleeding of unknown cause
• your ovaries do not work due to a disease called primary ovarian insufficiency
• you have ovarian cysts or enlargement of the ovaries that are not due to polycystic ovary syndrome (PCOS)
• you have malformations of the sex organs that make normal pregnancy impossible
• you have uterine fibroids that make normal pregnancy impossible
• you are an infertile man due to a disease called primary testicular insufficiency.

Warnings and precautions

Consult your doctor before starting treatment with Puregon if:

• you have had an allergic reaction to certain antibiotics (neomycin and/or streptomycin)
• you have uncontrolled pituitary gland or hypothalamic problems
• you have underactive thyroid gland (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 (e.g., diabetes, heart disease, or any other long-term disease)

If you are a woman:

Ovarian Hyperstimulation Syndrome (OHSS)

Your doctor will regularly check the effects of treatment to choose the right dose of Puregon at all times. You will have regular ultrasound scans of your ovaries. Your doctor may also check your hormone levels in your blood. This is very important because too high a dose of FSH can lead to rare but serious complications, in which the ovaries become overstimulated and the growing follicles become larger than normal. This disease is serious and is called Ovarian Hyperstimulation Syndrome (OHSS). In rare cases, severe OHSS can be life-threatening. OHSS causes fluid to accumulate suddenly in your stomach and chest, which can cause blood clots to form. Contact your doctor immediately if you feel severe abdominal swelling, stomach pain, nausea, vomiting, sudden weight gain due to fluid accumulation, diarrhea, decreased urine output, or difficulty breathing (see also section 4, Possible side effects).

? Periodic monitoring of the response to FSH treatment helps prevent ovarian overstimulation. Contact your doctor immediately if you feel stomach pain, and also if it occurs a few days after the last injection.

Multiple Pregnancy or Birth Defects

After treatment with gonadotropins, there is a higher chance of multiple pregnancies, even when only one embryo is transferred to the uterus. Multiple pregnancies pose an increased risk to the health of both the mother and the children before and after birth. Additionally, multiple pregnancy and the characteristics of patients undergoing fertility treatment (e.g., woman's age, semen characteristics, genetic history of both parents) may be associated with a higher risk of birth defects.

Pregnancy Complications

The risk of an ectopic pregnancy (a pregnancy outside the uterus) is slightly higher. Therefore, your doctor should perform an ultrasound at the beginning to rule out the possibility of an ectopic pregnancy.

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

Blood Clots (Thrombosis)

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

Blood clots can cause serious diseases, such as:

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

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

Ovarian Torsion

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

Before starting treatment with this medicine, tell your doctor if:

• you have had Ovarian Hyperstimulation Syndrome (OHSS)
• you are pregnant or think you may be pregnant
• you have had abdominal surgery
• you have had ovarian torsion
• you have had or have ovarian cysts.

Ovarian Tumors and Other Reproductive System Tumors

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

Other Diseases

Additionally, before starting treatment with this medicine, tell your doctor if:

• your doctor has informed you that pregnancy could be hazardous for you.

If you are a man:

Men with High FSH Levels in the Blood

High FSH levels in the blood are a sign of testicular damage. In such cases, Puregon is usually not effective. To monitor the effects of treatment, your doctor may ask for a semen sample for analysis 4 to 6 months after starting treatment.

Children and Adolescents

Puregon should not be used in children and adolescents.

Using Puregon with Other Medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

If Puregon is administered together with clomiphene citrate, the effect of Puregon may increase. If a GnRH agonist (a medicine to prevent premature ovulation) has been administered, higher doses of Puregon may be necessary.

Pregnancy and Breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine. You should not use Puregon if you are already pregnant or think you may be pregnant.

Puregon may affect milk production. It is unlikely that Puregon will pass into breast milk. If you are breast-feeding, ask your doctor for advice before using Puregon.

Driving and Using Machines

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

Puregon Contains Benzyl Alcohol

This medicine contains 10 mg of benzyl alcohol per ml.

Benzyl alcohol may cause allergic reactions.

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

Ask your doctor or pharmacist for advice if you are pregnant or breast-feeding. This is because large amounts of benzyl alcohol can accumulate in your body and cause side effects (metabolic acidosis).

Puregon Contains Sodium

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

3. How to Use Puregon

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are unsure, ask your doctor or pharmacist again.

Dosing in Women

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

There are large variations in ovarian response to FSH among women, making it impossible to establish a suitable dosing schedule for all patients. To find the correct dosage, your doctor will monitor follicle growth with ultrasound scans and measure estradiol (female sex hormone) levels in your blood.

• Women who do not ovulateYour doctor will set an initial dose that is maintained for at least 7 days. If no ovarian response is detected, the daily dose is gradually increased until follicle growth and/or estradiol levels in the blood indicate an appropriate response, and this daily dose is maintained until a follicle of the appropriate size is detected. Normally, 7 to 14 days of treatment are sufficient. Puregon treatment is then stopped, and ovulation is induced with human chorionic gonadotropin (hCG).
• Assisted reproduction programs, such as in vitro fertilizationYour doctor will set an initial dose that is maintained for the first 4 days, at a minimum. Subsequently, your dose may 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 with hCG. Oocyte (egg) retrieval is performed 34-35 hours later.

Dosing in Men

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

How to Administer the Injection

Puregon solution for injection in cartridges has been developed for use with the Puregon Pen injection device. The instructions for using the injection device, which are provided separately, must be followed carefully. Do not use the cartridge if the solution contains particles or is not transparent.

With the injection device, subcutaneous injections (e.g., in the lower abdomen) can be administered by you or your partner. Your doctor will tell you when and how to do this. If you inject Puregon yourself, follow the instructions for administration carefully 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 medicine 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 medicine. After administration of the last dose, the cartridge should be disposed of properly.

If you use more Puregon than you should

Tell your doctor immediately.

Taking too high a dose of Puregon can cause excessive stimulation of the ovaries (OHSS), which can manifest as stomach pain. If you feel unwell due to stomach pain, tell your doctor immediately. See also section 4, Possible side effects.

If you forget to use Puregon

If you miss a dose, do not apply a double dose to make up for the missed doses.

? Contact your doctor.

If you have any further questions on the use of this medicine, ask your doctor.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Tell your doctor if you notice:

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

Severe Adverse Effects in Women

A complication of FSH is ovarian hyperstimulation. Ovarian overstimulation can trigger a disease called Ovarian Hyperstimulation Syndrome (OHSS), which can be a serious clinical problem. The risk of this occurring can be reduced by carefully controlling follicle development during treatment. Your doctor will perform ultrasound scans of your ovaries to closely monitor the number of mature follicles. Your doctor may also check hormone levels in your blood. The first symptoms are stomach pain, discomfort, or diarrhea. In more severe cases, you may experience enlargement of the ovaries, fluid accumulation in the abdomen and/or chest, (which can cause sudden weight gain due to fluid accumulation) or the appearance of blood clots in the circulatory system. See section 2 Warnings and Precautions.

If you experience stomach pain or any of these symptoms of ovarian hyperstimulation, contact your doctor immediately, even if they occur several days after the last injection.

If you are a woman:

Adverse Effectsfrequently (may affect up to1in 10 people):

• Headache
• Reactions at the injection site (such as bruising, pain, redness, swelling

and itching)

• Ovarian Hyperstimulation Syndrome (OHSS)
• Pelvic pain
• Stomach pain and/or abdominal distension

Adverse Effectsinfrequently (may affect up to1 in 100 people):

• Breast tenderness (including pain on palpation).
• Diarrhea, constipation, and stomach 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

Adverse Effectsrarely(may affect up to1 in 1,000 people):

• Blood clots (this can also occur independently of unwanted ovarian overstimulation, see section 2, Warnings and Precautions)

Frequency Not Known (cannot be estimated from the available data):

• Allergic reactions

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

There have also been reports of ectopic pregnancies, spontaneous abortions, and multiple pregnancies. These adverse effects are not considered related to the use of Puregon, but rather to Assisted Reproduction Techniques (ART) or a subsequent pregnancy.

If you are a man:

Adverse Effectsfrequently (may affect up to1in 10 people):

• Acne
• Reactions at the injection site (such as hardening and pain)
• Headache
• Skin rash
• Breast development
• Testicular cysts

Frequency Not Known (cannot be estimated from the available data):

• Allergic reactions

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

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Puregon

Keep this medicine 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 single period of 3 months maximum.

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

Keep 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 28 days, maximum.

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

Do not use this medicine after the expiration date stated on the packaging after 'EXP'. The expiration date is the last day of the month indicated.

Discard used needles immediately after injection.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Puregon Composition

• Each cartridge contains the active ingredient folitropin beta, a hormone known as follicle-stimulating hormone (FSH) at a dose of 833 IU/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.

Product Appearance and Package Contents

Puregon injectable solution (injectable) is a clear, colorless liquid, presented in a glass cartridge. It is available in packs of 1 cartridge.

Marketing Authorization Holder and Manufacturer

N.V. Organon

Kloosterstraat 6

5349 AB Oss

Netherlands

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:Month YYYY

Other Sources of Information

Detailed information on this medicine is available on the European Medicines Agency website https://www.ema.europa.eu.