Package Insert: Information for the User

SYNAREL200 micrograms nasal spray solution

Nafarelina

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

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you alone, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist,even if they are not listed in this package insert. See section 4.

Contents of the package and additional information

Synarel belongs to a class of medications called synthetic analogs of gonadotropin-releasing hormone (a natural substance produced by the body that stimulates the ovaries in women - which contain the eggs - and the testicles in men). It acts by reducing the normal response of your body to this hormone, and as a result, the ovaries produce a lower amount of other hormones called estrogens. You will notice this decrease because your menstruation will stop or decrease in quantity after approximately one month of using this medication.

Synarel is used for:

• Endometriosis(abnormal location of the membrane that covers the uterus), including relief from symptoms that accompany it, such as for example: painful menstruation, painful intercourse, general pelvic pain, and significant blood loss during menstruation.
• Controlled ovary stimulation programs before performing in vitro fertilization, always under the supervision of a specialist doctor.

Do not use Synarel

• If you are allergic to nafarelin, to the natural gonadotropin-releasing hormone, to other gonadotropin-releasing hormone analog medications, or to any of the other components of this medication (listed in section 6).
• If you experience vaginal bleeding and the cause is not determined.
• If you are pregnant or think you may become pregnant during treatment. If you are using this medication as part of an in vitro fertilization program, your pregnancy will be planned for when treatment ends (see the section on Pregnancy and Breastfeeding).
• If you are breastfeeding.
• If you have already used Synarel for six months (see the section on Possible Adverse Effects).

Warnings and Precautions

Consult your doctor or pharmacist before starting to take this medication

• If you forget to take one or more doses, as this may pose a risk of becoming pregnant.
• It is recommended to use non-hormonal barrier contraceptive methods (diaphragm, intrauterine devices (IUDs), condoms) while taking this medication to avoid becoming pregnant (see the section on Pregnancy and Breastfeeding).
• If you have a history of multiple ovarian cysts, as these may increase in number or size. Although they usually disappear spontaneously within 4-6 weeks of treatment, in some cases, treatment may need to be interrupted and/or surgical intervention may be required.
• If you have a family history of osteoporosis (a condition in which the bones weaken, causing pain and increasing the risk of fractures), as treatment may cause a small loss of bone mineral (see the section on Possible Adverse Effects).
• If menstruation does not decrease after 2 months of treatment. Inform your doctor, as menstruation should be interrupted or decreased in quantity during treatment with Synarel. Also, if after 4-8 weeks of stopping treatment with Synarel, menstruation does not return to normal, consult your doctor.
• If you need to use a nasal decongestant, use it at least 30 minutes after using Synarel (see the section on Use of Other Medications).
• If you are to undergo exploration tests of the hypothalamic-pituitary-gonadal axis, as results may be altered up to 8 weeks after treatment ends.
• If after a period of treatment, you need to undergo a re-treatment, your doctor should determine your bone mineral density before starting to use the medication again.
• Severe depression has been reported in patients taking Synarel. If you are taking Synarel and experience depression, inform your doctor.
• The use of Synarel in combination with gonadotropin to treat infertility may cause an exaggerated reaction in the ovaries (ovarian hyperstimulation syndrome, OHSS). You may experience abdominal pain, abdominal swelling, and discomfort or nausea. If this occurs, consult your doctor. See also the section on Possible Adverse Effects.

Children and Adolescents

Use of Synarel is not recommended in individuals under 18 years of age.

Other Medications and Synarel

Inform your doctor or pharmacist if you are using or have used recently or may need to take other medications, including those purchased without a prescription.

No interactions with other medications are expected.

Nasal decongestants decrease the absorption of Synarel, so you should not use this type of medication within 30 minutes of administering Synarel. However, rhinitis (inflammation of the nasal mucosa due to allergy or cold, which may block your nose) does not appear to affect the absorption of Synarel, so you can continue to use Synarel normally (see the section on How to Use Synarel).

Pregnancy and Breastfeeding

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

Before starting treatment with Synarel, it should be confirmed that you are not pregnant. Do not use Synarel if you are pregnant or suspect you may be.

During treatment, avoid becoming pregnant using non-hormonal barrier contraceptive methods such as the diaphragm, IUDs, condoms, but NOT oral contraceptives, as they are hormonal. This may seem strange if you are taking Synarel as part of an in vitro fertilization program, but this is the case because your pregnancy will be planned for when treatment ends and should not occur before. If you become pregnant during treatment, you should stop treatment and inform your doctor, who will provide further information on this topic.

This medication should not be administered during breastfeeding.

Driving and Operating Machines

The influence on the ability to drive and operate machines is negligible or insignificant.

Synarel contains benzalkonium chloride.

This medication contains 0.01 mg of benzalkonium chloride in each spray.

Benzalkonium chloride may cause irritation or inflammation inside the nose, especially when used for a long treatment period.

Only those women with an age of 18 years or older can use Synarel, as clinical experience is limited to those ages.

Follow exactly the administration instructions of this medication indicated by your doctor.

The treatment with Synarel will be performed under the control and recommendations of your doctor, and requires periodic monitoring by him. Your doctor will indicate the duration of your treatment with Synarel. Do not suspend the treatment before.

Remember to use your medication.

Synarel must be administered only by nasal spray. As a general rule, the medication dose and administration frequency is as follows:

• Endometriosis:The treatment should start between day 2 and day 4 of the menstrual cycle. The recommended dose is 2 sprays per day (400 micrograms), divided into two administrations (one spray in one nostril in the morning and one spray in the other nostril at night). In some cases, it may be necessary to increase the dose to 4 sprays per day (800 micrograms); in this case, two sprays will be administered in the morning (one in each nasal fossa) and two in the evening (one in each nasal fossa).Your doctor will indicate which dose is recommended for you.

The maximum recommended treatment duration is 6 months.

• Controlled ovarian stimulation:If you are taking this medication as part of an in vitro fertilization program, your doctor will indicate when to start treatment. The recommended dose is 4 sprays per day (800 micrograms), i.e., one spray in both nasal orifices in the morning and one spray in both nasal orifices at night. Your doctor may decide to withdraw you from treatment if no response is observed.

Normally, the treatment period does not exceed 8 weeks.

Important guidelines for the use of Synarel

• The pump must produce a fine spray, which can only occur through a rapid and firm pumping action. It is normal to see some larger droplets of liquid within the spray. However, if Synarel comes out of the pump as a stream instead of a fine spray, Synarel may not work properly, and you should consult your pharmacist.

• Make sure to clean the spray tip before and after each use. If you do not do so, the spray tip may become clogged and the correct amount of medication may not be released. Always place the safety cap and plastic plug on the spray tip after use to prevent clogging.

• The pump is designed to administer only a certain amount of medication, regardless of the force with which you press the pump.

• Do not attempt to enlarge the hole in the spray tip. If the hole is enlarged, the pump will release an incorrect dose of Synarel.

Before the first use, follow these instructions:

Before the first use of each Synarel bottle, the pump must be primed. This step only needs to be done once, before you use this medication for the first time.

1.Remove and store the safety cap and plug to expose the nasal spray tip. Hold the bottle in a vertical position with 2 fingers in the pump's recesses and your thumb on the bottle's base.

2.Prime the pump by pressingwith your thumbupward several times firmly and quicklyuntilair comes out and a fine spray appears. Thisrequires 5 to 7 presses, keeping the container with the top end away from you. You do not need to repeat this operation with subsequent use of the medication, as it would waste the medication.

1. Clean the spray tip after use:

Hold the bottle in a horizontal position and rinse the spray tip with warm water while cleaning it with your fingers or a clean cloth for 15 seconds.

Do not clean the spray tip with a sharp object.This may cause an incorrect amount to be released. Do not separate the pump from the bottle, as this will release the pressure of the spray.

Dry the spray tip with a soft, clean cloth or a paper towel.

Using the spray tip::

1. Blow your nose gently to clear your nasal passages.

1. Remove and store the safety cap and plug from the containerto expose the nasal spray tip. Hold the bottle as previously shown.

1. Clean the nasal spray tip. To do this, hold the bottle in a horizontal position and rinse the nasal spray tip with warm water while cleaning it with your finger or a soft cloth for 15 seconds.

Do not clean the nasal spray tip with a sharp object.This may cause an incorrect amount to be released. Do not separate the pump from the bottle, as this will release the pressure.

Dry the nasal spray tip with a soft, clean cloth or a paper towel.

1. Incline your head slightly forward. Insert the spray tip into one nostril, directing it towards theposteriorandexternalpart of the nose. Close the other nostril with your finger.

1. Press the pump quickly and firmlyonce, and breathe in gently at the same time.

1. Remove the spray tip from the nose and tilt your head back for a few seconds to allow the liquid to pass to the back of the nose.

1. Cleanthe nasal spray tip. To do this, hold the bottle in a horizontal position and rinsethe nasal spray tipwith warm water while cleaning it with your finger or a soft cloth for 15 seconds.

Do not cleanthe nasal spray tipwith a sharp object.This may cause an incorrect amount to be released. Do not separate the pump from the bottle, as this will release the pressure.

Drythe nasal spray tipwith a soft, clean cloth or a paper towel.

Clean the nasal spray tip before and after each use to prevent clogging, as if it becomes clogged, it may release an incorrect amount of medication.

1. Place the safety cap and plug on the container to cover the nasal spray tip. This is important to prevent the nasal spray tip from becoming clogged.

Consult your doctor or pharmacist if you have any doubts about these instructions.

It is essential that you use this medication regularly, following the recommended doses, daily, in the morning and evening (see the section“If you forgot to use Synarel”).

Do not interrupt treatment if you have a common cold. If you want to use a nasal decongestant, it is recommended to administer it at least 30 minutes after using Synarel(see the section “Use of other medications”).

If you sneeze while using this medication or after using it, it is recommended that you repeat the administration. However, if you sneeze every time you use Synarel, inform your doctor.

To ensure proper administration of the doses, the bottle should not be used for more than 30 days (2 sprays per day) or 15 days (4 sprays per day); after these, you will see a small amount of solution remaining in the container, but you should not use it.

If you estimate that the action of Synarel is too strong or too weak, inform your doctor or pharmacist.

If you use more Synarel than you should,consult your doctor or pharmacist immediately.

In case of overdose or accidental ingestion, consult the Toxicology Information Service. Phone 91-562 04 20.

If you forgot to use Synarel:

You must use this medication habitually. If you forgot to use it at the right time, do it as soon as you remember, and then use it again as instructed, i.e., in the morning and evening.

If you forget to administer a dose, you may experience vaginal bleeding. If you forget several doses, you may become pregnant. If this happens, you should discontinue administration of this medication and inform your doctor immediately.

Do not take a double dose to compensate for the missed doses.

Like all medications, Synarel may have side effects, although not everyone will experience them. The estimated frequency of their occurrence in adults is as follows:

The very common side effects (occurring in at least 1 in 10 patients) are:

• Weight gain.
• Mood swings (emotional lability), decreased libido (sexual desire).
• Headache.
• Hot flashes.
• Rhinitis (inflammation of the nasal mucosa).
• Acne, seborrhea (excess skin oil).
• Muscle pain.
• Breast atrophy, vaginal dryness, decreased breast size.
• Edema (swelling).

The common side effects (occurring in at least 1 in 100 patients) are:

• Hypersensitivity to the drug characterized by chest pain, dyspnea (difficulty breathing), pruritus (itching), rash, urticaria (hives).
• Estrogen deficiency (female sex hormones).
• Weight loss.
• Depression, insomnia (difficulty sleeping), increased libido (sexual desire).
• Paresthesia (tingling sensation).
• Hypertension (elevated blood pressure), hypotension (low blood pressure).
• Nasal mucosa irritation.
• Hirsutism (excessive hair growth).
• Arthralgia (joint pain).
• Artificial menopause, uterine bleeding (uterine bleeding).
• Decreased bone density (increased bone porosity).

The uncommon side effects (occurring in at least 1 in 1,000 patients) are:

• Alopecia (hair loss).
• Increased breast size, ovarian cysts (fluid concentration within the ovary).

The rare side effects (occurring in at least 1 in 10,000 patients) are:

• Increased serum levels of GOT, GPT, and alkaline phosphatase (elevated liver enzymes, indicators of liver function).

The side effects whose frequency is unknown (cannot be estimated from available data) are:

• Migraine (headache).
• Blurred vision (visual deterioration).
• Palpitations (perception of heart activity).
• Ovarian hyperstimulation syndrome (exaggerated response to ovarian stimulation that may cause abdominal distension, nausea, and/or vomiting, and diarrhea. In severe cases, fluid in the abdomen).

Other side effects in children and adolescents

The side effects and their estimated frequency of occurrence in the pediatric population are as follows:

The very common side effects (occurring in at least 1 in 10 patients) are:

• Enlarged breasts.

The common side effects (occurring in at least 1 in 100 patients) are:

• Hypersensitivity to the drug characterized by chest pain, dyspnea (difficulty breathing), pruritus (itching), rash, urticaria (hives).
• Mood swings (emotional lability).
• Hot flashes.
• Rhinitis.
• Acne, hirsutism (excessive hair growth), seborrhea (excess skin oil), abnormal body odor.

The uncommon side effects (occurring in at least 1 in 1,000 patients) are:

• Vaginal bleeding, vaginal discharge (vaginal secretion).

The side effects whose frequency is unknown (cannot be estimated from available data) are:

• Transient increase in pubic hair).

During the first two months of treatment, some vaginal bleeding may occur. Do not worry, this is normal.

A small decrease in the mineral content of the bones may also occur, although it recovers within six months after treatment is stopped. If you have a family history of osteoporosis, you may be more likely to experience a loss of bone mineral during treatment (see the section “Be especially careful with Synarel”).

Most of these side effects are not severe, disappear at the end of treatment, and do not justify interrupting treatment.

Some patients have presented symptoms that may indicate an allergy to this medication, such as difficulty breathing, chest pain, rash, skin redness, and itching. If any of these symptoms appear, discontinue the medication and consult your doctor.

If you consider that any of the side effects you are experiencing are severe or if you notice any side effect not mentioned in this prospectus, inform your doctor or pharmacist.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not mentioned in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Do not store at a temperature above 86°F (30°C).

Keep the container in an upright position (standing).

Do not freeze.

Store in the outer container to protect it from light.

When not using this medication, keep the cap and safety closure in place.

Keep out of the reach and sight of children.

Do not use Synarel after the expiration date that appears on the container.

Each Synarel container can be used for a maximum of 30 days, with this time potentially reduced based on dosage (see section “How to use Synarel”).

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

Composition of Synarel

• The active ingredient is nafarelin (as acetate). Each spray releases 100 microliters of aqueous solution containing acetate of nafarelin equivalent to 200 micrograms of nafarelin base.
• The other components are: sorbitol (E-420), benzalkonium chloride, glacial acetic acid, and purified water.

Appearance of the product and contents of the packaging

Synarel is presented as a nasal spray solution, each package contains a 8 ml aqueous solution bottle, provided with a dosing valve. Each bottle contains 60 doses.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

Pfizer, S.L.

Avda. de Europa, 20-B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Spain

Responsible for manufacturing:

PFIZER SERVICE COMPANY BV

Hoge Wei 10 (Zaventem)

B-1930 – Belgium

Last review date of this leaflet: January 2022

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