Prescribing Information for the Patient

Ambiful 250 mg injectable solution in pre-filled syringe EFG

fulvestrant

Read this entire prescribing information carefully before starting to use this medication, as it contains important information for you.

-Keep this prescribing information, as you may need to refer to it again.
If you have any questions, consult your doctor, pharmacist, or nurse.

-This medication has been prescribed to you alone, and you should not give it to otherseven if they have the same symptoms as you, as it may harm them.

- If you experience any adverse effects, consult your doctor, pharmacist, or nurse,even if they are not listed in this prescribing information. See section 4.

6. Contents of the pack and additional information

Ambifulcontains the active ingredient fulvestrant, which belongs to the group of estrogen blockers. Estrogens, a type of female sex hormone, may be involved in the development of breast cancer in some cases.

Ambiful is used:

• in monotherapy, for the treatment of postmenopausal women with a type of breast cancer called estrogen receptor-positive breast cancer, which is locally advanced or has spread to other parts of the body (metastatic) or,
• in combination with palbociclib, to treat women with a type of breast cancer called hormone receptor-positive breast cancer, human epidermal growth factor receptor 2-negative breast cancer, which is locally advanced or has spread to other parts of the body (metastatic). Women who have not yet reached menopause will also be treated with a medication called a luteinizing hormone-releasing hormone (LHRH) agonist.

When Ambiful is administered in combination with palbociclib, it is essential that you also read the prospectus for palbociclib. If you have any doubts about palbociclib, consult your doctor.

No use fulvestrant:

• If you are allergic to fulvestrant or any of the other components of this medication (listed in section 6)

- if you are pregnant or breastfeeding

• if you have severe liver problems

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use fulvestrant if any of the following apply:

• kidney or liver problems
• low platelet count (which helps blood clotting) or bleeding disorders
• previous history of blood clots
• osteoporosis (bone density loss)
• alcoholism

Children and adolescents

Fulvestrant is not indicated for children and adolescents under 18 years.

Use of fulvestrant with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Particularly, tell your doctor if you are using anticoagulants (medications to prevent blood clots).

Pregnancy and lactation

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.

You should not use fulvestrant if you are pregnant. If you can become pregnant, you must use an effective contraceptive method while you are being treated with fulvestrant and for 2 years after your last dose.

You should not breastfeed while being treated with fulvestrant.

Driving and operating machines

Fulvestrant is not expected to affect your ability to drive or operate machines. However, if you feel tired after treatment, do not drive or operate machines.

Ambifulcontains up to 500 mg of alcohol (ethanol)per syringe, which is equivalent to a 10% volume.The amount in each syringe of this medication is equivalent to less than10 ml of beer or 4 ml of wine.

This reduced amount of alcohol in this medication will have no appreciable effect.

Ambiful contains benzyl alcohol

This medicationcontains 500 mg of benzyl alcohol in each syringe, equivalent to 100 mg/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).

Ambiful contains benzyl benzoate

Ambiful contains 750 mg of benzyl benzoate in each syringe, which is equivalent to 150 mg/ml.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The recommended dose is 500 mg of fulvestrant (two injections of 250 mg/5 ml) administered once a month with an additional dose of 500 mg administered 2 weeks after the initial dose.

Your doctor or nurse will administerfulvestrantvia a slow intramuscular injection in each of your buttocks.

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

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

You may need urgent medical treatment if you experience any of the following side effects:

• Allergic reactions (hypersensitivity), including swelling of the face, lips, tongue, and/or throat, which may be symptoms of anaphylactic reactions
• Thromboembolism (increased risk of blood clots)*
• Inflammation of the liver (hepatitis)
• Liver failure

Inform your doctor, pharmacist, or nurse if you notice any of the following side effects:

Very common side effects(may affect more than 1 in 10 people)

• Reactions at the injection site, such as pain and/or inflammation
• Abnormal levels of liver enzymes (in blood tests)*
• Nausea (feeling of discomfort)
• Weakness, fatigue*
• Joint and musculoskeletal pain
• Hot flashes
• Skin rash
• Allergic reactions (hypersensitivity), including swelling of the face, lips, tongue, and/or throat

All other side effects:

Common side effects(may affect up to 1 in 10 people)

• Headache
• Vomiting, diarrhea, or loss of appetite*
• Urinary tract infections
• Back pain*
• Increased bilirubin (a pigment produced by the liver)
• Thromboembolism (increased risk of blood clots)*
• Decreased platelet count (thrombocytopenia)
• Vaginal bleeding
• Lower back pain radiating to one leg (sciatica)
• Sudden weakness, numbness, tingling, or loss of movement in your leg, especially on one side of the body, sudden problems walking or balance (peripheral neuropathy)

Less common side effects(may affect up to 1 in 100 people)

• Thick, white vaginal discharge, and candidiasis (infection)
• Hematoma and bleeding at the injection site
• Increased gamma-GT, a liver enzyme identified in a blood test
• Inflammation of the liver (hepatitis)
• Liver failure
• Numbness, tingling, and pain
• Anaphylactic reactions

* Includes side effects for which the exact role of fulvestrant cannot be evaluated due to underlying disease.

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 that does not appear in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging or on the syringe labels after the abbreviation CAD. The expiration date is the last day of the month indicated.

This medication does not require special conditions for conservation.

Your healthcare professional will be responsible for the correct conservation, use, and disposal of Ambiful.

This medication may pose a risk to the aquatic environment.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. In this way, you will help protect the environment.

Composition of Ambiful

• The active ingredient is fulvestrant. Each pre-filled syringe (5 ml) contains 250 mg of fulvestrant. Each ml contains 50 mg of fulvestrant.
• The other components (excipients) are ethanol (96%), benzyl alcohol, benzyl benzoate, and virgin castor oil.

- Each pre-filled syringe contains 10% ethanol (alcohol), i.e., up to 500 mg of ethanol.

- Each pre-filled syringe contains 500 mg of benzyl alcohol, which is equivalent to 100 mg/ml.

- Each pre-filled syringe contains 750 mg of benzyl benzoate, which is equivalent to 150 mg/ml.

Aspect of the product and content of the package

Ambiful is a viscous, transparent, colorless to yellowish solution, practically free of particles, in a type I glass syringe, with a bromobutyl rubber stopper, a plunger, and a stopper, equipped with a tamper-evident closure, containing 5 ml of injectable solution. Two syringes should be administered to receive the recommended monthly dose of 500 mg.

Ambiful is available in two formats: either a package containing one pre-filled syringe or a package containing two pre-filled syringes. In addition, 21G needles with a safety system ("BD SafetyGlide") are provided for connection to the body of each syringe.

Grouping of packages:

Packages containing 4 pre-filled syringes (in 2 boxes, each containing 2 pre-filled syringes) or 6 pre-filled syringes (in 3 boxes, each containing 2 pre-filled syringes) (5 ml each).

Only some package sizes may be commercially available.

Holder of the marketing authorization

EVER Valinject GmbH

Oberburgau 3

4866 Unterach am Attersee

Austria

Responsible for manufacture

EVER Pharma Jena GmbH

Otto-Schott-Straße 15

07745 Jena

Germany

EVER Pharma Jena GmbH

Brüsseler Str. 18

07747 Jena

Germany

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

EVER Pharma Therapeutics Spain, S.L.

C/Toledo 170

28805 Madrid

Spain

This medicine is authorized in the member states of the European Economic Area, with the following names:

Last review date of this leaflet: July 2021

Other sources of information

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

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This information is intended solely for healthcare professionals:

Fulvestrant 500 mg (2 pre-filled syringes of 250 mg/5 ml injectable solution) should be administered using two pre-filled syringes, see section 3.

"BD SafetyGlide" is a registered trademark of "Becton Dickinson and Company" and has the CE mark: CE 0050.

Administration instructions

Administer the injection according to local guidelines for the intramuscular injection of large volumes.

NOTE: Due to the proximity of the underlying sciatic nerve, caution should be exercised if fulvestrant is injected in the gluteal region.

Warning: Do not sterilize the safety needle (BD SafetyGlide) in an autoclave before use. Hands should remain behind the needle at all times.

Disposal

The pre-filled syringes are only for single use.

This medicine may pose a risk to aquatic environments. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.