AMBIFUL 250 mg SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE

Introduction

Package Leaflet: Information for the Patient

Ambiful 250 mg Solution for Injection in Pre-filled Syringe EFG

fulvestrant

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, pharmacist, or nurse.
• 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Ambiful and what is it used for
2. What you need to know before you use Ambiful
3. How to use Ambiful
4. Possible side effects
5. Storage of Ambiful

1. Contents of the pack and other information

1. What is Ambiful and what is it used for

Ambiful contains the active substance 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:

• as monotherapy, for the treatment of postmenopausal women with a type of breast cancer called hormone 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, human epidermal growth factor receptor 2 (HER2) negative breast cancer, which is locally advanced or has spread to other parts of the body (metastatic). Women who have not reached menopause will also be treated with a medicine called a luteinizing hormone-releasing hormone (LHRH) agonist.

When Ambiful is administered in combination with palbociclib, it is important that you also read the package leaflet for palbociclib. If you have any questions about palbociclib, ask your doctor.

2. What you need to know before you use Ambiful

Do not use fulvestrant:

• if you are allergic to fulvestrant or any of the other ingredients of this medicine (listed in section 6)

• if you are pregnant or breastfeeding
  • if you have severe liver problems

Warnings and precautions

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

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

Children and adolescents

Fulvestrant is not indicated in children and adolescents under 18 years of age.

Using fulvestrant with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

In particular, you should tell your doctor if you are using anticoagulants (medicines to prevent blood clots).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

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

You should not breastfeed while being treated with fulvestrant.

Driving and using machines

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

Ambiful contains up to 500 mg of alcohol (ethanol)per syringe, which is equivalent to 10% by volume. The amount in each syringe of this medicine is equivalent to less than 10 ml of beer or 4 ml of wine.

This small amount of alcohol in this medicine will have no noticeable effect.

Ambiful contains benzyl alcohol

This medicine contains 500 mg of benzyl alcohol in each syringe, equivalent to 100 mg/ml. Benzyl alcohol may cause allergic reactions.

Talk to 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 side effects (metabolic acidosis).

Ambiful contains benzyl benzoate

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

3. How to use Ambiful

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

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

Your doctor or nurse will administer fulvestrant by slow intramuscular injection into each of your buttocks.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

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

Tell 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)

• Injection site reactions, such as pain and/or inflammation
• Abnormal levels of liver enzymes (in blood tests)*
• Nausea (feeling sick)
• Weakness, fatigue*
• Joint and musculoskeletal pain
• Hot flashes
• 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 bile pigment produced by the liver)
• Thromboembolism (increased risk of blood clots)*
• Decreased platelet count (thrombocytopenia)
• Vaginal bleeding
• Lumbar 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 with walking or balance (peripheral neuropathy)

Uncommon 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
• Hepatitis (inflammation of the liver)
• Liver failure
• Numbness, tingling, and pain
• Anaphylactic reactions

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

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Medicines and Healthcare Products Agency (AEMPS) via their website: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Ambiful

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

Do not use this medicine after the expiry date which is stated on the carton or on the label of the syringes after the abbreviation EXP. The expiry date refers to the last day of the month shown.

This medicine does not require any special storage conditions.

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

This medicine may pose a risk to the aquatic environment.

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

6. Contents of the pack and other information

Composition of Ambiful

• The active substance is fulvestrant. Each pre-filled syringe (5 ml) contains 250 mg of fulvestrant. Each ml contains 50 mg of fulvestrant.
• The other ingredients (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.

Appearance and packaging of the product

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

Ambiful is available in 2 formats: either a pack containing 1 pre-filled glass syringe or a pack containing 2 pre-filled glass syringes. 21G needles with a safety system ("BD SafetyGlide") are also provided for connection to the syringe body.

Packaging combinations:

Packs 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).

Not all pack sizes may be marketed.

Marketing authorization holder

EVER Valinject GmbH

Oberburgau 3

4866 Unterach am Attersee

Austria

Manufacturer

EVER Pharma Jena GmbH

Otto-Schott-Straße 15

07745 Jena

Germany

EVER Pharma Jena GmbH

Brüsseler Str. 18

07747 Jena

Germany

You can ask for more information about this medicine from 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 under the following names:

Date of last revision of this leaflet:July 2021

Other sources of information

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.gob.es/.

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This information is intended only for healthcare professionals:

Fulvestrant 500 mg (2 pre-filled syringes of 250 mg/5 ml solution for injection) 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 intramuscular injection of large volumes.

NOTE: Due to the proximity of the underlying sciatic nerve, caution should be exercised when injecting fulvestrant into the dorsogluteal area.

Warning: Do not autoclave the safety needle (Protected Hypodermic Needle BD SafetyGlide®) before use. Hands should remain behind the needle at all times.

For each of the two syringes:

Disposal

The pre-filled syringes are for singleuse only.

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