Ambiful 250 mg solution for injection in pre-filled syringe EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Ambiful 250 mg injection solution in pre-filled syringe EFG

fulvestrant

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet as you may need to read it again. If you have any questions, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if these are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Ambiful is and what it is used for

2. What you need to know before using Ambiful

3. How to use Ambiful

4. Possible side effects

5. How to store Ambiful

6. Contents of the pack and other information

1. What Ambiful is and what it is used for

Ambiful contains the active substance fulvestrant, which belongs to the group of estrogen blockers. Estrogens, a type of female sex hormones, may in some cases be involved in the development of breast cancer.

Ambiful is used:

• as 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, 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 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 palbociclib package leaflet. If you have any questions about palbociclib, consult your doctor.

2. What you need to know before using Ambiful

Do not use fulvestrant:

• if you are allergic to fulvestrant or to 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 using fulvestrant if any of the following apply to you:

• kidney or liver problems
• low platelet count (platelets help blood to clot) or bleeding disorders
• history of blood clots
• osteoporosis (loss of bone density)
• alcoholism

Children and adolescents

Fulvestrant is not indicated for use 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 need to take any other medicines.

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

You must not use fulvestrant if you are pregnant. If you could become pregnant, you should use an effective method of contraception during treatment with fulvestrant and for 2 years after the last dose.

You must 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 operate machinery.

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 the medicine will have no significant 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.

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

Ambiful contains benzyl benzoate

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

3. How to use Ambiful

Follow exactly the administration instructions for this medicine 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 given 2 weeks after the initial dose.

Your doctor or nurse will administer fulvestrant to you as a slow intramuscular injection into each of your buttocks.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

You may require urgent medical treatment if you experience any of the following adverse 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

Tell your doctor, pharmacist, or nurse if you notice any of the following adverse effects:

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

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

All other adverse effects:

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

• Headache
• Vomiting, diarrhoea, 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 levels (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 with walking or balance (peripheral neuropathy)

Uncommon adverse effects (may affect up to 1 in 100 people)

• Thick, whitish vaginal discharge and candidiasis (infection)

• Bruising and bleeding at the injection site

• Increased gamma-GT, a liver enzyme detected in blood tests

• Inflammation of the liver (hepatitis)

• Liver failure

• Numbness, tingling, and pain

• Anaphylactic reactions

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

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse 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 stated on the packaging or on the labels of the syringes, following the abbreviation EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Your healthcare professional is responsible for the proper storage, use, and disposal of Ambiful.

This medicine may pose a risk to the aquatic environment.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. 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 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, equivalent to 100 mg/ml.

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

Appearance of the product and contents of the pack

Ambiful is a viscous, transparent, colorless to yellow solution, practically free from particles, in a pre-filled Type I glass syringe with a bromobutyl rubber plunger, a plunger rod, and a cap, equipped with a tamper-evident seal, containing 5 ml of injectable solution. Two syringes must be administered to receive the recommended monthly dose of 500 mg.

Ambiful is available in two pack sizes: either a pack containing 1 pre-filled glass syringe or a pack containing 2 pre-filled glass syringes. Additionally, 21G needles with a safety system (“BD SafetyGlide”) are provided for attachment to each syringe barrel.

Packaging configurations:

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).

Only certain pack sizes may be commercially available.

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

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

EVER Pharma Therapeutics Spain, S.L.
C/Toledo 170
28805 Madrid
Spain

This medicinal product is authorized in the European Economic Area member states under the following names:

Date of the most recent review of this leaflet: July 2021

Other sources of information

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

This information is intended for healthcare professionals only:

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

“BD SafetyGlide” is a registered trademark of “Becton Dickinson and Company” and bears the CE marking: 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 site.

Warning: Do not sterilize the safety needle device (BD SafetyGlide® protected hypodermic needle) in an autoclave prior to use. Hands must remain behind the needle at all times.

For each of the two syringes:

Disposal

Pre-filled syringes are for single use only.

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