Rekovelle 36 micrograms/1.08 ml solution for injection in pre-filled pen

Patient Information Leaflet

Introduction

Patient Information Leaflet

REKOVELLE 36 micrograms/1.08 ml

pre-filled pen injection solution

folitropin delta

Read all of this 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, ask your doctor or pharmacist.
• 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 side effects, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What REKOVELLE is and what it is used for

REKOVELLE contains folitropin delta, a follicle-stimulating hormone belonging to the family of hormones known as gonadotropins. Gonadotropins are involved in reproduction and fertility.

REKOVELLE is used in the treatment of female infertility and in women undergoing assisted reproductive techniques such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). REKOVELLE stimulates the ovaries to grow and develop multiple sacs (‘follicles’), from which eggs are retrieved and fertilized in the laboratory.

2. What you need to know before using REKOVELLE

Before starting treatment with this medicine, a doctor should evaluate both you and your partner to investigate possible causes of infertility.

Do not use REKOVELLE

• if you are allergic to follicle-stimulating hormone or to any of the other ingredients of this medicine (listed in section 6)
• if you have a tumor of the uterus, ovaries, breasts, pituitary gland, or hypothalamus
• if you have enlarged ovaries or cysts not caused by polycystic ovary syndrome
• if you have vaginal bleeding of unknown cause
• if you have experienced premature menopause
• if you have malformations of the reproductive organs that make normal pregnancy impossible
• if you have uterine fibroids that make normal pregnancy impossible.

Warnings and precautions

Talk to your doctor before using REKOVELLE

Ovarian hyperstimulation syndrome

Gonadotropins, such as this medicine, may cause ovarian hyperstimulation syndrome. This occurs when your follicles become excessively stimulated and develop into large cysts.

Contact your doctor if:

• you experience abdominal pain, discomfort, or swelling
• you have nausea
• you have vomiting
• you have diarrhea
• you gain weight rapidly
• you have difficulty breathing

Your doctor may instruct you to stop treatment with this medicine (see section 4).

If you follow the recommended dose and administration schedule, the risk of developing ovarian hyperstimulation syndrome is reduced.

Blood clotting problems (thromboembolic events)

The formation of blood clots in blood vessels (veins or arteries) is more common in pregnant women. Infertility treatments may increase this risk, especially if you are overweight or if you or a family member (blood relative) have a known clotting disorder (thrombophilia). Talk to your doctor if you think this applies to you.

Ovarian torsion

Cases of ovarian torsion (twisting of the ovaries) have been reported following assisted reproductive treatments. Ovarian torsion can cut off blood supply to the ovaries.

Multiple pregnancy and birth defects

When undergoing assisted reproductive techniques, the likelihood of multiple pregnancy (such as twins) is primarily related to the number of embryos transferred into your uterus, embryo quality, and your age. Multiple pregnancy may lead to medical complications for you and your babies. Additionally, the risk of birth defects may be slightly increased with infertility treatments. This is thought to be due to parental factors (such as age and sperm characteristics) and multiple pregnancy.

Pregnancy loss

When undergoing assisted reproductive techniques, the risk of miscarriage is higher than with natural conception.

Ectopic pregnancy (pregnancy outside the uterus)

When undergoing assisted reproductive techniques, the risk of ectopic pregnancy (pregnancy outside the uterus) is higher than with natural conception. If you have a history of tubal disease, your risk of ectopic pregnancy is increased.

Ovarian tumors and other reproductive system tumors

Cases of ovarian tumors and other tumors of the reproductive system have been reported in women who have undergone infertility treatments. It is not known whether fertility medications increase the risk of these tumors in infertile women.

Other medical conditions

Before starting this medicine, inform your doctor if:

• another doctor has told you that pregnancy could be dangerous for you
• you have liver or kidney disease

Children and adolescents (under 18 years of age)

This medicine is not intended for use in children and adolescents.

Other medicines and REKOVELLE

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

Pregnancy and breastfeeding

Do not use this medicine if you are pregnant or breastfeeding.

Driving and using machines

This medicine does not affect your ability to drive or operate machinery.

REKOVELLE contains sodium

This medicine contains less than 1 mmol of sodium chloride (23 mg) per dose, i.e., essentially “sodium-free”.

3. How to use REKOVELLE

Follow exactly the administration instructions for this medicine given by your doctor.

If in doubt, consult your doctor or pharmacist again.

The dose of REKOVELLE for the first treatment cycle will be calculated by your doctor using your anti-Müllerian hormone (AMH) level (a marker of how your ovaries will respond to stimulation with gonadotropins) in your blood and your body weight. Therefore, before starting treatment, the AMH result from a blood sample (taken within the last 12 months) must be available. Your body weight will also be measured before starting treatment. The dose of REKOVELLE is expressed in micrograms.

The dose of REKOVELLE remains fixed throughout the treatment period, without adjustments to increase or decrease the daily dose. Your doctor will monitor the effect of treatment with REKOVELLE, and treatment will be stopped when an adequate number of follicles have developed. Generally, you will be given a single injection of a medicine called human chorionic gonadotropin (hCG) at a dose of 250 micrograms or 5,000 IU to trigger final follicular development.

If your body's response to treatment is very weak or very strong, your doctor may decide to stop treatment with REKOVELLE. For the next treatment cycle, your doctor may prescribe a higher or lower daily dose of REKOVELLE than the previous one.

How to administer the injections

The instructions for use of the pre-filled pen must be carefully followed. Do not use the pre-filled pen if the solution contains particles or does not appear clear.

The first injection of this medicine must be administered under the supervision of a doctor or nurse. Your doctor will decide whether you can self-administer this medicine at home, but only after you have received adequate training.

This medicine is intended for subcutaneous injection (just under the skin), usually in the abdominal area. The pre-filled pen may be used for multiple injections.

If you use more REKOVELLE than you should

The effects of using too much medicine are not known. Ovarian hyperstimulation syndrome (OHSS), described in section 4, may occur.

If you forget to use REKOVELLE

Do not administer a double dose to make up for a missed dose. Please contact your doctor or pharmacist as soon as you realize you have missed a dose.

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

4. Possible adverse effects

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

Serious adverse effects:

Hormones used in fertility treatment, such as this medicine, may cause high levels of ovarian activity (Ovarian Hyperstimulation Syndrome). Symptoms may include pain, discomfort, and swelling in the abdomen, nausea, vomiting, diarrhea, weight gain, or difficulty breathing. If you experience any of these symptoms, please contact your doctor immediately.

The risk of adverse reactions is classified into the following categories:

Frequent (may affect up to 1 in 10 people):

• Headache
• Nausea
• Ovarian hyperstimulation syndrome (see above)
• Pelvic pain and discomfort, including pain originating from the ovaries
• Tiredness (fatigue)

Uncommon (may affect up to 1 in 100 people):

• Mood changes
• Somnolence / Drowsiness
• Dizziness
• Diarrhea
• Vomiting
• Constipation
• Abdominal discomfort
• Vaginal bleeding
• Breast discomfort (including breast pain, breast swelling, breast tenderness, and/or nipple pain)

Reporting of adverse effects

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

5. Storage of REKOVELLE

Keep out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the label of the pre-filled pen and the packaging following "EXP". The expiry date refers to the last day of the month indicated.

Store in a refrigerator (2 °C – 8 °C). Do not freeze.

Keep in the original packaging to protect from light.

REKOVELLE may be stored at or below 25 °C for up to 3 months, including the period after first use. It must not be refrigerated again and should be discarded if not used within 3 months.

After first use: 28 days when stored at or below 25 °C.

At the end of treatment, any unused product should be discarded.

Medicines should not be disposed of via wastewater or household waste. If you are unsure how to dispose of unused containers or medicines, ask your pharmacist. This will help protect the environment.

6. Contents of the pack and other information

Composition of REKOVELLE

• The active substance is folitropin delta.

Each pre-filled multidose pen contains 36 micrograms of folitropin delta in 1.08 millilitres of solution. One millilitre of solution contains 33.3 micrograms of folitropin delta per millilitre of solution.

• The other components are phenol, polysorbate 20, L-methionine, sodium sulfate decahydrate, disodium phosphate dodecahydrate, concentrated phosphoric acid, sodium hydroxide, and water for injection.

Appearance of the product and contents of the pack

REKOVELLE is a clear, colourless solution for injection in a pre-filled pen. It is available in packs containing 1 pre-filled pen and 9 needles.

Marketing Authorisation Holder

Ferring Pharmaceuticals A/S

Amager Strandvej 405

2770 Kastrup

Denmark

Manufacturer responsible for batch release

Ferring GmbH

Wittland 11

D-24109 Kiel

Germany

More information about this medicinal product is available upon request by contacting the local representative of the Marketing Authorisation Holder:

Belgium/Belgium/Belgium Ferring N.V. Tel/Tel: +32 53 72 92 00 [email protected]	Lithuania CentralPharma Communications UAB Tel: +370 5 243 0444 [email protected]
Bulgaria Farmont Ltd Tel: +359 2 807 5022 [email protected]	Luxembourg/Luxembourg Ferring N.V. Belgium/Belgium Tel/Tel: +32 53 72 92 00 [email protected]
Czech Republic Ferring Pharmaceuticals CZ s.r.o. Tel: +420 234 701 333 [email protected]	Hungary Ferring Magyarország Gyógyszerkereskedelmi Kft. Tel: +36 1 236 3800 [email protected]
Denmark Ferring Lægemidler A/S Tlf: +45 88 16 88 17	Malta E.J. Busuttil Ltd. Tel: +356 21447184 [email protected]
Germany Ferring Arzneimittel GmbH Tel: +49 431 5852 0 [email protected]	Netherlands Ferring B.V. Tel: +31 235680300 [email protected]
Estonia CentralPharma Communications OÜ Tel: +372 601 5540 [email protected]	Norway Ferring Legemidler AS Tlf: +47 22 02 08 80 [email protected]
Greece Ferring Ελλάς ΜΕΠΕ Tel: +30 210 68 43 449	Austria Ferring Arzneimittel Ges.m.b.H Tel: +43 1 60 8080 [email protected]
Spain Ferring S.A.U. Tel: +34 91 387 70 00 [email protected]	Poland Ferring Pharmaceuticals Poland Sp. z o.o. Tel: +48 22 246 06 80 [email protected]
France Ferring S.A.S. Tél: +33 1 49 08 67 60 [email protected]	Portugal Ferring Portuguesa – Produtos Farmacêuticos, Sociedade Unipessoal, Lda. Tel: +351 21 940 51 90
Croatia Clinres farmacija d.o.o. Tel: +385 1 2396 900 [email protected]	Romania Ferring Pharmaceuticals Romania SRL Tel: +40 356 113 270
Ireland Ferring Ireland Ltd. Tel: +353 1 4637355 [email protected]	Slovenia SALUS, Veletrgovina, d.o.o. Tel: +386 1 5899 100 [email protected]
Iceland Vistor hf. Tel: +354 535 70 00	Slovakia Ferring Slovakia s.r.o. Tel: +421 2 54 416 010 [email protected]
Italy Ferring S.p.A. Tel: +39 02 640 00 11	Finland Ferring Lääkkeet Oy Tel: +358 207 401 440 [email protected]
Cyprus A.Potamitis Medicare Ltd Tel: +357 22583333 [email protected]	Sweden Ferring Läkemedel AB Tel: +46 40 691 69 00 [email protected]
Latvia CentralPharma Communications SIA Tel: +371 674 50497 [email protected]	United Kingdom (Northern Ireland) Ferring Ireland Ltd Tel: +353 1 4637355 [email protected]

Date of the most recent review of this leaflet in .

Detailed and up-to-date information on this medicine is available on the website of the European Medicines Agency (EMA): http://www.ema.europa.eu.

Instructions for use

REKOVELLE pre-filled pen

Follitropin delta

Your healthcare professional must teach you how to properly prepare and inject REKOVELLE before you administer it for the first time.

Do not attempt to inject yourself until you have been trained by your healthcare professional in the correct method of administering injections.

Read this entire manual before using the REKOVELLE pre-filled pen and each time you get a new pen. There may be new information. Follow these instructions carefully even if you have previously used a similar injection pen. Incorrect use of the pen may result in an incorrect dose of the medicine.

Contact your healthcare professional (physician, nurse, or pharmacist) if you have any questions about how to administer your REKOVELLE injection.

The REKOVELLE pre-filled pen is a disposable, dose-adjustable pen that can be used to administer more than one dose of REKOVELLE. The pen is available in 3 different concentrations:

• 12 micrograms/0.36 mL
• 36 micrograms/1.08 mL
• 72 micrograms/2.16 mL

REKOVELLE pre-filled pen and its parts

Instructions for use – REKOVELLE pre-filled pen (follitropin delta)

Important information

• The REKOVELLE pre-filled pen and needles are for single-person use and must not be shared with others.
• Use the pen only for the medical condition it was prescribed for and as instructed by your healthcare professional.
• If you are blind or have impaired vision and cannot read the dose scale on the pen, do not use this pen without assistance. Ask for help from a person with good vision who has been trained in how to use the pen.
• If you have any questions, contact your healthcare professional or the local representative of the marketing authorization holder (see the package leaflet for contact information) before administering your REKOVELLE injection.

Information about your REKOVELLE pre-filled pen

The pen can be adjusted to deliver doses ranging from 0.33 micrograms to 20 micrograms of REKOVELLE in increments of 0.33 micrograms. See “Examples of how to set a dose” on pages 20 to 211.

• The pen’s dose scale is numbered from 0 to 20 micrograms.
• Each number is separated by two lines; each line represents an increment of 0.33 micrograms.
• As you turn the dose selector to your prescribed dose, you will hear a click and feel resistance at each increment to help you set the correct dose.

Cleaning

• The exterior of your pen may be cleaned with a cloth dampened with water, if necessary.
• Do not immerse the pen in water or any other liquid.

Storage

• Always store the pen with the cap on and without a needle attached.
• Do not use the pen after the expiration date (CAD) printed on the pen label.
• Do not expose the pen to extreme temperatures, direct sunlight, or very cold conditions such as in a car or freezer.
• Keep the pen out of reach of children and of anyone who has not been trained in its use.

Before use:

• Store the pen in the refrigerator between 2 °C and 8 °C. Do not freeze.
• If stored outside the refrigerator (at a temperature not exceeding 25 °C), the pen may be kept for up to 3 months, including the period of use. Discard the pen if not used within 3 months.

After first use (period of use):

• The pen may be stored for up to 28 days at a temperature not exceeding 25 °C. Do not freeze.

Items you will need to administer your REKOVELLE injection

Before use – (Step 1)

Step 1:

• Wash your hands.
• Check the pen for any damage. Do not use the pen if it is damaged.
• Check the pen (cartridge) to ensure the medicine is clear and free of particles. Do not use a pen containing cloudy medicine or particles.
• Make sure you have the correct pen with the correct concentration.
• Check the expiration date on the pen label.

Attaching the needle – (Steps 2 to 6)

Important:

• Always use a new needle for each injection.
• Use only the single-use click-on needles provided with the pen.

Step 2:

• Remove the pen cap.

Step 3:

• Remove the protective tab from the needle.

Step 4:

• Attach the needle.
• You will hear or feel a “click” when the needle is securely attached.
• You may also screw the needle on. When you feel slight resistance, it is securely attached.

Step 5:

• Remove the outer protective needle cap.
• Do not discard the outer needle cap. You will need it to safely dispose of the needle after the injection.

Step 6:

• Remove the inner needle cap and discard it.

Preparation – (Steps 7 to 9)

• Before using the pen for the first time, you must remove air bubbles from the cartridge (priming) to ensure you receive the correct dose of medicine.
• Priming should only be performed the first time you use the pen.
• Perform steps 7 to 9 even if you do not see air bubbles.
• If the pen has already been used, proceed directly to step 10.

Step 7:

• Turn the dose button clockwise until the drop symbol aligns with the dose indicator.
• If you set the incorrect priming dose, you can correct it either up or down without loss of medicine by turning the dose button in either direction until the drop symbol aligns with the dose indicator.

Step 8:

• Hold the pen with the needle pointing upward.
• Tap the cartridge holder gently with your finger to allow any air bubbles present in the cartridge to rise to the top.

Step 9:

• With the needle still pointing upward (away from your face), press the injection button until the number ‘0’ aligns with the dose indicator.
• Check that a drop of liquid appears at the tip of the needle.
• If no drop appears, repeat steps 7 to 9 (Preparation) until a drop appears.
• If no drop appears after 5 attempts, remove the needle (see step 13), attach a new needle (see steps 3 to 6), and repeat the preparation (see steps 7 to 9).
• If you still do not see a drop after using a new needle, try a new pen.

Setting the dose – (Step 10)

See “Examples of how to set a dose” on pages 20 to 211.

Step 10:

• Turn the dose button clockwise until the prescribed dose aligns with the dose indicator in the dose display window.
• The dose can be adjusted either up or down without loss of medicine by turning the dose button in either direction until the correct dose aligns with the dose indicator.
• Do not press the injection button while setting the dose to avoid loss of medicine.

Dose splitting:

• You may need more than one pen to complete the prescribed dose.
• If you cannot set your full dose, this means there is not enough medicine left in the pen. You will need to administer your dose as two separate injections or discard your pen and use a new one for your injection.

See “Administering a split dose of REKOVELLE” on pages 22 to 231 for examples of how to calculate and record your split dose.

Injecting the dose – (Steps 11 to 12)

Important:

• Do not use the pen if the medicine contains particles or appears cloudy.
• Read steps 11 and 12 on pages 14 to 151 before administering your injection.
• This medicine must be administered by subcutaneous injection just under the skin in the abdominal area (stomach).
• Use a new injection site for each injection to reduce the risk of skin reactions such as redness and irritation.
• Do not inject into areas that are irritated (tender), bruised, red, hard, scarred, or have stretch marks.

Steps 11 and 12:

• Clean the skin at the injection site with an alcohol swab. Do not touch this area again before administering the injection.

• Hold the pen so that the dose display window is visible during the injection.

• Pinch your skin and insert the needle directly as instructed by your healthcare professional. Do not press the injection button yet.

• After inserting the needle, place your thumb on the injection button.

• Press the injection button fully and keep it pressed.

• Continue holding the injection button down and, when you see the number ‘0’ aligned with the dose indicator, wait 5 seconds (count slowly to 5). This ensures you receive your full dose.

• After holding the injection button for 5 seconds, release it. Then slowly withdraw the needle straight out of the skin.
• If blood appears at the injection site, apply light pressure with gauze or a cotton ball.

Note:

• Do not tilt the pen during injection or while removing the needle from the skin.
• Tilting the pen may cause the needle to bend or break.
• If a broken needle remains stuck in the body or under the skin, seek immediate medical assistance.

Removing the needle – (Step 13)

Step 13:

• Carefully replace the outer needle cap with a firm push (A).
• Unscrew the needle counterclockwise to remove it from the pen (B+C).
• Carefully dispose of the used needle (D).
• See “Disposal” on page 181.

Note:

• Always remove the needle after each use. Needles are for single use only.
• Do not store the pen with the needle attached.

Replacing the pen cap – (Step 14)

Step 14:

• Firmly replace the pen cap to protect it between injections.

Note:

• The pen cap will not fit if a needle is attached.
• If you are administering a split dose in two injections, discard the pen only when it is empty.
• If you are using a new pen to administer your full prescribed dose instead of splitting the dose into two injections, discard the pen when there is not enough medicine left for a full dose.
• Keep the pen cap on when not in use.

Disposal

Needles:

Place used needles immediately into a puncture-resistant container, such as a sharps container. Do not dispose of the used container with your household waste.

If you do not have a sharps container, you may use a household container that meets the following criteria:

• Made of solid, durable plastic,
• With a tight-fitting, puncture-resistant lid that prevents sharp objects from escaping,
• Able to remain upright and stable during use,
• Leak-proof, and
• Properly labeled to indicate it contains hazardous waste.

REKOVELLE pre-filled pens:

• Dispose of used pens according to local waste disposal regulations.

Examples of how to set a dose

Examples of how to set a dose using your REKOVELLE pre-filled pen

The following table shows examples of prescribed doses, how to set the prescribed dose examples, and what the dose display window looks like for the prescribed doses.

Examples of prescribed doses (in micrograms)	Dose to be set on the pen	Display window for the examples of prescribed doses
0.33	0 and 1 line (set to 0 plus 1 click)
0.66 (preparation dose)	0 and 2 lines (set to 0 plus 2 clicks)
2.33	2 and 1 line (set to 2 plus 1 click)
11.00	11 (set to 11)
12.33	12 and 1 line (set to 12 plus 1 click)
18.66	18 and 2 lines (set to 18 plus 2 clicks)
20.00	20 (set to 20)

Administration of a Split Dose of REKOVELLE

If you are unable to set the full prescribed dose on your pen, this means there is not enough medication left in the pen to administer the complete dose. You must either administer part of your prescribed dose using the pen you were using and the remainder of the dose using a new pen (split dose injection), or you should discard the pen you were using and use a new pen to administer your complete prescribed dose in a single injection. If you decide to administer a split dose via two injections, follow these instructions and record the amount of medication to be administered using the split dose diary on page 231.

• Column A shows an example of a prescribed dose. Write your prescribed dose in column A.
• Column B shows an example of the remaining dose in the pen (this equals the dose you are able to set).
• Write the remaining dose in your pen in column B. Administer the injection using the remaining amount of medication in your pen.
• Prepare a new pen (steps 1 to 9).
• Calculate and write the remaining dose to be injected in column C by subtracting the number in column B from the number in column A. Use a calculator to verify your calculation if necessary.
• See “Examples of how to set a dose” on pages 20 to 211 if needed.
• Doses must be rounded to the nearest increment: X.00, X.33, or X.66 micrograms. For example, if the number in column C is 5.34, round your dose down to 5.33. If the number in column C is 9.67, round your dose down to 9.66.
• Contact your healthcare professional if you have any doubts about how to calculate your split dose.
• Inject the remaining medication (the number in column C) using a new pen to complete the prescribed dose.

Split Dose Diary

Frequently Asked Questions

1. Is the preparation step necessary before each injection?

• No. Preparation should only be performed before administering the first injection with a new pen.

1. How can I tell if the injection is complete?

• The injection button has been firmly pressed all the way down until it stopped.
• The number ‘0’ is aligned with the dose indicator.
• You have counted slowly to 5 while holding the injection button and the needle is still injected into the skin.

1. Why should I count to 5 while holding the injection button?

• Holding the injection button for 5 seconds ensures that the full dose is delivered and absorbed under your skin.

1. What if the dose button cannot be turned to the prescribed dose?

• The cartridge in the pen may not contain enough medication to deliver the prescribed dose.
• The pen does not allow you to set a dose higher than the amount remaining in the cartridge.
• You may inject the amount of medication remaining in the pen and complete the prescribed dose with a new pen (split dose), or use a new pen to administer the full prescribed dose.

Precautions

• Do not use a pen that has been dropped or struck against hard surfaces.
• If the injection button is difficult to press, do not use force. Change the needle. If the injection button remains difficult to press after changing the needle, use a new pen.
• Do not attempt to repair a damaged pen. If a pen is damaged, contact your healthcare professional or the local representative of the marketing authorization holder (see the package leaflet for contact information).

Additional Information

Needles

Needles are provided with the pen. If you require additional needles, contact your healthcare professional. Only use the needles supplied with the REKOVELLE pre-filled pen or those prescribed by your healthcare professional.

Contact

If you have any questions or problems regarding the pen, contact your healthcare professional or the local representative of the marketing authorization holder (see the package leaflet for contact information).

1. Page numbers refer to the printed Instructions for Use manual and not to the page numbers in this document.