Rekovelle - patient leaflet, side effects, dosage

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What REKOVELLE is and what it is used for

• 2. What you need to know before you use 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 follitropin delta, a follicle stimulating hormone which belongs to the family of hormones called gonadotropins. Gonadotropins are involved in reproduction and fertility.

REKOVELLE is used in the treatment of female infertility and in women undergoing assisted reproduction programmes such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). REKOVELLE stimulates the ovaries to grow and develop many egg sacs (‘follicles’), from which eggs are collected and fertilised in the laboratory.

2. What you need to know before you use REKOVELLE

Before starting treatment with this medicine, a doctor should check you and your partner for possible causes of your fertility problems.

Do not use REKOVELLE

• if you are allergic to follicle stimulating hormone or any of the other ingredients of this medicine (listed in section 6)
• if you have a tumour of the uterus, ovaries, breasts, pituitary gland or hypothalamus
• if you have enlarged ovaries or cysts on your ovaries (unless caused by polycystic ovarian

disease)

• if you suffer from bleeding from the vagina without any known cause
• if you have had an early menopause
• if you have malformations of the sexual organs which make a normal pregnancy impossible
• if you have fibroids of the uterus which make a normal pregnancy impossible.

Warnings and precautions

Talk to your doctor before using REKOVELLE.

Ovarian hyperstimulation syndrome

Gonadotropins like this medicine may cause ovarian hyperstimulation syndrome. This is when your follicles develop too much and become large cysts.

Talk to your doctor if you:

• have abdominal pain, discomfort or swelling
• have nausea
• are vomiting
• get diarrhoea
• gain weight
• have difficulty in breathing

Your doctor may ask you to stop using this medicine (see section 4).

If the recommended dose and schedule of administration are followed, ovarian hyperstimulation syndrome is less likely.

Blood clotting problems (thromboembolic events)

Clots in the blood vessels (veins or arteries) are more likely in women who are pregnant. Infertility treatment can increase the risk of this happening, especially if you are overweight or you or someone in your family (blood relative) have a known blood clotting disease (thrombophilia). Tell your doctor if you think this applies to you.

Twisting of ovaries

There have been reports of twisting of ovaries (ovarian torsion) following assisted reproductive technology treatment. Twisting of the ovary could cut off the blood flow to the ovary.

Multiple pregnancy and birth defects

When undergoing assisted reproductive technology treatment the possibility of having a multiple pregnancy (such as twins) is mainly related to the number of embryos placed inside your womb, the quality of the embryos, and your age. Multiple pregnancy may lead to medical complications for you and your babies. Furthermore, the risk of birth defects may be slightly higher following infertility treatment, which is thought to be due to characteristics of the parents (such as your age, and your partner’s sperm characteristics) and multiple pregnancy.

Pregnancy loss

When undergoing assisted reproductive technology treatment, you are more likely to have a miscarriage than if you conceive naturally.

Pregnancy outside the uterus (ectopic pregnancy)

When undergoing assisted reproductive technology treatment, you are more likely to have a pregnancy outside the uterus (ectopic pregnancy) than if you conceive naturally. If you have a history of tubal disease, you have an increased risk of ectopic pregnancy.

Ovarian and other reproductive system tumours

There have been reports of ovarian and other reproductive system tumours in women who had undergone infertility treatment. It is not known if treatment with fertility medicines increase the risk of these tumours in infertile women.

Other medical conditions

Before starting to use this medicine, tell your doctor if:

• you have been told by another doctor that pregnancy would be dangerous for you
• you have kidney or liver disease

Children and adolescents (under 18 years of age)

This medicine is not indicated in children and adolescents.

Other medicines and REKOVELLE

Tell your doctor if you are using, have recently used or might use any other medicines.

Pregnancy and breast-feeding

Do not use this medicine if you are pregnant or breast-feeding.

Driving and using machines

This medicine does not affect your ability to drive and use machines.

REKOVELLE contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free”.

3. How to use REKOVELLE

Always use this medicine exactly as your doctor has told you and at the dose your doctor has told you. Check with your doctor if you are not sure.

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

The REKOVELLE dose is fixed for the whole treatment period with no adjustments to increase or decrease your daily dose. Your doctor will monitor the effect of REKOVELLE treatment, and treatment is stopped when an appropriate number of egg sacs are present. In general, you will be given a single injection of a medicine called human chorionic gonadotrophin (hCG) at a dose of 250 micrograms or 5,000 IU for final development of the follicles.

If your body's response to treatment is too weak or too strong, your doctor may decide to stop treatment with REKOVELLE. For the next treatment cycle, your doctor will in this case give you either a higher or a lower daily dose of REKOVELLE than before.

How are injections given

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

The first injection of this medicine should be given under the supervision of a doctor or a nurse. Your doctor will decide if you can give yourself further doses of this medicine at home, but only after receiving adequate training.

This medicine is to be given by injection just under the skin (subcutaneously) usually in the abdomen. The pre-filled pen may be used for several injections.

If you use more REKOVELLE than you should

The effects of taking too much of this medicine are unknown. Ovarian hyperstimulation syndrome may possibly occur, which is described in section 4.

If you forget to use REKOVELLE

Do not take a double dose to make up for a forgotten dose. Please contact your doctor as soon as you notice that you forgot a dose.

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

4. Possible side effects

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

Serious side effects:

Hormones used in the treatment of infertility such as this medicine may cause a high level of activity in the ovaries (ovarian hyperstimulation syndrome). Symptoms may include pain, discomfort or swelling of the abdomen, nausea, vomiting, diarrhoea, weight gain or difficulty breathing. If you have any of these symptoms you should contact a doctor immediately.

The risk of having a side effect is described by the following categories:

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

• Headache
• Nausea
• Ovarian hyperstimulation syndrome (see above)
• Pelvic pain and discomfort, including of ovarian origin
• Tiredness (fatigue)

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

• Mood swings
• Sleepiness/drow­siness
• Dizziness
• Diarrhoea
• Vomiting
• Constipation
• Discomfort of the abdomen
• Vaginal bleeding
• Breast complaints (include breast pain, breast tenderness)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Y ou can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store REKOVELLE

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 pre-filled pen label and carton after EXP. The expiry date refers to the last day of that month.

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

Store in the original package in order 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 must be discarded if it has not been used after 3 months.

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

At the end of the treatment any unused solution must be discarded.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What REKOVELLE contains

• – The active substance is follitropin delta.

Each pre-filled pen with multidose cartridge contains 12 micrograms of follitropin delta in 0.36 millilitre of solution. One millilitre of solution contains 33.3 micrograms of follitropin delta in each millilitre of solution.

• – The other ingredients are phenol, polysorbate 20, L-methionine, sodium sulphate decahydrate, disodium phosphate dodecahydrate, concentrated phosphoric acid, sodium hydroxide and water for injections.

What REKOVELLE looks like and contents of the pack

REKOVELLE is a clear and colourless solution for injection in a pre-filled pen (injection). It is available in packs of 1 pre-filled pen and 3 pen injection needles.

Marketing Authorisation Holder

Ferring Pharmaceuticals A/S

Kay Fiskers Plads 11

2300 Copenhagen S

Denmark

Manufacturer

Ferring GmbH

Wittland 11

D-24109 Kiel

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgie/Belgiqu­e/Belgien Ferring N.V. Tel/Tél: +32 53 72 92 00 Etnrapua AkBaxuM Afl Ten: +359 2 807 5022 Česká republika Ferring Pharmaceuticals CZ s.r.o. Tel: +420 234 701 333 Danmark Ferring L^gemidler A/S Tlf: +45 88 16 88 17 Deutschland Ferring Arzneimittel GmbH Tel: +49 431 5852 0

Lietuva CentralPharma Communications UAB Tel: +370 5 243 0444 Luxembourg/Lu­xemburg Ferring N.V. Belgique/Belgien Tel/Tel: +32 53 72 92 00 Magyarorszag Ferring Magyarorszag Gyogyszerkeres­kedelmi Kft. Tel: +36 1 236 3800 Malta E.J. Busuttil Ltd. Tel: +356 21447184 Nederland Ferring B.V. Tel: +31 235680300

Eesti CentralPharma Communications OÜ Tel: +372 601 5540	Norge Ferring Legemidler AS Tlf: +47 22 02 08 80
EZZaöa Ferring EZZág MEnE Tql: +30 210 68 43 449	Österreich Ferring Arzneimittel Ges.m.b.H Tel: +43 1 60 8080
España Ferring S.A.U. Tel: +34 91 387 70 00	Polska Ferring Pharmaceuticals Poland Sp. z o.o. Tel: +48 22 246 06 80
France Ferring S.A.S. Tél: +33 1 49 08 67 60	Portugal Ferring Portuguesa – Produtos Farmacéuticos, Sociedade Unipessoal, Lda. Tel: +351 21 940 51 90
Hrvatska Clinres farmacija d.o.o. Tel: +385 1 2396 900	Romania Ferring Pharmaceuticals Romania SRL Tel: +40 356 113 270
Ireland Ferring Ireland Ltd. Tel: +353 1 4637355	Slovenija SALUS, Veletrgovina, d.o.o. Tel: +386 1 5899 179
Ísland Vistor hf. Sími: +354 535 70 00	Slovenská republika Ferring Slovakia s.r.o. Tel: +421 2 54 416 010
Italia Ferring S.p.A. Tel: +39 02 640 00 11	Suomi/Finland Ferring Lääkkeet Oy Puh/Tel: +358 207 401 440
Kúnpog A.Potamitis Medicare Ltd Tql: +357 22583333	Sverige Ferring Läkemedel AB Tel: +46 40 691 69 00
Latvija CentralPharma Communications SIA Tälr: +371 674 50497	United Kingdom (Northern Ireland) Ferring Ireland Ltd.Tel.: +353 1

This leaflet was last revised in.

Detailed information on this medicine is available on the European Medicines Agency web site:

Instructions For Use

REKOVELLE pre-filled pen follitropin delta

Your healthcare provider should show you how to prepare and inject REKOVELLE the right way before you inject it for the first time.

Do not try to inject yourself until you have been shown the right way to give your injections by your healthcare provider.

Read this booklet completely before using your REKOVELLE pre-filled pen and each time you get a new pen. There may be new information. Follow the instructions carefully even if you have used a similar injection pen before. Using the pen incorrectly could result in receiving an incorrect dose of medicine.

Call your healthcare provider (doctor, nurse or pharmacist) if you have any questions about how to give your REKOVELLE injection.

The REKOVELLE pre-filled pen is a disposable, dial-a-dose pen that can be used to give more than

• 1 dose of REKOVELLE. The pen is available in 3 different strengths:

• 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 (follitropin delta) pre-filled pen

Important information

• The REKOVELLE pre-filled pen and the needles are for use by only one person and should not

be shared with others.

• Use the pen only for the medical condition it is prescribed for and as directed by your healthcare provider.
• If you are blind or have poor eyesight and cannot read the dose scale on the pen, do not use this

pen without help. Get help from a person with good eyesight who is trained to use the pen.

• Call your healthcare provider or local representative of the marketing authorisation holder (please refer to package leaflet for contact details) before giving your REKOVELLE injection if you have questions.

Information about your REKOVELLE pre-filled pen

The pen can be dialed to give doses from 0.33 micrograms to 20 micrograms of REKOVELLE in marked increments of 0.33 micrograms. See “Examples of how to dial a dose” at Page 20 to 2

• The dose scale of the pen is numbered from 0 to 20 micrograms.
• Each number is separated by two lines, each line is equal to one increment of 0.33 micrograms.

When turning the dial to your dose, you will hear a click sound and feel resistance on the dial for each increment to help you dial the correct dose.

Cleaning

• If needed, the outside of your pen may be cleaned with a cloth moistened with water.
• Do not put the pen in water or any other liquid.

Storage

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

Before use:

• Store the pen in a refrigerator at 2 °C to 8 °C. Do not freeze.
• If stored outside the refrigerator (at or below 25 °C), the pen will last up to 3 months

including the in-use period. Throw away (dispose of) the pen if it has not been used after 3 months.

After first use (in-use period):

• The pen may be stored for up to 28 days at or below 25°C. Do not freeze.

Supplies you will need to give your REKOVELLE injection

Before use – (Step 1)

Step 1:

• Wash your hands.
• Check the pen to see that it is not damaged. Do not use the pen if it is damaged.
• Check the pen (cartridge) to see that the medicine is clear and does not contain particles. Do not

use a pen with particles or unclear medicine in the cartridge.

• Make sure you have the correct pen with correct strength.
• Check the expiration on the pen label.

Attaching needle – (Step 2 to 6)

Important:

• Always use a new needle for each injection.
• Only use the single-use click-on needles supplied with the pen.

Step 2:

• Pull off the pen cap.

Step 3:

• Pull off the protective foil from the needle.

Step 4:

• Click on the needle.
• You will hear or feel a click when the needle is safely on.
• You may also screw on the needle. When you feel a light resistance it is safely on.

Step 5:

• Pull off the outer needle cap.
• Do not throw the outer needle cap away. You will need it to throw away (dispose of) the needle after injecting the medicine.

Step 6:

• Pull off the inner needle cap and throw it away.

Priming – (Step 7 to 9)

Before using the pen for the first time, you need to remove air bubbles from the cartridge (Priming) to receive the correct dose of medicine.

Only prime your pen the first time you use it.

Perform Step 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 knob clockwise until a symbol of a droplet lines up with the dose indicator.
• If you dial the incorrect priming dose, the priming dose can be corrected either up or down

without loss of medicine by turning the dose knob in either direction until the symbol of a droplet lines up with the dose indicator.

Step 8:

• Hold the pen with the needle pointing upwards.
• Tap with your finger on the cartridge holder to make any air bubbles in the cartridge rise to the top of the cartridge.

Step 9:

• With the needle still pointing upwards (away from the face) press in the injection button all the way in until you see the number ‘0’ lined up with the dose indicator.
• Check that a droplet of liquid appears at the tip of the needle.
• If no droplet(s) appear repeat Steps 7 to 9 (Priming) until a droplet appears.
• If no droplet appears after 5 tries, remove the needle (See Step 13), attach a new needle

(See Steps 3 to 6), and repeat priming (See Steps 7 to 9).

• If you still do not see a droplet after using a new needle, try a new pen.

Dialing the dose – (Step 10)

See “Examples of how to dial a dose” at Page 20 to 2

Step 10:

• Turn the dose knob clockwise until the prescribed dose lines up with the dose indicator in the dose display window.
• The dose can be corrected either up or down without loss of medicine by turning the dose knob in either direction until the correct dose lines up with the dose indicator.
• Do not press the injection button when dialing the dose to avoid loss of medicine.

Split-dosing:

• You may need more than one pen to complete your prescribed dose.
• If you are not able to dial your complete dose, this means there is not enough medicine left in

the pen. You will need to give a split-dose injection or throw away (dispose of) your current pen and use a new pen for your injection.

See “Giving a split-dose of REKOVELLE“ at Page 22 to 2for examples of how to calculate and record your split dose.

Injecting the dose – (Step 11 to 12)

Important:

• Do not use the pen if the medicine contains particles or if the medicine is not clear.
• Read Step 11 and 12 at Page 14 to 1before giving your injection.
• This medicine should be given by injection just under the skin (subcutaneously) in the stomach-area (abdomen).
• Use a new injection site for each injection to lower the risk of skin reactions as redness and irritation.
• Do not inject into an area that is sore (tender), bruised, red, hard, scarred or where you have stretch marks.

Step 11 and 12:

• Wipe the skin of your injection site with an alcohol swab to clean it. Do not touch this area again before you give your injection.
• Hold the pen so the dose display window is visible during injection.
• Pinch your skin and insert the needle straight into your skin as shown by your healthcare provider. Do not touch the injection button yet.
• After the needle is inserted, place your thumb on the injection button.

Press the injection button all the way in and hold.

Keep pressing the injection button in and when you see the number ‘0’ lined up with the dose indicator, wait for 5 seconds (slowly count to 5). This will make sure you get your full dose.

• After pressing in the injection button for 5 seconds, release the injection button. Then slowly remove the needle from the injection site by pulling it straight out of the skin.
• If blood appears at the injection site, press a gauze pad or cotton ball lightly to the injection site.

Note:

• Do not tilt the pen during injection and removal from skin.
• Tilting the pen can cause the needle to bend or break off.
• If a broken needle remains stuck in the body or remains under the skin, get medical help right away.

Disposal of Needle – (Step 13)

Step 13:

• Carefully replace the outer needle cap over the needle with a firm push (A).
• Unscrew the needle in counter-clockwise direction to remove the needle from the pen (B+C).
• Throw away (dispose of) the used needle carefully (D).
• See “Disposal” at Page 1

Note:

• Always remove the needle after every use. The needles are for single-use only.
• Do not store the pen with the needle attached.

Replace pen cap – (Step 14)

Step 14:

• Firmly replace the pen cap on the pen for protection between injections.

The pen cap will not fit over a needle.

If you will give a split-dose injection, only throw away (dispose of) the pen when it is empty.

If you will use a new pen to give your full prescribed dose instead of giving a split-dose injection, throw away (dispose of) your pen when there is not enough medicine in the pen for a full dose.

Keep the pen cap on the pen when it is not in use.

Disposal

Needles:

Put your used needles in a puncture-resistant container, such as a sharps disposal container right away after use. Do not throw away (dispose of) your used sharps disposal container in your household trash.

If you do not have a sharps disposal container, you may use a household container that is:

• made of a heavy-duty plastic,
• can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
• upright and stable during use,
• leak-resistant, and
• properly labeled to warn of hazardous waste inside the container.

REKOVELLE pre-filled pens:

• Throw away (dispose of) your used pens in accordance with local waste regulations.

Examples of how to dial a dose

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

The chart below shows examples of prescribed doses, how to dial the examples of prescribed doses, and what the dose display window looks like for the prescribed doses.

Giving a split-dose of REKOVELLE

If you are not able to dial the full prescribed dose in your pen, this means that there is not enough medicine left in the pen to give the full dose. You will need to give part of your prescribed dose using your current pen and the remainder of the dose using a new pen (split-dose injection) or you may throw away (dispose of) the pen you are using and use a new pen to give your full prescribed dose in 1 injection. If you decide to give a split-dose injection, follow these instructions and write down how much medicine to give using the split-dose diary on Page 2

Column A shows an example of a prescribed dose. Write down your prescribed dose in column A.

Column B shows an example of the dose that is left in the pen (this is equal to what you are able to dial).

Write down the dose that is left in your pen in column B. Give the injection using the rest of the medicine that is left in your pen.

Prepare and prime a new pen (Step 1 to 9).

Calculate and write down the remaining dose to inject in column C by subtracting the number in column B from the number in column A. Use a calculator to check your math if needed.

See “Examples of how to dial a dose” at Page 20 to 2if needed.

Doses should be rounded off to nearest increment, X.00, X.33 or X.66 micrograms. For example, if the number in column C is 5.34, round your remaining dose to 5.33. If the number in column C is 9.67, round your remaining dose to 9.66.

Call your healthcare provider if you have questions about how to calculate your split-dose. Inject the remaining dose of medicine (the number in column C) using your new pen to complete your prescribed dose.

Split-dose diary

A Prescribed Dose	B Dose left In pen (Dose shown at dose indicator in dose display window)	C = A minus B Dose to inject on new pen (Dose shown at dose Indicator In dose display window)
11.33	4.00(4)	7.33 (7 and 1 line (Dial to 7 plus 1 click))
12.66	12.33 (12 and 1 line (12 plus 1 click))	0.33 (0 and 1 line (Dial to 0 plus 1 dick))
11.00	3.00(3)	8.00 (8 (Dial to 8))
12.00	6.66 (6 and 2 lines (6 plus 2 clicks))	Round 5.3 4 to 5.33 (5 and 1 line (Dial to 5 and 1 click))
18.33	8.66 (8 and 2 lines (8 plus 2 clicks))	Round 9.67 to 9.66 (9 and 2 lines (Dial to 9 plus 2 clicks))

Frequently Asked Questions (FAQ)

• 1. Is the priming step necessary before each injection?

• No. Priming must be performed only before giving the first injection with a new pen.

• 2. How do I know that the injection is complete?

• The injection button is firmly pushed in all the way until it stops.
• The number ‘0’ is lined up with the dose indicator.
• You have slowly counted to 5 while you are still holding the injection button in and the

needle is still in your skin.

• 3. Why do I have to count to 5 while holding the injection button?

• Holding the injection button for 5 seconds allows for the full dose to be injected and absorbed under your skin.

• 4. What if the dose knob cannot be turned to the required dose?

• The cartridge in the pen may not have enough medicine left to deliver the prescribed dose.
• The pen does not allow you to dial a larger dose than the dose that is left in the cartridge.
• You can inject the medicine left in the pen and complete the prescribed dose with a new

pen (split-dose) or use a new pen to give the full prescribed dose.

Warnings

• Do not use a pen if it has been dropped or hit against hard surfaces.
• If the injection button is not easy to push in, do not use force. Change the needle. If the injection button still is not easy to push in after changing the needle, use a new pen.
• Do not try to repair a damaged pen. If a pen is damaged, contact your healthcare provider or local representative of the marketing authorisation holder (please refer to package leaflet for contact details).