Luveris

Patient Information Leaflet

Solvent in vials
Luveris 75 IU powder and solvent for injectable solution
lutropin alfa
Please read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Luveris is and what it is used for

What Luveris is
Luveris is a medicine containing lutropin alfa, a recombinant luteinizing hormone (LH) that is essentially identical to the hormone naturally present in the human body, but produced in the laboratory using biotechnological methods. It belongs to a family of hormones called gonadotropins, which are involved in the normal regulation of reproduction.

What Luveris is used for
Luveris is indicated for the treatment of adult women who have low levels of certain hormones involved in the natural reproductive cycle. The medicine is used in combination with another hormone called follicle-stimulating hormone (FSH) to induce the development of follicles—the structures responsible for the maturation of eggs (oocytes) in the ovary. Treatment with Luveris is followed by administration of a single dose of human chorionic gonadotropin (hCG) to trigger the release of an egg from the follicle (ovulation).

2. What you need to know before using Luveris

Do not use Luveris

• if you are allergic to gonadotropins (such as luteinizing hormone, follicle-stimulating hormone, or human chorionic gonadotropin) or to any of the other ingredients of this medicine (listed in section 6).
• if you have an ovarian, uterine, or breast tumour.
• if you have been diagnosed with a brain tumour.
• if you have ovarian enlargement or fluid-filled sacs in the ovaries (ovarian cysts) of unknown origin.
• if you have vaginal bleeding of unknown cause.

Do not use Luveris if you have any of the conditions listed above. If you are in any doubt, consult your doctor or pharmacist before using this medicine.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using Luveris.

Before starting treatment, your fertility and that of your partner should be assessed.

It is recommended not to use Luveris if you have any condition that usually makes a normal pregnancy impossible, such as non-functioning ovaries due to a condition called primary ovarian insufficiency, or malformations of the reproductive organs.

Porphyria

Before starting treatment, inform your doctor if you or any of your family members suffer from porphyria (an inability to break down porphyrins, which can be inherited).

Ovarian hyperstimulation syndrome (OHSS)

This medicine stimulates the ovaries, increasing the risk of developing ovarian hyperstimulation syndrome (OHSS). This occurs when follicles develop excessively and become large cysts. If you experience lower abdominal pain, rapid weight gain, nausea or vomiting, or breathing difficulties, consult your doctor immediately, as they may advise you to stop taking this medicine (see “Serious side effects” in section 4).

If ovulation does not occur and the recommended dosage and administration schedule are followed, the likelihood of developing OHSS is reduced. The use of Luveris rarely causes severe OHSS. However, the risk increases if the medicine used for final follicular maturation, containing human chorionic gonadotropin (hCG), is administered (see “Recommended dosage” in section 3). If you are developing OHSS, your doctor may decide to withhold hCG in this treatment cycle, and you may need to abstain from sexual intercourse or use barrier contraceptive methods for at least four days.

Your doctor will schedule careful monitoring of ovarian response through ultrasound and blood tests, both before and during treatment.

Multiple pregnancy

When using Luveris, your chance of having a multiple pregnancy is higher than with natural conception, most commonly twins. Multiple pregnancy can lead to medical complications for you and your babies. The risk of multiple pregnancy can be reduced by taking the correct dose of Luveris at the prescribed times. If undergoing assisted reproductive techniques, the risk of multiple pregnancy is related to age, egg/embryo quality, and the number of fertilized eggs or embryos implanted.

Spontaneous abortion

If undergoing assisted reproductive techniques or ovarian stimulation to produce eggs, the risk of spontaneous abortion is higher than in the general female population.

Ectopic pregnancies

Women with previous tubal disorders are at increased risk of ectopic pregnancies (pregnancies in which the embryo implants outside the uterus), whether the pregnancy results from spontaneous conception or infertility treatments.

Blood clotting problems (thromboembolic events)

Talk to your doctor before using Luveris if you or a family member has ever had blood clots in the legs or lungs, or if you have had a heart attack or stroke. Treatment with Luveris may increase your risk of developing serious blood clots or worsening existing ones.

Tumours of the reproductive organs

Cases of benign and malignant tumours of the ovaries and other reproductive organs have been reported in women undergoing repeated cycles of pharmacological infertility treatment.

Congenital abnormalities

The incidence of congenital abnormalities following assisted reproductive techniques may be slightly higher than after natural conception. This is thought to be due to differences in parental characteristics such as maternal age and genetic factors, as well as the assisted reproductive procedures themselves and the occurrence of multiple pregnancies.

Children and adolescents

Luveris is not indicated for use in children and adolescents under 18 years of age.

Other medicines and Luveris

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

Do not mix Luveris with other medicines in the same injection, except with follitropin alfa, if prescribed by your doctor.

Pregnancy and breastfeeding

Do not use Luveris during pregnancy or while breastfeeding.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Luveris has no effect or has a negligible effect on the ability to drive and use machines.

Luveris contains sodium

Luveris contains less than 1 mmol (23 mg) of sodium per dose and is therefore essentially “sodium-free”.

3. How to use Luveris

Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor.

Use of the medicine
Your doctor will determine the most appropriate dose and administration schedule during the course of treatment.

Recommended dosage
Luveris is generally taken daily for up to 3 weeks, in combination with FSH injections.

• The most common starting dose is 75 IU (1 vial) of Luveris together with 75 or 150 IU of FSH.
• Depending on your response, your doctor may increase the FSH dose, preferably by 37.5–75 IU at intervals of 7–14 days.

Your doctor may decide to extend treatment up to 5 weeks.
Once the desired response is achieved, a single dose of hCG should be administered 24–48 hours after the last injection of Luveris and FSH. It is recommended that you have sexual intercourse on the day of hCG administration and the following day. Alternatively, intrauterine insemination or another medically assisted reproductive procedure may be performed, according to your doctor’s judgment.

If you have an excessive response, treatment must be stopped and administration of hCG should be avoided (see “Ovarian hyperstimulation syndrome (OHSS)” in section 4). In the next cycle, your doctor will prescribe a lower dose of FSH than in the previous cycle.

Method of administration
Luveris is for subcutaneous use, i.e. by injection under the skin. Each vial is a single-dose preparation.

If you are self-administering Luveris, carefully read the following instructions:

• Wash your hands. It is important to ensure that your hands and all materials used are clean.
• Gather all necessary items and place them on a clean surface:
  • one vial of Luveris,
  • one vial of solvent,
  • two alcohol-impregnated cotton swabs,
  • one syringe,
  • one reconstitution needle for dissolving the powder with the solvent,
  • one fine needle for subcutaneous injections,
  • a designated container for safe disposal of glass and needles.
• Remove the protective cap from the solvent vial. Attach the reconstitution needle to the syringe and draw a small amount of air into the syringe

by pulling the plunger to the mark indicating approximately 1 mL.
Then insert the needle into the solvent vial, push the plunger to expel the air, turn the vial upside down, and slowly draw up all the solvent.
Carefully place the syringe on the work surface, taking care not to touch the needle.

• Prepare the injection solution: remove the protective cap from the vial containing Luveris powder, take the syringe and slowly inject

the solvent into the Luveris vial. Gently rotate the vial without removing the syringe. Do not shake.

• After the powder has dissolved (which should occur immediately), check that the resulting solution is clear and free from particles.

Invert the vial and slowly draw the solution back into the syringe.
You may also reconstitute Luveris and follitropin alfa together, rather than injecting each product separately. After dissolving the Luveris powder, draw the solution back into the syringe and reinject it into the vial containing the follitropin alfa powder. Once the powder has dissolved, draw the solution back into the syringe. Check for particles as described above; if the solution is not clear, do not use it.
Up to 3 vials of powder can be dissolved in 1 mL of solvent.

• Replace the needle with the fine injection needle and remove any air bubbles: if you see air bubbles in the syringe, hold the syringe with the needle pointing upward,

and gently tap the syringe until all the air collects at the top. Gently push the plunger until the air bubbles are expelled.

• Inject the solution immediately: your doctor or nurse should have already instructed you on the injection site (e.g. abdomen, front of the thigh). Clean the selected injection site with an alcohol-impregnated swab. Firmly pinch the skin and insert the needle at an angle between 45° and 90° with a quick, dart-like motion. Inject the solution subcutaneously as you have been taught. Do not inject directly into a vein. Inject the solution by slowly pushing the syringe plunger. Take your time to ensure the full dose is administered.
  Immediately remove the needle and clean the injection site in a circular motion with an alcohol-impregnated swab.

• Disposal of used materials: after completing the injection, immediately dispose of all used needles and empty vials in the designated sharps container provided. Any unused solution must also be discarded.

If you use more Luveris than you should
The effects of an overdose of Luveris are unknown, but ovarian hyperstimulation syndrome may occur (see section 4). However, this can only happen if hCG is also administered (see “Warnings and precautions” in section 2).

If you forget to use Luveris
Do not use a double dose to make up for a missed dose. Contact your doctor.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Contact your doctor immediately if you experience any of the following side effects.
Your doctor may ask you to stop using Luveris.
Allergic reaction
Allergic reactions such as rash, red skin, hives or swelling of the face accompanied by breathing difficulties can sometimes be severe. This side effect is very rare (may affect up to 1 in 10,000 people).
Ovarian hyperstimulation syndrome (OHSS)

• Lower abdominal pain with nausea or vomiting may be symptoms of ovarian hyperstimulation syndrome (OHSS). The ovaries may have over-responded to treatment and developed large fluid-filled sacs or cysts (see "Ovarian hyperstimulation syndrome (OHSS)" in section 2). This side effect is common (may affect up to 1 in 10 people). If this occurs, your doctor will need to examine you as soon as possible.
• Serious complications related to blood clots (thromboembolic events), usually associated with severe OHSS, occur very rarely. This could cause chest pain, breathing difficulties, stroke or heart attack (see "Blood clotting problems" in section 2).

Other common side effects

• Headache
• Nausea, vomiting, diarrhoea, abdominal discomfort or pain
• Fluid-filled sacs in the ovaries (ovarian cysts), breast tenderness and pelvic pain
• Local reactions at the injection site, such as pain, itching, bruising, swelling or irritation

Ovarian torsion and intra-abdominal bleeding have not been reported during the use of Luveris; however, rare cases have been reported after treatment with human menopausal gonadotropin (hMG), a urinary-derived product also containing LH.
Ectopic pregnancies (embryo implanted outside the uterus) may occur, especially in women with a previous history of tubal disorders.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Luveris

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial, following
Exp. The expiry date refers to the last day of that month.
Do not store above 25 °C. Store in the original packaging to protect the medicine from light.
Do not use this medicine if you notice any visible signs of deterioration, such as changes in the colour of the powder or damage to the container.
The medicine should be administered immediately after reconstitution of the powder.
Do not administer the solution if it contains particles or is not clear.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Luveris contains

• The active substance is lutropin alfa. One vial of powder for injectable solution contains 75 IU (International Units).
• Lutropin alfa is recombinant human luteinizing hormone (r-hLH), produced using recombinant DNA technology.
• The other components of the powder are polysorbate 20, sucrose, monobasic sodium phosphate monohydrate, dibasic sodium phosphate dihydrate, concentrated phosphoric acid, sodium hydroxide, L-methionine and nitrogen.
• The solvent is water for injections.

Description of the appearance of Luveris and contents of the pack

• Luveris is supplied as a powder and solvent for injectable solution.
• Each powder vial contains 75 IU of lutropin alfa and each solvent vial contains 1 mL of water for injections.
• Luveris is available in packs containing 1, 3 or 10 vials of powder with the same number of solvent vials.

Marketing Authorisation Holder
Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The Netherlands

Manufacturer
Merck Serono S.p.A.
Via delle Magnolie 15
70026 Modugno (Bari)
Italy

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu