Label: information for the user

Vehicle for solution

Luvéris 75UI powder and vehicle for injectable solution

Lutropin alfa

Read this label carefully before starting to use this medicationbecause it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribedonlyto you, and you should not give it to others even if they have the same symptomsas you, as it may harm them.
• Ifyou experienceadverse effects, consult your doctor, pharmacist, or nurse, even if they do notappearin this label. See section4.

What is Luveris

Luvris is a medication that contains lutropin alfa, a recombinant Luteinizing Hormone (LH), which is essentially similar to the hormone found naturally in humans, but obtained through biotechnology. It belongs to the family of hormones called gonadotropins, which are involved in the normal control of reproduction.

What is Luveris used for

Luvris is recommended for the treatment of adult women who produce very small amounts of some hormones involved in the natural reproductive cycle. The medication is used in conjunction with another hormone called follicle-stimulating hormone (FSH) to induce the development of follicles, which are the structures of the ovary where ova (eggs) mature. This treatment follows the administration of a single dose of human Chorionic Gonadotropin (hCG), which causes the release of an ovum from the follicle (ovulation).

Do not use Luveris

• If you are allergic to gonadotropins (such as luteinizing hormone, follicle-stimulating hormone, or human chorionic gonadotropin) or any of the other components of this medication (listed in section6).
• If you have ovarian, uterine, or breast cancer.
• If you have been diagnosed with a brain tumor.
• If you have an enlargement of the ovaries or fluid-filled sacs in the ovaries (ovarian cysts) of unknown origin.
• If you have unexplained vaginal bleeding.

Do not use Luveris if you present any of the above factors. If you are unsure, speak with your doctor or pharmacist before using this medication.

Warnings and precautions

Consult your doctor,pharmacist, or nurse before starting to use Luveris.

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

It is recommended that you do not use Luveris if you present a clinical condition that would make a normal pregnancy impossible, such as a condition in which the ovaries do not function correctly due to a disease called primary ovarian insufficiency or malformations of the reproductive organs.

Porphyria

Inform your doctor before starting treatment if you or a family member has porphyria (a disorder that affects the production of heme and can be inherited).

Hyperstimulation syndrome (HSS)

This medication stimulates the ovaries, increasing the risk of developing hyperstimulation syndrome (HSS) or ovarian hyperstimulation syndrome. This condition occurs when your follicles grow excessively and become large cysts. If you experience abdominal pain, rapid weight gain, nausea, vomiting, or difficulty breathing, seek immediate medical attention, as your doctor may advise you to stop using this medication (see section4 under “Serious side effects”).

If you are not ovulating and the recommended dose and treatment schedule are followed, the risk of HSS is lower. Treatment with Luveris rarely leads to severe HSS. This is more likely to occur if you are also taking the medication used to induce final follicular maturation (which contains human chorionic gonadotropin, hCG). See section3 under “How much to use” for more information. If you develop HSS, your doctor may not administer hCG in this treatment cycle and advise you to avoid intercourse or use barrier contraceptives for at least four days.

Your doctor will ensure careful monitoring of your ovarian response, using ultrasound and blood tests, before and during treatment.

Multiple pregnancy

Using Luveris increases the risk of conceiving multiple fetuses (twins, triplets, etc.) compared to natural conception. Multiple pregnancy can lead to complications for you and your babies. You can reduce the risk of multiple pregnancy by using the correct dose of Luveris at the right time. The risk of multiple pregnancy is associated with your age, the quality and number of eggs fertilized or embryos transferred during assisted reproduction techniques.

Spontaneous abortion

Women undergoing assisted reproduction or ovarian stimulation to produce eggs are more likely to experience spontaneous abortion than the general population.

Ectopic pregnancy

Women with a history of fallopian tube disease are at risk of ectopic pregnancy (pregnancy in which the embryo implants outside the uterus), regardless of whether the pregnancy occurs naturally or through fertility treatments.

Blood clotting disorders (thromboembolic events)

Consult your doctor before starting to use Luveris if you or a family member has ever experienced blood clots in the leg or lung, or a heart attack or stroke. You may be at a higher risk of severe blood clots or worsening existing clots when taking Luveris.

Sexual organ tumors

Tumors in the ovaries and other sexual organs, both benign and malignant, have been reported in women who have received various pharmacological treatments for infertility.

Congenital defects

Congenital defects after assisted reproduction may be slightly higher than after natural pregnancies. This may be due to differences related to the parents, such as the mother's age and genetic background, interventions related to assisted reproduction, and multiple pregnancy.

Children and adolescents

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

Other medications and Luveris

Inform your doctor or pharmacist if you are using, have used recentlyormayneed to use anyother medication.

Do not use Luveris mixed with other medications in the same injection, except for recombinant follicle-stimulating hormone (rFSH), if your doctor prescribes it.

Pregnancy and breastfeeding

Do not use Luveris if you are pregnant or breastfeeding.

Consult your doctor or pharmacist before using any medication.

Driving and operating machinery

The influence of Luveris on the ability to drive and operate machinery is negligible or insignificant.

Luveris contains sodium

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

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

Use of this medication

Your doctor will decide on the most appropriate dose and administration schedule for you throughout the treatment.

How much to use

Luveris is usually used daily for a maximum of three weeks, simultaneously with FSH injections.

• The usual initial dose is75UI (1 vial) of Luveris along with 75UI or 150UI of FSH.
• Depending on the response,your doctor may increase the FSH dose, preferably with increases of 37.5 to 75UI every 7‑14days.

Your doctor may decide to extend treatment up to 5 weeks.

When the desired response is obtained, you should administer a single injection of hCG, 24 to 48hours after the last injection of Luveris and FSH. It is recommended that you have intercourse on the same day as the hCG administration, as well as the following day. Alternatively, intrauterine insemination or other medically assisted reproduction procedures may be performed at your doctor's discretion.

If an excessive response is obtained, treatment should be interrupted and hCG should not be administered (see section4 under “Ovarian Hyperstimulation Syndrome (OHSS)”). For the next cycle, your doctor will prescribe a lower dose of FSH than the previous cycle.

Administration form

Luveris should be administered subcutaneously, i.e., by injecting it just below the skin. Each vial is for single use.

If you administer Luveris yourself, read the following instructions carefully:

• Wash your hands. It is essential that your hands and the materials you use are as clean as possible.

• Gather everything you will need. Find a clean place and prepare everything:

• a vial of Luveris,
• a vial of solvent,
• two cotton balls soaked in alcohol,
• a syringe,
• a reconstitution needle to dissolve the powder with the solvent,
• a fine needle for subcutaneous injection,
• a container for sharp objects to safely dispose of glass vials and needles.

• Remove the protective cap from thevial of solvent: Place thereconstitution needle

• Prepare the injection solution: Remove the protective cap from thevial containing the Luveris powder,

• Once the powder has dissolved (which usually occurs immediately), check that the

You can also mix Luveris and follitropin alfa, as an alternative to injecting each product separately. After dissolving the Luveris powder, load the solution into the syringe and inject it back into the vial containing the follitropin alfa powder. Once the powder has dissolved, extract the solution with the syringe. Check if there are any particles, as indicated above, and do not use the solution if it is not clear.

Up to 3vials of powder can be dissolved in 1ml of solvent.

• Change the needle by placing thefine needleand remove any possible air bubbles: If you see any

• Inject the solution immediately: Your doctor or nurse will have indicated where to administer the injection (e.g., abdomen, front of the thigh). Clean the chosen area with an alcohol-soaked cotton ball. Pinch the skin firmly and insert the needle at an angle of 45° to 90°, with a motion similar to that of a dart. Inject under the skin, according to the instructions received. Do not inject directly into a vein. Insert the solution by gently pressing on the plunger. Use as much time as needed to inject the entire solution. Remove the needle immediately and clean the skin with an alcohol-soaked cotton ball, making a circular motion.

• Discard all used material: Once the injection is complete, discard all needles and empty glass vials immediately in the container for sharp objects provided. Any unused portion of the solution should also be discarded.

If you use more Luveris than you should

The effects of a Luveris overdose are unknown; however, there is a possibility of ovarian hyperstimulation syndrome (see section4). However, this will only occur if hCG is administered (see section2 under “Warnings and Precautions”).

If you forgot to use Luveris

Do not use a double dose to compensate for the missed doses. Contact your doctor.

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

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

Severe side effects

Immediately contact your doctor if you notice any of the following side effects. Your doctor may instruct you to stop using Luveris.

Allergic reaction

Allergic reactions such as skin rash, skin redness, blisters, and facial inflammation with difficulty breathing can be severe in some cases. This side effect is very rare (may affect up to 1 in 10,000 people).

Hyperstimulation syndrome of the ovaries (SHO)

• Abdominal pain in the lower region accompanied by nausea or vomiting may be symptoms of hyperstimulation syndrome of the ovaries (SHO). The ovaries may have reacted excessively to treatment and may have formed large fluid-filled bags or cysts (see section2 under “Hyperstimulation syndrome of the ovaries (SHO)”). 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.
• In rare cases, severe blood clotting complications (thromboembolic episodes) may occur, usually with severe SHO. This can cause chest pain, shortness of breath, stroke, or heart attack (see section2 under “Blood clotting problems”).

Other frequent side effects

• Headache
• Nausea, vomiting, diarrhea, abdominal discomfort, or abdominal pain
• Fluid-filled bags in the ovaries (ovarian cysts), chest pain, and pelvic pain
• Local reactions at the injection site, such as pain, itching, hematomas, inflammation, or irritation

No cases of ovarian torsion or abdominal hemorrhage have been reported after treatment with Luveris; however, rare cases have been reported after treatment with human menopausal gonadotropin (hMG), a medication derived from urine, which also contains LH.

Pregnancy may occur outside the uterus (ectopic pregnancy), especially in women with a history of fallopian tube diseases.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, ornurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears on the box and on the vials afterCAD. The expiration date is the last day of the month indicated.

Do not store at a temperature above 25°C. Store in the original packaging to protect it from thelight.

Do not usethis medicationif visible signs of deterioration are observed, such as discoloration of the powder or damage to the container.

The medication must be administered immediately after dissolving the powder.

The solution should not be administered if it contains particles or is not clear.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications thatyouno longer need. In this way, you will help protect the environment.

Composition of Luveris

• The active principle is lutropin alfa. A vial of injectable powder contains 75UI (International Units).
• Lutropin alfa is human recombinant Luteinizing Hormone, r-hLH, produced by recombinant DNA technology.
• The other components of the powder are polysorbate 20, sucrose, monosodium phosphate monohydrate, disodium phosphate dihydrate, concentrated phosphoric acid, sodium hydroxide, L‑methionine and nitrogen.
• The solvent is water for injectable preparations.

Appearance of the product and contents of the packaging

• Luveris is presented as a powder and solvent for injectable solution.
• Each vial of powder contains 75UI of lutropin alfa and each vial of solvent contains 1ml of water for injectable preparations.
• Luveris is presented in boxes containing 1, 3 or 10vials of powder along with the same number of vials of solvent.

Holder of the marketing authorization

Merck Europe B.V.

Gustav Mahlerplein 102

1082 MA Amsterdam

Netherlands

Responsible for manufacturing

Merck Serono S.p.A.

Via delle Magnolie 15

70026 Modugno (Bari)

Italy

Last review date ofthis leaflet:06/2022

Detailed information about this medicine is available on the European Medicines Agency website:http://www.ema.europa.eu.