Luveris 450 IU solution for injection

What Luveris is

Luveris is a medicine containing lutropin alfa, a recombinant Luteinising Hormone (LH) which is essentially similar to the hormone found naturally in humans, but is made by means of biotechnology. It belongs to the family of hormones called gonadotropins, which are involved in the normal control of reproduction.

What Luveris is used for

Luveris is recommended for the treatment of adult women who have been shown to produce very low levels of some of the hormones involved in the natural reproductive cycle. The medicine is used together with another hormone called Follicle Stimulating Hormone (FSH) to bring about the development of follicles which are in the ovary, the structures maturing the eggs (ova). It is followed by treatment with a single dose of human chorionic gonadotropin (hCG), which leads to the release of an egg from the follicle (ovulation).

Do not use Luveris
- If you are allergic (hypersensitive) to gonadotropins (such as luteinising hormone, follicle stimulating hormone or human chorionic gonadotropin), or any of the other ingredients of Luveris.
- If you have cancer of ovaries, uterus or breast.
- If you have had a brain tumour diagnosed.
- If you have ovarian enlargement or sacs of fluid within the ovaries (ovarian cyst) of unknown origin.
- If you have unexplained vaginal bleeding.

Do not use Luveris if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before using this medicine.

Take special care with Luveris

You and your partner's fertility should be evaluated before the treatment is started.

It is recommended not to use Luveris if you have any condition that usually makes a normal pregnancy impossible, such as ovaries that do not work because of a condition called primary ovarian failure, or malformations of sexual organs.

Porphyria
Tell your doctor before you start treatment, if you or any member of your family have porphyria (an inability to break down porphyrins that may be passed on from parents to children).

Ovarian Hyper-Stimulation Syndrome (OHSS)
This medicine increases your risk of developing a condition called ovarian hyperstimulation syndrome (OHSS). This is when your follicles develop too much and become large cysts. If you get lower abdominal pain, gain any weight rapidly, feel sick or are vomiting or if you have difficulty in breathing, talk to your doctor straight away who might ask you to stop using this medicine (see section 4).

In case you are not ovulating, and if the recommended dose and schedule of administration are adhered to, the occurrence of OHSS is less likely. Luveris treatment seldom causes severe OHSS unless the medicine that is used for final follicular maturation (containing human Chorionic Gonadotropin, hCG) is administered. If you are developing OHSS your doctor may not give you any hCG in this treatment cycle and you may be told not to have sex or to use a barrier contraceptive method for at least four days.

Your doctor will ensure, careful monitoring of ovarian response, based on ultrasound and blood sampling before and during the course of treatment.

Multiple pregnancyWhen using Luveris, you have a higher risk of being pregnant with more than one child at the same time (?multiple pregnancy?, mostly twins), than if you conceived naturally. Multiple pregnancy may lead to medical complications for you and your babies. You can reduce the risk of multiple pregnancy by using the right dose of Luveris at the right times. When undergoing assisted reproductive technology the risk of having a multiple pregnancy is related to your age, the quality and the number of fertilised eggs or embryos placed inside you.

Miscarriage
When undergoing assisted reproductive technology or stimulation of your ovaries to produce eggs, you are more likely to have a miscarriage than the average woman.

Ectopic pregnancy
Women with a history of tubal disease are at risk of ectopic pregnancy (pregnancy where the embryo is implanted outside the womb), whether the pregnancy is obtained by spontaneous conception or with fertility treatments.

Blood clotting problems (thromboembolic events)
If you had in the past or recently blood clots in the leg or in the lung, or a heart attack or stroke, or if those happened in your family, then you might have a higher risk that these problems occur or become worse with Luveris treatment.

Tumours of sexual organs
There have been reports of tumours of the ovary and other reproductive organs, both benign and malignant, in women who have undergone multiple drug regimens for infertility treatment.

Birth defects
Birth defects after Assisted Reproductive Technology (ART) may be slightly higher than after spontaneous conceptions. This could be due to differences in parental factors like maternal age,

genetics, as well as the ART procedures and multiple pregnancies.

Children
Luveris is not for use in children.

Using other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

Luveris is not indicated if you are pregnant or breast-feeding.
Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

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

Important information about some of the ingredients of Luveris

Luveris contains less than 1 mmol sodium (23 mg) per dose of 75 IU, i.e. it is essentially ?sodium free?.

Always use Luveris exactly as your doctor has told you. You should check with your doctor if you are not sure.

Using this medicine

Your doctor will decide on the dose and schedule of administration, which are most appropriate for you during this course of treatment.

How much to use

Luveris is usually used every day for up to three weeks simultaneously with injections of FSH.

The usual starting doseis 75 IU of Luveris together with 75 IU or 150 IU of FSH. According to your response, your doctor may increase your dose of FSH by preferably 37.5-75 IU at 7 to 14-day intervals.
Your physician may decide to extend your treatment up to 5 weeks.

When the desired response has been obtained, a single injection of hCG is given 24 to 48 hours after the last injections of Luveris and FSH. You are recommended to have sexual intercourse on the day of, and the day following, administration of the hCG. Alternatively, Intrauterine Insemination (IUI) may be performed.

If an excessive response is obtained, treatment should be stopped and hCG withheld (see section headed ?Possible Side Effects?). For the following cycle, your doctor will prescribe FSH at a lower dose than that of the previous cycle.

Luveris is intended for subcutaneous use which means it is given by injection under the skin. The cartridge is intended for multiple injections (6 doses).

Luveris cartridge is to be used with the autoinjector device provided separately.

If you administer Luveris to yourself:

- Wash your hands. It is important that your hands and the items you use be as clean as possible. - Wipe the area chosen for the injection with an alcohol swab.
- For injection, please read carefully the autoinjector device Instructions for Use provided with the device.

Do not inject directly into a vein. After the injection clean the skin with an alcohol swab using a circular motion. Once you have finished your injection, immediately discard the needle.

If you use more Luveris than you should

The effects of an overdose of Luveris are unknown, nevertheless there is a possibility that ovarian hyperstimulation syndrome may occur, which is further described in ?Possible side effects'. However this will only occur if hCG is administered (see section headed ?Take special care with Luveris?).

If you forget to use Luveris

Do not use a double dose to make up for a forgotten dose. Please contact your doctor.

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

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

The frequency of possible side effects listed below is defined using the following convention very common affects more than 1 user in 10 common affects 1 to 10 users in 100 uncommon affects 1 to 10 users in 1,000 rare affects 1 to 10 users in 10,000 very rare affects less than 1 user in 10,000 not known frequency cannot be estimated from the available data

Serious side effects

- Allergic reactions such as rash, red skin, hives, swelling of your face with difficulty breathing can sometimes be serious. This side effect is very rare.
- Lower abdominal pain together with nausea or vomiting may be the symptoms of Ovarian Hyper-Stimulation Syndrome (OHSS). This may indicate that the ovaries over-reacted to the treatment and that large ovarian cysts developed (see also section 2 ?Take special care with Luveris?). This side effect is common.
- Serious blood clotting complications (thromboembolic events) usually with severe OHSS may be found very rarely. This could cause chest pain, breathlessness, stroke or heart attack (see also section 2 ?Take special care with Luveris?).

Other common side effects Headache Nausea, vomiting, diarrhoea, abdominal discomfort or abdominal pain Ovarian cysts, breast pain and pelvic pain. Local reactions at the injection site, such as pain, redness or swelling

Torsion of the ovary and bleeding into the abdomen have not been reported with Luveris, however, there have been rare cases reported following treatment with human menopausal gonadotropin (hMG), a urine-derived medication also containing LH.

Ectopic pregnancy (embryo implanted outside the womb) may occur especially in women with a history of prior tubal disease.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Luveris after the expiry date, which is stated on the cartridge after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2ºC ? 8ºC). Do not freeze.
Store in the original package in order to protect from light.
After first use do not remove the cartridge from the autoinjector device.
Once opened, the cartridge with the autoinjector must be stored for a maximum of 28 days in a refrigerator.

Do not use Luveris if you notice any visible signs of deterioration.
The solution should not be administered if it contains particles or is not clear.

Any unused solution must be discarded not later than 28 days after first opening.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Luveris contains

The active substance is lutropin alfa .
Lutropin alfa is recombinant human luteinising hormone, r-hLH, produced by recombinant DNA technology. \

Each cartridge of Luveris contains 450 IU of lutropin alfa in 0.72 ml water for injections that allows delivering six doses of 75 IU of lutropin alfa.

The other ingredients are L-arginine HCl, disodium phosphate dihydrate, sodium dihydrogen phosphate monohydrate, sodium hydroxide, phosphoric acid, polysorbate 20, L-methionine, phenol and water for injections.

What Luveris looks like and contents of the pack

Luveris 450 IU/0.72 ml is presented as a solution for injection in a cartridge.

It is supplied in packs of 1 cartridge containing 6 doses.

An appropriate autoinjector device is supplied separately.
The solution is clear and colourless.

Marketing Authorisation Holder

Merck Serono Europe Limited
56 Marsh Wall
London E14 9TP
United Kingdom

Manufacturer

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

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

BelgiëBelgiqueBelgien MERCK NVSA Brusselsesteenweg 288 B-3090 Overijse TélTel 32-2-686 07 11 LuxembourgLuxemburg MERCK NVSA Brusselsesteenweg 288 B-3090 Overijse, BelgiqueBelgien TélTel 32-2-686 07 11

Magyarország Merck Kft. Bocskai út 134-146. H-1113 Budapest Tel 36-1-463-8100 . . 83 1582 Te 359 28075 111

eská republika Merck spol. s r.o. Na Hrebenech II. 171810 CZ-140 00 Praha 4 Tel. 420 272084 211 Malta Cherubino Ltd Delf Building Sliema Road MT-GZR 06 Gzira Malta Tel 356-21-3432701234

Danmark Merck AS Strandvejen 102 B, 4th DK-2900 Hellerup Tlf 45 35253550 Nederland Merck BV Tupolevlaan 41-61 NL-1119 NW Schiphol-Rijk Tel 31-20-6582800

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Eesti Merck Serono OÜ Tornimäe 7 - 132 EE-10145, Tallinn Tel 372 682 5882 Österreich Merck GesmbH. Zimbagasse 5 A-1147 Wien Tel 43 1 57600-0

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Slovenija MERCK d.o.o. Dunajska cesta 119 SI-1000 Ljubljana Tel 386 1 560 3 800 Ireland Merck Serono Ltd Bedfont Cross, Stanwell Road Feltham, Middlesex TW14 8NX United Kingdom Tel 44-20 8818 7200

Ísland Icepharma hf Lynghálsi 13 IS-110 Reykjavík Tel 354 540 8000 Slovenská republika Merck spol. s r.o. Tuhovská 3 SK-831 06 Bratislava Tel 421 2 49 267 111

Italia Merck Serono S.p.A. Via Casilina 125 I-00176 Roma Tel 39-06-70 38 41 SuomiFinland Merck Oy Pihatörmä 1 C FIN-02240 Espoo PuhTel 358-9-8678 700

. . ef 35, CY-2234 ats, 357-22-490305 Sverige Merck AB Box 3033 169 03 Solna Tel 46-8-562 445 00

Latvija Merck Serono SIA Duntes iela 23A LV-1005, Rga Tel 371 67152500 United Kingdom Merck Serono Ltd Bedfont Cross, Stanwell Road Feltham, Middlesex TW14 8NX UK Tel 44-20 8818 7200

Lietuva
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LT-44151 Kaunas
Tel: +370 37320603

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