SUMMARY CMI

LUVERIS^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using LUVERIS?

LUVERIS contains the active ingredient lutropin alfa (rch). LUVERIS is used for the stimulation of follicular development in women with severe LH and FSH deficiency.

For more information, see Section 1. Why am I using LUVERIS? in the full CMI.

2. What should I know before I use LUVERIS?

Do not use if you have ever had an allergic reaction to LUVERIS or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, are pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use LUVERIS? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with LUVERIS and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use LUVERIS?

• It is usually recommended that your treatment with LUVERIS starts at 75 IU daily along with 75 IU or 150 IU of follitropin alfa. Your doctor may adjust your dose depending on your individual response to treatment.
• LUVERIS is given as a course of daily subcutaneous (under the skin) injection at the same time as another medicine, follitropin alfa.
• Follow all directions given to you by your doctor or pharmacist carefully, including the Instructions for Use provided in the pack.

More instructions can be found in Section 4. How do I use LUVERIS? in the full CMI.

5. What should I know while using LUVERIS?

For more information, see Section 5. What should I know while using LUVERIS? in the full CMI.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention. Most common side effects include injection site reactions, headache, nausea, vomiting, diarrhoea, abdominal pain or discomfort. Tell your doctor if you experience any side effects.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

LUVERIS^®

Active ingredient: lutropin alfa (rch)

Consumer Medicine Information (CMI)

This leaflet provides important information about using LUVERIS. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using LUVERIS.

Where to find information in this leaflet:

1. Why am I using LUVERIS?
2. What should I know before I use LUVERIS?
3. What if I am taking other medicines?
4. How do I use LUVERIS?
5. What should I know while using LUVERIS?
6. Are there any side effects?
7. Product details

1. Why am I using LUVERIS?

LUVERIS contains the active ingredient lutropin alfa (rch), a recombinant luteinising hormone (LH). This hormone is essentially similar to the hormone found naturally in human, but it is made by means of biotechnology. LUVERIS belongs to the family of hormones called gonadotrophins, which are involved in the normal control of reproduction.

LUVERIS is used for the stimulation of follicular development in women with severe LH and FSH deficiency.

2. What should I know before I use LUVERIS?

Warnings

Do not use LUVERIS if:

• you are allergic to lutropin alfa (rch), or any of the ingredients listed at the end of this leaflet.
  Always check the ingredients to make sure you can use this medicine.
• you are pregnant or breastfeeding
• you have an unexplained ovarian cyst or ovarian enlargement
• you have unexplained vaginal or uterine bleeding
• you have cancer of the ovaries, uterus or breasts
• you have tumours of the pituitary gland or hypothalamus

Check with your doctor if you:

• take any medicines for any other condition
• have or have had any other medical conditions, such as:
  - kidney disease
  - liver disease
  - you or your family have increased risk factors for developing blood clots, e.g. stroke, heart attacks
  - porphyria or a family history of porphyria

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant while using LUVERIS.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Compared to natural conception, the frequency of multiple pregnancies and births is increased in patients receiving this treatment. Your doctor will monitor your ovarian response to minimise the chance of multiple pregnancies.

There may be a slightly increased risk of birth defects in women using assisted reproductive technologies. This may be due to increased maternal age, genetic factors, multiple pregnancies or the procedures.

Talk to your doctor about any concerns you may have before undergoing treatment with LUVERIS.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect LUVERIS.

4. How do I use LUVERIS?

How much to use

• It is recommended that your treatment with LUVERIS starts with 75 IU daily, together with 75 IU to 150 IU of follitropin alfa.
• Your treatment should be tailored according to your individual response. Your doctor will tell you how much LUVERIS to use.

When to use LUVERIS

• Your doctor will tell you when to take LUVERIS.
• LUVERIS is given as a course of daily injections. You should have your injection at the same time each day.

How to use LUVERIS

• LUVERIS should be injected daily under the skin (subcutaneous) in the lower abdominal area or thigh.
• Each vial is for single use only.
• The injection site should be changed daily to lessen possible injection site reactions.
• Before using LUVERIS, your doctor or nurse can teach you the injection technique.
• Read the Instructions for Use carefully, as follows:

1. Wash your hands

It is important that your hands and the items you use be as clean as possible.

2. Assemble everything you need

Please note that alcohol swabs, syringes and needles are not provided in the package. Find a clean area and lay out everything:

• Two alcohol swabs
• One solvent vial
• One vial containing LUVERIS
• One syringe
• One big needle for reconstitution
• A fine-bore needle for subcutaneous injection

3. Draw up the solvent

Remove the protective cap from the solvent vial. Attach the needle for reconstitution (the bigger needle) to the syringe and draw up some air into the syringe by pulling the plunger to approximately the 1 mL mark. Then insert the needle into the vial, push the plunger to expel the air, turn the vial upside down and gently draw up all the solvent.

4. Prepare the injection solution

Remove the protective cap from LUVERIS powder vial, slowly inject the solvent in the syringe into the vial of LUVERIS.

Swirl gently without removing the syringe. Do not shake.

The powder will dissolve into a clear solution immediately. Do not use the solution if it is not clear.

Turn the vial upside down, gently draw the solution back into the syringe

5. Injection

Change the needle for the fine-bore needle and remove any air bubbles: If you see air bubbles in the syringe, hold the syringe with the needle pointing upwards and gently flick the syringe until all the air collects at the top.

Gently push the plunger until the air bubbles are gone.

Immediately inject the solution. Your doctor or nurse will tell you where to inject (e.g. tummy, front of thigh).

Wipe the chosen area with an alcohol swab. Firmly pinch the skin together and insert the needle at a 45° to 90° angle using a dart-like motion. Inject under the skin, as you were taught. Do not inject directly into a vein.

Inject the solution by pushing gently on the plunger. Take as much time as you need to inject all the solution.

Immediately withdraw the needle and clean the skin with an alcohol swab or cotton pad.

6. Dispose of all used items

Once you have finished your injection, immediately discard all needles and empty glass containers in a sharps container. Any unused solution must be discarded.

If you forget to use LUVERIS

LUVERIS should be used regularly at the same time each day. If you miss your dose at the usual time, contact your doctor or nurse immediately for advice.

If you use too much LUVERIS

If you think that you have used too much LUVERIS, you may need urgent medical attention.

You should immediately:

• phone the Poisons Information Centre
  (by calling 13 11 26), or
• contact your doctor, or
• go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using LUVERIS?

Things you should do

See your doctor regularly. Your doctor will monitor you closely throughout your treatment.

Tell your doctor immediately if you become pregnant while using LUVERIS.

If you plan to have surgery, tell your doctor or dentist that you are using LUVERIS.

Remind any doctor, dentist or pharmacist you visit that you are using LUVERIS.

Things you should not do

• Do not stop using this medicine suddenly without telling your doctor.
• Do not change the dose unless your doctor tells you to.
• Do not give this medicine to anyone else even if they have the same condition as you.

Ovarian Hyperstimulation Syndrome (OHSS)

Treatment with LUVERIS may increase your risk of developing a condition called ovarian hyperstimulation syndrome (OHSS). This is when the ovaries overact to the hormonal treatment and become larger.

The most common symptom is lower abdominal pain. Your doctor will monitor your treatment using ultrasound and blood tests to help determine if you are likely to develop OHSS. If necessary, your doctor will delay or cancel your LUVERIS injection. You may also be advised to refrain from sexual intercourse or use barrier methods until the end of the cycle if this occurs.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how LUVERIS affects you.

Looking after your medicine

• Prior to reconstitution keep the vials in a dry cool place where the temperature is below 25°C.
• Store in the original package in order to protect from light.
• Once the LUVERIS powder is dissolved with the solvent provided, it should be injected immediately. This is due to the solvent not containing any preservative. Any solution that is left over must be discarded.
• Do not use the dissolved solution if it contains particles or is not clear.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

• in the bathroom or near a sink, or
• in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Side effects

Serious side effects

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems (for Australia) or at pophealth.my.site.com/carmreportnz/s/ (for New Zealand). By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What LUVERIS contains

Do not take this medicine if you are allergic to any of these ingredients.

What LUVERIS looks like

LUVERIS is a sterile white powder in a vial.

Each vial of LUVERIS contains 75 IU lutropin alfa.

LUVERIS is available in packs of 1 vial. Each pack also contains a vial of 1 mL water for injections.

Australian Registration Number: AUST R 95042

Who distributes LUVERIS

Luveris is supplied in Australia by:

Merck Healthcare Pty Ltd
Suite 1, Level 1, Building B
11 Talavera Road
Macquarie Park NSW 2113
For enquiries call: 1800 633 463
E-mail: [email protected]

Luveris is supplied in New Zealand by:

Healthcare Logistics
58 Richard Pearse Drive
Airport Oaks, Auckland
For enquiries call: 0800 426 252
E-mail: [email protected]

This leaflet was prepared in June 2024.

Published by MIMS August 2024

1 Name of Medicine

Lutropin alfa (rch).

2 Qualitative and Quantitative Composition

Lutropin alfa is a recombinant human luteinising hormone (r-hLH) derived from a Chinese Hamster Ovary cell line that has been modified by the addition of human genes encoding the LH α- and β-chains.
Each vial of Luveris contains 75 IU of lutropin alfa as lyophilised powder.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection in vial(s).
Luveris is available as a sterile, lyophilised powder.
It is intended for co-administration with follitropin alfa as subcutaneous injection after reconstitution with sterile water for injections.

4 Clinical Particulars

4.1 Therapeutic Indications

Luveris in association with a recombinant follicle stimulating hormone (FSH) preparation is indicated for the stimulation of follicular development in women with severe LH and FSH deficiency.

4.2 Dose and Method of Administration

Treatment with Luveris should be initiated under the supervision of a physician experienced in the treatment of fertility problems. Self-administration of Luveris should only be performed by patients who are well-motivated, adequately trained and with access to expert advice.
In LH and FSH deficient women, the objective of Luveris therapy, in association with FSH is to promote follicular development followed by final maturation after the administration of human chorionic gonadotrophin (hCG). Luveris should be given as a course of daily injections concomitantly with FSH. If the patient is amenorrhoeic and has low endogenous oestrogen secretion, treatment can commence at any time. Nevertheless, the possibility of pregnancy should be first excluded by clinical or other means.
All clinical experience to date with Luveris in this indication has been gained with concomitant daily administration of follitropin alfa.
Luveris is intended for daily subcutaneous administration. The powder should be reconstituted, immediately prior to use, with the solvent provided.
The majority of the women with very low LH levels (< 1.2 IU/L as used in clinical studies, but this may vary from laboratory to laboratory) will have a poor ovarian response to r-hFSH alone. However, some women may have adequate follicular response. Clinicians will need to decide on a case by case basis whether to commence ovulation induction with r-hFSH alone or in combination with Luveris.
The efficacy studies have suggested that the minimum effective dose of Luveris is 37.5 IU. However, dose titration is recommended according to individual patient response.
A recommended regimen commences at 75 IU of Luveris daily with 75-150 IU FSH. Treatment should be tailored to the individual patient's response as assessed by measuring: (i) follicle size by ultrasound and (ii) oestrogen response.
Clinical studies have employed doses of up to 225 IU of lutropin alfa and 150 IU follitropin alfa per day to induce follicular development. If a patient fails to respond after 3 weeks of treatment, the cycle should be abandoned and the patient should recommence treatment with a higher starting dose of follitropin alfa and/or Luveris than in the abandoned cycle.
If there is insufficient follicular growth, it is reasonable to increase the FSH dose, but if there is good follicular development with a low oestradiol level, this suggests that more LH may be required.
In clinical trials, Luveris has been associated with higher oestradiol levels than follitropin alfa alone. If an FSH dose increase is deemed appropriate, dose adaptation should preferably be at 7 to 14 day intervals and preferably with 37.5 to 75 IU increments.
When an optimal response is obtained, a single injection of 250 microgram of recombinant hCG (r-hCG) or 5,000 IU to 10,000 IU hCG should be administered 24 to 48 hours after the last Luveris and FSH injections. The patient is recommended to have coitus on the day of, and on the day following, hCG administration. Alternatively, intrauterine insemination (IUI) or another medically assisted reproduction procedure may be performed based on the physician's judgement of the clinical case.
Luteal phase support should be considered since lack of endogenous gonadotrophins after ovulation may lead to premature failure of the corpus luteum.
If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment should recommence in the next cycle at an FSH dosage lower than that of the previous cycle.
Product is for single use in one patient only. Discard any residue.

4.3 Contraindications

Luveris is contraindicated in patients with:
hypersensitivity to gonadotrophins or to any of the excipients;
ovarian, uterine or mammary carcinoma;
active, untreated tumours of the hypothalamus or pituitary gland;
ovarian enlargement or cyst of unknown aetiology;
gynaecological haemorrhages of unknown origin;
pregnancy and lactation.

4.4 Special Warnings and Precautions for Use

Before starting treatment, the couple's infertility should be assessed as appropriate and putative contraindications for pregnancy evaluated. It is recommended that Luveris is not used in conditions where an effective response is usually not expected, such as primary ovarian failure, malformation of the sexual organs or fibroid tumours of the uterus that are incompatible with pregnancy. In addition, patients should be evaluated for hypothyroidism, adrenocortical deficiency and hyperprolactinemia, and appropriate specific treatment given.

Ovarian hyperstimulation syndrome (OHSS).

Multiple pregnancy.

Pregnancy loss.

Thromboembolic events.

Porphyria.

Congenital anomalies.

Use in hepatic or renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Luveris should not be administered as a mixture with other medicines in the same injection, except follitropin alfa, for which studies have shown that co-administration does not significantly alter the activity, stability, pharmacokinetic nor pharmacodynamic properties of the active substances.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed.

4.8 Adverse Effects (Undesirable Effects)

Luveris is used for the stimulation of follicular development in association with follitropin alfa. In this context, undesirable effects may be due to either or both of the substances used, or to their pharmacodynamic consequences.
There is considerable post-marketing safety experience with human luteinising hormone (hLH) containing products of urinary origin. The safety profile of Luveris is expected to be very similar to that of urine derived hLH, with the exception of hypersensitivity reactions and application site disorders.
In clinical trials, a maximal score of all mild and moderate injection site reactions (bruising, pain, redness, itching or swelling) was reported in 12.7% (mild) and 2.7% (moderate) of the 2282 injections in 271 treatment cycles, respectively. Among the 170 patients treated, only 2 patients (1.2%) reported a severe injection site reaction.
OHSS was observed in 3.9% of treatment cycles with Luveris. Six serious OHSS reports (2.3%) occurred in 259 treatment cycles.
Ovarian cysts and enlargement are common. Complications including adnexal torsion and haemoperitoneum have been reported rarely with human menopausal gonadotrophin therapy.
Ectopic pregnancy may also occur, especially in women with a history of prior tubal disease.
The following definitions apply to the frequency terminology used hereafter: Very Common ≥ 1/10; Common ≥ 1/100 to < 1/10; Uncommon ≥ 1/1,000 to < 1/100; Rare ≥ 1/10,000 to < 1/1,000; Very Rare < 1/10,000.

General disorders and administration site condition.

Nervous system disorders.

Gastrointestinal disorders.

Reproductive system and breast disorders.

Vascular disorders.

Immune system disorders.

Reporting suspected adverse effects.

4.9 Overdose

The effects of overdosage of Luveris are unknown; nevertheless, there is a possibility that OHSS may occur which is further described in Section 4.4 Special Warnings and Precautions for Use.
Single doses of up to 40,000 IU of Luveris have been administered to healthy female volunteers without serious adverse events and were well tolerated.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia) or 0800 764 766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

Study 6253.

Study 21008.

5.2 Pharmacokinetic Properties

The pharmacokinetics of lutropin alfa have been studied in pituitary desensitised female volunteers from 75 IU up to 40,000 IU.
The pharmacokinetic profile of lutropin alfa is similar to that of urinary-derived hLH. Following intravenous administration, lutropin alfa is rapidly distributed with an initial half-life of approximately one hour and eliminated from the body with a terminal half-life of about 10-12 hours. The steady state volume of distribution is around 10-14 L. Lutropin alfa shows linear pharmacokinetics, as assessed by AUC, which is directly proportional to the dose administered. Total clearance is around 2 L/h, and less than 5% of the dose is excreted in the urine. The mean residence time is approximately 5 hours.
Following subcutaneous administration, the absolute bioavailability is approximately 60%; the terminal half-life is slightly prolonged. The lutropin alfa pharmacokinetics following single and repeated administration of Luveris are comparable and the accumulation ratio of lutropin alfa minimal. There is no pharmacokinetic interaction with follitropin alfa when administered simultaneously.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sucrose, dibasic sodium phosphate dihydrate, methionine, monobasic sodium phosphate monohydrate, polysorbate 20, sodium hydroxide, phosphoric acid and sodium hydroxide for pH adjustment.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

Information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG) in Australia or on Medsafe Product Detail in New Zealand. The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

The lyophilised product must be stored below 25°C. Protect from light.
The reconstituted solution must be injected immediately as it contains no antimicrobial agent.

6.5 Nature and Contents of Container

Luveris is supplied in packs of 1, 3 or 10 vials* with the corresponding number of vials containing 1 mL water for injections.
* Not all pack sizes are available.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription Only Medicine).

Summary Table of Changes