SUMMARY CMI

REKOVELLE^®

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 REKOVELLE?

REKOVELLE is used in the treatment of infertility (reproduction related conditions) in women. It contains the active ingredient follitropin delta, which is a recombinant form of human follicle-stimulating hormone (FSH).

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

2. What should I know before I use REKOVELLE?

Do not use REKOVELLE if you have ever had an allergic reaction to follitropin delta, or to any of the ingredients listed at the end of the CMI (see Section 7. Product details in the full CMI).

There are several circumstances in which a person should not use this medicine or may need to use it with caution. It is important to understand if any of these apply to you before using REKOVELLE.

Talk to your doctor if you have any other medical conditions or take any other medicines.

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

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.

Some medicines may interfere with REKOVELLE and affect how it works. For more information, see Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use REKOVELLE?

• You should only use REKOVELLE under the supervision of a doctor experienced in the treatment of infertility.
• Always use this medicine exactly as your doctor has told you. You should check with your doctor if you are unsure. Your doctor will determine your dose of REKOVELLE depending on your condition.
• Before using REKOVELLE, you must be educated on how to use the injection pen and how to perform injections. Your first injection must be supervised by a trained healthcare practitioner.

More instructions can be found in Section 4. How do I use REKOVELLE? in the full CMI and in the ‘Instructions for Use’ leaflet inside the carton.

5. What should I know while using REKOVELLE?

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

6. Are there any side effects?

All medicines can have side effects. Most of them are minor and temporary but some may need medical attention.

Tell your doctor if you experience any side effects.

Pain and/or swelling in the abdomen or pelvic region, nausea, vomiting, diarrhoea, weight gain, having difficulty breathing and/or reduced urination may be a sign of too much activity in the ovaries and may require urgent medical attention in hospital. For more information see Section 6. Are there any side effects? in the full CMI.

FULL CMI

REKOVELLE^® Solution for injection in a pre-filled multidose pen

Active ingredient: follitropin delta

Consumer Medicine Information (CMI)

This leaflet provides important information about using REKOVELLE. 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 REKOVELLE.

Where to find information in this leaflet:

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

1. Why am I using REKOVELLE?

REKOVELLE is used in the treatment of infertility (reproduction related conditions) in women. It belongs to a class of medicines called gonadotrophins.

REKOVELLE contains the active ingredient follitropin delta, which is a recombinant form of human follicle-stimulating hormone (FSH).

REKOVELLE is used to stimulate the ovaries to grow and develop egg sacs (‘follicles’), from which eggs are collected and fertilised in the laboratory.

REKOVELLE is used to stimulate the follicles in women undergoing Assisted Reproductive Technology (ART) procedures to help them become pregnant. ART procedures include IVF/ET (in vitro fertilisation/embryo transfer), and ICSI (intracyctoplasmic sperm injection).

2. What should I know before I use REKOVELLE?

Warnings

Do not use REKOVELLE if:

• you are allergic to follitropin delta, 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 a cancer of the uterus (womb), ovaries, or breasts
• you have a tumour of the pituitary gland or hypothalamus
• you have enlarged ovaries or cysts on your ovaries not caused by polycystic ovarian syndrome (PCOS)
• you have had bleeding from the vagina where the cause is not known
• your ovaries have failed
• you have malformations of the sexual organs, which make a normal pregnancy impossible
• you have fibroids, or tumours, of the uterus (womb) which make a normal pregnancy impossible.

Do not use the REKOVELLE pre-filled pen if:

• the expiry date printed on the pack has passed
• the solution contains particles
• the solution does not look clear.

Tell your doctor if you:

• have or have had any other medical conditions, especially the following:
  - thyroid problems
  - high prolactin levels in the blood
  - blood clots, a history of blood clots, or any condition that puts you at risk of blood clots
  - polycystic ovarian syndrome (PCOS)
  - ovarian hyperstimulation syndrome (OHSS)
  - fallopian tube disease
• take any medicines for any other condition.

Your doctor will assess you and your partner's fertility. This may include tests for other medical conditions, including medical conditions which may interfere with your ability to become pregnant. If necessary, other medical conditions may be treated before starting infertility treatments including the use of REKOVELLE.

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

Do not use REKOVELLE if you are pregnant or breastfeeding.

It may affect your developing baby if you use it during pregnancy. Talk to your doctor immediately if you become pregnant while using REKOVELLE.

Pregnancy risks

• The risk of a pregnancy outside of the womb (ectopic pregnancy) may be higher after assisted reproduction than if you conceive naturally. If you have a history of tubal disease, you have an increased risk of ectopic pregnancy.
• Compared to natural conception, the frequency of pregnancy loss is higher in patients undergoing fertility treatments.
• Multiple pregnancy, more than one baby at a time, carries greater risks for mothers and babies. In patients undergoing ART procedures, the risk of multiple pregnancy is related to the number of embryos replaced, their quality and your age. Your doctor will monitor your response to treatment 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.

Some women who have been given multiple medicines for infertility treatment have developed tumours in the ovaries and other reproductive organs. It is not yet known if treatment with hormones like REKOVELLE causes these problems.

Ovarian hyperstimulation syndrome (OHSS)

Some people have an exaggerated response to hormones used in ART, including REKOVELLE. This may lead to ovarian hyperstimulation syndrome (OHSS). This is when your follicles develop too much causing your ovaries to swell and become painful.

Talk to your doctor if you have:

• abdominal pain, discomfort or swelling
• nausea
• vomiting
• diarrhoea
• weight gain
• difficulty in breathing
• decreased urination.

Blood clots

Tell your doctor if you or a family member have or have had blood clots or signs of blood clots (e.g. pain, warmth, redness, numbness or tingling in the arm or leg).

Blood clots are more likely to form inside your blood vessels when you are pregnant. This is more likely if you have had treatment to help you become pregnant and:

• you are overweight (BMI > 30 kg/m2)
• you have a condition that increases your risk of having blood clots ‘thrombophilia’
• you or someone in your family (blood relative) has had blood clots.

Twisting of ovaries

Tell your doctor immediately if you experience a sudden pain in your lower abdomen, followed by nausea and vomiting during treatment with REKOVELLE.

There have been reports of twisting of ovaries (ovarian torsion) following assisted reproductive technology treatment. If untreated, twisting of the ovary could cut off the blood flow and damage the ovary.

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.

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

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

4. How do I use REKOVELLE?

Treatment with REKOVELLE should be started under the supervision of a specialist doctor experienced in the treatment of infertility.

How much to use

Always use this medicine exactly as your doctor has told you. You should check with your doctor if you are unsure.

Your dose of REKOVELLE and length of treatment will be determined by your doctor depending on your condition. Your dose of REKOVELLE for the first cycle will be determined for you depending on your weight and your fertility as measured by a diagnostic test.

Your REKOVELLE dose is intended to be fixed for the treatment cycle with no adjustments to increase or decrease your daily dose. Your doctor may adjust your dose for any subsequent treatment cycle depending on your response to the last treatment cycle with REKOVELLE.

Follow the instructions provided and use REKOVELLE until your doctor tells you to stop.

When to use REKOVELLE

• Your doctor will advise you to start REKOVELLE 2 or 3 days after the start of your menstrual bleeding.
• You will need to inject REKOVELLE once a day.
• Your doctor will monitor you with ultrasound alone or may also use blood tests to check when enough follicles are present.
• Usually enough follicles have developed, on average, 9 days after starting treatment however this can range from 5 to 20 days.
• If enough follicles have developed, you will be given another medicine to stimulate the final maturation of the eggs in the follicles prior to collection and fertilisation.
• Your doctor will monitor the effect of REKOVELLE treatment. If you have responded too strongly to REKOVELLE, your doctor may advise you to stop treatment with REKOVELLE and not give you the medicine to stimulate the final maturation of the eggs. In this case, you will be instructed to use a barrier method of contraception (e.g. condom) or not have sexual intercourse until your next period has started.

How to inject REKOVELLE

• REKOVELLE is to be injected under the skin of your abdomen using a new area of the abdomen on each occasion.
• Before using REKOVELLE, you must be educated on how to use the injection pen and how to perform injections.
• Your first injection must be supervised by a trained healthcare practitioner.
• Step-by-step instructions on how to inject REKOVELLE with the injection pen are provided in the ‘Instructions for Use’ leaflet in the carton.

Do not self-inject REKOVELLE until you are sure of how to do it.

If you forget to use REKOVELLE

If you forget an injection or are not sure what to do, contact your doctor or nurse immediately for advice.

Do not inject a double dose to make up for the dose you missed.

If you use too much REKOVELLE

REKOVELLE may cause hyperstimulation of the ovaries known as ovarian hyperstimulation syndrome (OHSS). OHSS is a potentially serious complication of infertility treatment and could be fatal without proper management in hospital. The initial symptoms may consist of abdominal pain, abdominal swelling and/or nausea and vomiting.

If you think that you have used too much REKOVELLE, 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 Accident and Emergency 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 REKOVELLE?

Things you should do

Call your doctor straight away if you:

• feel pain in the abdomen or pelvic region
• notice swelling in the abdomen
• experience nausea (feeling sick) or vomiting
• develop diarrhoea
• gain weight
• have trouble breathing
• notice you are urinating less.

Tell your doctor straight away if you notice any of the above symptoms, even if the symptoms develop some days after the last injection has been given.

This can be a sign of high levels of activity in the ovaries known as OHSS and the symptoms could become severe.

If these symptoms become severe, treatment with REKOVELLE should be stopped and you should receive urgent medical attention in hospital.

Keeping to your recommended dose and careful monitoring of your treatment will reduce your chances of getting these symptoms.

You should also contact your doctor right away if you:

• become pregnant
• have unusual vaginal bleeding.

Be sure to keep all your doctor's appointments so your progress can be checked.

Your doctor will normally arrange for you to have ultrasound scans and do some blood and other tests from time to time to check on your progress and detect any unwanted side effects.

Tell any doctor, dentist or pharmacist you visit that you are using REKOVELLE. If you are going to have surgery, tell the surgeon or anaesthetist that you are using REKOVELLE.

Things you should not do

• Do not stop using this medicine or change your dose without talking to your doctor.
• Do not give this medicine to anyone else, even if they have the same condition as you.

Driving or using machines

REKOVELLE should not normally interfere with your ability to drive a car or operate machinery.

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

Looking after your medicine

• Keep REKOVELLE in a refrigerator at a temperature of 2°C to 8°C. Do not freeze.
• Always store the REKOVELLE pre-filled pen in the original package with the cap on to protect from light.
• REKOVELLE may be removed from the refrigerator and stored at or below 25°C for up to 3 months as long as the expiry date has not passed. It must be discarded afterwards.
• After opening, the pre-filled pen can be stored at or below 25°C for up to 28 days. After 28 days, the pre-filled pen containing any unused medicine should be discarded.

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.

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

Keep it where young children cannot reach it.

When to discard your medicine

Discard REKOVELLE pre-filled pen if it has been opened for more than 28 days.

Do not use this medicine after the expiry date.

Once you have injected REKOVELLE, do not re-use the needle. Discard the used needle into an approved, puncture-resistant sharps container and keep it out of the reach of children. Never put a used needle into your normal household rubbish bin.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it has expired, take it to any pharmacy for safe disposal.

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, nurse 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. 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 REKOVELLE contains

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

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

What REKOVELLE looks like

REKOVELLE is a clear and colourless solution for injection in a pre-filled pen and comes in three presentations, 12 micrograms, 36 micrograms and 72 micrograms:

REKOVELLE 12 micrograms pack contains:

1 x pre-filled multidose pen containing 12 micrograms of follitropin delta (rhu) in 0.36 mL of solution for injection and 3 x injection needles (AUST R 289310)

REKOVELLE 36 micrograms pack contains:

1 x pre-filled multidose pen containing 36 micrograms of follitropin delta (rhu) in 1.08 mL of solution for injection and 9 x injection needles (AUST R 289311)

REKOVELLE 72 micrograms pack contains:

1 x pre-filled multidose pen containing 72 micrograms of follitropin delta (rhu) in 2.16 mL of solution for injection and 15 x injection needles (AUST R 289312)

Who distributes REKOVELLE

REKOVELLE is distributed in Australia by:

Ferring Pharmaceuticals Pty Ltd
Suite 2, Level 1, Building 1
20 Bridge Street, Pymble, NSW 2073

This leaflet was prepared in May 2022.

DOCS#45471-v1C

Published by MIMS July 2022

1 Name of Medicine

Follitropin delta*.

2 Qualitative and Quantitative Composition

* Follitropin delta (rhu) is a recombinant human follicle-stimulating hormone (FSH) produced in a human cell line (PER.C6) by recombinant DNA technology.
Rekovelle 12 micrograms: contains 12 micrograms follitropin delta (rhu) in 0.36 mL. One pre-filled multidose pen contains 12 micrograms follitropin delta (rhu)* in 0.36 mL solution.
Rekovelle 36 micrograms: contains 36 micrograms follitropin delta (rhu) in 1.08 mL. One pre-filled multidose pen contains 36 micrograms follitropin delta (rhu)* in 1.08 mL solution.
Rekovelle 72 micrograms: contains 72 micrograms follitropin delta (rhu) in 2.16 mL. One pre-filled multidose pen contains 72 micrograms follitropin delta (rhu)* in 2.16 mL solution.
For all products, one mL of the solution contains 33.3 micrograms of follitropin delta (rhu).
This medicinal product contains less than 1 mmol (23 mg) sodium per dose.
Rekovelle (follitropin delta) solution for injection includes the following excipients: phenol, polysorbate 20, methionine, sodium sulfate decahydrate, dibasic sodium phosphate dodecahydrate, phosphoric acid (for pH adjustment), sodium hydroxide (for pH adjustment) and water for injections.

3 Pharmaceutical Form

Follitropin delta is a recombinant human follicle-stimulating hormone (FSH) produced in a human cell line (PER.C6) by recombinant DNA technology.
The average molecular weights of the glycosylated α and β subunits are approximately 15,200 and 18,500 Daltons (Da), respectively. Thus, approximately 40% of the total molecular weight of the molecule is due to glycosylation. No animal-derived materials are used in the Rekovelle manufacturing processes.
Solution for injection in a pre-filled multidose pen with injection needles.
Clear and colourless solution. The pH of the solution is 6.0-7.0.

4 Clinical Particulars

4.1 Therapeutic Indications

Controlled ovarian stimulation for the development of multiple follicles in women undergoing assisted reproductive technologies (ART) such as an in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycle.

4.2 Dose and Method of Administration

Treatment with Rekovelle should be initiated under the supervision of a physician experienced in the treatment of fertility problems. Patients must be educated on how to use the Rekovelle injection pen and to perform injections.
The dosage of Rekovelle is individualised for each patient to obtain an ovarian response with favourable safety/efficacy profile (see Section 5.1 Pharmacodynamic Properties). Rekovelle is dosed in micrograms and not in international units (IU) of biological activity (see Section 5.1 Pharmacodynamic Properties). The dosing regimen is specific for Rekovelle and the microgram dose cannot be applied to other gonadotropins.
For the first treatment cycle, the individual daily dose will be determined on the basis of the woman's serum anti-Müllerian hormone (AMH) concentration, which is a biomarker of ovarian response to gonadotropins, and her body weight. The dose should be based on a recent (i.e. within the last 12 months) determination of AMH concentration measured by one of the following diagnostic tests: Elecsys AMH Plus immunoassay from Roche (i.e. assay used in clinical development trials) or, alternatively, the Access AMH Advanced immunoassay from Beckman Coulter.
The dosing recommendations (based on AMH concentration and body weight) are presented in Table 1. These dosing recommendations rely on the use of the Roche Elecsys AMH Plus or the Beckman Coulter Access AMH Advanced immunoassays. The use of other AMH assays for this purpose is not recommended, as there is currently no standardisation of available AMH assays.
Patients with low AMH levels are likely to have low ovarian reserve.
The individual daily dose is to be maintained throughout the stimulation period. For women with AMH < 15 picomol/L the daily dose is 12 micrograms, irrespective of body weight. For women with AMH ≥ 15 picomol/L the daily dose decreases from 0.19 to 0.10 micrograms/kg by increasing AMH concentration (Table 1). The dose is to be rounded off to the nearest 0.33 micrograms to match the dosing scale on the injection pen. The maximum daily dose for the first treatment cycle is 12 micrograms.
The AMH concentration is to be expressed in picomol/L and is to be rounded off to the nearest integer (Table 1). If the AMH concentration is in nanogram/mL, the concentration should be converted to picomol/L by multiplying by 7.14 (nanogram/mL x 7.14 = picomol/L) before use.
For calculation of the Rekovelle dose, body weight is to be measured without shoes and overcoat just prior to start of stimulation.
Dosing with Rekovelle should be initiated day 2 or 3 after start of menstrual bleeding, and continue until adequate follicular development has been achieved as assessed by monitoring with ultrasound alone or in combination with measurement of serum oestradiol levels. Adequate follicular development is achieved on average by the ninth day of treatment (range 5 to 20 days). As soon as ≥ 3 follicles ≥ 17 mm are observed, a single injection of 250 micrograms recombinant human chorionic gonadotropin (hCG) or 5,000 IU hCG is administered to induce final follicular maturation. In patients with excessive ovarian response at risk of ovarian hyperstimulation syndrome (OHSS), administration of a GnRH agonist instead of hCG could be considered for triggering of final follicular maturation. Administration of GnRH agonist can reduce, but not eliminate, the risk for OHSS and is applicable only for GnRH antagonist cycles. In case of GnRH agonist administration, embryos should not be replaced in the fresh cycle but cryopreserved for later use. In patients with excessive ovarian response of > 35 follicles with a diameter ≥ 12 mm, triggering of final follicular maturation should not be performed and the cycle cancelled.
For subsequent treatment cycles, the daily dose of Rekovelle should be maintained or modified according to the patient's ovarian response in the previous cycle. The maximum daily dose is 24 micrograms.
If the patient had adequate ovarian response in the previous cycle without developing OHSS, the same daily dose of Rekovelle should be used.
In case of ovarian hypo-response in the previous cycle, the daily dose of Rekovelle in the subsequent cycle should be increased by 25% or 50%, according to the extent of response observed.
In case of ovarian hyper-response in the previous cycle, the daily dose of Rekovelle in the subsequent cycle should be decreased by 20% or 33%, according to the extent of response observed.
In patients who developed OHSS or were at risk of OHSS in a previous cycle, the daily dose of Rekovelle for the subsequent cycle is 33% lower than the dose used in the cycle where OHSS or risk of OHSS occurred.
There is no clinical trial experience with Rekovelle in the long GnRH agonist protocol (see Section 5.1 Pharmacodynamic Properties).

Patients with renal and hepatic impairment.

Polycystic ovarian syndrome patients with anovulatory disorders.

Elderly (more than 65 years).

Paediatric population.

Method of administration.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Qualitative and Quantitative Composition.
Tumours of the hypothalamus or pituitary gland.
Ovarian enlargement or ovarian cyst not due to polycystic ovarian syndrome.
Gynaecological haemorrhages of unknown aetiology.
Ovarian, uterine or mammary carcinoma.
Pregnancy and lactation.
Rekovelle must not be used when an effective response cannot be obtained, such as:
primary ovarian failure;
malformations of sexual organs incompatible with pregnancy;
fibroid tumours of the uterus incompatible with pregnancy.

4.4 Special Warnings and Precautions for Use

Rekovelle contains a potent gonadotropic substance capable of causing mild to severe adverse reactions, and should only be used by physicians who are thoroughly familiar with infertility problems and their management.
Gonadotropin therapy requires time commitment by physicians and supportive healthcare professionals, as well as the availability of appropriate monitoring facilities. Safe and effective use of Rekovelle calls for monitoring of ovarian response with ultrasound alone, or in combination with measurement of serum oestradiol levels, on a regular basis. The dose of Rekovelle is individualised for each patient to obtain an ovarian response with a favourable safety/efficacy profile. There may be a degree of inter-patient variability in response to FSH administration, with poor response to FSH in some patients and exaggerated response in others.
Before starting treatment, the couple's infertility should be assessed as appropriate and putative contraindications for pregnancy evaluated. In particular, patients should be evaluated for hypothyroidism and hyperprolactinaemia, and the appropriate specific treatment should be given.
Patients undergoing stimulation of follicular growth may experience ovarian enlargement and may be at risk of developing ovarian hyperstimulation syndrome. Adherence to the Rekovelle dose and regimen of administration and careful monitoring of therapy will minimise the incidence of such events.

Ovarian hyperstimulation syndrome (OHSS).

Thromboembolic events.

Ovarian torsion.

Multiple pregnancy.

Pregnancy loss.

Ectopic pregnancy.

Reproductive system neoplasms.

Congenital malformation.

Other medical conditions.

Sodium content.

Use in women over 40 years of age.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies have been performed with Rekovelle.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

Rekovelle is expected to have no or negligible influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Table 2 combines all three controlled ovarian stimulation (COS) cycles in the ESTHER trials and thus provides the most frequent adverse events based on 1,012 treatment cycles with Rekovelle and 1,015 treatment cycles with GONAL-F in the phase 3 program conducted in IVF/ICSI patients.
The most frequently reported adverse drug reactions during treatment with Rekovelle in pivotal clinical trials (1,012 cycles) are headache (4.2%), pelvic discomfort (2.9%), ovarian hyperstimulation syndrome (2.3%), pelvic pain (1.6%), nausea (1.4%), adnexa uteri pain (1.4%) and fatigue (1.2%).
Table 3 displays the adverse drug reactions in patients treated with Rekovelle in the pivotal clinical trials according to system organ class and frequency; common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to < 1/100). Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness.
OHSS is an intrinsic risk of ovarian stimulation. Known gastrointestinal symptoms associated with OHSS include abdominal pain, discomfort, and distension, nausea, vomiting and diarrhoea. Ovarian torsion and thromboembolic events are known to be rare complications of ovarian stimulation treatment.

Reporting suspected adverse effects.

4.9 Overdose

The effect of an overdose in humans is unknown, nevertheless, there is a risk that OHSS may occur (see Section 4.4 Special Warnings and Precautions for Use).
For information on the management of overdose, contact the Poisons Information Centre on 131 126 (Australia).
Advise your patients to immediately contact their doctor or the Poisons Information Centre (telephone 131 126) if they are concerned that they have given themselves too much Rekovelle.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital systems, gonadotropins and other ovulation stimulants, gonadotropins.
ATC code: G03GA10.

Mechanism of action.

Pharmacodynamic effects compared to follitropin alfa.

Factors influencing response.

Clinical trials.

Ovarian response and total FSH dose.

Safety - OHSS risk management.

Safety - immunogenicity.

5.2 Pharmacokinetic Properties

The pharmacokinetic profile of Rekovelle has been investigated in healthy female subjects and in in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) patients undergoing controlled ovarian stimulation (COS). Following repeated daily subcutaneous administration, Rekovelle reaches steady-state within 6 to 7 days with a three-fold higher concentration compared with the concentration after the first dose. Circulating levels of Rekovelle are inversely related to the body weight, which supports individualised dosing based on body weight.
Within the therapeutic dose range, exposure to Rekovelle increases proportionally with the dose.

Absorption.

Distribution.

Metabolism.

Excretion.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store in a refrigerator (2°C-8°C). Do not freeze.
Within its shelf life, Rekovelle may be removed from the refrigerator, without being refrigerated again, and stored at or below 25°C for up to 3 months and must be discarded afterwards.
Before use: store in the original package in order to protect from light.
After the first injection: the pre-filled pen can be stored at or below 25°C and it must be discarded after 28 days. Reattach pen cap after each injection.

6.5 Nature and Contents of Container

Rekovelle is a clear and colourless solution for injection presented in a pre-filled multidose pen with a dose selection knob, display window and cap. Each pen contains an integrated non-replaceable cartridge containing the solution for injection.

12 micrograms.

36 micrograms.

72 micrograms.

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)

(S4) Prescription Only Medicine.

Summary Table of Changes