Consumer medicine information

Elonva

Corifollitropin alfa

BRAND INFORMATION

Brand name

Elonva

Active ingredient

Corifollitropin alfa

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Elonva.

What is in this leaflet

This leaflet answers some common questions about ELONVA.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using ELONVA against the benefits they expect it will have for you.

If you have any concerns about using this medicine, tell your doctor or pharmacist.

Keep this leaflet with the medicine. You may want to read it again.

What ELONVA is used for

ELONVA contains corifollitropin alfa, a medicine belonging to the group of gonadotrophic hormones. These hormones play an important part in human fertility and reproduction. One of these gonadotrophic hormones is follicle-stimulating hormone (FSH), which is needed in women for the growth and development of follicles (small round sacs in your ovaries that contain the eggs).

ELONVA is especially designed to work much longer than FSH. One single injection of ELONVA can replace a whole week of daily FSH injections in women participating in in vitro fertilisation (IVF).

ELONVA is used to help achieve pregnancy in women having infertility treatment, such as IVF. ELONVA causes the growth and development of several follicles at the same time by controlled stimulation of the ovaries. The eggs are collected from the ovary, fertilised in the laboratory and the embryos are transferred into the uterus a few days later.

ELONVA is not addictive.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Before you use ELONVA

When you must not use it

Do not use ELONVA if you:

  • are allergic (hypersensitive) to corifollitropin alfa or to any of the ingredients in ELONVA listed at the end of this leaflet.
  • are pregnant or think you may be pregnant.
  • are breastfeeding.
  • have cancer of the ovary, breast, uterus, or brain (pituitary gland or hypothalamus).
  • have recently had unexpected vaginal bleeding (other than periods) where the cause is unknown.
  • have ovaries that do not work because of a condition called primary ovarian failure.
  • have ovarian cysts or enlarged ovaries.
  • have malformations of the sexual organs which make a normal pregnancy impossible.
  • have fibroid tumours in the uterus which make a normal pregnancy impossible.
  • have risk factors of OHSS (OHSS is a serious medical problem that can happen when the ovaries are overly stimulated. See below for further explanation):
    - have polycystic ovarian syndrome (PCOS)
    - have had ovarian hyperstimulation syndrome (OHSS)
    - have previously had a treatment cycle of controlled stimulation of the ovaries that resulted in the growth of more than 30 follicles with a size of 11 mm or larger
    - have a basal antral follicle count (the number of small follicles present in your ovaries at the beginning of a menstrual cycle) higher than 20

Do not use ELONVA:

  • if the syringe or needle is damaged
  • if the solution is not clear
  • if the packaging is torn or shows signs of tampering
  • after the expiry date printed on the pack has passed

If it has expired or is damaged, return it to your pharmacist or clinic.

If you are not sure whether you should start using ELONVA, talk to your doctor.

Before you start to use it

Take special care with ELONVA

Before starting to use this medicine, tell your doctor if you:

  • have ever had ovarian hyperstimulation syndrome (OHSS)
  • are pregnant or think you might be pregnant
  • have ever had stomach (abdominal) surgery
  • have ever had a twisting of an ovary (ovarian torsion). Twisting of an ovary could cause the blood flow to the ovary to be cut off.
  • have past or current cysts in you ovary or ovaries
  • have kidney disease
  • have uncontrolled pituitary gland or hypothalamic problems
  • have an underactive thyroid (hypothyroidism)
  • have adrenal glands that are not working properly (adrenocortical insufficiency)
  • have high prolactin levels in the blood (hyperprolactinemia)
  • have any other medical conditions (for example, diabetes, heart disease, or any other long-term disease)
  • have been told by a doctor that pregnancy would be dangerous for you

Ovarian Hyperstimulation Syndrome (OHSS)
Treatment with gonadotrophic hormones like ELONVA may cause ovarian hyperstimulation syndrome (OHSS). This is a serious medical condition where the ovaries are overly stimulated and the growing follicles become larger than normal.

OHSS causes fluid to build up suddenly in your stomach and chest areas and can cause blood clots to form.

Call you doctor right away if you have:

  • severe abdominal swelling and pain in the stomach area (abdomen)
  • feeling sick (nausea)
  • vomiting
  • sudden weight gain due to fluid build up
  • diarrhoea
  • decreased urine output
  • trouble breathing

In rare cases, severe OHSS may be life-threatening. Therefore close supervision by your doctor is very important. To check the effects of treatment, your doctor will do ultrasound scans of your ovaries. Your doctor may also check blood hormone levels (see also Side Effects).

Use ELONVA only once during the same treatment cycle otherwise the chance of having OHSS may increase.

Thrombosis (blood clot)
Treatment with gonadotrophic hormones like ELONVA may (as in pregnancy) increase the risk of having a blood clot (thrombosis). Thrombosis is the formation of a blood clot in a blood vessel.

Blood clots can cause serious medical conditions, such as:

  • blockage in your lungs (pulmonary embolus)
  • stroke
  • heart attack
  • blood vessel problems (thrombophlebitis)
  • a lack of blood flow (deep venous thrombosis) that may result in a loss of your arm or leg

Please discuss this with your doctor, before starting treatment, especially if:

  • you know you already have an increased chance of having a thrombosis
  • you, or anyone in your immediate family, have ever had a thrombosis
  • you are severely overweight

Multiple pregnancies
In women having fertility treatment, the risk of multiple pregnancies (having twins or even more than two babies) is mainly related to the number of embryos transferred into the uterus.

Multiple pregnancies carry an increased health risk for both the mother and her babies. Multiple pregnancies and specific characteristics of couples with fertility problems (e.g. a woman's age, certain sperm problems, genetic background of both parents) may also be associated with an increased chance of birth defects.

Pregnancy complications
If treatment with ELONVA results in pregnancy, there is a higher chance of pregnancy outside the uterus (an ectopic pregnancy). Therefore your doctor should perform an early ultrasound examination to exclude the possibility of pregnancy outside the uterus.

Ovarian and other reproductive system tumours
There have been reports of ovarian and other reproductive system tumours in women who have had infertility treatment. It is not known if treatment with fertility medicines increases the risk of these tumours in infertile women.

Taking other medicines

Tell your doctor if you are taking or have recently taken any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

How to use ELONVA

Follow all directions given to you by your doctor, nurse or pharmacist carefully. You should check with your doctor or pharmacist if you are not sure.

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

How much to inject

In the treatment of women of reproductive age, the dose of ELONVA is based on weight and age.

A single 100 - microgram dose is recommended in women who weigh less than or equal to 60 kilograms and who are 36 years of age or younger.

A single 150 - microgram dose is recommended in women:

  • who weigh more than 60 kilograms, regardless of age.
  • who weigh 50 kilograms or more and who are older than 36 years of age.

Women older than 36 years of age who weighed less than 50 kilograms were not studied.

Your doctor will explain exactly when to give the injection.

Your doctor may also give you other medication (such as a GnRH antagonist) to prevent early release of eggs from your ovary.

Seven days after the injection of ELONVA, your doctor may decide to continue your treatment cycle with another gonadotrophic hormone, like follicle-stimulating hormone (FSH) medicine. This may be continued for a few days until enough follicles of adequate size are present. This can be checked by ultrasound examination. FSH treatment is then stopped and the eggs are matured by giving hCG (human Chorionic Gonadotrophin). The eggs are collected from the ovary 34-36 hours later.

How to inject

ELONVA must be injected under the skin (subcutaneous) into a skin fold (that you pinch between your thumb and index finger), preferably just below the navel.

Do not inject ELONVA into a muscle.

The doctor or nurse may give you the injection.

ELONVA can also be injected by yourself or by your partner.

If the doctor decides you can give the injection yourself, the doctor or nurse will teach you the injection technique.

A step-by-step "instructions for use" is given at the end of this leaflet.

Do not attempt self-injection until you are sure of how to do it. Your partner may be trained to give the injection at home.

ELONVA is supplied in pre-filled syringes that have an automatic safety system to help prevent needle stick injuries after use.

If you forget to inject ELONVA

Contact your doctor immediately if you forget to inject ELONVA on the day you should have. Do not inject ELONVA without talking to your doctor.

If you use too much (overdose)

Contact your doctor immediately if you think you have used more ELONVA or additional medicines (for example, follicle-stimulating hormone) that make your ovaries continue to grow mature eggs.

While you are using ELONVA

Your doctor will carefully monitor your response using ultrasound scans of your ovaries during treatment with ELONVA. Your doctor may also check blood hormone levels.

Things you must do

See your doctor regularly so you can be monitored closely throughout your treatment.

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking ELONVA.

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

Tell all doctors and dentists who are treating you that you are using ELONVA.

Things you must not do

Be careful driving or operating machinery until you know how ELONVA affects you. ELONVA may cause dizziness. If you feel dizzy, you should not drive a car, operate machinery or do anything else that could be dangerous.

Do not give your medicine to anyone else, even if they have the same condition as you.

Side effects

Tell your doctor as soon as possible if you do not feel well while you are taking ELONVA.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Common (affects 1 to 10 users in 100):

  • Ovarian hyperstimulation syndrome (OHSS)
  • Pelvic pain
  • Feeling sick (nausea)
  • Headache
  • Tiredness (fatigue)
  • Pelvic discomfort
  • Breast tenderness

Uncommon (affects 1 to 10 users in 1,000):

  • Ovarian torsion (twisting of the ovary resulting in extreme lower stomach pain)
  • Liver enzyme increases
  • Miscarriage
  • Pain after oocyte retrieval
  • Procedural pain
  • Releasing an egg too early (premature ovulation)
  • Abdominal distension
  • Vomiting
  • Diarrhoea
  • Constipation
  • Back pain
  • Breast pain
  • Bruising or pain at the injection site
  • Irritability
  • Mood swings
  • Dizziness
  • Hot flush

A possible complication of treatment with gonadotrophic hormones like ELONVA is unwanted overstimulation of the ovaries.

The chance of having this complication can be reduced by carefully monitoring the number of maturing follicles. Your doctor will do ultrasound scans of your ovaries to carefully monitor the number of maturing follicles. Your doctor may also check blood hormone levels.

The first symptoms of ovarian overstimulation may be noticed as: pain in the stomach (abdomen), feeling sick or diarrhoea.

Ovarian overstimulation may develop into a serious medical condition called ovarian hyperstimulation syndrome (OHSS). Signs and symptoms of severe OHSS may include:

  • acute stomach pain, weight gain, shortness of breath and passing less urine.
  • in rare cases blood clots. Signs of a blood clot include pain, warmth, redness, numbness or tingling in your arm or leg.

Tell your doctor immediately or go to the accident and emergency at your nearest hospital if you have stomach pains or any of the other symptoms of ovarian hyperstimulation, even if they happen some days after the injection has been given.

In general use there have been reports of allergic reactions (hypersensitivity reactions, both local and generalised, including rash).

The following side effects are considered to be related to Assisted Reproductive Technology (ART) or subsequent pregnancy.

  • ectopic pregnancy (pregnancy that occurs outside the uterus)
  • multiple pregnancies

The incidence of congenital malformations (a physical defect present in a baby at birth) after ART may be slightly higher than after spontaneous conceptions. The slightly higher incidence is thought to be due to differences in patients undergoing fertility treatment (e.g. age of the female, sperm characteristics) and to the higher incidence of multiple pregnancies after ART.

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may occur in some patients.

After using it

Storage

Store ELONVA in the refrigerator (2°C to 8°C) until the expiry date. Do not freeze.

Do not use after the expiry date on the carton.

OR

Store at or below 25°C for a total period of not more than one month. Make a note of when you start storing the product out of the refrigerator, and use it within one month of that date.

Keep the syringe in the outer carton in order to protect from light until you are ready to use it.

Keep ELONVA in a safe place away from the sight and reach of children.

Do not use ELONVA:

  • If it has been stored out of the refrigerator for more than one month.
  • If it has been stored out of the refrigerator at a temperature of more than 25°C.

Disposal

Do not dispose of an empty or unused syringe in household waste.

Ask your pharmacist or doctor how to dispose of medicines no longer required. These measures will help protect the environment.

Product description

What it looks like

ELONVA is a clear and colourless solution in a pre-filled syringe for single use.

The syringe has an automatic safety system, which prevents needle stick injuries after use.

One pre-filled syringe contains 100 micrograms or 150 micrograms of corifollitropin alfa in 0.5 mL.

ELONVA is available in packs containing 1 pre-filled syringe and a sterile injection needle.

Ingredients

Active ingredient

  • corifollitropin alfa (rch)

Inactive ingredients

  • sodium citrate dihydrate
  • sucrose
  • polysorbate 20
  • methionine
  • water for injections
  • sodium hydroxide and/or hydrochloric acid for adjustment of pH.

ELONVA contains less than 1 mmol sodium (23 mg) per injection, i.e. essentially "sodium-free".

Supplier

Organon Pharma Pty Ltd
Building A
26 Talavera Road
Macquarie Park NSW 2113
Australia

Organon New Zealand Limited
P O Box 99 851
Newmarket
Auckland 1149
New Zealand

Australian Registration Numbers:

AUST R 160646 (100 mcg/0.5 mL)

AUST R 160645 (150 mcg/0.5 mL)

Date of preparation: January 2021

Instructions for use

Components of the ELONVA syringe with needle:

Preparing the injection

  1. Wash your hands with soap and water and dry them before you use ELONVA.
    Swab the injection site (the area just below your belly button) with a disinfectant (for example, alcohol) to remove any surface bacteria.
    Clean about 5 cm around the point where the needle will go in and let the disinfectant dry for at least one minute before proceeding.

  1. While waiting for the disinfectant to dry, break the label perforation and pull off the needle-cap.
    Leave the needle shield on the needle.
    Place the needle shield (containing the needle) on a clean dry surface, while preparing the syringe.

  1. Hold the syringe with the grey cap pointing upwards.
    Tap the syringe gently with your finger to help air bubbles rise to the top.

  1. Keep the syringe pointing upwards.
    Unscrew the syringe cap counter-clockwise.

  1. Keep the syringe pointing upwards.
    Screw the needle shield (containing the needle) clockwise onto the syringe.

  1. Keep the syringe pointing upwards.
    Remove the needle shield straight up and discard it.
    BE CAREFUL with the needle.

Injecting

  1. Now take the syringe between index and middle finger in the upward position.
    Place your thumb on the plunger.
    Carefully push the plunger upwards until a tiny droplet appears at the tip of the needle.

  1. Pinch a fold of the skin between thumb and index finger.
    Insert the entire needle at an angle of 90 degrees into the fold of the skin.
    CAREFULLY press the plunger until it can not go further and hold the plunger down
    COUNT TO FIVE to ensure that all of the solution is injected.

  1. Release your thumb from the plunger.
    The needle will withdraw automatically into the syringe where it will be locked permanently.

Published by MIMS April 2021

BRAND INFORMATION

Brand name

Elonva

Active ingredient

Corifollitropin alfa

Schedule

S4

 

1 Name of Medicine

Corifollitropin alfa (rch).

2 Qualitative and Quantitative Composition

Corifollitropin alfa solution for injection.
Elonva (corifollitropin alfa) 100 micrograms/0.5 mL.
Elonva (corifollitropin alfa) 150 micrograms/0.5 mL.
Each pre-filled syringe contains 100 micrograms or 150 micrograms of corifollitropin alfa in 0.5 mL solution for injection.
Corifollitropin alfa is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology, using a chemically defined cell culture medium without the addition of antibiotics, human or animal derived proteins (protein free) or any other components of human or animal origin.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
Elonva is presented as a sterile, ready for use, clear and colourless aqueous solution for subcutaneous administration.

4 Clinical Particulars

4.1 Therapeutic Indications

Controlled ovarian stimulation (COS) for the development of multiple follicles and pregnancy in women undergoing in vitro fertilisation techniques.

4.2 Dose and Method of Administration

Treatment with Elonva should be initiated under the supervision of a physician experienced in the treatment of fertility problems.
Elonva may be administered by the woman herself or her partner, provided that proper instructions are given by the physician. Self administration of Elonva should only be performed by women who are well motivated, adequately trained and with access to expert advice.
Do not use if the solution contains particles or if the solution is not clear. Product is for single use in one patient only. Contains no antimicrobial preservative. Discard any residue.
In the treatment of women of reproductive age, the dose of Elonva is based on weight and age. See Table 1.
A single 100 microgram dose is recommended in women who weigh less than or equal to 60 kilograms and who are 36 years of age or younger.
A single 150 microgram dose is recommended in women:
who weigh more than 60 kilograms, regardless of age;
who weigh 50 kilograms or more and who are older than 36 years of age.
The recommended doses of Elonva have only been established in a treatment cycle with a GnRH antagonist that was administered from stimulation day 5 or day 6 onwards (see Section 4.4 Special Warnings and Precautions for Use; Section 5.1 Pharmacodynamic Properties, Clinical trials).

Stimulation day 1.

Elonva should be administered as a single subcutaneous injection, preferably in the abdominal wall, during the early follicular phase of the menstrual cycle.

Stimulation day 5 or 6.

Treatment with Gonadotrophin Releasing Hormone (GnRH) antagonist should be started on stimulation day 5 or day 6 depending on the ovarian response, i.e. the number and size of growing follicles. The concurrent determination of serum estradiol levels may also be useful. The GnRH antagonist is used to prevent premature Luteinising Hormone (LH) surges.

Stimulation day 8.

Seven days after the injection with Elonva on stimulation day 1, COS treatment may be continued with daily injections of (rec)FSH until the criterion for triggering final oocyte maturation (3 follicles ≥ 17 mm) has been reached. The daily dose of (rec)FSH may depend on the ovarian response, which should be monitored by regular ultrasonographic assessments from stimulation day 5 or 6 onwards. In normal responders a daily dose of 150 IU (rec)FSH is advised. Administration of (rec)FSH on the day of human Chorionic Gonadotrophin (hCG) administration can be omitted, depending on the ovarian response. In general, adequate follicular development is achieved on average by the ninth day of treatment (range 6 to 18 days).
As soon as three follicles ≥ 17 mm are observed, a single injection of 5,000 up to 10,000 IU urinary hCG is administered the same day or the day thereafter to induce final oocyte maturation. In case of an excessive ovarian response, see the recommendation given (see Section 4.4 Special Warnings and Precautions for Use) in order to reduce the risk for developing ovarian hyperstimulation syndrome (OHSS).

Special populations.

Renal impairment.

No clinical studies have been performed in patients with renal insufficiency. Since the rate of elimination of corifollitropin alfa maybe reduced in patients with renal insufficiency, the use of Elonva in these women is not recommended (see Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties).

Hepatic impairment.

Although data in hepatically impaired patients are not available, hepatic impairment is unlikely to affect the elimination of corifollitropin alfa (see Section 5.2 Pharmacokinetic Properties).

4.3 Contraindications

Tumours of the ovary, breast, uterus, pituitary or hypothalamus.
Abnormal (not menstrual) vaginal bleeding without a known/ diagnosed cause.
Primary ovarian failure.
Ovarian cysts or enlarged ovaries.
Factors associated with risk of OHSS including:
a history of ovarian hyperstimulation syndrome (OHSS);
a previous COS cycle that resulted in more than 30 follicles ≥ 11 mm measured by ultrasound examination;
a basal antral follicle count > 20;
polycystic ovarian syndrome (PCOS).
Fibroid tumours of the uterus incompatible with pregnancy.
Malformations of the reproductive organs incompatible with pregnancy.
Pregnancy or lactation (see Section 4.4 Special Warnings and Precautions for Use).
Hypersensitivity to the active substance or to any of the excipients.

4.4 Special Warnings and Precautions for Use

Infertility evaluation before starting treatment.

Before starting treatment, the couple's infertility should be assessed as appropriate. In particular, women should be evaluated for hypothyroidism, adrenocortical insufficiency, hyperprolactinemia and pituitary or hypothalamic tumours, and appropriate specific treatment given. Medical conditions that contraindicate pregnancy should also be evaluated before starting treatment with Elonva.

Dosing during the stimulation cycle.

Elonva is intended for single subcutaneous injection only. Additional injections of Elonva should not be given within the same treatment cycle (see Section 4.2 Dose and Method of Administration).
After administration of Elonva, no additional FSH containing product should be administered prior to stimulation day 8 (see Section 4.2 Dose and Method of Administration).

Not recommended with a GnRH agonist protocol.

There are limited data on the use of Elonva in combination with a Gonadotrophin Releasing Hormone (GnRH) agonist. Therefore, the use of Elonva is not recommended in combination with a GnRH agonist (see Section 4.2 Dose and Method of Administration).

Ovarian hyperstimulation syndrome (OHSS).

OHSS is a medical event distinct from uncomplicated ovarian enlargement.
Clinical signs and symptoms of mild and moderate OHSS are abdominal pain, nausea, diarrhoea, mild to moderate enlargement of ovaries and ovarian cysts.
Severe OHSS may be life threatening. Clinical signs and symptoms of severe OHSS are large ovarian cysts, acute abdominal pain, ascites, pleural effusion, hydrothorax, dyspnoea, oliguria, haematological abnormalities and weight gain.
In rare instances, venous or arterial thromboembolism may occur in association with OHSS.
Transient liver function test abnormalities suggestive of hepatic dysfunction with or without morphologic changes on liver biopsy have also been reported in association with OHSS.
OHSS may be caused by administration of human Chorionic Gonadotrophin (hCG) and by pregnancy (endogenous hCG).
Early OHSS usually occurs within 10 days after hCG administration and may be associated with an excessive ovarian response to gonadotrophin stimulation.
Late OHSS occurs more than 10 days after hCG administration, as a consequence of the hormonal changes with pregnancy.
Because of the risk of developing OHSS, patients should be monitored for at least two weeks after hCG administration.
Women with known risk factors for a high ovarian response may be especially prone to the development of OHSS during or following treatment with Elonva (see Section 4.3 Contraindications). For women having their first cycle of ovarian stimulation, for whom risk factors are only partially known, close observation for early signs and symptoms of OHSS is recommended.
Follow current clinical practice for reducing the risk of OHSS during Assisted Reproductive Technology (ART). Adherence to the recommended Elonva dose and treatment regimen and careful monitoring of ovarian response is important to reduce the risk of OHSS.
To monitor the risk of OHSS, ultrasonographic assessments of follicular development should be performed prior to treatment and at regular intervals during treatment, the concurrent determination of serum estradiol levels may also be useful. In ART there is an increased risk of OHSS with 18 or more follicles of 11 mm or more in diameter.
If OHSS develops, standard and appropriate management of OHSS should be implemented and followed.

Ovarian torsion.

Ovarian torsion has been reported after treatment with gonadotrophins, including Elonva. Ovarian torsion may be related to other conditions, such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, and previous or current ovarian cysts. Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.

Multifoetal gestation and birth.

Multiple pregnancies and births have been reported for all gonadotrophin treatments, including Elonva. The woman and her partner should be advised of the potential risks for the mother (pregnancy and delivery complications) and the neonate (low birth weight) before starting treatment. In women undergoing ART procedures the risk of multiple pregnancy is mainly related to the number of embryos transferred.

Ectopic pregnancy.

Infertile women undergoing ART have an increased incidence of ectopic pregnancies. It is important to have early ultrasound confirmation that a pregnancy is intrauterine, and to exclude the possibility of extrauterine pregnancy.

Congenital malformations.

The incidence of congenital malformations after ART may be slightly higher than after spontaneous conceptions. This is thought to be due to differences in parental characteristics (e.g. maternal age, sperm characteristics) and the higher incidence of multiple pregnancies.

Ovarian and other reproductive system neoplasms.

There have been reports of ovarian and other reproductive system neoplasms, both benign and malignant, in women who have undergone multiple treatment regimens for infertility treatment. It is not established whether or not treatment with gonadotrophins increases the risk of these tumours in infertile women.

Vascular complications.

Thromboembolic events, both in association with and separate from OHSS, have been reported following treatment with gonadotrophins, including Elonva. Intravascular thrombosis, which may originate in venous or arterial vessels, can result in reduced blood flow to vital organs or the extremities. In women with generally recognised risk factors for thromboembolic events, such as a personal or family history, severe obesity or thrombophilia, treatment with gonadotrophins, including Elonva may further increase this risk. In these women the benefits of gonadotrophin administration, including Elonva, need to be weighed against the risks. It should be noted, however, that pregnancy itself also carries an increased risk of thrombosis.

Use in hepatic impairment.

See Section 5.2 Pharmacokinetic Properties, Other special populations; Section 4.2 Dose and Method of Administration, Special populations.

Use in renal impairment.

In patients with renal insufficiency the rate of elimination of corifollitropin alfa may be reduced. Therefore, the use of Elonva in these women is not recommended (see Section 4.2 Dose and Method of Administration; Section 5.2 Pharmacokinetic Properties).

Use in the elderly.

No data available.

Paediatric use.

The use of Elonva in the paediatric population is not relevant within the approved indication.

Effects on laboratory tests.

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

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies with Elonva and other medicines have been performed. Since corifollitropin alfa is not a substrate of cytochrome P450 enzymes, no metabolic interactions with other medicinal products are anticipated.
Elonva may cause a false positive hCG pregnancy test if the test is administered during the ovarian stimulation portion of the ART cycle. This may be due to cross-reactivity of some hCG pregnancy tests with the carboxy-terminal peptide of the beta subunit of Elonva.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Corifollitropin alfa administered to rats and rabbits prior to mating did not impair fertility; treatment stimulated the development of multiple follicles.
(Category B3)
The use of Elonva during pregnancy is contraindicated. In case of inadvertent exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect of corifollitropin alfa. Administration of corifollitropin alfa to rats and rabbits, prior to and directly after mating, and during early pregnancy, resulted in embryotoxicity. In rabbits, when administered prior to mating, teratogenicity has been observed. Both embryotoxicity and teratogenicity are considered a consequence of the superovulatory state of the animal not able to support a number of embryos above a physiological ceiling. The relevance of these findings for the clinical use of Elonva is limited.
 The use of Elonva during lactation is contraindicated.

4.7 Effects on Ability to Drive and Use Machines

No studies on the ability to drive and use machines have been performed.
Elonva may cause dizziness. Patients should be advised that if they feel dizzy, they should not drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

The most frequently reported adverse drug reactions during treatment with Elonva in clinical trials (N=2,397) are pelvic discomfort (6.0%), OHSS (4.3%, see Section 4.4 Special Warnings and Precautions for Use), headache (4.0%), pelvic pain (2.9%), nausea (2.3%), fatigue (1.5%), and breast tenderness (1.3%).
Table 2 displays the main adverse drug reactions in women treated with Elonva in clinical trials according to body system and frequency; common (≥ 1%, < 10%), uncommon (≥ 0.1%, < 1%).
There have been post-marketing reports of hypersensitivity reactions, both local and generalised, including rash.
In addition, ectopic pregnancy, and multiple gestations have been reported. These are considered to be related to ART or subsequent pregnancy.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

More than one injection of Elonva within one treatment cycle or too high a dose of Elonva and/or (rec)FSH may increase the risk of OHSS. After administration of Elonva, no additional FSH containing product should be administered prior to stimulation day 8, as this may also increase the risk of OHSS. See Section 4.4 Special Warnings and Precautions for Use, Ovarian hyperstimulation syndrome (OHSS).
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: gonadotrophins.
ATC code: G03GA09 corifollitropin alfa.

Mechanism of action.

Corifollitropin alfa has the same pharmacodynamic profile as (rec)FSH, but with a markedly prolonged duration of FSH activity due to a relatively long elimination half-life. This was achieved by the addition of the carboxy-terminal peptide (CTP) of the beta-subunit of hCG to the beta-chain of human FSH. Due to its ability to initiate and sustain multiple follicular growth for an entire week, a single subcutaneous injection of the recommended dose of Elonva may replace the first seven injections of any daily (rec)FSH preparation in a COS treatment cycle. Corifollitropin alfa does not display any intrinsic luteinising hormone (LH)/hCG activity.

Clinical trials.

In three randomised, double blind, clinical trials (ENSURE, ENGAGE, and PURSUE), treatment with a single subcutaneous injection of Elonva, 100 micrograms (ENSURE study) or 150 micrograms (ENGAGE and PURSUE study), for the first seven days of COS was compared to treatment with a daily dose of 150, 200, or 300 IU of recFSH, respectively. Pituitary suppression with a GnRH antagonist (ganirelix acetate injection at a daily dose of 0.25 mg) was used in each of the three clinical trials.
In the ENSURE study, 396 healthy normal ovulatory women, aged 18 to 36 years with a body weight less than or equal to 60 kg, were treated for one cycle with 100 micrograms of Elonva and pituitary suppression with a GnRH antagonist as part of an ART program. The primary efficacy endpoint was number of oocytes retrieved. The median total duration of stimulation was 9 days for both groups, indicating that two days of recFSH were required to complete ovarian stimulation from stimulation day 8 onwards (recFSH was given on the day of hCG for this study).
In the ENGAGE study, 1,506 healthy normal ovulatory women, aged 18 to 36 years with a body weight greater than 60 kg and less than or equal to 90 kg, were treated for one cycle with 150 micrograms of Elonva and pituitary suppression with a GnRH antagonist as part of an ART program. The co-primary efficacy endpoints were ongoing pregnancy rate and number of oocytes retrieved. The median total duration of stimulation was 9 days for both groups, indicating that two days of recFSH were required to complete ovarian stimulation from stimulation day 8 onwards (recFSH was given on the day of hCG for this study).
In the PURSUE study, 1,390 healthy normal ovulatory women, aged 35 to 42 years with a body weight greater than or equal to 50 kg, were treated for one cycle with 150 micrograms of Elonva and pituitary suppression with a GnRH antagonist as part of an ART program. The primary efficacy endpoint was vital pregnancy rate. The number of oocytes retrieved was a key secondary efficacy endpoint. The median total duration of stimulation was 9 days for both groups, indicating that one day of recFSH was required to complete ovarian stimulation from stimulation day 8 onwards (no recFSH was given on the day of hCG for this study).

Number of oocytes retrieved.

In all three studies, treatment with a single injection of Elonva, 100 or 150 micrograms, for the first seven days of COS, resulted in a higher number of oocytes retrieved compared with a daily dose of recFSH. However, the differences were within the predefined equivalence (ENGAGE and ENSURE) or non-inferiority (PURSUE) margins. See Table 3.

Pregnancy from the fresh cycles of ENGAGE and PURSUE.

In the ENGAGE study, non-inferiority was demonstrated in ongoing pregnancy rates between Elonva and recFSH, with ongoing pregnancy rate defined as presence of at least one foetus with heart activity assessed at least 10 weeks after embryo transfer.
In the PURSUE study, non-inferiority was demonstrated in vital pregnancy rate between Elonva and recFSH, with vital pregnancy rate defined as the percentage of subjects with at least one foetus with heart activity assessed 5 to 6 weeks after embryo transfer.
The pregnancy results from the fresh cycles of ENGAGE and PURSUE are summarised in Table 4.
In these clinical trials, the safety profile of a single injection of Elonva was comparable to daily injections with recFSH.

Pregnancy from the frozen-thawed embryo transfer (FTET) cycles of ENGAGE and PURSUE.

The follow-up FTET trial for ENGAGE included women who had at least one embryo thawed for use up to at least one year after cryopreservation. The mean number of embryos transferred in the FTET cycles of ENGAGE was 1.7 in both treatment groups.
The follow-up FTET trial for PURSUE included women who had at least one embryo thawed for use within two years of the date of the last cryopreservation for this trial. The mean number of embryos transferred in the FTET cycles of PURSUE was 2.4 in both treatment groups. This trial also provided safety data on the infants born from cryopreserved embryos.
The pregnancy results from the FTET cycles of ENGAGE and PURSUE are summarised in Table 5.

Pregnancy from the addition of FTET cycles to the fresh cycles of ENGAGE and PURSUE (cumulative vital pregnancy rates).

The cumulative vital pregnancy rate (per subject and per cycle) was calculated based on the results of the fresh and subsequent FTET cycles of a single cohort of women who received Elonva or recFSH in ENGAGE or PURSUE.
The cumulative vital pregnancy rate from ENGAGE in subjects treated with a single injection of 150 microgram Elonva was similar to that in subjects treated with daily 200 IU recFSH.
The cumulative vital pregnancy rate from PURSUE in subjects treated with a single injection of 150 microgram Elonva was similar to that in subjects treated with daily 300 IU recFSH.
The pregnancy results are summarised in Table 6.

Congenital malformations reported in infants born after a frozen-thawed embryo transfer (FTET) cycle.

Following use of Elonva, 61 infants were born after an FTET cycle in the PURSUE study follow-up, and 607 infants were born after fresh ART cycles in the ENSURE, ENGAGE and PURSUE studies combined. The rates for congenital malformations (major and minor combined) reported for infants born after an FTET cycle in the PURSUE study follow-up (16.4%) were similar to those reported for infants born after fresh ART cycles in the ENSURE, ENGAGE and PURSUE studies combined (16.8%).

Immunogenicity.

Of the 2,511 women treated with Elonva who were evaluated for the formation of post-treatment antibodies, four (0.16%) had evidence of antibody formation, including three who had been exposed once to Elonva and one who had been exposed twice to Elonva. In each case, these antibodies were non-neutralising and did not interfere with the response to stimulation or the normal physiologic responses of the Hypothalamic-Pituitary-Ovarian (HPO) axis. Two of these four women became pregnant during the same treatment cycle in which antibodies were detected, suggesting that the presence of non-neutralising antibodies after stimulation with Elonva is not clinically relevant.

Cardiac electrophysiology.

In a randomised, double blind, placebo and active controlled, 4 period crossover study, 70 healthy postmenopausal women received a single therapeutic dose of 150 microgram of corifollitropin alfa subcutaneously, a single supratherapeutic dose of 240 microgram of corifollitropin alfa subcutaneously, 400 mg moxifloxacin orally, and placebo. Both doses of corifollitropin alfa did not appear to prolong the QTc interval for up to 216 hours postdose. After baseline and placebo adjustment, the maximum mean QTc interval change after administration of a therapeutic dose of 150 microgram of corifollitropin alfa was 1.4 msec (1-sided 95% upper CI: 3.4 msec). After administration of the supratherapeutic dose of 240 microgram of corifollitropin alfa, the maximum mean QTc interval change was 1.2 msec (1-sided 95% upper CI: 3.6 msec).

5.2 Pharmacokinetic Properties

Pharmacokinetic parameters of corifollitropin alfa were evaluated after subcutaneous administration in women undergoing a COS treatment cycle.
Due to the long elimination half-life, after administration of the recommended dose, serum concentrations of corifollitropin alfa are sufficient to sustain multiple follicular growth for an entire week. Therefore, a single subcutaneous injection of Elonva may be used as an alternative to the first seven days of daily ref(FSH) in COS for the development of multiple follicles and pregnancy in women undergoing in vitro fertilisation techniques (see Section 4.2 Dose and Method of Administration).
Body weight is a determinant of exposure to corifollitropin alfa. The mean corifollitropin alfa exposure (AUC) after a single subcutaneous injection is 665 hours*nanogram/mL (426-1,037 hours*nanogram/mL1) and is similar after administration of 100 micrograms corifollitropin alfa to women with a body weight less than or equal to 60 kilograms and of 150 micrograms corifollitropin alfa to women with a body weight greater than 60 kilograms. [1Predicted range for 90% of subjects].

Absorption.

After a single subcutaneous injection of Elonva, the mean maximum serum concentration (Cmax) of corifollitropin alfa is 4.24 nanogram/mL (2.49-7.21 nanogram/mL1) and is reached at the mean Tmax of 44 hours (35-57 hours1) postdose. The absolute bioavailability is 58% (48-70%1). [1Predicted range for 90% of subjects].

Distribution.

Distribution, metabolism and elimination of corifollitropin alfa are very similar to other gonadotrophins, such as FSH, hCG and LH. After absorption into the blood, corifollitropin alfa is distributed mainly to the ovaries and the kidneys. Elimination of corifollitropin alfa predominantly occurs via the kidneys. The steady state volume of distribution is 9.2 L (6.5-13.1 L1). Exposure to corifollitropin alfa increases proportionally with dose within the range of 60 micrograms to 240 micrograms. [1Predicted range for 90% of subjects].

Metabolism.

Hepatic metabolism contributes to a minor extent to the elimination of corifollitropin alfa.

Excretion.

Corifollitropin alfa has a mean elimination half-life (t1/2) of 70 hours (59-82 hours1) and a clearance of 0.13 L/h (0.10-0.18 L/h1). Elimination of corifollitropin alfa predominantly occurs via the kidneys, and the rate of elimination may be reduced in patients with renal insufficiency (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use). [1Predicted range for 90% of subjects].

Other special populations.

Hepatic impairment.

Although data in hepatically impaired patients are not available, hepatic impairment is unlikely to affect the pharmacokinetic profile of corifollitropin alfa.

5.3 Preclinical Safety Data

Genotoxicity.

Corifollitropin alfa was not mutagenic or clastogenic in the standard battery of tests.

Carcinogenicity.

Long-term carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of corifollitropin alfa.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium citrate dihydrate, sucrose, polysorbate 20, methionine, sodium hydroxide and/or hydrochloric acid (for pH adjustment) and water for injections.
Elonva contains less than 1 mmol sodium (23 mg) per injection, i.e. essentially 'sodium-free'.

6.2 Incompatibilities

In the absence of compatibility studies, the solution for injection must not be mixed with other medicinal products.

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 at 2°C to 8°C (Refrigerate. Do not freeze). Keep the syringe in the outer carton. Do not use after the expiry date on the carton.
Elonva can also be stored below 25°C for up to 1 month. Do not use after this period.

6.5 Nature and Contents of Container

Elonva is supplied in disposable 1 mL luerlock syringes of hydrolytic glass (type I), closed with a rubber plunger and a tip cap. The syringes are packed together with a sterile injection needle.

Pack size.

1 prefilled syringe equipped with an automatic safety system to prevent needle stick injuries after use.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Corifollitropin alfa, a gonadotrophin designed as a sustained follicle stimulant is a glycoprotein consisting of two noncovalently linked nonidentical subunits called α and β. The α-subunit is identical to that of human follicle stimulating hormone (FSH); the β-subunit is composed of the complete β-subunit of human FSH (residues 1-111) extended with the carboxy terminal peptide (CTP) of the β-subunit of human chorionic gonadotrophin (hCG) (residues 118-145).

Chemical structure.


CAS number.

195962-23-3.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes