Elonva

New Zealand - English - Medsafe (Medicines Safety Authority)

Buy It Now

Active ingredient:
Corifollitropin alfa 0.2 mg/mL;  
Available from:
Merck Sharp & Dohme (New Zealand) Limited
INN (International Name):
Corifollitropin alfa 0.2 mg/mL
Dosage:
100 mcg/0.5mL
Pharmaceutical form:
Solution for injection
Composition:
Active: Corifollitropin alfa 0.2 mg/mL   Excipient: Hydrochloric acid Methionine Polysorbate 20 Sodium citrate Sodium hydroxide Sucrose Water for injection
Units in package:
Syringe, glass, Pre-filled glass syringe closed with rubber plunger and tip cap., 1 dose unit
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
NV Organon
Therapeutic indications:
Controlled ovarian stimulation (COS) for the development of multiple follicles and pregnancy in women undergoing in-vitro fertilisation techniques.
Product summary:
Package - Contents - Shelf Life: Syringe, glass, Pre-filled glass syringe closed with rubber plunger and tip cap. - 1 dose units - 36 months from date of manufacture stored at 2° to 8°C (Refrigerate, do not freeze) protect from light 1 months from date of manufacture stored at or below 25°C
Authorization number:
TT50-8309
Authorization date:
2009-05-22

S-CCPPI-MK8962-SOi-022019

ELONVA

®

Corifollitropin alfa (rch)

Consumer Medicine Information

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 ovarian

hyperstimulation syndrome

(OHSS). OHSS is a serious

medical problem that can happen

when the ovaries are overly

stimulated (see

Before you start

to use it: Ovarian

Hyperstimulation Syndrome

(OHSS)

for further explanation).

have polycystic ovarian

syndrome (PCOS)

have had 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.

S-CCPPI-MK8962-SOi-022019

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

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.

S-CCPPI-MK8962-SOi-022019

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

Pelvic discomfort

S-CCPPI-MK8962-SOi-022019

Breast tenderness

Tiredness (fatigue)

Uncommon (affects 1 to 10 users in

1,000):

Ovarian torsion (twisting of the

ovary resulting in extreme lower

stomach pain)

Liver enzyme increase

Miscarriage

Pain after oocyte retrieval

Procedure 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.

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

S-CCPPI-MK8962-SOi-022019

corifollitropin alfa (rch)

Inactive ingredients

sodium citrate

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

Merck Sharp & Dohme (New

Zealand) Limited

P O Box 99 851

Newmarket

Auckland 1149

New Zealand

Date of preparation:

March 2019

S-CCPPI-MK8962-SOi-022019

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.

2.

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.

3.

Hold the syringe with the grey cap

pointing upwards.

Tap the syringe gently with your

finger to help air bubbles rise to the

top.

4.

Keep the syringe pointing upwards.

Unscrew the syringe cap counter-

clockwise.

5.

Keep the syringe pointing upwards.

Screw the needle shield (containing

the needle) clockwise onto the

syringe.

6.

Keep the syringe pointing upwards.

Remove the needle shield straight up

and discard it.

BE CAREFUL with the needle.

Injecting

7.

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.

S-CCPPI-MK8962-SOi-022019

8.

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.

9

Release your thumb from the

plunger.

The needle will withdraw

automatically into the syringe where

it will be locked permanently.

NEW ZEALAND DATA SHEET

1. PRODUCT NAME

ELONVA

100 micrograms solution for injection

ELONVA

150 micrograms solution for injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

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

solution for injection.

Corifollitropin alfa, a gonadotrophin designed as a sustained follicle stimulant is a glycoprotein

consisting of two non-covalently linked non-identical 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). CAS No.: 195962-23-

α-subunit

APDVQDCPEC TLQENPFFSQ PGAPILQCMG CCFSRAYPTP

* *

LRSKKTMLVQ KNVTSESTCC VAKSYNRVTV MGGFKVENHT

ACHCSTCYYH KS

β-subunit

* *

NSCELTNITI AIEKEECRFC ISINTTWCAG YCYTRDLVYK

DPARPKIQKT CTFKELVYET VRVPGCAHHA DSLYTYPVAT

&&

QCHCGKCDSD STDCTVRGLG PSYCSFGEMK ESSSSKAPPP

& & & &

SLPSPSRLPG PSDTPILPQ

* = N-glycosylation sites

& = O-glycosylation sites

Corifollitropin

alfa

produced

Chinese

Hamster

Ovary

(CHO)

cells

recombinant

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.

Excipient(s) with known effect:

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

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection.

Clear and colourless aqueous solution.

Page 2 of 14

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.

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.

Body Weight

Less than 50 kg

50 – 60 kg

More than 60 kg

Age

36 years or younger

100 micrograms

100 micrograms

150 micrograms

Older than 36 years

Not studied.

150 micrograms

150 micrograms

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 also sections 4.4 and

5.1).

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

started

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 oestradiol 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).

Page 3 of 14

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 in section 4.4 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 and section 5.2).

Hepatic

impairment:

Although

data

hepatically

impaired

patients

available,

hepatic

impairment is unlikely to affect the elimination of corifollitropin alfa (see section 5.2).

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.

Fibroid tumours of the uterus incompatible with pregnancy.

Malformations of the reproductive organs incompatible with pregnancy.

Pregnancy or lactation (see section 4.4).

Hypersensitivity to the active substance or to any of the excipients.

Risk factors for OHSS

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).

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).

After administration of ELONVA, no additional FSH-containing products should be administered prior

to stimulation day 8 (see section 4.2).

Renal Insufficiency

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 and section

5.2).

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).

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

Page 4 of 14

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. 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

reducing

risk

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 oestradiol 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.

Multi-foetal 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.

Page 5 of 14

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 recognized 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.

4.5

Interaction with other medicines and other forms of interaction

Interactions with other medicines

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

Use in pregnancy (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.

Use in lactation

The use of ELONVA during lactation is contraindicated.

Effects on fertility

Corifollitropin alfa administered to rats and rabbits prior to mating did not impair fertility; treatment

stimulated the development of multiple follicles.

4.7

Effects on ability to drive and use machines

Effect 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

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 4.2), headache (4.0%), nausea

(2.3%), fatigue (1.5%), and breast tenderness (1.3%).

The table below 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%).

Page 6 of 14

Body system

Frequency

Undesirable effect

Psychiatric disorders

Uncommon

Mood swings

Nervous system

disorders

Common

Uncommon

Headache

Dizziness

Vascular disorders

Uncommon

Hot flush

Gastrointestinal

disorders

Common

Uncommon

Nausea

Abdominal distension,

vomiting, diarrhoea,

constipation.

Musculoskeletal and

connective tissue

disorders

Uncommon

Back pain

Pregnancy, puerperium

and perinatal conditions

Uncommon

Abortion spontaneous

Reproductive system and

breast disorders

Common

Uncommon

OHSS, pelvic pain, pelvic

discomfort, breast

tenderness

Ovarian torsion, adnexa

uteri pain, premature

ovulation, breast pain

General disorders and

administration site

conditions

Common

Uncommon

Fatigue

Injection

site

haematoma,

injection site pain, irritability

Investigations

Uncommon

Alanine

aminotransferase

increased,

aspartate

aminotransferase increased

Injury, poisoning and

procedural complications

Uncommon

Procedural pain

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 of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows

continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked

to report any suspected adverse reactions https//nzphvc.otago.ac.nz/reporting/.

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 (see section 4.4). 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 OHSS in section 4.4).

For advice on the management of overdose please contact the National Poisons Centre on 0800

POISON (0800 764766).

Page 7 of 14

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 efficacy and safety

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 1 below.

Page 8 of 14

Table 1: Mean Number of Oocytes Retrieved from ENSURE, ENGAGE, and PURSUE

Intent-to-Treat Population (ITT)

Parameter

ENSURE

(18-36 years of age)

(body weight less than or

equal to 60 kg)

ENGAGE

(18-36 years of age)

(body weight greater than

60 kg and less than or

equal to 90 kg)

PURSUE

(35-42 years of age)

(body weight greater than

or equal to 50 kg)

ELONVA

100 µg

recFSH

150 IU

ELONVA

150 µg

recFSH

200 IU

ELONVA

150 µg

recFSH

300 IU

N=268

N=128

N=756

N=750

N=694

N=696

Mean

number of

oocytes

13.3

10.6

13.8

12.6

10.7

10.3

Difference

[95% CI]

2.5 [1.2; 3.9]

1.2 [0.5, 1.9]

0.5 [-0.2, 1.2]

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 summarized in Table 2

below.

Page 9 of 14

Table 2: Pregnancy Results from the Fresh Cycles of ENGAGE and PURSUE

Intent-to-Treat Population (ITT)

Parameter

Fresh Cycles of ENGAGE

(18-36 years of age)

(body weight greater than 60 kg and

less than or equal to 90 kg)

Fresh Cycles of PURSUE

(35-42 years of age)

(body weight greater than or equal to

50 kg)

ELONVA

150 µg

recFSH

200 IU

Difference

[95% CI]

ELONVA

150 µg

recFSH

300 IU

Difference

[95% CI]

N=756

N=750

N=694

N=696

Vital

pregnancy rate

39.9%

39.1%

1.1 [-3.8, 5.9]

23.9%

26.9%

-3.0 [-7.3, 1.4]

Ongoing

pregnancy rate

39.0%

38.1%

1.1 [-3.8, 5.9]

22.2%

24.0%

-1.9 [-6.1, 2.3]

Live birth rate*

35.6%

34.4%

1.3 [-3.5, 6.1]

21.3%

23.4%

-2.3 [-6.5, 1.9]

The primary efficacy endpoint in the ENGAGE study was ongoing pregnancy (assessed at least 10 weeks after

embryo transfer).

The primary efficacy endpoint in the PURSUE study was 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.

*Live birth rate was a secondary efficacy endpoint in ENGAGE and PURSUE.

In these comparative 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 3

below.

Page 10 of 14

Table 3: Pregnancy Results from the FTET cycles of ENGAGE and PURSUE

Intent-to-Treat Population (ITT)

FTET Cycles of ENGAGE

(18-36 years of age)

(body weight greater than 60 kg

and less than or equal to 90 kg)

FTET Cycles of PURSUE

(35-42 years of age)

(body weight greater than or equal to

50 kg)

ELONVA

150 µg

recFSH

200 IU

ELONVA

150 µg

recFSH

300 IU

FTET Cycle 1

a

Ongoing

pregnancy

37.2

30.6

28.3

29.0

Live birth

28.3

28.3

FTET Cycle 2

a

Ongoing

pregnancy

23.7

29.0

34.8

42.9

Live birth

34.8

42.9

FTET Cycle 3

a

Ongoing

pregnancy

11.1

40.0

25.0

Live birth

40.0

25.0

FTET Cycle 4

a

Ongoing

pregnancy

100.0

Live birth

100.0

FTET Cycle 5

a

Ongoing

pregnancy

Live birth

n = number of subjects with the event; N = total number of subjects

Per embryo transfer.

Pregnancy

from

addition

FTET

cycles

fresh

cycles

ENGAGE

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

μg 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 μg

ELONVA was similar to that in subjects treated with daily 300 IU recFSH .

The pregnancy results are summarised in Table 4 below.

Page 11 of 14

Table 4: Pregnancy Results

from fresh ART cycles combined with FTET cycles of ENGAGE and PURSUE

Intent-to-Treat Population (ITT)

Parameter

ENGAGE

(18-36 years of age)

(body weight greater than 60 kg and

less than or equal to 90 kg)

PURSUE

(35-42 years of age)

(body weight greater than or equal to

50 kg)

ELONVA

150 µg

recFSH

200 IU

ELONVA

150 µg

recFSH

300 IU

Cumulative

vital

pregnancy

rate

per subject

N=756

N=750

N=694

N=696

48.1%

46.0%

31.1%

33.0%

Cumulative

vital

pregnancy

rate

per cycle

Nc=980

Nc=974

Nc=875

Nc=861

37.7%

35.8%

25.6%

28.0%

N=Number of subjects

Nc=Number of cycles

The cumulative vital pregnancy rate was calculated per subject and is based on fresh and frozen-thawed

embryo transfer (FTET) cycles from ENGAGE and PURSUE.

The cumulative vital pregnancy rate was calculated per cycle and is based on fresh and frozen-thawed embryo

transfer (FTET) cycles from ENGAGE and PURSUE.

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 randomized, double-blind, placebo- and active-controlled, 4-period crossover study, 70 healthy

postmenopausal

women

received

single

therapeutic

dose

corifollitropin

alfa

subcutaneously, a single supratherapeutic dose of 240 mcg 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 mcg of corifollitropin alfa

was 1.4 msec (1-sided 95% upper CI: 3.4 msec). After administration of the supratherapeutic dose of

240 mcg 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.

Page 12 of 14

long

elimination

half-life,

after

administration

recommended

dose,

serum

concentrations of corifollitropin alfa are sufficient to sustain multiple follicular growth for an entire

week. Therefore, with a single subcutaneous injection of ELONVA may be used as an alternative to

the first seven days of daily rec(FSH) in COS for the development of multiple follicles and pregnancy

in women undergoing in vitro fertilisation techniques (see section 4.2).

Body weight is a determinant of exposure to corifollitropin alfa. The mean corifollitropin alfa exposure

(AUC) after a single subcutaneous injection is 665 hours*ng/mL (426-1,037 hours*ng/mL

) 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. [

Predicted range for 90% of subjects].

Absorption

After a single subcutaneous injection of ELONVA, the mean maximum serum concentration (C

) of

corifollitropin alfa is 4.24 ng/mL (2.49-7.21 ng/mL

) and is reached at the mean T

of 44 hours (35-

57 hours

) postdose. The absolute bioavailability is 58% (48-70%

). [

Predicted 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 L

). Exposure to corifollitropin alfa increases

proportionally with dose within the range of 60 micrograms to 240 micrograms. [

Predicted range for

90% of subjects].

Elimination

Corifollitropin alfa has a mean elimination half-life (t

) of 70 hours (59-82 hours

) and a clearance of

0.13 L/h (0.10-0.18 L/h

). Elimination of corifollitropin alfa predominantly occurs via the kidneys, and

the rate of elimination may be reduced in patients with renal insufficiency (see sections 4.4 and 4.2). [

Predicted range for 90% of subjects]. Hepatic metabolism contributes to a minor extent to the

elimination of corifollitropin alfa.

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

Administration of corifollitropin alfa to rats and rabbits, prior to and directly after mating, and during

early

pregnancy,

resulted

embryotoxicity.

rabbits,

when

administered

prior

mating,

teratogenicity

been

observed.

Both

embryotoxicity

teratogenicity

considered

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.

Carcinogenicity

Long-term carcinogenicity studies in animals have not been performed to evaluate the carcinogenic

potential of corifollitropin alfa.

Genotoxicity

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

Page 13 of 14

6. PHARMACEUTICAL PARTICULARS

6.1

List of excipients

ELONVA also contains the excipients sodium citrate, sucrose, polysorbate 20, methionine, sodium

hydroxide and/or hydrochloric acid (for pH adjustment), and Water for Injections.

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

3 years

6.4

Special precautions for storage

Store at 2°C to 8°C (Refrigerate. Do not freeze). Keep the syringe in the outer carton. Product is for

single use in one patient only. Contains no antimicrobial preservative. Discard any residue. 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 pre-filled syringe equipped with an automatic safety system to prevent needle stick

injuries after use.

6.6

Special precautions for disposal

No information

7. MEDICINE SCHEDULE

Prescription Only Medicine

8. SPONSOR

Merck Sharp & Dohme (NZ) Ltd

PO Box 99 851

Newmarket

Auckland 1149

Tel: 0800 500 673

9. DATE OF FIRST APPROVAL

8 March 2012

10. DATE OF REVISION OF THE TEXT

28 March 2019

Page 14 of 14

SUMMARY TABLE OF CHANGES

Version

#

CCDS document code

Release Date

Sections revised

Brief Description

of Change

S-CCDS-MK8962-SOi-022019

February 2019

4.3, 4.4, 4.9

4.3: Consolidated

OHSS risk factors

as sub-bullets

under main bullet.

4.4: Updated

safety information

regarding OHSS

clinical practice

4.9: Updated

reference to

section 4.4.

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