GONAL-F follitropin alfa (rch) 300IU /0.5mL (21.84microgram) solution for injection cartridge, pre-assembled in a pen

Australia - English - Department of Health (Therapeutic Goods Administration)

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Active ingredient:
Follitropin alfa
Available from:
Merck Healthcare Pty Ltd
INN (International Name):
Follitropin alfa
Authorization status:
Registered
Authorization number:
96230

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GONAL-f

®

(follitropin alfa [rch]) solution for injection

Consumer Medicine Information

What is in this leaflet

This leaflet answers some common

questions about GONAL-f.

It does not contain all the available

information.

It does not take the place of talking to

your doctor, nurse or pharmacist.

All medicines have risks and

benefits. Your doctor has weighed

the risks of you using GONAL-f

against the benefits it is expected to

have for you.

If you have any concerns about

using this medicine, ask your

doctor, nurse or pharmacist.

Keep this information with your

medicine.

You may need to read it again later.

What is GONAL-f used

for

GONAL-f contains follitropin alfa,

which is similar to follicle

stimulating hormone (FSH) found

naturally in humans.

GONAL-f belongs to a class of

hormones called gonadotrophins.

FSH is necessary for the growth and

development of egg cells (follicles)

in women, and sperm production in

men.

In women

GONAL-f can be used to bring about

the development of follicles in

women who are not ovulating and

who have not responded to treatment

with clomiphene citrate.

GONAL-f is also used to stimulate

the development of several follicles

in women undergoing assisted

reproductive technologies (ART)

such as in vitro fertilisation (IVF).

In men

GONAL-f is used in combination

with human chorionic gonadotrophin

(hCG) to stimulate the production of

sperm.

Ask your doctor if you have any

questions about why GONAL-f has

been prescribed for you.

Your doctor may have prescribed it

for another reason.

GONAL-f is available only on a

doctor's prescription.

GONAL-f is not habit-forming.

Before you are given

GONAL-f

When you must not use

GONAL-f

Do not use GONAL-f if you have a

history of allergy to any of the

ingredients listed at the end of this

leaflet.

Symptoms of an allergic reaction

may include:

shortness of breath

wheezing or difficulty breathing

swelling of the face, lips, tongue

or other parts of the body

rash, itching or hives on the skin.

Do not use GONAL-f if you have

tumours of the hypothalamus or

pituitary gland.

For women

Do not use GONAL-f if:

you are pregnant

you are breastfeeding

your ovaries are enlarged

you have an unexplained ovarian

cyst

you have unexplained vaginal or

uterine bleeding

you have cancer of the ovaries,

uterus or breasts

your ovaries have failed

you have fibroids in your uterus

which would make pregnancy

impossible

For men

Do not use GONAL-f if:

you have increased levels of

gonadotrophins indicating failure

of the testes

your infertility is due to disorders

other than hypogonadotrophic

hypogonadism (low levels of

gonadotrophins)

If you are not certain whether

these conditions apply to you, or

you are worried about anything on

this list, tell your doctor.

Do not give this medicine to a child

or elderly person.

Do not use this medicine after the

expiry date (month/year) on the

packaging has passed, or if the

packaging is torn or shows signs of

tampering.

If your medicine has expired or is

damaged, return it to your

pharmacist / clinic for disposal.

If you are not sure whether you

should start using GONAL-f, talk

to your doctor.

GONAL-F

Before you start to use

GONAL-f

Your doctor will assess you and your

partner's fertility. This may include

tests for other medical conditions,

which may interfere with your ability

to become pregnant. If necessary,

other medical conditions may be

treated before starting infertility

treatments including GONAL-f.

Tell your doctor if you have any

allergies to any foods, dyes,

preservatives or any other

medicines.

Tell your doctor if you have or

have had any of the following

medical conditions:

disorders of the thyroid gland

disorders of the adrenal glands

high prolactin levels in the blood

porphyria or a family history of

porphyria

For women

Your doctor will assess if you have

any medical conditions which

interfere with your ability to become

pregnant.

Treatment with GONAL-f may

increase your risk of developing a

condition called ovarian

hyperstimulation syndrome (OHSS).

This is when the ovaries over-react to

the hormonal treatment and become

larger.

The most common symptom is lower

abdominal pain. During stimulation

your doctor will monitor your

treatment by the use of ultrasound

and/or blood tests to help determine

if you are likely to develop OHSS. If

necessary your doctor will delay or

cancel your GONAL-f injection. You

may also be advised to refrain from

sexual intercourse until the end of the

cycle if this occurs.

Compared to natural conception, the

frequency of multiple pregnancies

and births is higher in patients

receiving treatments that stimulate

follicle growth for ovulation

induction. The majority of these are

twins. Your doctor will monitor your

response to treatment to minimise the

chance of multiple pregnancies,

because of the greater risks they

carry for mothers and babies.

Compared to natural conception, the

frequency of pregnancy loss is higher

in patients undergoing treatments to

stimulate follicle growth for

ovulation induction.

There may be a slightly increased

risk of birth defects in women using

assisted reproductive technologies.

This may be due to increased

maternal age, genetic factors,

multiple pregnancies or the

procedures. An effect of medicines

used to induce ovulation has not been

excluded.

Tell your doctor if you or a family

member have or have had signs of

blood clots (e.g. pain, warmth,

redness, numbness or tingling in

the arm or leg).

Treatment with GONAL-f and hCG

may increase the risk of blood clots

forming in your blood vessels.

Talk to your doctor about any

concerns you may have before

undergoing treatment or before

you start using GONAL-f.

For men

Elevated FSH blood levels are

indicative of testicular failure. Your

doctor may ask you for a semen

analysis to assess your response to

treatment.

Talk to your doctor about any

concerns you may have before you

start using GONAL-f

Taking other medicines

Tell your doctor if you are taking

any other medicines, including:

all prescription medicines

any medicines, vitamins, herbal

supplements or natural

therapies you buy without

prescription from your

pharmacy, supermarket,

naturopath or health food shop

Some medicines may be affected by

GONAL-f or may affect how well it

works.

Your doctor has more information on

medicines to be careful with or avoid

while using GONAL-f.

How GONAL-f is given

Follow all directions given to you

by your doctor, nurse or

pharmacist carefully.

They may differ from the

information contained in this leaflet.

Treatment with GONAL-f should be

started under the supervision of a

specialist doctor experienced in

fertility treatment.

GONAL-f is given as a course of

daily injections.

You should have your injection at the

same time each day.

Do not use GONAL-f on anyone

else.

It is for your use only.

How much to inject

Your doctor will decide the correct

dose of GONAL-f for you. Your

dose of GONAL-f may be adjusted

depending on your individual

response to treatment. Please consult

your doctor if you are in any doubt.

The following is a guide to the

common dose.

1.

Women who are not ovulating

The common dose usually starts at

75IU (5.46 microgram) daily. The

dose may be adjusted as your

treatment progresses. The maximal

daily dose is usually not higher than

225 IU (16.5 microgram).

2.

Women undergoing assisted

reproductive technologies

The common dose usually starts at

150 IU (10.92 microgram) daily,

commencing on day 2 or 3 of the

cycle. The dose may be adjusted as

your treatment progresses. The

maximal daily dose is usually not

higher than 450 IU (32.76

microgram).

3.

Men with hypogonadotrophic

hypogonadism

GONAL-F

GONAL-f is commonly given with

hCG. The common dose usually

starts at 150 IU (10.92 microgram)

three times a week.

How to inject

GONAL-f is given as a subcutaneous

(under your skin) injection in the

lower abdominal area or thigh.

GONAL-f is intended to be injected

by you or your partner.

Alternatively your doctor or a nurse

may give you these injections.

If your doctor or nurse decides you

can give the injections yourself, the

doctor or nurse will teach you the

injection technique.

Do not self-inject until you are sure

of how to do it.

Read the Instructions for Use

provided in the pack carefully

before commencing injections.

Your partner may be trained to give

the injection at home.

Where to inject

GONAL-f is usually given in the

lower abdominal area (except around

the navel and waistline) or the front

of your thigh. The injection site

should be changed daily to lessen

possible injection site reactions.

Do not inject into any areas in

which you feel lumps, firm knots,

depressions, pain, or see any

discolouration.

Talk to your doctor if you find

anything unusual when injecting.

How long to use GONAL-f

for

For women

The length of treatment varies with

each patient. It is possible to have

more than one treatment cycle of

GONAL-f.

For men

The combination treatment of

GONAL-f and hCG could continue

for at least 4 months and may

continue for up to 18-24 months.

If you forget to inject

GONAL-f

If you forget an injection or are not

sure what to do, contact your doctor

or nurse immediately for advice.

Do not inject a double dose on any

day.

Ask your doctor if you are not sure

what to do or have trouble

remembering to inject your

medicine.

If you injected too much

Immediately contact your doctor

or the Poisons Information Centre

(In Australia telephone 131 126. In

New Zealand telephone 0800 764

766) if you are concerned that you

have given yourself too much or

someone else has injected

themselves with GONAL-f.

While you are using

GONAL-f

Your doctor will carefully monitor

your response to GONAL-f by using

ultrasound, blood tests or semen

analysis.

Things you must do

See your doctor regularly.

Your doctor will monitor you closely

throughout your treatment.

If you are about to be started on

any new medicine, tell your doctor

and pharmacist that you are using

GONAL-f.

If you plan to have surgery, tell

your doctor or dentist that you are

using GONAL-f.

Tell all doctors, dentists and

pharmacists who are treating you

that you are using GONAL-f.

For Women

Tell your doctor immediately if

you become pregnant while using

GONAL-f.

Things you must not do

If you are self-injecting do not:

Stop using GONAL-f without

telling your doctor.

Change the dose unless your

doctor tells you to.

Changing your dose without

advising your doctor can increase

your risk of unwanted side effects

or can prevent the drug from

working properly.

Give this medicine to anyone

else, even if their symptoms

seem similar to yours or if they

have the same condition as you.

Things to be careful of

Be careful driving or operating

machinery until you know how

GONAL-f affects you.

Side Effects

Tell your doctor as soon as possible

if you do not feel well while using

GONAL-f.

All medicines can have side effects.

Sometimes they are serious, most of

the time they are not.

Do not be alarmed by this list of

possible side effects.

You may not experience any of them.

Ask your doctor or pharmacist to

answer any questions you may

have.

If you get any side effects, do not

stop using GONAL-f without first

talking to your doctor.

Tell your doctor immediately, or

go to Accident and Emergency at

your nearest hospital if you notice

any of the following:

signs of an allergic reaction,

including swelling of the face,

lips, tongue, or other parts of the

body; shortness of breath,

wheezing or difficulty breathing;

severe skin rash, itching or hives.

GONAL-F

Tell your doctor if you notice any

of the following and they worry

you:

pain, redness, itching or swelling

at the site of injection during your

treatment with GONAL-f

For women

vaginal bleeding

inflammation, swelling or pain in

your legs

signs of severe OHSS such as

severe lower abdominal pain,

severe pelvic pain, nausea,

vomiting, diarrhoea followed by

rapid weight gain, reduced

amounts of urine and shortness of

breath

warning signs of stroke or heart

attack

warning signs of blood clots such

as pain, warmth, redness,

numbness or tingling in your arm

or leg

Ectopic pregnancy (embryo

implanted outside the womb) may

occur, especially in women with

prior tubal disease.

Tell your doctor if you notice any

of the following and they worry

you:

headache, dizziness

stomach pain, abdominal

distension or abdominal

discomfort

nausea, vomiting

diarrhoea

For men

acne

some breast development

weight gain

These are common side effects.

Tell your doctor if you notice

anything else that is making you

feel unwell.

Other side effects not listed above

may also occur in some patients.

After Using GONAL-f

Storage

Prior to using, store GONAL-f in the

original package at 2°C to 8°C

(Refrigerate. Do not freeze.). Protect

from light.

Should refrigeration be unavailable,

GONAL-f can be stored below 25°C

for up to 3 months and away from

light.

After first piercing GONAL-f pen

with a needle, GONAL-f may be

stored below 25°C for a maximum of

21 days with the cap on, in order to

protect the product from light.

Do not use GONAL-f if the

solution contains particles or is not

clear.

Do not use the product after the

expiry date printed on the label.

Do not use GONAL-f if you notice

any visible signs of deterioration or

damage to the container.

Do not store it or any other

medicine in the bathroom or near a

sink.

Do not leave it in the car.

Keep this medicine where children

cannot reach it.

A locked cupboard at least one-and-

a-half-metres above the ground is a

good place to store medicines.

Disposal

If you are self-injecting, you should

discard all sharps into a disposal unit.

If you have any GONAL-f that has

expired or is left over from your

treatment refer this to your clinic/

pharmacy.

Product description

What it looks like

GONAL-f contains sterile solution

for injection in a cartridge, pre-

assembled in a pen.

GONAL-f solution for injection is

available in the following strengths

and pack sizes:

300 IU/0.5 mL (21.84

microgram). The pack contains 1

cartridge of solution for injection

pre-assembled in a pen and 8

needles for administration.

450 IU/0.75 mL (32.76

microgram). The pack contains 1

cartridge of solution for injection

pre-assembled in a pen and 12

needles for administration.

900 IU/1.5 mL (65.52

microgram). The pack contains 1

cartridge of solution for injection

pre-assembled in a pen and 20

needles for administration.

Each cartridge contains the following

ingredients:

Active ingredient

Follitropin alfa (rch)

Other ingredients

Sucrose

Dibasic sodium phosphate

dihydrate

Monobasic sodium phosphate

monohydrate

Sodium hydroxide

Phosphoric acid

Poloxamer

Methionine

Metacresol

Water for injections

Australian Registration

Numbers:

GONAL-f follitropin alfa (rch) 300

IU/0.5 mL solution for injection

cartridge pre-assembled in a pen:

AUST R 96230

GONAL-f follitropin alfa (rch) 450

IU/0.75 mL solution for injection

cartridge pre-assembled in a pen:

AUST R 96236

GONAL-f follitropin alfa (rch) 900

IU/1.5 mL solution for injection

cartridge pre-assembled in a pen:

AUST R 96237

GONAL-F

Supplier

GONAL-f is supplied in Australia

by:

Merck Healthcare Pty Ltd

Suite 1, Level 1, Building B

11 Talavera Road

Macquarie Park NSW 2113

E-mail:

medinfo.australia@merckgroup.com

For enquiries call: 1800 633 463

GONAL-f is supplied in New

Zealand by:

Healthcare Logistics

58 Richard Pearse Drive

Airport Oaks, Auckland

E-mail:

medinfo.australia@merckgroup.com

For enquiries call: 0800 426 252

This leaflet was prepared in

December 2019.

A011-1219

GONAL-F

Read the complete document

Version: A015-1219 1 Supersedes: A014-0219

AUSTRALIAN PRODUCT INFORMATION – GONAL-F

®

(follitropin alfa

(rch)) solution for injection

1

NAME OF THE MEDICINE

Follitropin alfa (rch)

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

GONAL-f is produced by a Chinese Hamster Ovary cell line transfected with the human FSH

subunit genes (i.e. by recombinant DNA technology). Each cartridge contains the active

ingredient follitropin alfa (rch) (recombinant human follicle stimulating hormone) 300 IU/0.5

mL, 450 IU/0.75 mL or 900 IU/1.5 mL.

For the full list of excipients, see Section 6.1 LIST OF EXCIPIENTS.

3

PHARMACEUTICAL FORM

Solution for injection in a cartridge pre-assembled in a pen.

4

CLINICAL PARTICULARS

4.1

T

HERAPEUTIC INDICATIONS

The treatment of anovulatory infertility in women who have been unresponsive to

clomiphene citrate or where clomiphene citrate is contraindicated.

For controlled ovarian hyperstimulation in women undergoing assisted reproductive

technologies.

GONAL-f is indicated with concomitant human chorionic gonadotrophin (hCG) therapy for

the stimulation of spermatogenesis in gonadotrophin-deficient men in whom hCG alone is

ineffective.

4.2

D

OSE AND METHOD OF ADMINISTRATION

Treatment with GONAL-f should be initiated under the supervision of a physician experienced

in the treatment of fertility disorders.

GONAL-f should be administered subcutaneously. The injection site should be alternated daily

to prevent lipoatrophy. Self-administration of GONAL-f should only be performed by patients

who are well motivated, adequately trained and who have access to expert advice. Each GONAL-

f pen is for individual patient use only.

Women with Anovulatory Infertility (WHO Group II)

The objective of GONAL-f therapy is to develop a single mature Graafian follicle from which the

ovum will be liberated after the administration of hCG.

GONAL-f may be given as a course of daily injections. In menstruating patients, treatment

should commence within the first 7 days of the menstrual cycle. Treatment should be tailored to

Version: A015-1219 2 Supersedes: A014-0219

the individual patient's response as assessed by measuring 1) follicle size by ultrasound and/or

2) oestrogen secretion. A commonly used regimen commences at 75 – 150 IU (5.46 to 10.92

microgram) FSH daily and is increased by 37.5 IU (2.73 microgram) up to 75 IU (5.46

microgram) at 7- or 14- day intervals if necessary, to obtain an adequate, but not excessive

response. If a patient fails to respond adequately after 5 weeks of treatment, that cycle should

be abandoned.

When an optimal response is obtained, a single injection of 250 microgram r-hCG or 5000 IU up

to 10,000 IU urinary human chorionic gonadotropin (u-hCG) should be administered 24 – 48

hours after the last GONAL-f injection. The patient is recommended to have coitus on the day of,

and the day following hCG administration.

If an excessive response is obtained, treatment should be stopped and hCG withheld (see

Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE). Treatment should recommence

in the next cycle at a dosage lower than that of the previous cycle.

Women undergoing Assisted Reproductive Technologies

A commonly used regimen for superovulation involves the administration of 150 IU (10.92

microgram) to 225 IU (16.5 microgram) of GONAL-f daily, commencing on days 2 or 3 of the

cycle. Treatment is continued until adequate follicular development has been achieved (as

assessed by monitoring of serum oestrogen concentrations and/or ultrasound examination),

with the dose adjusted according to the patient's response, to usually not higher than 450 IU

(32.76 microgram) daily.

A single injection of 250 microgram r-hCG or 5000 IU up to 10,000 IU u-hCG is administered 24

– 48 hours after the last GONAL-f injection to induce final follicular maturation. In clinical trials,

final follicular maturation was judged to be when at least two follicles were ≥ 16 mm mean

diameter and when E2 levels were within the physician’s acceptable range for the number of

follicles present.

Down-regulation with either a GnRH agonist or antagonist is now commonly used in order to

suppress the endogenous LH surge and to control tonic levels of LH. Dosage regimens should be

customised in order to achieve the desired result. In a commonly used protocol GONAL-f is

started approximately 2 weeks after the start of agonist treatment, both being continued until

adequate follicular development is achieved. For example, following two weeks treatment with

an agonist, 225 IU (16.5 microgram) GONAL-f is administered (subcutaneously) for the first 7

days. The dose is then adjusted according to the ovarian response.

Men with Hypogonadotrophic Hypogonadism

Prior to combined therapy with GONAL-f and hCG, pre-treatment should begin with hCG alone

at the appropriate dosage to achieve masculinisation and serum testosterone level within the

eugonadal range (> 9 – 10 nmol/L). This starting dose should be increased to the necessary

dosage in order to obtain normal testosterone values. If after an inadequate trial of hCG alone

(usually 6 months) at effective doses, GONAL-f should be given concomitantly at the dosage of

150 IU (10.92 microgram) three times a week. This regimen should be continued for a minimum

of 4 months. If after this period, the patient has not responded, the combination treatment (hCG

plus GONAL-f 150 IU (10.92 microgram) 3 times a week) may be continued. Current clinical

Version: A015-1219 3 Supersedes: A014-0219

experience indicates that prolonged treatment for up to 18 – 24 months may be necessary to

achieve spermatogenesis or fertility.

4.3

C

ONTRAINDICATIONS

GONAL-f is contraindicated for safety reasons in:

cases of prior hypersensitivity to follitropin alfa, or to any excipients of GONAL-f

tumours of the hypothalamus or pituitary gland

FSH therapy is contraindicated for safety reasons where the following exist:

In women:

pregnancy and lactation

ovarian enlargement or ovarian cyst of unknown aetiology

gynaecological haemorrhages of unknown aetiology

ovarian, uterine or breast carcinoma

FSH is contraindicated when an effective response cannot be obtained, such as:

In women

primary ovarian failure as indicated by high levels of FSH (ovarian dysgenesis, premature

menopause)

malformations of sexual organs incompatible with pregnancy

fibroid tumours of the uterus incompatible with pregnancy

In men

elevated gonadotrophin levels that indicate primary testicular failure

infertility disorders other than hypogonadotrophic hypogonadism

Use in Elderly and Children

GONAL-f should not be used in the elderly or children.

4.4

S

PECIAL WARNINGS AND PRECAUTIONS FOR USE

GONAL-f is a potent gonadotrophic substance capable of causing mild to severe adverse

reactions, and should only be used by physicians who are thoroughly familiar with infertility

problems and their management.

Gonadotrophin therapy requires a certain time commitment by physicians and supportive

health professionals, as well as the availability of appropriate monitoring facilities. In women,

safe and effective use of GONAL-f calls for monitoring of ovarian response with ultrasound,

alone or preferably in combination with measurement of serum oestradiol levels, on a regular

basis. There may be a degree of inter-patient variability in response to FSH administration, with

a poor response to FSH in some patients and exaggerated response in others. The lowest

effective dose in relation to the treatment objective should be used in both men and women.

Version: A015-1219 4 Supersedes: A014-0219

Before starting treatment, the couple's infertility should be assessed as appropriate and

putative contraindications for pregnancy evaluated. In particular, patients should be evaluated

for hypothyroidism, adrenocortical deficiency, hyperprolactinaemia, and appropriate specific

treatment given.

GONAL-f should be used with caution in patients with known hypersensitivity to gonadotrophin

presentations that do not contain FSH, due to the risk of cross-sensitivity. The first injection of

GONAL-f in such patients must be performed under direct medical supervision.

Self-administration of GONAL-f should only be performed by patients who are well motivated,

adequately trained and with access to expert advice. During training of the patient for self-

administration, special attention should be given to specific instructions for the use of the pre-

filled pen.

Treatment in women

Patients should be selected carefully according to the following guidelines: a thorough

gynaecological and endocrinological evaluation must be performed; presence of early

pregnancy should be ruled out; aetiology of any abnormal vaginal bleeding should be

established before starting GONAL-f therapy; evaluation of semen quality of the partner should

be performed; or other appropriate investigations should be performed as required.

Ovarian Hyperstimulation Syndrome (OHSS)

Mild to moderate uncomplicated ovarian enlargement, which may be accompanied by

abdominal distension and/or abdominal pain, occurs in approximately 20% of those treated

with follitropin and hCG, and generally regresses without treatment within two or three weeks.

In the presence of marked ovarian enlargement, treatment should be discontinued.

Patients undergoing superovulation are at an increased risk of developing Ovarian

Hyperstimulation Syndrome (OHSS) in view of the excessive oestrogen response and multiple

follicular development. Distinct from uncomplicated ovarian enlargement, OHSS is a condition

that can manifest itself with increasing degrees of severity. It comprises marked ovarian

enlargement, high serum sex steroids and an increase in vascular permeability which can result

in an accumulation of fluid in the peritoneal, pleural and, rarely, in the pericardial cavities.

OHSS can become a serious complication of human gonadotrophin therapy and sometimes leads

to fatal complications if not adequately treated.

Mild manifestations of OHSS include abdominal pain, abdominal discomfort and distension, and

enlarged ovaries. Moderate OHSS may additionally present with nausea, vomiting, ultrasound

evidence of ascites and marked ovarian enlargement. Severe OHSS further includes symptoms

such as severe ovarian enlargement, weight gain, dyspnoea or oliguria. Clinical evaluation may

reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, pleural effusions or

acute pulmonary distress. Rarely, severe OHSS may be complicated by ovarian torsion or

thromboembolic events, such as pulmonary embolism, ischaemic stroke or myocardial

infarction.

Independent risk factors for developing OHSS have been reported to include young age, lean

body mass, polycystic ovarian syndrome (PCOS), higher doses of exogenous gonadotrophins,

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high absolute or rapidly rising serum oestradiol levels and previous episodes of OHSS, large

number of developing ovarian follicles and large number of oocytes retrieved in ART cycles.

Careful monitoring of ovarian response with ultrasound alone or preferably in combination

with measurement of oestradiol levels is recommended prior to and during stimulation therapy,

especially in patients with PCOS.

OHSS may progress rapidly (within 24 hours) or over several days to become a serious medical

event. It most often occurs after treatment with follitropin or hCG has been discontinued,

reaching its maximum at about seven to ten days following treatment. Therefore, patients

should be followed for at least two weeks after follitropin or hCG administration.

If there are any symptoms or signs of OHSS, the patient must be evaluated, investigated, and

monitored. Adherence to recommended GONAL-f dosage and regimen of administration can

minimise the risk of OHSS. Monitoring of stimulation cycles by ultrasound scans as well as

oestradiol measurements are recommended to identify risk factors early.

Excessive oestrogenic response seldom gives rise to significant hyperstimulation unless hCG is

administered to induce ovulation. Cases of OHSS are more common, more severe and more

protracted if pregnancy occurs. Therefore, if signs of OHSS occur, it is recommended that hCG be

withheld and the physician should advise the patient to refrain from intercourse for at least 4

days. Intercourse should be prohibited in those patients in whom significant ovarian

enlargement occurs after ovulation because of the danger of haemoperitoneum resulting from

ruptured ovarian cysts.

Mild or moderate OHSS requires careful monitoring and may resolve spontaneously. Worsening

of symptoms suggests progression of OHSS and requires prompt clinical reassessment. If

necessary, the physician should recommend cessation of treatment or withholding hCG

injection, and closely monitor the ovarian response. Severe OHSS requires admission to hospital

and commencement of appropriate therapy in addition to cessation of gonadotrophins

treatment. Treatment of OHSS is primarily symptomatic, consisting of bed rest, fluid and

electrolyte management, and analgesics if needed.

The phenomenon of haemoconcentration associated with fluid loss into the peritoneal cavity,

pleural cavity and pericardial cavity has been seen to occur and should be thoroughly assessed

in the following manner: 1) fluid intake and output, 2) weight, 3) haematocrit, 4) serum and

urinary electrolytes, 5) urine specific gravity, 6) BUN and creatinine, and 7) abdominal girth.

These determinations are to be performed daily or more often if the need arises. Appropriate

imaging examination, especially ultrasound, should also be used for identifying, localising and

quantifying fluid loss.

There is an increased risk of injury to the ovary with OHSS. The ascitic, pleural and pericardial

fluids should not be removed unless absolutely necessary to relieve symptoms such as

pulmonary distress or cardiac tamponade. Pelvic examination may cause rupture of an ovarian

cyst, which may result in haemoperitoneum and should therefore be avoided. If this does occur,

and if bleeding becomes such that surgery is required, the surgical treatment should be

designed to control bleeding and to retain as much ovarian tissue as possible.

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Thromboembolic events

Thromboembolic events, including thrombophlebitis, pulmonary embolism, stroke and arterial

occlusion both in association with, and separate from OHSS, have been reported following

gonadotrophin therapy. In rare cases, thromboembolic events have resulted in death.

In women with recent or ongoing thromboembolic disease or women with generally recognised

risk factors for thromboembolic events, such as personal or family history, treatment with

gonadotrophins may further increase the risk for aggravation or occurrence of such events. In

these women, the benefits of gonadotrophin administration need to be weighed against the

risks. It should be noted, however, that pregnancy itself, as well as OHSS, also carries an

increased risk of thromboembolic events.

Multiple pregnancies

In patients undergoing induction of ovulation, the incidence of multiple pregnancy is increased

compared with natural conception. The majority of multiple conceptions are twins. Multiple

pregnancies, especially higher order, carry an increased risk of adverse maternal and perinatal

outcomes. The patient should be advised of the potential risk of multiple births before starting

treatment.

To minimise the risk of twins or higher order multiple pregnancy, careful monitoring of ovarian

response is recommended. Appropriate management, such as cycle cancellation, should be

considered in line with current clinical practice. The incidence of multiple pregnancy can be

minimised by using the recommended dose and schedule of administration (see Section 4.2

DOSE AND METHOD OF ADMINISTRATION).

In patients undergoing ART procedures, the risk of multiple pregnancy is related mainly to the

number of embryos replaced, their quality and the patient’s age. Single embryo transfer in good

prognosis cycles substantially reduces the risk of multiple pregnancy with little effect on live

birth rates.

Pregnancy loss

The incidence of pregnancy loss by miscarriage or abortion is higher in patients undergoing

stimulation of follicular growth for ovulation induction or ART than following natural

conception, but comparable with the rates found in women with other fertility problems.

Congenital anomalies

The prevalence of congenital anomalies after the use of ART may be slightly higher than after

spontaneous conceptions. Possible contributing factors include aspects inherent in the couple’s

infertility, ovulation induction agents, other medicines used in treatment and the ART

procedures. While there is no specific evidence from clinical trials or post-marketing data

implicating gonadotrophin use in adverse effects on pregnancy, embryonal or foetal

development, parturition or postnatal development, ovulation induction agents cannot be

excluded as a contributing factor.

Version: A015-1219 7 Supersedes: A014-0219

Treatment in men

Elevated endogenous FSH levels are indicative of primary testicular failure. Such patients are

unresponsive to GONAL-f/hCG therapy. Semen analysis is recommended in assessing the

response to treatment.

Porphyria

In patients with porphyria or a family history of porphyria, GONAL-f may increase the risk of an

acute attack. Deterioration or a first appearance of this condition may require cessation of

treatment.

Use in the elderly

GONAL-f should not be used in the elderly population (see Section 4.3 CONTRAINDICATIONS).

Paediatric use

GONAL-f should not be used in the paediatric population (see Section 4.3

CONTRAINDICATIONS).

Effects on laboratory tests

No data available.

4.5

I

NTERACTIONS WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTIONS

No clinically significant drug interactions have been reported during GONAL-f therapy.

Concomitant use of GONAL-f with other agents used to stimulate ovulation may potentiate the

follicular response, whereas concurrent use of a GnRH) agonist or antagonist to induce pituitary

desensitisation may increase the dosage of GONAL-f needed to elicit an adequate ovarian

response.

4.6

F

ERTILITY

,

PREGNANCY AND LACTATION

Effects on fertility

See Section 4.1 THERAPEUTIC INDICATIONS.

Use in pregnancy – Pregnancy Category D

Follitropin alfa is not intended for use during pregnancy (see Section 4.3

CONTRAINDICATIONS). In rats and rabbits, follitropin alfa caused dystocia and marked post

implantation loss at subcutaneous doses of greater than 5 IU/kg/day, indicating that it is

embryotoxic and fetotoxic. Follitropin alfa was not teratogenic at subcutaneous doses up to 320

IU/kg/day in rats or 5 IU/kg/day in rabbits.

Use in lactation.

It is not known whether follitropin alfa is excreted in human milk. In lactating rats, follitropin

alfa at doses up to 40 IU/kg did not influence lactation or have any effects on the postnatal

growth and development of the offspring. Follitropin alfa was measured in the milk in early

lactation.

Version: A015-1219 8 Supersedes: A014-0219

Because many drugs are excreted in human milk and because of the potential for serious

adverse reactions in the nursing infant from GONAL-f, a decision should be made whether to

discontinue breastfeeding or to discontinue the drug, taking into account the importance of the

drug to the mother.

4.7

E

FFECTS ON ABILITY TO DRIVE AND USE MACHINES

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

However, adverse events of these medicines include dizziness which could affect the ability to

drive or use machines (see Section 4.8 ADVERSE EFFECTS (UNDESIRABLE EFFECTS)).

4.8

A

DVERSE EFFECTS

(U

NDESIRABLE EFFECTS

)

The reactions reported below are classified according to frequency of occurrence as follows:

Very Common

≥ 1/10

Common

≥ 1/100 to < 1/10

Uncommon

≥ 1/1,000 to < 1/100

Rare

≥ 1/10,000 to < 1/ 1,000

Very Rare

< 1/10,000

Treatment in general

Immune system disorders

Very rare:

Mild to severe hypersensitivity reactions including anaphylactic reactions and

shock

Respiratory, thoracic and mediastinal disorders

Very rare:

Exacerbation or aggravation of asthma

General disorders and administration site conditions

Very common: Injection site reactions (e.g. pain, erythema, haematoma, swelling and/or

irritation at the site of injection)

Treatment in women

The following adverse events have been reported during gonadotrophin therapy:

Reproductive system and breast disorders

Very common: Ovarian cyst, mild to moderate ovarian enlargement

Common:

Mild or moderate OHSS (including symptomatology), intermenstrual bleeding

Uncommon:

Severe OHSS (including symptomatology)

Rare:

Complications of severe OHSS, ectopic pregnancy, adnexal torsion associated

with ovarian enlargement

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Gastrointestinal disorders

Common:

Abdominal pain, abdominal distension, abdominal discomfort, diarrhoea, nausea,

vomiting

Nervous system disorders

Very common: Headache, dizziness

Vascular disorders

Rare:

Thromboembolism

Refer to PRECAUTIONS for information on symptoms and management of OHSS.

Treatment in men

Reproductive system and breast disorders

Common:

Gynaecomastia

Skin and subcutaneous tissue disorders

Common:

Acne

Investigations

Common:

Weight gain

Reporting suspected adverse reactions

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 in Australia, or at https://nzphvc.otago.ac.nz/reporting/

in New Zealand.

4.9

O

VERDOSE

The effects of an overdose of GONAL-f are unknown, nevertheless, there is the possibility that

OHSS may occur (see Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE).

For information on the management of overdose, contact the Poisons Information Centre on

13 11 26 (Australia) or 0800 764 766 (New Zealand).

5

PHARMACOLOGICAL PROPERTIES

5.1

P

HARMACODYNAMIC PROPERTIES

Mechanism of action

In females, the most important effect resulting from parenteral administration of FSH is the

development of mature Graafian follicles. To complete follicular maturation and to stimulate

ovulation in the absence of an endogenous luteinising hormone (LH) surge, human chorionic

gonadotrophin (hCG) is given once monitoring of the patient indicates that sufficient follicular

Version: A015-1219 10 Supersedes: A014-0219

development has occurred. There may be a degree of inter-patient variability in response to FSH

administration, with lack of response to FSH in some patients. In males, FSH stimulates

spermatogenesis without significant effect on the androgen secreting interstitial cells.

Clinical trials

WHO Group II anovulatory infertile women

In a controlled study involving 222 randomised patients, cumulative ovulation rate was not

significantly different between GONAL-f and urofollitropin or urinary-derived hFSH (u-hFSH)

groups whether analysed on an intention-to-treat or evaluable patient basis. The ovulation rate

in each cycle was also not different between the two medicines.

Superovulation in Assisted Reproduction Techniques (ART)

Study 21884: The safety and efficacy of GONAL-f (r-hFSH; filled-by-mass) versus u-hFSH and its

equivalence as compared to GONAL-f old formulation (filled by bioactivity), all administered

subcutaneously, were assessed in a multicentre, randomised, single blind, phase III study in

infertile women undergoing in vitro fertilisation (IVF) and embryo transfer. All patients

underwent pituitary desensitisation (down-regulation) with a gonadotrophin-releasing

hormone (GnRH) agonist prior to and during stimulation of multiple follicular development

with one of the three study treatments. Randomisation occurred when pituitary down-

regulation was confirmed by an E

level of

50 pg/mL.

The primary efficacy parameter in this study was the number of fertilised oocytes retrieved per

patient. 837 patients entered the study, of whom 713 were randomised. Of these, 711 received

at least one dose of FSH: 237 patients received GONAL-f (r-hFSH; filled-by-mass), 237 patients

received u-hFSH

and 237 patients received GONAL-f old formulation (filled by bioactivity). The

number of oocytes retrieved was similar in all treatment groups. The efficacy of GONAL-f (r-

hFSH; filled-by-mass) although not superior, led to statistically higher response rates in the

number of fertilised oocytes as compared to u-hFSH. The efficacy results are summarised below

in Tables 1 and 2:

Table 1.

Number of Oocytes Fertilised: Summary Statistics (mean (SD)) by Treatment

(Study 21884)

Number of

patients

Missing

GONAL-f

(filled-by-

mass)

u-hFSH

Old GONAL-f

(filled by

bioactivity)

Overall

6.7 (4.1)

6.0 (3.7)

6.1 (4.3)

6.3 (4.0)

Read the complete document

Public Summary

Summary for ARTG Entry:

96230

GONAL-F follitropin alfa (rch) 300IU /0.5mL (21.84microgram) solution for injection cartridge,

pre-assembled in a pen

ARTG entry for

Medicine Registered

Sponsor

Merck Serono Australia Pty Ltd

Postal Address

Units 3-4/25 Frenchs Forrest Road East,FRENCHS FOREST, NSW, 2086

Australia

ARTG Start Date

1/12/2003

Product category

Medicine

Status

Active

Approval area

Drug Safety Evaluation Branch

Conditions

Conditions applicable to all therapeutic goods as specified in the document "Standard Conditions Applying to Registered or Listed Therapeutic Goods

Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Conditions applicable to the relevant category and class of therapeutic goods as specified in the document "Standard Conditions Applying to Registered

or Listed Therapeutic Goods Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Products

1. GONAL-F follitropin alfa (rch) 300IU /0.5mL (21.84microgram) solution for injection cartridge,

pre-assembled in a pen

Product Type

Single Medicine Product

Effective date

14/07/2017

Warnings

See Product Information and Consumer Medicine Information for this product

Standard Indications

Specific Indications

The treatment of anovulatory infertility in women who have been unresponsive to clomiphene citrate or where clomiphene citrate is contraindicated. For

controlled ovarian hyperstimulation in women undergoing assisted reproductive technologies. GONAL-f is indicated with concomitant human chorionic

gonadotrophin (hCG) therapy for the stimulation of spermatogenesis in gonadotrophin-deficient men in whom hCG alone is ineffective.

Additional Product information

Container information

Type

Material

Life Time

Temperature

Closure

Conditions

Cartridge

Glass Type I Clear

2 Years

Store at 2 to 8

degrees Celsius

Not recorded

Do not Freeze

Refrigerate

Pack Size/Poison information

Pack Size

Poison Schedule

1 cartridge + 8 needles

(S4) Prescription Only Medicine

Components

1. Medicine Component

Dosage Form

Injection, solution

Route of Administration

Subcutaneous

Visual Identification

Clear Colourless Solution.

Active Ingredients

Follitropin alfa

600 IU/mL

© Commonwealth of Australia.This work is copyright.You are not permitted to re-transmit, distribute or commercialise the material without obtaining prior

written approval from the Commonwealth.Further details can be found at http://www.tga.gov.au/about/website-copyright.htm.

Public Summary

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This is not an ARTG Certificate document.

The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown.

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