Consumer medicine information

Bemfola

Follitropin alfa

BRAND INFORMATION

Brand name

Bemfola

Active ingredient

Follitropin alfa

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Bemfola.

What is in this leaflet

This leaflet answers some common questions about Bemfola.

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 Bemfola 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 Bemfola used for

Bemfola contains follitropin alfa, which is similar to follicle stimulating hormone (FSH) found naturally in humans.

Bemfola 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.

Bemfola is an approved biosimilar to the reference product Gonal-f®. Comparability in safety, efficacy and quality between Bemfola and Gonal-f® have been established.

In women

Bemfola 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.

Bemfola is also used to stimulate the development of several follicles in women undergoing assisted reproductive technologies (ART) such as in vitro fertilisation (IVF).

Bemfola can be used together with another hormone called Luteinising Hormone (LH) to stimulate development of follicles in women who have been shown to produce very low levels of some of the hormones involved in the natural reproductive cycle.

In men

Bemfola 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 Bemfola has been prescribed for you. Your doctor may have prescribed it for another reason.

Bemfola is available only on a doctor's prescription.

Bemfola is not habit-forming.

Before you are given Bemfola

When you must not use Bemfola

Do not use Bemfola 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 Bemfola if you have tumours of the hypothalamus or pituitary gland.

For women

Do not use Bemfola 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 Bemfola 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 the packaging is damaged, return it to your pharmacist / clinic for disposal.

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

Before you start to use Bemfola

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 Bemfola.

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 Bemfola 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 Bemfola 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 babies of 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 Bemfola 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 Bemfola.

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 Bemfola.

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 Bemfola or may affect how well it works.

Your doctor has more information on medicines to be careful with or avoid while using Bemfola.

How Bemfola 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 Bemfola should be started under the supervision of a specialist doctor experienced in fertility treatment.

Bemfola is given as a course of daily injections.

You should have your injection at the same time each day.

How much to inject

Your doctor will decide the correct dose of Bemfola for you. Your dose of Bemfola 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 75 IU (5.5 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 (11 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 (33 microgram).
  3. Women who are not ovulating and have been diagnosed with very low levels of FSH and LH hormones
    The common dose usually starts at Bemfola 75 IU to 150 IU (5.5 to 11 microgram) together with 75 IU of lutropin alfa daily. The dose may be adjusted as your treatment progresses.
  4. Men with hypogonadotrophic hypogonadism
    Bemfola is commonly given with hCG. The common dose usually starts at 150 IU (11 microgram) three times a week.

How to inject

Bemfola is given as a subcutaneous (under your skin) injection in the lower abdominal area or thigh.

Bemfola 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 you the injection at home.

Where to inject

Bemfola 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 Bemfola for

For women

The length of treatment varies with each patient. It is possible to have more than one treatment cycle of Bemfola.

For men

The combination treatment of Bemfola and hCG could continue for at least 4 months and may continue for up to 18-24 months.

If you forget to inject Bemfola

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 Bemfola.

While you are using Bemfola

Your doctor will carefully monitor your response to Bemfola 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 Bemfola.

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

Tell all doctors, dentists and pharmacists who are treating you that you are using Bemfola.

For Women

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

Things you must not do

If you are self-injecting do not:

  • Stop using Bemfola 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 Bemfola affects you.

Side Effects

Tell your doctor as soon as possible if you do not feel well while using Bemfola.

All medicines can have side effects. Sometimes they are serious, most of the time they are not.

Ask your doctor or pharmacist to answer any questions you may have.

If you get any side effects, do not stop using Bemfola 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.

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 Bemfola

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.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

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 Bemfola

Storage

Prior to using, store Bemfola PEN in the original package at 2 °C to 8 °C (Refrigerate. Do not freeze).

Protect from light.

Before opening and within its shelf-life, the medicine may be removed from the refrigerator, without being refrigerated again, for up to 3 months kept at or below 25 °C.

The product if stored at or below 25 °C, must be discarded if it has not been used after 3 months.

Discard used pen and needle immediately after injection.

Do not use Bemfola PEN 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 Bemfola if you notice any visible signs of deterioration or damage to the container.

Do not use Bemfola on anyone else. It is for your use only.

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.

The Bemfola PEN once used should be disposed of in sharps container or return to your clinic or pharmacist for safe disposal.

If you have any Bemfola that has expired or is left over from your treatment take this to your clinic.

Product description

What it looks like

Bemfola Pen Injector is available in five strengths:

75 IU/0.125 mL (5.5 micrograms/0.125 mL);

150 IU/0.25 mL (11 micrograms/0.25 mL);

225 IU/0.375 mL (16.5 micrograms/0.375 mL);

300 IU/0.50 mL (22 micrograms/0.5 mL); and

450 IU/0.75 mL (33 micrograms/0.75 mL).

Bemfola Pen Injector is pre-filled with a clear, colourless solution of 0.125 mL (75 IU), 0.25 mL (150 IU), 0.375 mL (225 IU), 0.5 mL (300 IU) or 0.75 mL (450 IU).

Each cartridge contains the following ingredients:

Active ingredient

  • Recombinant human follicle stimulating hormone (follitropin alfa [rch])
    75 IU (5.5 microgram), 150 IU (11 microgram), 225 IU (16.5 microgram), 300 IU (22 microgram) or 450 IU (33 microgram)

Other ingredients

  • Sucrose
  • Dibasic sodium phosphate dihydrate
  • Monobasic sodium phosphate dihydrate
  • Phosphoric acid
  • Polaxamer
  • Methionine
  • Water for Injections

Pack sizes

Pack sizes of 1, 5 and 10 pre-filled pens. Not all pack sizes may be marketed. Each pack also contains the corresponding number of needles to be used with the pen for administration.

Bemfola Pens are not designed to allow the cartridge to be removed.

Australian Registration Numbers:

Bemfola 75 IU Pen Injector AUST R 231039

Bemfola 150 IU Pen Injector AUST R 231046

Bemfola 225 IU Pen Injector AUST R 231051

Bemfola 300 IU Pen Injector AUST R 231052

Bemfola 450 IU Pen Injector AUST R 231053

Supplier

Bemfola is supplied in Australia by:

Gedeon Richter Australia Pty Ltd
Suite 902, 15 Blue Street
North Sydney NSW 2060
Belrose NSW 2085
Australia

Phone number: 1300 GEDEON (1300 433 366)

BEMFOLA is supplied in New Zealand by:

Pharmacy Retailing (NZ) Ltd t/a
Healthcare Logistics
58 Richard Pearse Drive
Airport Oaks Mangere
AUCKLAND

Phone: 0800 GEDEON (0800 433 366)

This leaflet was prepared in October 2022

Instructions for Use

CONTENTS

  1. How to use the Bemfola pre-filled pen
  2. Before you start using your pre-filled pen
  3. Getting your pre-filled pen ready for injection
  4. Setting the dose
  5. Injecting the dose
  6. After the injection

1. How to use the Bemfola pre-filled pen

  • Before starting to use your pre-filled pen, please read these instructions the whole way through first.
  • Only use this pen for you – do not let anyone else use it.
  • The numbers on the dose display are measured in International Units or IU. Your doctor will have told you how many IU to inject each day.
  • Your doctor/pharmacist will tell you how many Bemfola pens you need to use for your complete treatment course.
  • Give yourself the injection at the same time each day.

2. Before you start using your pre-filled pen

2.1. Wash your hands

  • It is important that your hands and the things you use to get your pen ready are as clean as possible.

2.2. Find a clean area

  • A good place is a clean table or surface.

3. Getting your pre-filled pen ready for injection

Perform the injection every day at the same time. Take the pen out of the fridge 5 to 10 minutes before using it.

Note: Please check that the medicine is not frozen. If frozen, do not inject and immediately contact your pharmacist or nurse or doctor

Remove the peel tab from the injection needle.

Attach the needle by pushing directly on to the pen, until you hear a ‘click’. Do not twist or screw the needle onto the pen. Do not click on at an angle.

Caution: Do not push the dosage knob while clicking on the injection needle.

Remove the outer and inner needle protection caps.

4. Setting the dose

Hold the pen with the needle pointing upright. Tap the pen slightly in order to make eventual air bubbles rise.

Hold the pen with needle pointing Upright. Push the dosage knob until the stop.

Note: The activation bar disappears and a small amount of liquid splashes out.

If a small amount of liquid is not splashed out, the pen should not be used.

Turn the dosage knob until the desired dose (dose bar) is set in the display window.

Note: The pen is now ready for injection.

Caution: Do not push the dosage knob.

5. Injecting the dose

Immediately inject the solution: Your doctor or nurse will have already advised you where to inject (e.g. tummy, front of thigh). To minimise skin irritation, select a different injection site each day.

Fold the skin lightly and insert the injection needle completely at a 45° to 90° angle using a dart-like motion.

Caution: Do not push the dosage knob while inserting injection needle.

Push the dosage knob until the stop.

Note: Push slowly but continuously; the dose bar disappears.

End of the injection: The dose bar has disappeared completely behind the display window (the display window shows the injected dose). Wait for 5 seconds, then pull out the injection needle.

6. After the injection

Following injection do not remove the needle.

Place the needle and the used pre-filled pen into a suitable sharps container for disposal.

Throw away the packaging box, needle caps, peel tab, and the instructions for use in the household waste.

Published by MIMS December 2022

BRAND INFORMATION

Brand name

Bemfola

Active ingredient

Follitropin alfa

Schedule

S4

 

1 Name of Medicine

Follitropin alfa (rch).

2 Qualitative and Quantitative Composition

Bemfola is a biosimilar medicinal product, i.e. a medicine that has been demonstrated to be similar in quality, safety and efficacy to the reference medicinal product Gonal-f.
Bemfola contains the active ingredient follitropin alfa (rch). This is produced by a Chinese Hamster Ovary cell line transfected with the human FSH subunit genes (i.e. by recombinant DNA technology).
Clear glass cartridges containing Bemfola solution for injection are designed for subcutaneous injection pre-assembled in a disposable pen. Bemfola is available as solution for injection, containing follitropin alfa (rch) 75 IU/0.125 mL (5.5 microgram/0.125 mL), 150 IU/0.25 mL (11 microgram/0.25 mL), 225 IU/0.375 mL (16.5 microgram/0.375 mL), 300 IU/0.5 mL (22 microgram/0.5 mL) or 450 IU/0.75 mL (33 microgram/0.75 mL) in pre-filled pens.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Bemfola is a clear, colourless solution for injection for subcutaneous injection pre-assembled in a disposable pen.

4 Clinical Particulars

4.1 Therapeutic Indications

In adult women.

Bemfola is indicated for the treatment of anovulatory infertility in women who have been unresponsive to clomiphene citrate or where clomiphene citrate is contraindicated.
Controlled ovarian hyperstimulation in women undergoing assisted reproductive technologies.
Bemfola in association with a luteinising hormone (LH) preparation is recommended for the stimulation of follicular development in women with severe LH and FSH deficiency. In clinical trials these patients were defined by an endogenous serum LH level < 1.2 IU/L.

In adult men.

Bemfola 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 Dose and Method of Administration

Treatment with Bemfola should be initiated under the supervision of a physician experienced in the treatment of fertility disorders.
Bemfola should be administered subcutaneously. The injection site should be alternated daily to prevent lipoatrophy. Self administration of Bemfola should only be performed by patients who are well motivated, adequately trained and who have access to expert advice.
The solution should not be administered if it contains particles or is not clear.

Women with anovulatory infertility (WHO group II).

The objective of Bemfola therapy is to develop a single mature Graafian follicle from which the ovum will be liberated after the administration of hCG.
Bemfola 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 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 (5.5 to 11 microgram) FSH daily and is increased in increments of 37.5 IU (2.75 microgram) up to 75 IU (5.5 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. The Bemfola Pen provides treating physicians with capability of 12.5 IU increments to adapt patient's dose with flexibility.
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 Bemfola 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 (11 microgram) to 225 IU (16.5 microgram) of Bemfola 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 (33 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 Bemfola 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.
Downregulation 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 regimes should be customised in order to achieve the desired result. In a commonly used protocol Bemfola 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) Bemfola is administered (subcutaneously) for the first 7 days. The dose is then adjusted according to the ovarian response.

Women with anovulation resulting from severe LH and FSH deficiency.

In LH and FSH deficient women (hypogonadotrophic hypogonadism), the objective of Bemfola therapy in association with lutropin alfa is to develop a single mature Graafian follicle from which the oocyte will be liberated after the administration of human chorionic gonadotropin (hCG). Follitropin alfa should be given as a course of daily injections simultaneously with lutropin alfa. Since these patients are amenorrhoeic and have low endogenous oestrogen secretion, treatment can commence at any time.
A recommended regimen commences at 75 IU of lutropin alfa daily with 75-150 IU FSH. Treatment should be tailored to the individual patient's response as assessed by measuring follicle size by ultrasound and oestrogen response.
If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7-14 day intervals and preferably by 37.5-75 IU increments. It may be acceptable to extend the duration of stimulation in any one cycle to up to 5 weeks.
When an optimal response is obtained, a single injection of 250 microgram r-hCG or 5,000 IU up to 10,000 IU hCG should be administered 24-48 hours after the last follitropin alfa and lutropin alfa injections. The patient is recommended to have coitus on the day of, and on the day following, hCG administration.
Alternatively, IUI may be performed.
Luteal phase support may be considered since lack of substances with luteotrophic activity (LH/hCG) after ovulation may lead to premature failure of the corpus luteum.
If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment should recommence in the next cycle at a dose of FSH lower than that of the previous cycle.

Men with hypogonadotrophic hypogonadism.

Prior to combined therapy with Bemfola and hCG, pretreatment should begin with hCG alone at the appropriate dosage to achieve masculinisation and serum testosterone level within the eugonadal range (> 9-10 nanomol/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, Bemfola should be given concomitantly at the dosage of 150 IU (11 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 Bemfola 150 IU (11 microgram) 3 times a week) may be continued. Current clinical experience indicates that prolonged treatment for up to 18-24 months may be necessary to achieve spermatogenesis or fertility.

4.3 Contraindications

Bemfola is contraindicated for safety reasons in:
cases of prior hypersensitivity to follitropin alfa, or to any excipients of Bemfola;
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.

Bemfola should not be used in the elderly or children.

4.4 Special Warnings and Precautions for Use

Bemfola 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 Bemfola 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 interpatient 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.
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.
Bemfola 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 Bemfola in such patients must be performed under direct medical supervision.
Self administration of Bemfola 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 prefilled 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 Bemfola 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, 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 Bemfola 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.

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 postmarketing data implicating gonadotrophin use in adverse effects on pregnancy, embryonal or fetal development, parturition or postnatal development, ovulation induction agents cannot be excluded as a contributing factor.

Treatment in men.

Elevated endogenous FSH levels are indicative of primary testicular failure. Such patients are unresponsive to Bemfola/hCG therapy. Semen analysis is recommended in assessing the response to treatment.

Paediatric use.

Bemfola should not be used in the paediatric population (see Section 4.3 Contraindications).

Use in the elderly.

Bemfola should not be used in the elderly population (see Section 4.3 Contraindications).

Porphyria.

In patients with porphyria or a family history of porphyria, Bemfola may increase the risk of an acute attack. Deterioration or a first appearance of this condition may require cessation of treatment.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No clinically significant drug interactions have been reported during Bemfola therapy. Concomitant use of Bemfola 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 Bemfola needed to elicit an adequate ovarian response.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Bemfola is indicated for use in infertility (see Section 4.1 Therapeutic Indications).
(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 postimplantation 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.
 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.
Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in the nursing infant from Bemfola, 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 Effects 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 effect of Bemfola included dizziness which could affect the ability to drive or use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable 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.

Gastrointestinal disorders.

Common: abdominal pain, abdominal distension, abdominal discomfort, diarrhoea, nausea, vomiting.

Nervous system disorders.

Very common: headache, dizziness.

Vascular disorders.

Very rare: thromboembolism.
See Section 4.4 Special Warnings and Precautions for Use 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 events after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

The effects of an overdose of Bemfola are unknown, nevertheless, there is the possibility that OHSS may occur (see Section 4.4 Special Warnings and Precautions for Use).
Advise your patients to immediately contact their doctor or the Poisons Information Centre (in Australia telephone 131 126, in New Zealand telephone 0800 764 766) if they are concerned that they have given themselves too much Bemfola.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

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 development has occurred. There may be a degree of interpatient 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 follitropin alfa 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 follitropin alfa (r-hFSH; filled by mass) versus u-hFSH and its equivalence as compared to follitropin alfa 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 (downregulation) 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 downregulation was confirmed by an E2 level of ≤ 50 picogram/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 follitropin alfa (r-hFSH; filled by mass), 237 patients received u-hFSH, and 237 patients received follitropin alfa old formulation (filled by bioactivity). The number of oocytes retrieved was similar in all treatment groups. The efficacy of follitropin alfa (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 in Tables 1 and 2.
441 of 713 patients experienced 1474 adverse events: 145 patients in the follitropin alfa (r-hFSH; filled by mass) group, 143 patients in the u-hFSH group and 153 patients in the old follitropin alfa (filled by bioactivity) group. Most of the reported events were less in the follitropin alfa (r-hFSH; filled by mass) group when compared to the old follitropin alfa (filled by bioactivity) group. Overall, the pattern of adverse events was similar between treatment groups and was consistent with the profile of events reported in this indication.
Men with hypogonadotrophic hypogonadism. Male hypogonadotrophic hypogonadism (HH) is a rare condition therefore study sizes are limited. Two phase III (open and noncomparative) studies were conducted to assess the efficacy and safety of follitropin alfa in combination with hCG in inducing spermatogenesis in men with HH. The primary efficacy endpoint was the achievement of a mature sperm density of ≥ 1.5 x 106/mL. Follitropin alfa was administered subcutaneously at a dosage of 150 IU three times a week in combination with hCG (≥ 2000 IU twice weekly) for up to 18 months.
The first study was conducted in university clinical centres in France, Germany and UK. A total of 32 patients with complete, primary isolated HH were recruited into this study. They were azoospermic before entering the study, remained so after the pretreatment phase and none had prior treatment with FSH or GnRH. In the pretreatment phase, the patients were treated with hCG alone (2000 IU twice weekly for 3-6 months) to first normalise serum testosterone levels before initiating the treatment with follitropin alfa. Of 26 patients who received follitropin alfa, 19 patients were found to be eligible for efficacy evaluation.
The primary endpoint of a sperm density of ≥ 1.5 x 106/mL was achieved in 12/19 (63%) patients. Overall 15/19 (79%) patients achieved some spermatogenesis. The median time to initiate spermatogenesis was 9 months.
The second study was conducted in 2 university clinical centres in Australia. A total of 10 patients with severe HH entered the study, but only 8 patients completed the follitropin alfa treatment phase. Similar results to the first study were obtained.
The primary endpoint of a sperm density of ≥ 1.5 x 106/mL were achieved in 5/8 (63%) patients. Overall 7/8 (88%) patients achieved some spermatogenesis. The median time to initiate spermatogenesis was 6 months. The studies also demonstrated that follitropin alfa has a good safety profile and is well tolerated over the treatment period of up to 18 months.
Comparability of Bemfola with Gonal-f. Therapeutic equivalence of Bemfola and Gonal-f was demonstrated in a multinational, multicentre, randomised, controlled, assessor blind, parallel group study in women undergoing assisted reproductive technologies.
The primary efficacy endpoint was the number of oocytes retrieved. Equivalence of Bemfola and Gonal-f was considered to be shown if the two sided 95% CI for the difference in the number of oocytes retrieved was within the equivalence range [-2.9 oocytes, +2.9 oocytes].
The secondary endpoints 'total r-hFSH dose', 'number of days of r-hFSH stimulation', 'mean number of follicles on stimulation day 8 and day of hCG administration', 'median estradiol levels on stimulation day 8', and 'number of patients with cycle cancellation' were comparable between both treatment groups.
Differences were noted in the first treatment cycle in the 'proportion of patients requiring dose reductions due to risk of imminent OHSS' and 'median estradiol levels on the day of hCG administration'. However, these differences are considered small, i.e. 3.3% difference between Bemfola and Gonal-f in proportion of patients with dose reductions. Further, the difference in median estradiol levels is also considered small considering the range in estradiol concentrations.

5.2 Pharmacokinetic Properties

Absorption/ distribution/ metabolism/ excretion.

Following intravenous administration, follitropin alfa is distributed to the extracellular fluid space with an initial half-life of around 2 hours and eliminated from the body with a terminal half-life of about 1 day. The steady-state volume of distribution and total clearance are 10 L (0.17 L/kg) and 0.6 L/h (0.01 L/h/kg), respectively. One-eighth of the follitropin alfa dose is excreted in the urine.
Following subcutaneous administration, the absolute bioavailability is about 70%. Following repeated administration, follitropin alfa accumulates 3-fold at steady state within 3-4 days. In women whose endogenous gonadotrophin secretion is suppressed, follitropin alfa has nevertheless been shown to effectively stimulate follicular development and steroidogenesis, despite unmeasurable LH levels.
A phase I (study IMP 23572), open, randomised, 2 way crossover study to assess the relative bioavailability and the tolerability of r-hFSH of a reference follitropin alfa as a monodose freeze dried formulation and a new multidose liquid formulation, administered subcutaneously in male and premenopausal female volunteers with pituitary gonadotrope cell downregulation was conducted. The pharmacokinetic parameters from this study can be seen in Table 3.
Following the subcutaneous administration of both formulations, the 90% confidence intervals of the mean ratios for the bioavailability metrics, Cmax and AUClast lie within the predefined limits of 0.8-1.25 showing bioequivalence of liquid (test) and freeze dried (reference) formulations. Because the observed variability (< 10%) was much lower than expected a priori, the study allowed the detection of a small difference between the two formulations in rate (about 8%) and extent (about 5%). Suppression of endogenous FSH production was incomplete, probably more so in period 2 compared to period 1 and this probably explains the significant period effect observed. The significant difference seen on tmax is probably a function of the diverse mechanisms by which the drug enters the systemic circulation. In subjects where the diffusion processes from the subcutis to the adjacent small blood vessels dominate, earlier tmax is observed, whereas, in subjects where flow of FSH through the lymph to the systemic circulation is dominant, a later tmax probably occurs. This latter process may be nonlinear generating an apparent zero order input over sustained periods in some subjects. The mixture of these processes in the population leads to very high variability in tmax so a larger study would be necessary to truly assess the relative magnitude of this parameter for the two formulations.

Comparability of Bemfola with Gonal-f.

Equivalent pharmacokinetic (PK) profiles of Bemfola and Gonal-f have been demonstrated in a randomised, open label, two period, two treatment crossover study in 23 healthy female volunteers, with a duration of 11 weeks. The pharmacokinetic parameters are summarized in Table 4.

5.3 Preclinical Safety Data

Genotoxicity.

Follitropin alfa showed no genotoxic activity in a series of assays performed to evaluate its potential to cause gene mutations (Salmonella typhimurium, Escherichia coli and Chinese hamster lung cells) and chromosomal damage (human lymphocytes and mouse micronucleus test).

Carcinogenicity.

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

6 Pharmaceutical Particulars

6.1 List of Excipients

Sucrose, methionine, phosphoric acid, dibasic sodium phosphate dihydrate, monobasic sodium phosphate dihydrate, polaxamer and water for injections.

6.2 Incompatibilities

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

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). In New Zealand, information on the shelf-life can be found on the pubic Medsafe Product Detail information. The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Storage.

Store in a refrigerator (2°C - 8°C). Do not freeze.
Before opening and within its shelf life, the medicinal product may be removed from the refrigerator, without being refrigerated again, for up to 3 months at or below 25°C. The product must be discarded if it has not been used after 3 months.
Store in the original package in order to protect from light.
Each Bemfola Pen is for individual patient use only. Discard used pen and needle immediately after injection.

6.5 Nature and Contents of Container

Solution for injection in 1.5 mL cartridge (clear type I glass), with a plunger stopper (halobutyl rubber) and an aluminium crimp cap with a rubber inlay.
Bemfola is available in packs of 1, 5 and 10 pre-filled pens. Not all pack sizes may be marketed. Each pack also contains the corresponding number of needles to be used with the pen for administration.
Bemfola Pens are not designed to allow the cartridge to be removed.

6.6 Special Precautions for Disposal

Any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Human follicle stimulating hormone (FSH) is a glycoprotein (MW about 30,000) and is characterised by two amino acid chains known as α and β. The β-chain confers biological activity. The α-chain is common to all gonadotrophins with specificity residing in the β-chain.

Chemical structure.

The 92-amino-acid FSH alpha subunit in humans has the following sequence:
NH2-Ala-Pro-Asp-Val-Gln-Asp-Cys-Pro-Glu-Cys-Thr-Leu-Gln-Glu-Asn-Pro-Phe-Phe-Ser-Gln-Pro-Gly-Ala-Pro-Ile-Leu-Gln-Cys-Met-Gly-Cys-Cys-Phe-Ser-Arg-Ala-Tyr-Pro-Thr-Pro-Leu-Arg-Ser-Lys-Lys-Thr-Met-Leu-Val-Gln-Lys-Asn-Val-Thr-Ser-Glu-Ser-Thr-Cys-Cys-Val-Ala-Lys-Ser-Tyr-Asn-Arg-Val-Thr-Val-Met-Gly-Gly-Phe-Lys-Val-Glu-Asn-His-Thr-Ala-Cys-His-Cys-Ser-Thr-Cys-Tyr-Tyr-His-Lys-Ser-OH.
Note: The carbohydrate moiety is linked to the asparagine at positions 52 and 78.
The 111-amino-acid FSH beta subunit in humans has the following sequence:
NH2-Asn-Ser-Cys-Glu-Leu-Thr-Asn-Ile-Thr-Ile-Ala-Ile-Glu-Lys-Glu-Glu-Cys-Arg-Phe-Cys-Ile-Ser-Ile-Asn-Thr-Thr-Trp-Cys-Ala-Gly-Tyr-Cys-Tyr-Thr-Arg-Asp-Leu-Val-Tyr-Lys-Asp-Pro-Ala-Arg-Pro-Lys-Ile-Gln-Lys-Thr-Cys-Thr-Phe-Lys-Glu-Leu-Val-Tyr-Glu-Thr-Val-Arg-Val-Pro-Gly-Cys-Ala-His-His-Ala-Asp-Ser-Leu-Tyr-Thr-Tyr-Pro-Val-Ala-Thr-Gln-Cys-His-Cys-Gly-Lys-Cys-Asp-Ser-Asp-Ser-Thr-Asp-Cys-Thr-Val-Arg-Gly-Leu-Gly-Pro-Ser-Tyr-Cys-Ser-Phe-Gly-Glu-Met-Lys-Glu-OH.
Note: The carbohydrate moiety is linked to the asparagine at positions 7 and 24.

CAS number.

146479-72-3.

7 Medicine Schedule (Poisons Standard)

Schedule 4 Prescription Medicine.

Summary Table of Changes