GONAL-f^®

• GONAL-f (follitropin alfa for injection) is follicle-stimulating hormone (FSH) with no urinary proteins, which stimulates oocyte (egg) development in women
• GONAL-f is a highly purified recombinant form of FSH, manufactured using the latest technology with proven effectiveness and safety in clinical studies
• GONAL-f is provided in liquid formulation in the prefilled pen, for easy administration under the skin (subcutaneous injection)
• GONAL-f belongs to a group of medicines called “gonadotropins”

• GONAL-f is used to stimulate the maturation of follicles in ovulating patients undergoing Assisted Reproductive Technologies (ART), such as in vitro fertilization (IVF)
• GONAL-f is also used to stimulate the maturation of follicles in some patients whose menstrual cycle is either irregular or absent; in both cases, another hormone, hCG (human chorionic gonadotropin) is given to complete the maturation of follicles

Before GONAL-f treatment, be sure to ask your doctor…

• How long will my treatment last?
• How are you monitoring my response?

Every treatment is individualized. Your treatment has been carefully designed for you by your doctor. Over the course of your treatment, doses may range between 75 to 450 IU depending on your specific medical condition and your response to the medicine.

IU is International Units

Do not use GONAL-f if you:

• Have high levels of FSH indicating primary ovarian failure
• Have uncontrolled thyroid or adrenal dysfunction
• Are allergic (hypersensitive) or have a history of hypersensitivity to FSH or to any of the other ingredients of GONAL-f
• Are pregnant or breastfeeding
• Have ovarian enlargement or a cyst not due to polycystic ovarian disease (PCO)
• Have vaginal bleeding of unknown cause
• Have tumours of the ovary, uterus, breast/soft chest tissue or brain (hypothalamus or pituitary gland)

GONAL-f is often used with other medicines to stimulate ovulation (e.g., hCG and LH), which may help the maturation of follicles that contain the eggs. If a GnRH agonist or antagonist medicine is also given along with your GONAL-f in your treatment program, you may be told by your doctor to change your dose of GONAL-f over the course of your treatment.

No other significant interactions with other medicines have been reported.

Fertility drugs are safe to take with close monitoring by your doctor. As with all medication, there is a potential for side effects; the following have been reported with the use of GONAL-f during clinical trials and post-market use:

Common and Very Common: may affect 1 to 10 users in 100

• Ovarian cysts
• Mild to moderate ovarian enlargement
• Breast tenderness/tenderness of soft tissue in the chest/underarm area
• Mild to moderate ovarian hyperstimulation syndrome (OHSS)
• Mild to severe injection site reaction (such as pain, redness, bruising, swelling and/or irritation)
• Headache
• Stomach pain or bloating
• Feeling sick (nausea), vomiting, diarrhea

Uncommon, Rare and Very Rare: may affect less than 1 to 10 users in 1,000

• Severe OHSS
• Blood clots (thrombosis)
• Difficulty breathing (acute pulmonary distress)
• Worsening of asthma
• Mild to severe allergic reactions (hypersensitivity) such as rash, red skin, hives, swelling of your face with difficulty breathing may occur; these reactions can sometimes be serious

The greatest concern your doctor will have is OHSS. To avoid this, your doctor will carefully monitor your response to GONAL-f. Ovarian enlargement, sometimes accompanied by abdominal bloating and pain, may occur in about 20% of patients taking gonadotropins. This is generally reversed with cessation of treatment and severe life-threatening cases are rare.

A causal relationship between treatment with fertility drugs and ovarian cancer has not been established.

The following medical events have been reported subsequent to pregnancies resulting from gonadotropin therapy in controlled clinical trials: spontaneous abortion, tubal pregnancy, premature labour, postpartum fever and congenital abnormalities.

None of these events were thought to be drug-related; incidence is not more than that found in the general population.

This is not a complete list of side effects. If you experience any unusual symptoms or side effects while taking GONAL-f, report them to your doctor or pharmacist immediately. You should discuss the possibility of side effects with your doctor before you begin treatment.

General

To help avoid side effects and ensure proper use, talk to your doctor or pharmacist before you take GONAL-f. Your fertility should be evaluated before the treatment is started by a doctor experienced in treating fertility disorders.

Porphyria

If you have porphyria or a family history of porphyria, GONAL-f may increase the risk of an acute attack. Tell your doctor immediately if:

• Your skin becomes fragile and easily blistered, especially skin that has been frequently in the sun, and/or
• You have stomach, arm or leg pain

In case of the above events your doctor may recommend that you stop treatment.

Overstimulation of the Ovary During FSH Therapy

Ovarian Enlargement

• Use of FSH therapy to stimulate follicular development may result in the growth of more than one follicle
• This may result in mild to moderate uncomplicated ovarian enlargement which may be accompanied by abdominal distention and/or abdominal pain; it is more commonly seen in those with polycystic ovarian syndrome

Ovarian Hyperstimulation Syndrome (OHSS)

• Treatment increases your risk of developing ovarian hyperstimulation syndrome (OHSS) – when multiple follicles develop and may become large cysts; in rare cases, severe OHSS may be life-threatening
• OHSS may cause fluid build-up in your abdominal and chest areas and can cause blood clots to form; call your doctor right away if you notice severe abdominal swelling, pain in the stomach area (abdomen), feeling sick (nausea), vomiting, sudden weight gain due to fluid build-up, diarrhea, decreased urine output or trouble breathing
• However, if you follow your doctor’s instructions for the recommended dose and schedule of administration, the occurrence of OHSS is uncommon; GONAL-f treatment seldom causes significant OHSS unless the medicine used to induce final follicular maturation and ovulation (containing human chorionic gonadotropin – hCG) is administered
• In cases where OHSS is developing it is recommended to not give hCG, and pregnancy should be prevented at this time by not having sexual intercourse or taking any other steps to achieve pregnancy.

Breathing and Blood Clotting

• Serious breathing problems (e.g., lung collapse, extreme shortness of breath and worsening of asthma) have been reported with use of gonadotropin therapy
• Treatment with gonadotropin therapy may increase the risk of having a blood clot (thrombosis) which may or may not be associated with Ovarian Hyperstimulation Syndrome
• Blood clots can lead to serious medical conditions, such as blockage in the lungs (pulmonary embolus), blood vessel problems (thrombophlebitis), heart attack, stroke, blockage in the arteries in your arms and legs (which may result in a loss of your arm or leg)
• In rare cases, lung complications and/or blood clots have resulted in death

Reproductive Issues

• Since patients undergoing assisted reproduction, particularly IVF, may have tubal abnormalities, the incidence of ectopic pregnancies (pregnancy in the fallopian tubes) might be increased
• Early ultrasound to confirm pregnancy is in the uterus is important; miscarriages may be higher than in the normal population, but comparable with the rates found in patients with fertility problems
• Reports of multiple births have been associated with fertility treatments – you should discuss the potential risk of multiple births with your doctor before beginning treatment
• Incidence of multiple births with GONAL-f is no different from any other gonadotropin and depends on protocol used by the clinic; your doctor will monitor you closely to help minimize the possibility of a multiple pregnancy
• Majority of births (about 80%) are single babies; of those women who do have multiple births, the majority of these are twins – only very few people conceive 3 or more babies; even so, neither single nor multiple births can be guaranteed
• There have been reports of ovarian and other reproductive system tumours in patients who have had infertility treatment; it is not known if treatment with fertility medicines increases the risk of these tumours in infertile women

GONAL-f is available in 3 pre-filled pen formats:

• 300 IU Pen – 300 IU/0.5 mL (22 μg/0.5 mL)
• 450 IU Pen – 400 IU/0.75 mL (33 μg/0.75 mL)
• 900 IU Pen – 900 IU/1.5 mL (66 μg/1.5 mL)

• Store at 2-8°C (in a refrigerator) or store for a single period between 2 and 25°C (in the refrigerator or at room temperature) for a maximum of 3 months
  • After first use, the pen may be stored at 25°C (room temperature) for a maximum of 28 days
• Do not use the GONAL-f Pen if the solution contains particles or is not clear
• Do not freeze
• Protect the GONAL-f Pen from light
• Keep in a safe place out of the reach of children
• Do not use after the expiry date

No, this product does not contain latex.

If you dialed the dose past your prescribed dose, simply turn the injection button back to the correct dose. To adjust the dose, you can turn the injection button either clockwise or counter-clockwise. After confirming the correct dose from the display window, you can proceed with the injection.

If you have accidentally injected too much GONAL-f, do not panic. Simply contact your physician or healthcare professional for further instructions.

IMPORTANT: The maximum dose that can be dialed is 450 IU for the 900 & 450 IU Pen & 300 IU for the 300 IU Pen.

Do not take a double dose to make up for any doses you have missed. Contact your doctor for advice if you forget to take a dose of GONAL-f.

When you cannot push the injection button down, it means your pen is empty and it is unable to provide you with your desired dose; you may still see a small amount of medication remaining in the pen – this is normal.

If the dose display shows a number higher than 0 after your injection, this indicates that the pen is empty and that the complete dose has not been given. If this happens, the number shown in the dose display indicates the missing amount of GONAL-f solution that is needed to complete your dose. This is the dose you need to inject using a new pen. To complete your dose, set the dose to the missing amount (displayed on the empty pen) that you have just finished, and proceed with the injection.