COMPOSTTION

Each vial of Follitrope Inj. is accompanied by 1 mL solvent vial for injection. 1 vial of Follitrope contains 75 IU or 150 IU recombinant follicle stimulating hormone (FSH) as active ingredient, sucrose. Tris and 1 vial of solvent contain 0.01% polysorbate 20 in saline solution.

DESCRIPTION

White lyophilized powder for injection in a clear vial and clear solution in a clear vial for reconstitution.

INDICATIONS

Treatment of female infertility in the following clinical situations:

Controlled ovarian hyperstimulation to induce the development of multiple follicles in medically assisted reproduction program (e. g. in vitro fertilization/embryo transfer; IVF/ET, gamete intra-fallopian transfer; GIFT, zygote intra-fallopian transfer; ZIFT, intracytoplasmic sperm injection; ICSI).

DOSAGE AND ADMINISTRATION

Treatment with Follitrope should be initiated under the supervision of a physician experienced in the treatment of fertility problems. Follitrope is intended for subcutaneous and intramuscular administration. The powder should be reconstituted prior to the first use with the solvent provided. 3 vials of Follitrope 75 IU or 150 IU can be reconstituted with 1 mL solvent.

Women undergoing ovarian stimulation for multiple follicular development prior to in vitro fertilization of other assisted reproductive technologies:

Various stimulation protocols are applied in order to suppress the endogenous LH surge and to control tonic levels of LH. A commonly used regimen for hyperovulation involves the administration of 150 - 300 IU of Follitrope daily, commencing on days 2 to 5 of the cycle. Treatment is continued until adequate follicular development has been achieved (as assessed by monitoring of serum oestrogen levels and/or ultrasound examination), with the dose adjusted according to the patient’s response, to usually not higher than 450 IU daily. In general, adequate follicular development was achieved on average by the tenth day of treatment. A single injection up to 10,000 IU hCG (Human Chorionic Gondadotropin) is administered 48 hours after the last Follitrope injection.

WARNINGS AND PRECAUTIONS

1. Contra-indications

1. Tumors of the ovary, breast, uterus, hypothalamus or pituitary gland
2. Undiagnosed vaginal bleeding
3. Hyperactivity to the active substance or to any of the excipients
4. Primary ovarian failure
5. Ovarian cysts or enlarged ovaries, not related to polycystic ovarian disease (PCOD)
6. Malformations of the sexual organs incompatible with pregnancy
7. Fibroid tumors of the uterus incompatible with pregnancy
8. The presence of uncontrolled non-gonadal endocrinopathies (e.g. thyroid, adrenal or pituitary disorders).

2. Warnings

1. Since infertile women undergoing assisted reproduction, and particularly IVF, often have tubal abnormalities, the incidence of ectopic pregnancies might be increased.
   Early ultrasound confirmation that a pregnancy is intrauterine is therefore important.

2. The diagnosis of ovarian hyperstimulation may be confirmed by ultrasound examination. Ultrasonographic assessment of follicular development, and determination of oestradiol levels should be performed prior to treatment and at regular intervals during treatment. If unwanted ovarian hyperstimulation occurs, the administration of FSH should be discontinued and hCG must be withheld, because it may induce the ovarian hyperstimulation syndrome (OHSS).

   Clinical symptoms and sign of mild ovarian hyperstimulation syndrome are abdominal pain, nausea, vomiting and weight gain. In rare cases, severe ovarian hyperstimulation syndrome can happen characterized by large ovarian cysts (prone to rupture), ascites, often hydrothorax, which may be life threatening. In rare instances, venous or arterial thromboembolism may occur in association with OHSS. But if hCG administration is withheld and intercourse is avoided at least for 4 days, excessive estrogen response does not cause ovarian hyperstimulation.

3. Precautions

1. There were no report of hypersensitivity of human FSH, but the possibility of anaphylaxis response is present. The first infection of Follitrope should be performed under direct medical supervision.
2. Rates of pregnancy loss in women undergoing assisted reproduction techniques are higher than in the normal population.

4. Undesirable Effects

1. Unwanted ovarian hyperstimulation is observed.
2. Clinical use of Follitrope by the intramuscular or subcutaneous routes may lead to local reactions at the site of infection such as bruising, pain, swelling and itching, the majority of which are mild and transient in nature. Systemic reaction uses not observed.
3. A slightly increased risk of ectopic pregnancy and multiple pregnancies can be seen.
4. In rare instances, threomboembolism can be associated with Human Menopausal Gonadotropin (hMG)/hCG therapy. This may also occur with Follitrope/hCG therapy.

5. Interaction

1. Concomitant use of Follitrope and Clomiphene citrate may enhance the follicular response.
2. After pituitary desensitization induced by a Gonadotropin Release Hormone (GnRH) analogue, a higher dose of Follitrope may be necessary to achieve an adequate follicular response.
3. No drug/drug interaction studies have been performed.

6. Pregnancy and lactation

Follitrope must not be used during pregnancy and lactation.

7. Effects on ability to drive and use machines

No effects on ability to drive and use machines have been observed.

8. Overdose

No data on acute toxicity of Follitrope in humans is available, but the acute toxicity of Follitrope and of urinary gonadotropin preparations in animal studies has been shown to be very low. Very high dose of FSH may lead to hyperstimulation of the ovaries.

9. Instruction for use, handling and disposal

1. Follitrope should be reconstituted with the solvent provided first and gently inverted (avoid vigorous shaking).
2. Do not use if the solution contains particles or the solution is not clear.
3. Once the vial opened, it should be used immediately.
4. Any solution left should be disposed after using one time.

HOW SUPPLIED

75 IU 1 vial with 1 solvent vial/pack
150 IU 1, 5 vials with 1 solvent vials/pack

STORAGE CONDITION

• Store below 25° C in hermetic container protected from light.

SHELF LIFE

• 36 months