Follitrope^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Lg Life Sciences, Ltd. (Republic Of Korea)

ATC Code

G03GA05 (Follitropin alfa)

Active Substance

Follitropin alfa (Rec.INN registered by WHO)

Dosage Form

Follitrope®

Lyophilizate for preparation of solution for intramuscular and subcutaneous administration 75 IU: vial 1 pc. in a set with solvent

Dosage Form, Packaging, and Composition

Lyophilizate for preparation of solution for intramuscular and subcutaneous administration in the form of a white or almost white mass; the supplied solvent is a transparent colorless liquid.

Excipients: sucrose, trometamol, sodium hydroxide, hydrochloric acid.

Solvent: sodium chloride, polysorbate 20, water for injections.

75 IU – colorless glass vials with a volume of 3 ml (1) in a set with a solvent (vial 1 ml 1 pc.) – plastic contour cell packaging (1) – cardboard packs.

Clinical-Pharmacological Group

Recombinant human follicle-stimulating hormone

Pharmacotherapeutic Group

Follicle-stimulating agent

Pharmacological Action

Recombinant FSH, obtained by genetic engineering from Chinese hamster ovary cells.

It has a gonadotropic effect – it stimulates the growth and maturation of the follicle/follicles, promotes the development of several follicles during controlled ovarian hyperstimulation, including for assisted reproductive technology programs.

Pharmacokinetics

After subcutaneous administration, the absolute bioavailability is approximately 70%.

After repeated injections, a threefold accumulation of follitropin alfa in the blood is observed compared to a single injection.

Steady-state concentration is achieved within 3-4 days.

The volume of distribution is 10 L, total clearance is 0.6 L/h.

Indications

Anovulation (including polycystic ovary syndrome (PCOS)) in women in case of ineffectiveness of previous clomifene therapy.

Controlled ovarian hyperstimulation in assisted reproductive technology programs.

Ovarian stimulation in women with severe deficiency of FSH and LH (in combination with an LH preparation, in the appropriate dosage form).

Stimulation of spermatogenesis in hypogonadotropic hypogonadism in men (in combination with hCG, in the appropriate dosage form).

ICD codes

Dosage Regimen

Administer Follitrope^® subcutaneously or intramuscularly.

Determine the dosage regimen individually for each patient based on the indication, ovarian response, and semen analysis results.

For anovulation in women, initiate treatment with 75 IU daily. Adjust the dose after 14 days if necessary; increase by 37.5 IU at subsequent treatment steps. Do not exceed a maximum daily dose of 225 IU. Continue until adequate follicular development is observed. Administer hCG 24-48 hours after the last Follitrope^® injection to finalize follicular maturation and induce ovulation.

For controlled ovarian hyperstimulation in ART cycles, start with 150-225 IU daily, beginning on days 2 or 3 of the cycle. Adjust the dose based on the ovarian response monitored via ultrasound and serum estradiol levels. Use the lowest effective dose. Administer hCG to induce final follicular maturation once an adequate number of follicles of sufficient size are present.

For ovarian stimulation in women with severe FSH and LH deficiency, use Follitrope^® in combination with a luteinizing hormone (LH) preparation. Initiate treatment with 75-150 IU of Follitrope^® daily. Adjust the dose based on ovarian monitoring.

For stimulation of spermatogenesis in men with hypogonadotropic hypogonadism, use Follitrope^® in combination with hCG pretreatment. Administer Follitrope^® at a dose of 75-150 IU two to three times per week. Continue treatment for a minimum of 4 months. Adjust the dose based on semen analysis and hormone levels.

Reconstitute the lyophilisate immediately before use with the supplied solvent. Inject the prepared solution subcutaneously or intramuscularly. Rotate injection sites to minimize local reactions.

Monitor patients closely for signs of ovarian hyperstimulation syndrome (OHSS). Withhold hCG and advise the patient to refrain from intercourse if an excessive ovarian response occurs.

Adverse Reactions

In women

Immune system disorders very rarely – hypersensitivity reactions, from mild and moderate (skin redness, rash, facial swelling, urticaria, difficulty breathing) to severe, including anaphylactic reactions and shock.

Nervous system disorders very often – headache.

Cardiovascular system disorders very rarely – thromboembolism, usually associated with OHSS.

Respiratory system disorders very rarely – in patients with bronchial asthma, worsening of the course or exacerbation of the disease.

Gastrointestinal system disorders often – abdominal pain, heaviness, abdominal discomfort, nausea, vomiting, diarrhea.

Reproductive system disorders very often – ovarian cysts; often – mild and moderate OHSS; infrequently – severe form of OHSS; rarely – complication of OHSS, ectopic pregnancy (in women with a history of fallopian tube diseases), multiple pregnancy.

Local reactions very often – pain, redness, hematoma, swelling at the injection site.

Other fever, arthralgia.

In men

Immune system disorders very rarely – hypersensitivity reactions, from mild and moderate (skin redness, rash, facial swelling, urticaria, difficulty breathing) to severe, including anaphylactic reactions and shock.

Respiratory system disorders very rarely – in patients with bronchial asthma, worsening of the course or exacerbation of the disease.

Skin and subcutaneous tissue disorders often – acne.

Reproductive system disorders: often – gynecomastia, varicocele.

Metabolism and nutrition disorders often – weight gain.

Local reactions very often – pain, redness, hematoma, swelling at the injection site.

Other fever, arthralgia.

Contraindications

Hypersensitivity to follitropin alfa; tumors of the pituitary gland or hypothalamus.

In women: pregnancy; space-occupying lesions or ovarian cysts (not associated with PCOS), gynecological bleeding of unknown etiology, ovarian cancer, uterine cancer, breast cancer; in cases where the goal of therapy cannot be achieved – with developmental anomalies of the genital organs and uterine fibroids incompatible with pregnancy, with primary ovarian insufficiency, premature menopause.

Not used in adolescent girls under 18 years of age.

Use is not indicated after menopause.

In men: with primary hypogonadism (primary testicular failure).

With caution

In patients with porphyria, as well as in the presence of porphyria in relatives.

In women with a history of or current thromboembolic disease, or in women at high risk of developing thromboembolic complications (presence of thrombosis or thromboembolism in close relatives).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy.

Not used during breastfeeding.

Pediatric Use

Not used in adolescent girls under 18 years of age.

Geriatric Use

The safety and efficacy of follitropin alfa in elderly patients have not been established.

Special Precautions

Before starting treatment, the fact of marital infertility and possible contraindications to pregnancy should be established.

Concomitant endocrine diseases (hypothyroidism, adrenal insufficiency, hyperprolactinemia, tumor of the hypothalamus and pituitary gland) must be excluded.

The patency of the fallopian tubes should be assessed to select the method of ART.

Fallopian tube obstruction should be ruled out if the patient is not participating in an in vitro fertilization program.

In patients with porphyria, as well as in the presence of porphyria in relatives, careful monitoring is required during therapy with follitropin alfa.

If the condition worsens or the first signs of this disease appear, discontinuation of therapy may be required.

When conducting therapy with follitropin alfa, assessment of the condition of the ovaries using ultrasound is required – both separately and in combination with determining the concentration of estradiol in the blood plasma.

The response to FSH administration may differ among different patients, so the minimum effective doses should be used in both women and men.

When prescribing hCG, the possibility of ovarian hyperstimulation syndrome increases, therefore, if an excessive estrogenic response occurs, hCG is not prescribed, and patients are advised to refrain from coitus for at least 4 days.

The likelihood of hyperstimulation can be reduced by aspirating all follicles before ovulation.

The frequency of multiple pregnancy and childbirth during ovulation induction is higher compared to natural conception, with twins being the most common variant in multiple pregnancies.

Multiple pregnancy, especially with a large number of embryos, increases the risk of adverse outcomes for the mother and fetus.

To minimize the risk of multiple pregnancy, careful monitoring of the ovarian response is necessary.

In ART, the risk of multiple pregnancy is mainly associated with the number of embryos transferred, their viability, and the age of the patient.

The frequency of congenital fetal malformations after the use of ART programs may be slightly higher than with natural pregnancy and childbirth.

However, it is unknown whether this is related to the characteristics of the parents (for example, maternal age, sperm quality) and multiple pregnancy, or directly to the ART procedures themselves.

An increased concentration of follicle-stimulating hormone in the blood serum of men may indicate primary testicular failure.

In this case, therapy with follitropin alfa is not effective, its use is contraindicated.

Drug Interactions

With simultaneous use with other means for stimulating ovulation, an increase in the follicular formation response is possible, while simultaneous desensitization of the pituitary gland with a GnRH agonist may lead to the need to increase the dose of follitropin alfa that causes an adequate ovarian response.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.