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| Primary information |
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| ID | 11637 |
| Therapeutic ID | Th1252 |
| Protein Name | Follitropin |
| Sequence | >Th1252_Follitropin
APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSYNRVTVMGGFKVENHTACHCSTCYYHKS
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| Molecular Weight | 22672.9 |
| Chemical Formula | C975H1513N267O304S26 |
| Isoelectric Point | 7.5 |
| Hydrophobicity | -0.33 |
| Melting point | 55 °C |
| Half-life | Circulation half life of 3-4 hours, elimination half life of 35-40 hours |
| Description | Follitropin is a human follicle stimulating hormone (FSH) preparation of recombinant DNA origin, which consists of two non-covalently linked, non-identical glycoproteins designated as the alpha- and beta- subunits. The alpha- and beta- subunits have 92 and 111 amino acids. The alpha subunit is glycosylated at Asn 51 and Asn 78 while the beta subunit is glycosylated at Asn 7 and Asn 24. Follitropin beta is produced in genetically engineered Chinese hamster cell lines (CHO). The nomenclature “beta” differentiates it from another recombinant human FSH product that was marketed earlier as follitropin alpha. Follitropin is important in the development of follicles produced by the ovaries. Given by subcutaneous injection, it is used in combination with human chorionic gonadotropin (hCG) to assist in ovulation and fertility. Follitropin may also be used to cause the ovary to produce several follicles, which can then be harvested for use in gamete intrafallopian transfer (GIFT) or in vitro fertilization (IVF). Numerous physio-chemical tests and bioassays indicate that follitropin beta and follitropin alpha are indistinguishable. However, a more recent study showed there is may be a slight clinical difference, with the alpha form tending towards a higher pregnancy rate and the beta form tending towards a lower pregnancy rate, but with significantly higher estradiol (E2) levels. Structural analysis shows that the amino acid sequence of follitropin beta is identical to that of natural human follicle stimulating hormone (FSH). Further, the ogliosaccharide side chains are very similar, but not completely identical to that of natural FSH. However, these small differences do not affect the bioactivity compared to natural FSH. |
| Indication/Disease | In women having been diagnosed with primary ovarian failure, it is used in combination with human chorionic gonadotropin (hCG) to assist in ovulation and fertility. In men with hypogonadotrophic hypogonadism, it is used to induce spermatogenesis. Follitropin may also be used to cause the ovary to produce several follicles, which can then be harvested for use in gamete intrafallopian transfer (GIFT) or in vitro fertilization (IVF). |
| Pharmacodynamics | Used for the treatment of female infertility, Follitropin beta or follicle stimulating hormone (FSH) stimulates ovarian follicular growth in women who do not have primary ovarian failure. FSH, the active component of Follitropin beta is the primary hormone responsible for follicular recruitment and development. |
| Mechanism of Action | Follitropin is a recombinant form of endogenous follicle stimulating hormone (FSH). FSH binds to the follicle stimulating hormone receptor which is a G-coupled transmembrane receptor. Binding of the FSH to its receptor seems to induce phosphorylation and activation of the PI3K (Phosphatidylinositol-3-kinase) and Akt signaling pathway, which is known to regulate many other metabolic and related survival/maturation functions in cells. |
| Toxicity | Headaches, ovarian cysts, nausea and upper respiratory tract infections occurred in more than 10% of women in clinical trials. In men, the most serious adverse events reported were testicular surgery for cryptorchidism which existed prestudy, hemoptysis, an infected pilonidal cyst, and lymphadenopathy associated with an Epstein-Barr viral infection. Other concerns include overstimulation of the ovaries, pulmonary and vascular complications and multiple births. Post-marketing reports revealed hypersensitivity reactions including anaphylactoid reactions and asthma. Follitropin is contraindicated in pregnant women. No studies have been done in nursing mothers. |
| Metabolism | NA |
| Absorption | The absorption rate is the main driving force behind the pharmokinetics of Follitropin alpha as the rate of absorption was found to be slower than the elimination rate after administration subcutaneously and intramuscularly. The bioavailability is approximately 66-76%. The time to peak after subcutaneous injection in healthy volunteers was 8-16 hours in females and 11-20 hours in males. |
| * 8 L [female subjects following intravenous administration of a 300 IU dose] |
| Clearance | * 0.01 1*h-1kg-1 [European women with a single intramuscular dose of 300 IU] * 0.01 1*h-1kg-1 [Japanese women with a single intramuscular dose of 300 IU] |
| Categories | Gonadotropins, Pituitary |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Follicle-stimulating hormone receptor |
| Brand Name | Bravelle |
| Company | Ferring Pharmaceuticals Inc. |
| Brand Description | Ferring Pharmaceuticals Inc. |
| Prescribed For | Subcutaneous |
| Chemical Name | 75 [iU]/1mL |
| Formulation | BRAVELLE® is contraindicated in women who exhibit: Prior hypersensitivity to BRAVELLE® or urofollitropins High levels of FSH indicating primary ovarian failure [see INDICATIONS AND USAGE] Pregnancy BRAVELLE® may cause fetal harm when administered to a pregnant woman [see Use In Specific Populations]. BRAVELLE® is contraindicated in women who are pregnant. If this drug is used during pregnancy, or if the woman becomes pregnant while taking this drug, the woman should be apprised of the potential hazard to a fetus. Presence of uncontrolled non-gonadal endocrinopathies (e.g., thyroid, adrenal, or pituitary disorders) [see INDICATIONS AND USAGE] Sex hormone dependent tumors of the reproductive tract and accessory organ Tumors of pituitary gland or hypothalamus Abnormal uterine bleeding of undetermined origin Ovarian cysts or enlargement of undetermined origin, not due to polycystic ovary syndrome |
| Physical Appearance | headache, nausea, vomiting, mild stomach/abdominal pain, bloating, mild pelvic pain, cramps, constipation, injection site reactions (redness, pain, swelling, itching, or irritation), breast tenderness/pain, skin rash, hot flashes, or acne |
| Route of Administration | Bravelle is a purified form of a hormone called follicle-stimulating hormone (FSH). This hormone is important in the development of follicles (eggs) that are produced by the ovaries in women. Bravelle is used together with other medicines to treat infertility in women with FSH deficiency. This medicine... |
| Recommended Dosage | Bravelle is a prescription medicine used to treat the symptoms of Ovulation Induction, Assisted Reproductive Technology (ART), and Spermatogenesis. Bravelle may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | BRAVELLE® is a product containing a highly purified preparation of human follicle stimulating hormone (hFSH) extracted from the urine of postmenopausal women. Human FSH is a gonadotropin and consists of two non-covalently linked glycoproteins designated as the α and β subunits. The α subunit has 92 amino acids of which two are modified by attachment of carbohydrates. The β subunit has 111 amino acids of which two are modified by attachment of carbohydrates. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |