Product Information
Registration Status: ActiveSIN15711P
PERGOVERIS SOLUTION FOR INJECTION IN PRE-FILLED PEN (300 IU + 150 IU)/0.48ML is approved to be sold in Singapore with effective from 2019-06-11. It is marketed by MERCK PTE LTD, with the registration number of SIN15711P.
This product contains Follitropin Alfa 300 IU/0.48ml, and Lutropin Alfa 150 IU/0.48ml in the form of INJECTION, SOLUTION. It is approved for Not Available use.
This product is manufactured by Merck Serono S.p.A in ITALY.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}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
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).
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.
Pharmacokinetics
- 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.
- Distribution
- * 8 L [female subjects following intravenous administration of a 300 IU dose]
- Metabolism
- Elimination
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]
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.
Active Ingredient/Synonyms
Follicle stimulating hormone | Follitrophin alfa | Follitrophin alpha | Follitrophin beta | Follitropin alfa | Follitropin alfa/beta | Follitropin alpha | Follitropin beta | Follitropin delta | Follitropin gamma | Follotropin recombinant | FSH | FSH alpha | FSH-a | FSH-b | FSH-beta | Recombinant human follicle stimulating hormone beta | Recombinant human follicle-stimulating hormone (r-HFSH) | rFSH-alpha | Follitropin |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Description
Lutropin alfa is a recombinant human luteinizing hormone produced in yeast with 2 subunits, alpha = 92 residues, beta = 121 residues. It is a heterodimeric glycoprotein. Each monomeric unit is a glycoprotein molecule. In females, an acute rise of LH ("LH surge") triggers ovulation and the development of the corpus luteum. In males, it stimulates Leydig cell production of testosterone. Lutropin alfa was the first and only recombinant human form of luteinizing hormone (LH) developed for use in the stimulation of follicular development.
Indication
For treatment of infertility in women with hypothalamic or pituitary insufficiency (hypogonadotropic hypogonadism) and profound LH deficiency (LH
Mechanism of Action
Luteinizing hormone binds to a receptor shared with the human chorionic gonadotropin hormone (hCG) on the ovarian theca (and granulosa) cells and testicular Leydig cells. This LH/CG transmembrane receptor is a member of the super-family of G protein-coupled receptors. Adenylate cyclase then activates many other pathways leading to steroid hormone production and other follicle maturation processes.
Pharmacokinetics
- Absorption
- Mean absolute bioavailability is 56%, following sub-Q administration, maximum serum concentrations reached after 4–16 hours. Time to peak, serum: 9 hours
- Distribution
- The steady state volume of distribution is around 10-14 L.
- Metabolism
- Elimination
Clearance
* 2 – 3 L/h [healthy female following subcutaneous administration]
Toxicity
Lutropin alfa is not indicated for people under 16 and over 60, pregnant and lactating women, patients with uncontrolled thyroid and adrenal failure, patients with active, untreated tumours of the hypothalamus and pituitary gland, and in any patient with a condition that makes a normal pregnancy possible such as primary ovarian failure or fibroid tumors of the uterus.
Active Ingredient/Synonyms
ICSH | Insterstiial cell-stimulating hormone | LH | LH-B | LSH- beta | LSH-B | Luteinizing hormone | Luteinizing hormone beta subunit | Lutrophin | Lutropin alpha | Lutropin beta chain precursor | Lutropin alfa |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.