Pergoveris (FOLLITROPIN ALFA_Lutropin Alfa)

Uses

Lutropin alfa is a form of recombinant human luteinizing hormone used to treat female infertility due to hypothalamic or pituitary insufficiency, or due to profound luteinizing hormone deficiency.

For treatment of infertility in women with hypothalamic or pituitary insufficiency (hypogonadotropic hypogonadism) and profound LH deficiency (LH <1.2 international units [IU]/L)

Urofollitropin lyophilized powder for injection containing 82.5 International Units of FSH, to deliver 75 International Units FSH after reconstituting, supplied as lyophilized powder in sterile vials with diluent vials

Urofollitropin is a gonadotropin used for:

• Induction of ovulation in women who have previously received pituitary suppression: intramuscular and subcutaneous administration
• Development of multiple follicles as part of an Assisted Reproductive Technology (ART) cycle in ovulatory women who have previously received pituitary suppression

Pergoveris (FOLLITROPIN ALFA_Lutropin Alfa) is also used to associated treatment for these conditions: Hypogonadism, InfertilityInfertility, Assisted Reproductive Technology therapy, Ovulation induction therapy

How Pergoveris (FOLLITROPIN ALFA_Lutropin Alfa) works

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.

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.

Dosage

Pergoveris (FOLLITROPIN ALFA_Lutropin Alfa) dosage

Ovulation Induction:

• Initial starting 150 International Units per day for 5 days, administered subcutaneously or intramuscularly
• Individualization of dosing after 5 days
• Dosage adjustments not to occur more frequently than once every 2 days and not to exceed 75 to 150. International Units per adjustment
• Do not administer greater than 450 International Units per day

Assisted Reproductive Technology (ART):

• Initial starting dose of the first cycle-225 International Units per day for 5 days, administered subcutaneously
• Individualization of dosing after 5 days
• Dosage adjustments not to occur more frequently than once every 2 days and not to exceed 75 to 150. International Units per adjustment
• Do not administer greater than 450 International Units per day

Side Effects

The most common adverse reactions (≥5% incidence) in ovulation induction include headache, hot flashes, OHSS, pain, and respiratory disorder.

The most common adverse reactions (≥2% incidence) in ART include: abdominal cramps, abdominal fullness/enlargement, headache, nausea, OHSS, pain, pelvic pain, and post retrieval pain

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.

Precaution

• Abnormal Ovarian Enlargement
• Ovarian Hyperstimulation Syndrome
• Pulmonary and Vascular Complications
• Ovarian Torsion
• Multi-fetal Gestation and Birth
• Congenital Malformations
• Ectopic Pregnancy
• Spontaneous Abortion
• Ovarian Neoplasms

Interaction

No drug/drug interaction studies have been conducted for Urofollitropin in humans

Volume of Distribution

The steady state volume of distribution is around 10-14 L.

Time to peak in plasma: IM: 17 hours (single dose), 11 hours (multiple doses) SubQ: 21 hours (single dose), 10 hours (multiple doses)

Elimination Route

Mean absolute bioavailability is 56%, following sub-Q administration, maximum serum concentrations reached after 4–16 hours. Time to peak, serum: 9 hours

74%

Half Life

Biphasic; terminal half-life is approximately 18 hours.

Circulation half life of 3-4 hours, elimination half life of 35-40 hours

Clearance

• 2 – 3 L/h [healthy female following subcutaneous administration]

Elimination Route

Total body clearance is approximately 2 to 3 L/h with less than 5 percent of the dose being excreted unchanged renally.

Via liver and kidneys

Pregnancy & Breastfeeding use

Pregnancy Category X. Do not use Urofollitropin in pregnant women. It is not known whether Urofollitropin is excreted in human milk

Contraindication

Urofollitropin is contraindicated in women who exhibit:

• Prior hypersensitivity to urofollitropins
• High levels of FSH indicating primary ovarian failure
• Pregnancy
• Presence of uncontrolled non-gonadal endocrinopathies
• 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

Special Warning

Pediatric Use: Safety and efficacy not established.

Renal and Hepatic Insufficiency: Safety, efficacy, and pharmacokinetics of Urofollitrophin in women with renal or hepatic insufficiency have not been established.

Storage Condition

Lyophilized powder may be stored refrigerated or at room temperature (3° to 25° C). Protect from light. Use immediately after reconstitution. Discard unused material.

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