Follitropin Delta

Uses

Follitropin Delta beta injection is used for the development of multiple follicles in ovulatory patients participating in an Assisted Reproductive Technology (ART) program. Follitropin Delta beta is also used for the induction of ovulation and pregnancy in anovulatory infertile patients in whom the cause of infertility is functional and not due to primary ovarian failure.

Follitropin Delta is also used to associated treatment for these conditions: Assisted Reproductive Technology therapy, Ovulation induction therapy, Stimulation of spermatogenesis therapy

How Follitropin Delta works

Follitropin Delta 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.

Dosage

Follitropin Delta dosage

Ovulation induction: IM or SC admin: Initiate with 75 IU daily for up to 14 days, may increase by 37.5 IU at wkly intervals. Once follicular growth or serum estradiol levels indicates an adequate response, administer a single dose of hCG (5,000-10,000 IU) after the last dose to induce ovulation. Withhold hCG if the ovaries are abnormally enlarged or if abdominal pain occurs. Max: 300 IU/day.

Assisted reproductive technologies: IM or SC admin: 150-225 IU /day for at least 1st 4 days of treatment. Adjust dose based on individual ovarian response. Usual maintenance dose: 75-300 IU for 6-12 days; 375-600 IU for poor responders. Max (clinical studies): 600 IU/day. Upon adequate follicular development, a single dose of hCG (5,000-10,000 IU) is administered for final oocyte maturation. Oocyte retrieval can be done 34-36 hr later. Withhold hCG if ovaries are abnormally enlarged on the last day of follicular treatment.

Side Effects

Ovarian cysts, mild to severe inj site reactions, headache, mild to moderate OHSS, abdominal pain, GI disturbances. Rarely, severe OHSS, ovarian torsion, thromboembolism, mild systemic allergic reactions.

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 Delta is contraindicated in pregnant women. No studies have been done in nursing mothers.

Precaution

May result in multiple births. Ovarian hyperstimulation syndrome (OHSS), serious pulmonary conditions and thromboembolic events may occur. Evaluate patients for hypothyroidism, adrenocortical deficiency, hyperprolactinaemia, pituitary and hypothalamic tumors before starting therapy.

Interaction

No drug-drug interaction studies have been performed.

Food Interaction

Volume of Distribution

• 8 L [female subjects following intravenous administration of a 300 IU dose]

Elimination Route

The absorption rate is the main driving force behind the pharmokinetics of Follitropin Delta 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.

Half Life

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

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]

Elimination Route

Via liver and kidneys.

Pregnancy & Breastfeeding use

Category X: Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Contraindication

Abnormal genital bleeding of undetermined origin, hormone sensitive malignancies; ovary, breast, uterus, hypothalamus, testes or pituitary gland tumor; ovarian cysts or enlargement not due to the polycystic ovary syndrome; high levels of FSH indicating primary gonadal failure (ovarian or testicular); uncontrolled thyroid or adrenal dysfunction; presence of any cause of infertility other than anovulation; hypersensitivity; pregnancy, lactation.

Acute Overdose

May lead to OHSS and multiple gestations.

Storage Condition

Store at 2-8°C.

Innovators Monograph

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