Follitropin

Identification

Summary

Follitropin is a form of recombinant human follicle stimulating hormone used to stimulate follicle development in women with primary ovarian hypogonadism and in men with hypogonadotropic hypogonadism.

Brand Names
Bemfola, Follistim, Gonal F, Gonal-F, Menopur, Ovaleap, Pergoveris, Puregon
Generic Name
Follitropin
DrugBank Accession Number
DB00066
Background

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.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Hormones
Protein Structure
Protein Chemical Formula
C975H1513N267O304S26
Protein Average Weight
22672.9 Da
Sequences
>Alpha chain
APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCC
VAKSYNRVTVMGGFKVENHTACHCSTCYYHKS
>Beta chain
NSCELTNITIAIEKEECRFCISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYET
VRVPGCAHHADSLYTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKE
Download FASTA Format
Synonyms
  • Folitropina alfa
  • Folitropina beta
  • Folitropina delta
  • 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

Pharmacology

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).

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Associated Therapies
Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
AFollicle-stimulating hormone receptor
agonist
Humans
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.

Volume of distribution
  • 8 L [female subjects following intravenous administration of a 300 IU dose]
Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Via liver and kidneys.

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]
Adverse Effects
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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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcalabrutinibThe therapeutic efficacy of Follitropin can be decreased when used in combination with Acalabrutinib.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Follitropin.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Follitropin.
AfatinibThe therapeutic efficacy of Follitropin can be decreased when used in combination with Afatinib.
AldesleukinThe therapeutic efficacy of Follitropin can be decreased when used in combination with Aldesleukin.
Food Interactions
No interactions found.

Products

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International/Other Brands
Cinnal-F
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BemfolaInjection, solution450 IU/0.75mlSubcutaneousGedeon Richter Plc.2016-09-08Not applicableEU flag
BemfolaInjection, solution150 IU/0.25mlSubcutaneousGedeon Richter Plc.2016-09-08Not applicableEU flag
BemfolaInjection, solution300 IU/0.50mlSubcutaneousGedeon Richter Plc.2016-09-08Not applicableEU flag
BemfolaInjection, solution225 IU/0.375mlSubcutaneousGedeon Richter Plc.2016-09-08Not applicableEU flag
BemfolaInjection, solution75 IU/0.125mlSubcutaneousGedeon Richter Plc.2016-09-08Not applicableEU flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
FollistimFollitropin (75 [iU]/1mL) + Water (5 mL/5mL)KitIntramuscular; SubcutaneousOrganon USA, Inc.1997-09-292005-01-01US flag
Humegon Inj 75 I.U.Follitropin (75 unit / kit) + Luteinizing hormone (75 unit / kit) + Sodium chloride (.9 % / kit)Liquid; Powder, for solutionIntramuscularOrganon Canada Ltd Ltee1993-12-312006-08-17Canada flag
MENOGON 75 IU LIYOFILIZE TOZ ICEREN AMPUL,5 ADETFollitropin (75 iu) + Luteinizing hormone (75 iu)Injection, powder, lyophilized, for solutionIntramuscular; SubcutaneousFERRİNG İLAÇ SAN. VE TİC. LTD. ŞTİ.2006-04-11Not applicableTurkey flag
MenopurFollitropin (75 [iU]/1) + Luteinizing hormone (75 [iU]/1) + Sodium chloride (9 mg/1)InjectionSubcutaneousFerring Pharmaceuticals Inc.2004-10-29Not applicableUS flag
MENOPUR 1200 IU MULTI DOZ ICIN SC ENJEKSIYONLUK COZELTI TOZU ICEREN FLAKON VE KULLANIMA HAZIR ENJEKTORDE COZUCU (1 ADET FLAKON + 2 ADET KULLANIMA HAZIR ENJEKTOR)Follitropin (1200 iu/1ml) + Luteinizing hormone (1200 iu/1ml)Injection, powder, lyophilized, for solutionSubcutaneousFERRİNG İLAÇ SAN. VE TİC. LTD. ŞTİ.2015-07-06Not applicableTurkey flag

Categories

ATC Codes
G03GA06 — Follitropin betaG03GA10 — Follitropin deltaG03GA05 — Follitropin alfa
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
2M2GGL7HUP
CAS number
146479-72-3

References

General References
  1. Goa KL, Wagstaff AJ: Follitropin alpha in infertility: a review. BioDrugs. 1998 Mar;9(3):235-60. [Article]
UniProt
P01225
Genbank
M16647
PubChem Substance
46508818
RxNav
227518
ChEMBL
CHEMBL1201692
Therapeutic Targets Database
DAP001028
PharmGKB
PA449693
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Follicle-stimulating_hormone
FDA label
Download (468 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedDiagnosticEndometrial Diseases / Female Infertility1
4CompletedHealth Services ResearchFemale Infertility1
4CompletedOtherAnovulatory cycle / Healthy Volunteers (HV) / Hyperandrogenism / Polycystic Ovarian Syndrome (PCOS)1
4CompletedPreventionInfertility1
4CompletedTreatmentEgg Donation1

Pharmacoeconomics

Manufacturers
  • Organon usa inc
  • Emd serono inc
Packagers
  • EMD Canada Inc.
  • Organon Pharmaceuticals
  • Vetter Pharma Fertigung GmbH and Co. KG
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous150 IU/0.25ML
Injection, solutionSubcutaneous225 IU/3.75ML
Injection, solutionSubcutaneous225 IU/0.375ML
Injection, solutionSubcutaneous300 IU/0.50ML
Injection, solutionSubcutaneous75 IU/0.125ML
SolutionSubcutaneous150 UI
SolutionSubcutaneous150 IU
SolutionSubcutaneous300 IU
SolutionSubcutaneous75 IU
KitIntramuscular; Subcutaneous
Injection, solutionIntramuscular; Subcutaneous150 [iU]/0.5mL
Injection, solutionIntramuscular; Subcutaneous75 [iU]/0.5mL
Injection, solutionSubcutaneous175 [iU]/0.210mL
Injection, solutionSubcutaneous300 [iU]/0.36mL
Injection, solutionSubcutaneous350 [iU]/0.42mL
Injection, solutionSubcutaneous600 [iU]/0.72mL
Injection, solutionSubcutaneous650 [iU]/0.78mL
Injection, solutionSubcutaneous900 [iU]/1.08mL
Injection, solutionSubcutaneous975 [iU]/1.17mL
Solution150 iu/1vial
Injection, powder, for solution
Powder75 iu/1vial
SolutionSubcutaneous75 UI
Injection, powder, lyophilized, for solutionSubcutaneous37.5 IU
Injection, powder, for solutionParenteral; Subcutaneous1050 IU/1.75ML
Injection, powder, for solutionParenteral; Subcutaneous150 IU
Injection, powder, for solutionParenteral; Subcutaneous300 IU/0.5ML
Injection, powder, for solutionParenteral; Subcutaneous37.5 IU
Injection, powder, for solutionParenteral; Subcutaneous450 IU/0.75ML
Injection, powder, for solutionParenteral; Subcutaneous75 IU
Injection, powder, for solutionSubcutaneous1050 IU/1.75ml
Injection, powder, for solutionSubcutaneous150 IU
Injection, powder, for solutionSubcutaneous300 IU/0.5ml
Injection, powder, for solutionSubcutaneous450 IU/0.75ml
Injection, powder, for solutionSubcutaneous75 IU/ML
Injection; injection, solutionSubcutaneous300 IU/0.5ml
KitSubcutaneous1050 [iU]/2mL
KitSubcutaneous450 [iU]/1mL
Powder, for solutionIntramuscular; Subcutaneous1200 unit / vial
Powder, for solutionIntramuscular; Subcutaneous150 unit / vial
Powder, for solutionIntramuscular; Subcutaneous33 mcg / vial
Powder, for solutionIntramuscular; Subcutaneous37.5 unit / vial
Powder, for solutionIntramuscular; Subcutaneous5.5 mcg / vial
Powder, for solutionIntramuscular; Subcutaneous75 unit / vial
Powder, for solutionIntramuscular; Subcutaneous77 mcg / vial
Injection, powder, lyophilized, for solutionSubcutaneous1050 iu/1.75ml
InjectionSubcutaneous150 iu
Injection, solutionSubcutaneous300 iu/0.5ml
Injection, solutionSubcutaneous22.23 mcg
Solution300 iu/0.5ml
InjectionSubcutaneous37.5 iu
Injection, solutionSubcutaneous450 iu/0.75ml
Injection, powder, lyophilized, for solutionSubcutaneous450 iu/0.75ml
Injection, solutionSubcutaneous33.34 mcg
Solution450 iu/0.75ml
Injection, powder, lyophilized, for solutionSubcutaneous75 iu
Injection, solutionSubcutaneous66.69 mcg
Injection, solutionSubcutaneous900 iu/1.5ml
Solution900 iu/1.5ml
Injection, powder, for solutionSubcutaneous75 IU
Injection, powder, for solutionSubcutaneous600 iu/ml
SolutionSubcutaneous300 unit / 0.5 mL
SolutionSubcutaneous450 unit / 0.75 mL
SolutionSubcutaneous900 unit / 1.5 mL
KitSubcutaneous75 [iU]/1mL
Injection, solutionSubcutaneous300 [iU]/0.5mL
Injection, solutionSubcutaneous450 [iU]/0.75mL
Injection, solutionSubcutaneous900 [iU]/1.5mL
Injection, solutionSubcutaneous150 [iU]/0.25mL
Injection, powder, for solutionSubcutaneous
Injection, solutionSubcutaneous22 mcg/0.5ml
Liquid; powder, for solutionIntramuscular
InjectionSubcutaneous
Injection, powder, for solutionIntramuscular; Subcutaneous
Injection, powder, lyophilized, for solutionSubcutaneous
Injection, powder, lyophilized, for solutionIntramuscular; Subcutaneous
Powder, for solutionIntramuscular
Injection, powder, for solutionSubcutaneous
Kit; powder, for solutionSubcutaneous
PowderParenteral; Subcutaneous
SolutionSubcutaneous
Injection, powder, for solutionSubcutaneous150 IU
Injection, solutionSubcutaneous300 IU/0.48ml
Injection, solutionSubcutaneous450 IU/0.72ml
Injection, solutionSubcutaneous900 IU/1.44ml
Injection, solutionIntramuscular; Subcutaneous100 IU/0.5ML
Injection, solutionIntramuscular; Subcutaneous150 IU/0.5ML
Injection, solutionIntramuscular; Subcutaneous200 IU/0.5ML
Injection, solutionIntramuscular; Subcutaneous225 IU/0.5ML
Injection, solutionIntramuscular; Subcutaneous250 IU/0.5ML
Injection, solutionIntramuscular; Subcutaneous300 IU/0.36ML
Injection, solutionIntramuscular; Subcutaneous600 IU/0.72ML
Injection, solutionIntramuscular; Subcutaneous75 IU/0.5ML
Injection, solutionSubcutaneous150 IU/0.18mL
Injection, solutionSubcutaneous300 IU/0.36mL
Injection, solutionSubcutaneous900 IU/1.08ml
Solution833 iu/1ml
SolutionIntramuscular; Subcutaneous100 IU/0.5ml
SolutionIntramuscular; Subcutaneous100 unit / 0.5 mL
SolutionIntramuscular; Subcutaneous150 IU/0.5ml
SolutionIntramuscular; Subcutaneous50 unit / 0.5 mL
SolutionIntramuscular; Subcutaneous50 IU/0.5ml
SolutionIntramuscular; Subcutaneous75 IU/0.5ml
SolutionParenteral150.000 UI
SolutionSubcutaneous833 unit / mL
Powder, for solution; solutionIntramuscular; Subcutaneous737 unit / cartridge
Injection, powder, lyophilized, for solutionParenteral100 IU
Injection, powder, lyophilized, for solutionParenteral150 IU
SolutionParenteral400 IU
SolutionIntramuscular; Subcutaneous300 IU/0.36ml
Injection, solution300 iu/0.36ml
Liquid; powder, for solutionIntramuscular; Subcutaneous
Injection, powder, for suspensionParenteral50 IU
SolutionIntramuscular; Subcutaneous600 IU/0.72ml
Injection, solution600 iu/0.72ml
Injection, powder, lyophilized, for solutionParenteral75 IU
SolutionParenteral75 IU
Injection, solution900 iu/1.08ml
SolutionIntramuscular; Subcutaneous900 IU/1.08ml
InjectionIntramuscular; Subcutaneous100 iu/0.5ml
InjectionSubcutaneous833 IU/ml
InjectionIntramuscular; Subcutaneous50 iu/0.5ml
Injection, solutionSubcutaneous600 IU/0.72ml
Injection, solutionSubcutaneous833 IU/ml
Injection, solutionIntramuscular; Subcutaneous50 IU/0.5ml
SolutionIntramuscular; Subcutaneous100 IU
SolutionIntramuscular; Subcutaneous50 IU
Injection, solutionCutaneous; Parenteral36 MCG/1.08ML
Injection, solutionCutaneous; Parenteral72 MCG/2.16ML
Injection, solutionIntramuscular; Subcutaneous12 MCG/0.36ML
Injection, solutionIntramuscular; Subcutaneous36 MCG/1.08ML
Injection, solutionSubcutaneous12 ?g/0.36ml
Injection, solutionSubcutaneous36 ?g/1.08ml
Injection, solutionSubcutaneous72 ?g/2.16ml
SolutionSubcutaneous12 mcg / 0.36 mL
SolutionSubcutaneous12.000 mcg
SolutionSubcutaneous36 mcg / 1.08 mL
SolutionSubcutaneous72 mcg / 2.16 mL
Injection, solutionSubcutaneous
Injection, solutionSubcutaneous12.0 mcg
Injection, solutionSubcutaneous36.0 mcg
Injection, solutionSubcutaneous72.0 mcg
SolutionSubcutaneous33.3 mcg
Solution75 IU/0.15ml
Injection, solution150 iu/1ml
Injection, solution75 iu/1ml
Injection, solutionSubcutaneous
Solution100 iu/0.5ml
Prices
Unit descriptionCostUnit
Gonal-f rff 900 unit pen1409.62USD ml
Follistim AQ 900unt/1.08ml Solution 1 Cartridge = 1.17ml1366.71USD cartridge
Follistim AQ 600unt/0.72ml Solution 0.78ml Cartridge911.14USD cartridge
Gonal-f 450 unit Solution Vial733.0USD vial
Gonal-f rff 450 unit pen704.81USD pen
Gonal-f rff 300 unit pen469.87USD pen
Follistim AQ 300unt/0.36ml Solution 0.42ml Cartridge455.57USD cartridge
Follistim aq 300 unit cartridge438.05USD cartridge
Follistim aq 150 unit vial219.02USD vial
Gonal-f rff 75 unit vial117.47USD vial
Follistim aq 75 unit vial109.51USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5270057No1993-12-142011-03-20US flag
CA2037884No2003-10-212011-03-08Canada flag
US7563763No2009-07-212019-08-23US flag
US5929028No1999-07-272018-01-14US flag
US7446090No2008-11-042019-08-23US flag
US7741268No2010-06-222024-04-02US flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)55 °CForastieri, H., Ingham, K.C. J. Biol. Chem. 257:7976-7981 (1982)
hydrophobicity-0.330Not Available
isoelectric point7.50Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
G-protein coupled peptide receptor activity
Specific Function
Receptor for follicle-stimulating hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Induces cAMP production through the activation of PI3K-AKT and S...
Gene Name
FSHR
Uniprot ID
P23945
Uniprot Name
Follicle-stimulating hormone receptor
Molecular Weight
78264.07 Da
References
  1. Layman LC: Mutations in the follicle-stimulating hormone-beta (FSH beta) and FSH receptor genes in mice and humans. Semin Reprod Med. 2000;18(1):5-10. [Article]
  2. Leng N, Dattatreyamurty B, Reichert LE Jr: Identification of amino acid residues 300-315 of the rat FSH receptor as a hormone binding domain: evidence for its interaction with specific regions of FSH beta-subunit. Biochem Biophys Res Commun. 1995 May 16;210(2):392-9. [Article]
  3. Santa Coloma TA, Dattatreyamurty B, Reichert LE Jr: A synthetic peptide corresponding to human FSH beta-subunit 33-53 binds to FSH receptor, stimulates basal estradiol biosynthesis, and is a partial antagonist of FSH. Biochemistry. 1990 Feb 6;29(5):1194-200. [Article]
  4. Dattatreyamurty B, Reichert LE Jr: Identification of regions of the follitropin (FSH) beta-subunit that interact with the N-terminus region (residues 9-30) of the FSH receptor. Mol Cell Endocrinol. 1993 May;93(1):39-46. [Article]
  5. Lindau-Shepard B, Roth KE, Dias JA: Identification of amino acids in the C-terminal region of human follicle-stimulating hormone (FSH) beta-subunit involved in binding to human FSH receptor. Endocrinology. 1994 Sep;135(3):1235-40. [Article]
  6. Goa KL, Wagstaff AJ: Follitropin alpha in infertility: a review. BioDrugs. 1998 Mar;9(3):235-60. [Article]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 28, 2024 06:02