Pegvisomant

Pegvisomant
Clinical data
Trade names Somavert
AHFS/Drugs.com monograph
Pregnancy cat.  ?
Legal status  ?
Identifiers
CAS number 218620-50-9 Y
ATC code H01AX01
UNII N824AOU5XV Y
KEGG D05394 Y
ChEMBL CHEMBL1201515 N
Chemical data
Formula C990H1532N262O300S7 
Mol. mass 22129.0 g/mol (unpegylated)
 N(what is this?)  (verify)

Pegvisomant (trade name Somavert) is a growth hormone receptor antagonist used in the treatment of acromegaly.[1] It is used if the tumor of the pituitary gland causing the acromegaly cannot be controlled with surgery or radiation, and the use of somatostatin analogues is unsuccessful. It is delivered as a powder that is mixed with water and injected under the skin.[2]

Contents

Structure

Pegvisomant is a protein containing 191 amino acid residues to which several polyethylene glycol polymers have been covalently bound in order to slow clearance from the blood. The protein is a modified version of human growth hormone designed to bind to and block the growth hormone receptor. It is manufactured using genetically modified E. coli bacteria. The polyethylene glycol polymers are subsequently added chemically.[2]

Mechanism of action

Pegvisomant blocks the action of growth hormone at the growth hormone receptor to reduce the production of IGF-1. IGF-1 is responsible for most of the symptoms of acromegaly thus normalising its levels is effective to control the symptoms.

Side effects

Side effects of Pegvisomant include reactions at the injection site, swelling of the limbs, chest pain, hypoglycemia, nausea and hepatitis.[3]

Blocking of the growth hormone's receptor reduces feedback control of the growth hormone regulation leading to approximately doubled GH levels.[4]

References

  1. ^ Schreiber, I; Buchfelder M, Droste M et al. (January 2007). "Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: safety and efficacy evaluation from the German Pegvisomant Observational Study". European Journal of Endocrinology 156 (1): 75–82. doi:10.1530/eje.1.02312. PMID 17218728. http://www.eje-online.org/cgi/content/full/156/1/75?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=Schreiber&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&volume=156&resourcetype=HWCIT. 
  2. ^ a b "Scientific Discussion of Somavert". European Medicines Agency. 2004. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000409/WC500054625.pdf. 
  3. ^ Feenstra, J; Van Aken, MO; De Herder, WW; Feelders, RA; Van Der Lely, AJ (2006). "Drug-induced hepatitis in an acromegalic patient during combined treatment with pegvisomant and octreotide long-acting repeatable attributed to the use of pegvisomant". European Journal of Endocrinology 154 (6): 805–806. doi:10.1530/eje.1.02160. PMID 16728538.  edit
  4. ^ Moore, D.; Adi, Y.; Connock, M.; Bayliss, S. (2009). "Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation". BMC endocrine disorders 9: 20. doi:10.1186/1472-6823-9-20. PMC 2768727. PMID 19814797. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2768727.  edit
Hypothalamic
Agonists: Lanreotide • Octreotide • Pasireotide
Anterior pituitary
Agonists: IGF-1 (Mecasermin/Mecasermin rinfabate) • Sermorelin • Somatrem
Antagonists: Pegvisomant
Agonists: Thyrotropin
Posterior pituitary
Agonists: Carbetocin • Demoxytocin
Antagonists: Atosiban

M: END

anat/phys/devp/horm

noco(d)/cong/tumr, sysi/epon

proc, drug (A10/H1/H2/H3/H5)