Pegvisomant(DB00082) Approved Drug Chemical Formula: C990H1532N262O300S7 Molecular Weight: 22129 Pegvisomant is a highly selective growth hormone (GH) receptor antagonist. It is used to treat acromegaly. Unlike dopamine or somatostatin analogs (which inhibit growth hormone secretion), this drug actually blocks the hepatic (GH-mediated) production of insulin like growth factor (IGF-1), which is the main mediator of growth hormone activity. Indication/Usage Pegvisomant is a growth hormone receptor antagonist used for the treatment of acromegaly. Pharmacodynamics Somavert is used for the treatment of acromegaly, which arises from excessive IGF-1 levels. Somavert selectively binds to growth hormone (GH) receptors on cell surfaces, where it blocks the binding of endogenous GH, and thus interferes with GH signal transduction. Inhibition of GH action results in decreased serum concentrations of insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3). This reduces the symptoms of acromegaly. Mechanism of Action Somavert selectively binds to growth hormone (GH) receptors on cell surfaces, where it blocks the binding of endogenous GH. This leads to the normalization of serum IGF-1 levels.

Volume of Distribution Half Life ~6 days Volume of Distribution * 7 L Clearence * 36 - 28 mL/h [SC doses ranging from 10 to 20 mg/day] Category Hormone Replacement Agents Affected Organisms Human and other Mammals Patents Patent no. 5849535, USA, approved: 1997-03-25 expired: 2017-03-25 Patent no. 5350836, USA, approved: 1994-09-27 expired: 2011-09-27 Patent no. 2230492, Canada, approved: 2009-05-26 expired: 2016-09-20 Patent no. 2102129, Canada, approved: 2003-04-01 expired: 2012-05-01 Drug Interactions DB01551 (Dihydrocodeine): Opioids may diminish the therapeutic effect of pegvisomant. It is recommended to monitor therapy. Sequence FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF

Experimental Properties Melting Point: 76 °C at pH 3.5 Hydrophobicity: 0.411 Isoelectric Point: 5.27 Targets Growth Hormone Receptor Brands SOMAVERT – Pfizer

SOMAVERT Formulation Used/Prescribed for Dosage Contraindications SOMAVERT contains pegvisomant, an analog of human growth hormone (GH) that has been structurally altered to act as a GH receptor antagonist.Pegvisomant is a protein of recombinant DNA origin containing 191 amino acid residues to which several polyethylene glycol (PEG) polymers are covalently bound (predominantly 4 to 6 PEG/protein molecule). The molecular weight of the protein of pegvisomant is 21,998 Daltons. SOMAVERT for injection is supplied as a sterile, white lyophilized powder to be administered as subcutaneous Injection. Formulation SOMAVERT is available in single-dose sterile vials containing 10, 15, or 20 mg of pegvisomant protein (approximately 10, 15, and 20 U activity, respectively). Each vial also contains 1.36 mg of glycine, 36.0 mg of mannitol, 1.04 mg of sodium phosphate dibasic anhydrous, and 0.36 mg of sodium phosphate monobasic monohydrate Used/Prescribed for SOMAVERT is indicated for the treatment of acromegaly in patients who have had an inadequate response to surgery or radiation therapy, or for whom these therapies are not appropriate. The goal of treatment is to normalize serum insulin-like growth factor-I (IGF-I) levels. Dosage The recommended loading dose of SOMAVERT is 40 mg given subcutaneously, under healthcare provider supervision. Increase the dosage by 5 mg increments every 4-6 weeks if IGF-I concentrations are elevated.Decrease the dosage by 5 mg decrements every 4-6 weeks if IGF-I concentrations are below the normal range Contraindications None

Side- effects Drug Interactions References Hypoglycemia associated with GH lowering in patients with Diabetes Mellitus, Liver test elevations, Cross-reactivity with GH assay, Lipohypertrophy, Systemic hypersensitivity, pain, nausea ,diarrhea, dizziness, Sinusitis Drug Interactions After initiation of SOMAVERT, patients with acromegaly and diabetes mellitus treated with insulin and/or oral hypoglycemic agents may require dose reductions of insulin and/or oral hypoglycemic agents. In clinical studies, patients taking opioids often needed higher SOMAVERT doses to normalize IGF-I concentrations compared with patients not receiving opioids. The mechanism of this interaction is not known. References http://www.rxlist.com/somavert-drug.htm http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=222a28ca-70c3-474c-850e-fae39eaaf40f