Pegvisomant, a biosynthetic analog of human growth hormone (somatotropin), is a selective, competitive somatotropin receptor antagonist.1, 3, 5, 6, 7
Pegvisomant injection is used for the treatment of acromegaly in patients who have had inadequate responses to or are not candidates for surgical resection, pituitary irradiation, and/or other medical therapies (e.g., bromocriptine mesylate, octreotide).1, 3, 4 The goal of pegvisomant therapy in patients with acromegaly is to normalize serum concentrations of insulin-like growth factor I (IGF-I, a somatomedin).1, 3, 4
In a placebo-controlled, dose-ranging study in patients with acromegaly previously treated with other medical or surgical therapies, therapy with pegvisomant reduced serum concentrations of IGF-I to normal after 12 weeks of therapy in 39, 75, or 82% of patients receiving 10, 15, or 20 mg daily, respectively, by subcutaneous injection (following a loading dose of 80 mg) compared with 10% of those receiving placebo.1, 3, 6, 10 Pegvisomant therapy also was associated with reductions in serum concentrations of other growth hormone-responsive proteins (e.g., free IGF-I, IGF binding protein-3 [IGFBP-3], acid labile subunit of IGFBP-3) and with improvements in certain manifestations of acromegaly (decreases in ring size and in a composite measure of soft tissue swelling, arthralgia, headache, excessive perspiration, and fatigue).1, 3, 6 Response (normalization of serum IGF-I concentrations) in patients receiving pegvisomant has been maintained for at least 12 months in clinical studies.1, 5, 6
Dosage of pegvisomant is expressed in terms of pegvisomant protein.1 Each mg of pegvisomant protein contains approximately 1 unit of activity.1, 10
Reconstitution and Administration
Pegvisomant is administered by subcutaneous injection into the upper arm, upper thigh, abdomen, or buttocks.1, 2 Injection sites should be rotated daily.2
Pegvisomant powder for injection is reconstituted by adding 1 mL of the manufacturer-supplied diluent (sterile water for injection) to a vial labeled as containing 10, 15, or 20 mg of pegvisomant protein to provide a solution containing 10, 15, or 20 mg/mL, respectively.1, 2 The diluent should be injected slowly onto the inner wall of the vial and the vial rolled gently between the palms of both hands until the powder is completely dissolved;1, 2 any unused diluent must be discarded.2, 10 The vial containing pegvisomant should not be shaken since denaturation of the protein may occur.1, 2, 10 Reconstituted solutions of the drug should be clear; cloudy solutions should not be injected.1 Reconstituted solutions of pegvisomant should be used within 6 hours.1, 2, 10
Subcutaneous: For the treatment of acromegaly in adults, a loading dose of 40 mg of pegvisomant should be administered under medical supervision; subsequently, the patient should be instructed to self-inject 10 mg once daily.1, 2, 6
The goal of pegvisomant therapy in patients with acromegaly is to reduce serum IGF-I concentrations to normal levels.1, 3, 4 Dosage of pegvisomant should be adjusted in 5-mg increments (or decrements, if serum IGF-I concentrations are below normal) at intervals of no less than 4-6 weeks until the desired effect on serum IGF-I concentrations is observed or a maximum dosage of 30 mg daily is reached.1, 5, 6 Monitor serum IGF-I concentrations at least semiannually after such concentrations have normalized.1, 10 It is not known whether patients who continue to have symptoms after achieving normal IGF-I levels would benefit from increased dosage of pegvisomant.1
Known hypersensitivity to pegvisomant or any ingredient in the formulation.1 Vial stopper contains natural rubber latex,1, 2 which may cause sensitivity reactions in susceptible individuals.8, 9
Elevations in serum aminotransferase (transaminase) concentrations (i.e., AST [SGOT], ALT [SGPT]) exceeding 3 times but not exceeding 10 times the upper limit of normal1, 3 were reported in approximately 1.2 or 2.1% of patients receiving pegvisomant or placebo, respectively, in clinical trials.1 These increases did not appear to be dose-related and occurred within the first 4-12 weeks of therapy.1 Elevated serum aminotransferase concentrations (exceeding 10 times the upper limit of normal) occurred in 2 patients (0.8%) receiving pegvisomant in premarketing clinical trials.1, 10 Elevations in serum transaminase concentrations recurred following rechallenge with the drug in one patient and were associated with chronic hepatitis (indicated by liver biopsy) in the other patient; aminotransferase concentrations normalized following discontinuance of the drug in both patients.1, 3, 5
Periodic liver function tests (i.e., serum aminotransferase, total bilirubin, and alkaline phosphatase concentrations) are recommended prior to and during pegvisomant therapy (i.e., monthly for first 6 months, every 3 months for the next 6 months, then every 6 months for the next year) for patients with normal liver function at baseline.1 In patients who develop certain abnormalities in liver function tests (elevations 3-5 times the upper limit of normal without signs or symptoms of hepatotoxicity or an increase in total bilirubin) during pegvisomant therapy, the drug may be continued with caution.1 Liver function tests should be monitored weekly, and a comprehensive hepatic examination performed to investigate possible alternative causes of liver dysfunction.1
If serum aminotransferase elevations of 3 times the upper limit of normal or higher occur in conjunction with any increase in total bilirubin concentration or if liver function test elevations of at least 5 times the upper limit of normal occur (with or without manifestations of hepatitis or liver injury), pegvisomant therapy should be discontinued immediately.1 In addition, a thorough examination of hepatic function should be undertaken in such patients, including serial liver function tests to determine if and when liver dysfunction resolves.1 If liver function test results normalize, cautious reinitiation of pegvisomant therapy, with frequent monitoring of liver function tests, may be considered.1
In patients who develop manifestations suggestive of hepatitis or other liver injury (e.g., jaundice, bilirubinuria, fatigue, nausea, vomiting, upper right quadrant pain, ascites, unexplained edema, easy bruising), a comprehensive hepatic examination should be performed and the drug discontinued if liver injury is confirmed.1, 2
Pegvisomant should be used with caution in patients with preexisting mild hepatic impairment (elevations in serum aminotransferase, total bilirubin, or alkaline phosphatase concentrations not exceeding 3 times the upper limit of normal).1 Monitor liver function tests frequently (monthly for at least 1 year after initiation of therapy, then every 6 months for the next year) during therapy in such patients.1 Do not initiate pegvisomant therapy in patients with liver function test elevations exceeding 3 times the upper limit of normal until a comprehensive examination establishes the cause of liver dysfunction.1 Determine if cholelithiasis or choledocholithiasis is present, particularly in patients with a history of prior therapy with somatostatin analogs.1, 10 If therapy with pegvisomant is implemented in these patients, monitor liver function tests and clinical symptoms very closely.1
Progressive tumor growth occurred in 2 patients with underlying somatotropin-secreting pituitary tumors receiving pegvisomant in clinical trials.1, 5 Both patients had at baseline large globular tumors impinging on the optic chiasm that had been relatively resistant to previous antiacromegalic therapies.1, 10
Patients with pituitary growth hormone secreting neoplasms, including those receiving pegvisomant, should be monitored carefully with periodic imaging scans of the sella turcica.1, 10
Endocrine and Metabolic Effects
Patients with acromegaly and diabetes mellitus should be monitored carefully for hypoglycemia and dosage of insulin and/or antidiabetic drugs reduced as necessary.1
Growth hormone deficiency may occur despite the presence of elevated serum growth hormone concentrations.1 (See Laboratory Test Interference under Cautions: Warnings/Precautions.) Patients should be monitored for signs and symptoms of growth hormone deficiency, and dosage of pegvisomant should be adjusted using serum IGF-I concentrations to maintain such concentrations within the age-adjusted normal range.1
Pegvisomant has substantial structural similarity to endogenous growth hormone, which causes it to cross-react in commercially available growth hormone assays.1, 10 Since therapeutic serum concentrations of pegvisomant generally are 100-1000 times higher than those of endogenous growth hormone, commercially available growth hormone assays will overestimate true endogenous growth hormone concentrations.1, 10 Also, even when accurately measured, growth hormone concentrations usually increase during pegvisomant therapy.1, 6, 11 Treatment with pegvisomant should not be adjusted based on serum growth hormone concentrations.1, 10 Instead, monitoring and dosage adjustments should only be based on serum IGF-I concentrations.1
Category B. (See Users Guide)
Not known whether pegvisomant is distributed in milk.1 Caution is advised if the drug is administered in nursing women.1
Safety and efficacy not established in children.1
Experience in patients 65 years of age or older is insufficient to determine whether they respond differently from younger adults.1
Use with caution. (See Hepatic Effects under Warnings/Precautions: General Precautions, in Cautions.)
Adverse effects occurring in at least 4% of patients receiving pegvisomant and at frequencies greater than with placebo include abnormal liver function test results,1 accidental injury,1, 5 back pain,1, 5 chest pain,1 diarrhea,1, 3, 5 dizziness,1 flu syndrome,1, 5 hypertension,1 infection, 1, 5 injection site reaction,1, 3, 5 nausea,1, 3 pain, 1, 3, 5 paresthesia,1 peripheral edema,1 and sinusitis.1, 5
Potential pharmacologic interaction (improved insulin sensitivity and glucose tolerance resulting from reduction in IGF-I concentrations) in patients with acromegaly and diabetes mellitus taking insulin and/or oral antidiabetic agents.1, 6, 10, 11 Adjustment of the dosage of concurrent antidiabetic therapy may be necessary.1, 10
Potential pharmacokinetic/pharmacologic interaction when pegvisomant is administered with opiate agonists (for unknown reasons, higher serum concentrations of pegvisomant needed to produce appropriate suppression of IGF-I); may require an increase in the dosage of pegvisomant.1, 10
Pegvisomant, a biosynthetic analog of human growth hormone (somatotropin), is a selective, competitive somatotropin receptor antagonist.1, 3, 5, 6, 7 Pegvisomant binds to somatotropin receptors and competitively blocks binding of endogenous growth hormone, thereby interfering with signal transduction and the subsequent production of insulin-like growth factor I (IGF-I).1, 3, 6, 7 Current evidence indicates that acromegaly is a chronic endocrine disorder involving the hypersecretion of growth hormone, resulting in an increase in serum IGF-I concentrations.3, 4 IGF-I mediates most of the somatotropic effects of growth hormone.1, 3, 6, 7 Pegvisomant has been shown to produce a rapid decrease in serum concentrations of IGF-I and other growth hormone-responsive serum proteins (e.g., IGF binding protein-3 [IGFBP-3], acid labile subunit of IGFBP-3) in patients with acromegaly.1, 3, 5, 6
Importance of understanding instructions for proper storage, preparation, and injection technique.2
Importance of monitoring for signs and symptoms of functional growth hormone deficiency.1, 2 Importance of obtaining periodic determinations of serum insulin growth factor-I (IGF-I) concentrations in order to achieve and maintain therapeutic response.1, 2
Importance of obtaining serial monitoring of liver function tests and of discontinuing therapy and reporting signs or symptoms of possible liver dysfunction (e.g., jaundice, dark urine, light stools, loss of appetite, nausea, fatigue, abdominal pain) to clinicians immediately.1, 2
Importance of alerting clinician about allergy to latex.1, 2
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (particularly insulin, other antidiabetic agents, or opiate agonists).1, 2, 10 (See Drug Interactions.)
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1, 2
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for subcutaneous use | 10 mg (as protein) | Somavert® (with 10 mL sterile water for injection diluent; may contain natural latex components in packaging) | |
15 mg (as protein) | Somavert® (with 10 mL sterile water for injection diluent; may contain natural latex components in packaging) | Pfizer | ||
20 mg (as protein) | Somavert® (with 10 mL sterile water for injection diluent; may contain natural latex components in packaging) | Pfizer |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions January 1, 2005. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Pfizer. Somavert® (pegvisomant) for injection prescribing information. Kalamazoo, MI; 2003 Jun.
2. Pfizer. Somavert® (pegvisomant) for injection patient information. Kalamazoo, MI; 2003 Jun.
3. Trainer PJ, Drake WM, Katznelson L et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med . 2000; 342:1171-7. [PubMed 10770982]
4. Utiger RD. Treatment of acromegaly. N Engl J Med . 2000; 342:1210-1. [PubMed 10770989]
5. van der Lely AJ, Hutson RK, Trainer PJ et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet . 2001; 358:1754-9. [PubMed 11734231]
6. Pfizer. Somavert® (pegvisomant) for injection general review. Kalamazoo, MI; 2003 Mar.
7. Friend KE. Cancer and the potential place for growth hormone receptor antagonist therapy. Growth Horm IGF Res . 2001; 11(Suppl A):S121-3.
8. Food and Drug Administration. Amended economic impact analysis of final rule requiring use of labeling on natural rubber containing devices; 21 CFR Part 801. Final rule. (Docket no. 96N-0119). Fed Regist. 1998; 63:50660-704.
9. Food and Drug Administration. Latex-containing devices; user labeling. 21 CFR Part 801. Proposed rule. (Docket No. 96N-0119). Fed Regist. 1996; 61:32617-21.
10. Pfizer, New York, NY: Personal communication.
11. Parkinson C, Drake WM, Roberts ME et al. A comparison of the effects of pegvisomant and octreotide on glucose, insulin, gastrin, cholecystokinin, and pancreatic polypeptide responses to oral glucose and a standard mixed meal. J Endocrinol Metab . 2002; 87:1797-1804.