Jane S. Ricciuti, RPh, MS


April 22, 2003

In This Article

Growth Hormone Receptor Antagonists


Manufacturer: Pharmacia and Upjohn Co.

Drug Approval Classification: Original New Drug Application (Approval Date: 03/25/03)

Indication: Somavert (pegvisomant) is indicated for the treatment of acromegaly in patients who have had an inadequate response to surgery and/or radiation therapy and/or other medical therapies, or for whom these therapies are not appropriate. The goal of treatment is to normalize serum insulin-like growth factor-I (IGF-I) levels.

Dosing: A loading dose of 40 mg of Somavert should be administered subcutaneously under physician supervision. The patient should then be instructed to begin daily subcutaneous injections of 10 mg of Somavert.

Serum IGF-I concentrations should be measured every 4 to 6 weeks, at which time the dose of Somavert should be adjusted in 5-mg increments if IGF-I levels are still elevated (or 5-mg decrements if IGF-I levels have decreased below the normal range). While the goals of therapy are to achieve (and then maintain) serum IGF-I concentrations within the age-adjusted normal range and to alleviate the signs and symptoms of acromegaly, titration of dosing should be based on IGF-I levels. It is unknown whether patients who remain symptomatic while achieving normalized IGF-I levels would benefit from increased dosing with Somavert.

The maximum daily maintenance dose should not exceed 30 mg.

Clinical Summary: Somavert contains pegvisomant for injection, an analogue of human growth hormone (GH) that has been structurally altered to act as a GH receptor antagonist. Pegvisomant selectively binds to growth hormone (GH) receptors on cell surfaces, where it blocks the binding of endogenous GH. Inhibition of GH action results in decreased serum concentrations of IGF-I.

Pegvisomant was studied in 112 patients with acromegaly in a single 12-week, randomized, double-blind, multicenter study comparing placebo and pegvisomant. Patients received a subcutaneous (SC) loading dose of pegvisomant, followed by 10, 15, or 20 mg/day SC. The 3 groups that received pegvisomant showed dose-dependent reductions in serum levels of IGF-I, free IGF-I, IGFBP-3, and antilymphocyte compared with placebo at all post-baseline visits. Eighty-two percent of patients receiving 20 mg/day of pegvisomant experienced normalized IGF-I levels compared with only 10% of placebo patients.

Adverse Effects: Patients should be advised that liver function tests may be elevated with pegvisomant use. In clinical trials, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated in 2 patients (0.8%). Pegvisomant labeling contains detailed information for the management of patients who experience elevated liver function tests.

Injection site pain was a common adverse event reported, followed by diarrhea and nausea.

Pharmacokinetics: Pegvisomant reaches peak serum concentrations 33-77 hours after administration. The volume of distribution is 7 L. The serum half-life is approximately 6 days.

Opioid use affected the serum concentration of pegvisomant in clinical trials, necessitating increased serum concentrations of pegvisomant to achieve appropriate IGF-I suppression.

No pharmacokinetic studies were performed in special populations (eg, patients with hepatic/renal insufficiency or geriatric/pediatric patients).

Somavert (pegvisomant) Labeling


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