Pegvisomant

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-1 (IGF-1) levels. SOMAVERT is a growth hormone receptor antagonist 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.

Pegvisomant 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 IGF-1, as well as other GH-responsive serum proteins such as free IGF-1, the acid-labile subunit of IGF-1 (ALS), and insulin-like growth factor binding protein-3 (IGFBP-3).

• Administer a 40 mg loading dose subcutaneously under physician supervision. • After proper injection instruction, on day after loading dose, patients or caregivers begin daily subcutaneous injections of 10 mg. • Adjust dosage in 5 mg increments or decrements until serum IGF-1 concentrations are maintained within age-adjusted normal range. Do not adjust dosage based on growth hormone (GH) levels or signs or symptoms of acromegaly. • Dosage range is 10 mg to 30 mg once daily. • Perform liver tests prior to first dosage and if greater than 3 times upper limit of normal should work-up prior to SOMAVERT administration. • Follow reconstitution and injection procedures.

None. None.

• Hypoglycemia: Monitor blood glucose in patients with diabetes mellitus and reduce anti-diabetic drug therapy as necessary. • Liver Toxicity: Should have more frequent liver tests and/or discontinue SOMAVERT. • Systemic Hypersensitivity: Monitor closely when re-initiating SOMAVERT in patients with systemic hypersensitivity.

Clinically significant adverse reactions that appear in other section of the labeling include: • Hypoglycemia Associated with GH Lowering in Patients with Diabetes Mellitus • Liver Toxicity • Cross-Reactivity with GH Assays • Lipohypertrophy • Systemic Hypersensitivity Elevations of serum concentrations of ALT and AST greater than ten times the ULN were reported in two patients (0.8%) exposed to SOMAVERT in pre-approval clinical studies. One patient was rechallenged with SOMAVERT, and the recurrence of elevated transaminase levels suggested a probable causal relationship between administration of the drug and the elevation in liver enzymes. A liver biopsy performed on the second patient was consistent with chronic hepatitis of unknown etiology. In both patients, the transaminase elevations normalized after discontinuation of the drug.

• Insulin and/or Oral hypoglycemic Agents: Patients with acromegaly and with diabetes mellitus may require careful monitoring and dose reductions of insulin and/or oral hypoglycemic agents. • Opioids: Patients on opioids may need higher SOMAVERT doses to achieve appropriate IGF-1 suppression.

If not used within 30 days at room temperature, the vial(s) should be discarded. The prefilled syringe(s) may be stored at a temperature up to 30°C (86°F) until the expiration date printed on the carton, at which point they should be discarded. Do not freeze. Prior to reconstitution: • The One Day Package of SOMAVERT should be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). • For the 30-Day Package, remove the three intermediate cartons containing the SOMAVERT vials and store in a refrigerator at 2°C to 8°C (36°F to 46°F).