Pegvisomant

Pegvisomant is a prescription drug used for the treatment of acromegaly. Acromegaly is a syndrome characterized by physical disfigurement resulting from excess growth hormone (hGH) production. The Food and Drug Administration approved the use of pegvisomant on March 25, 2003. Pegvisomant is marketed as Somavert by Pfizer.

Uses

Pegvisomant is used to reduce the secretion of insulin-like growth factor I (IGF-I) in people with acromegaly. It is reserved for use in people for whom surgery, radiation, or other therapies are either ineffective or inappropriate.

How Pegvisomant is Taken

Pegvisomant is available in 10 mg, 15 mg, and 20 mg vials for injection. A doctor injects a 40 mg dose subcutaneously (under the skin) as the first treatment. Subsequent daily 10 mg injections are self-administered by the patient. The dosage can be increased up to a maximum of 30 mg daily if a satisfactory reduction in circulating IGF-I levels is not reached.

How Pegvisomant Works

Acromegaly is a physically disfiguring syndrome caused by excessive production of hGH by the pituitary gland. The hormone is a growth factor and, as such, causes growth of tissues and organs. The hormone elicits many of its effects by stimulating the release of IGF-I. Pegvisomant is a synthetic form of hGH and binds to the same receptors on cell surfaces. Unlike hGH however, pegvisomant does not activate the receptor, but rather prevents natural hGH from binding. The result is a reduction in the secretion of IGF-I.

How the Body Affects Pegvisomant

Following injection, peak circulating levels of pegvisomant are reached within 33–77 hours. Pegvisomant is designed to have a slow clearance from the body. Clearance of pegvisomant following multiple doses is lower than seen following a single dose. The time needed for the concentration of pegvisomant in the blood to be reduced by half, the half-life, is approximately six days. The majority of a single dose is eliminated from the body within 96 hours.

Side Effects

Some side effects of pegvisomant include the following:

• reactions at the site of injection
• flu-like symptoms
• fluid accumulation in some tissues (edema)
• nausea
• hepatitis
• high blood pressure

Risks and Precautions

• Under pegvisomant therapy, tumors that secrete hGH may grow and cause serious complications. The risk of complications is reduced if regular brain scans are taken in patients with these tumors.

• Pegvisomant could influence blood sugar control in people with diabetes because hGH reduces insulin sensitivity.

• Some people may have signs of hGH deficiency, even if hGH levels are high. This is because pegvisomant prevents hGH from activating its receptor. Symptoms of hGH deficiency include weight loss, loss of energy, and loss of strength.

• Pegvisomant has been shown to cause elevations in liver enzymes, which could indicate liver damage. Blood tests that detect these enzymes can reduce the risk of injury.

Drug Interactions

Dosages of insulin or other medications that lower blood sugar may need to be reduced when pegvisomant is started.

In clinical studies, patients on opioids (such as methadone and oxycodone (Percocet)) often needed high doses of pegvisomant in order to suppress IGF-I adequately.

Clinical trials

Pegvisomant and placebo were compared in a study of 112 patients with acromegaly.^[1]

Pegvisomant was given at doses of 10 mg, 15 mg, or 20 mg after the initial 40 mg dose. Pegvisomant reduced IGF-I levels at all doses compared to treatment with the placebo. After 12 weeks of treatment, IGF-I levels were normal in 10%, 39%, 75%, and 82% of patients treated with placebo, 10, 15, or 20 mg/day of pegvisomant, respectively.

References

1. ↑ Trainer PJ, Drake WM, Katznelson L, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med. 2000 Apr 20;342(16):1171-7. Abstract | Full Text | PDF

External Links

FDA: Patient Information Sheet