Pegvisomant

Summary

Pegvisomant (Somavert) is a pegylated GH receptor antagonist approved for the treatment of acromegaly in patients who have had an inadequate response to surgery, radiation, or other medical therapies. It directly blocks GH receptor signaling and normalizes IGF-1 levels in the majority of treated patients.

Mechanism of Action

Pegvisomant is a genetically engineered analog of human growth hormone that binds to GH receptors on cell surfaces and blocks endogenous GH from binding, thereby preventing GH-induced signal transduction. This reduces hepatic IGF-1 production and normalizes serum IGF-1 levels in acromegaly patients.

Routes of Administration

Goals & Uses

• Combination therapy with somatostatin analogsEndocrine / Combination TherapyModerate
• Normalization of IGF-1 levels in acromegalyEndocrine / MetabolicHigh
• Management of acromegaly in patients not candidates for surgeryMedical ManagementHigh
• Symptom control in acromegaly (headache, soft tissue swelling, diaphoresis)Symptomatic ReliefHigh

Contraindications

• Significant hepatic impairment or active liver diseaseHepaticHigh
• Hypersensitivity to pegvisomant or any excipientAllergy / ImmunologicHigh
• Rapidly growing pituitary tumor at risk for chiasmal compressionOncologic / NeurologicHigh

Adverse Effects

• Elevated liver transaminases (hepatotoxicity)HepaticUncommon
• Injection site reactionsLocalCommon
• HeadacheNeurologicCommonPain in the head or upper neck
• Pituitary tumor growthOncologic / EndocrineUncommon
• Fatigue and dizzinessGeneral / NeurologicCommon
• Hyperglycemia or altered glucose metabolismMetabolic / EndocrineUncommon

Drug Interactions

• Somatostatin analogs (octreotide, lanreotide)Low
• Insulin / Oral antidiabetic agentsModerate
• OpioidsLow

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patientsAgeRelative
• Patients with diabetes mellitusMetabolicRelative
• BreastfeedingReproductiveRelative

Regulatory Status

• European UnionApprovedApproved: Treatment of acromegaly in adult patients with inadequate response to surgery and/or radiation therapy and in whom appropriate medical treatment with somatostatin analogues did not normalize IGF-1 concentrations or was not toleratedEMA approved; marketed as Somavert by Pfizer.
• United StatesApprovedApproved: Treatment of acromegaly in patients with inadequate response to surgery and/or radiation therapy and other medical therapies, or for whom these therapies are not appropriateFDA approved in 2003 (NDA 021106). Available under REMS program (Somavert REMS) requiring monitoring of liver function and pituitary imaging.
• United KingdomApprovedApproved: Treatment of acromegaly in adult patients with inadequate response to surgery and/or radiation and in whom appropriate somatostatin analogue treatment did not normalize IGF-1 or was not toleratedApproved by MHRA; follows similar criteria to EMA approval post-Brexit.

Approved by the FDA in 2003 and by the EMA for the treatment of acromegaly. Distributed under a Risk Evaluation and Mitigation Strategy (REMS) in the US due to potential for tumor growth and hepatotoxicity monitoring requirements.

Evidence & Sources

No sources recorded yet.