Growth hormone receptor blockers

Pegvisomant — Somavert

Class

• Growth hormone (GH) receptor antagonist

• Primary and only widely approved agent: Pegvisomant (brand name: Somavert)

• Pharmacologic category: Endocrine metabolic agent, anti-acromegaly

Mechanism of Action

• Pegvisomant is a genetically modified human GH analogue

• Binds to GH receptors without activating them

• Occupies receptor sites and prevents receptor dimerization

• Inhibits JAK2–STAT5, MAPK, and PI3K intracellular signalling pathways

• Reduces hepatic production of insulin-like growth factor 1 (IGF-1)

• GH secretion from the pituitary gland remains unaffected

• IGF-1 is the only reliable biochemical parameter for therapy monitoring (GH assays are unreliable due to interference and continued secretion)

Indications

• Acromegaly in adults:

  • Persistent elevated IGF-1 after surgery and/or radiotherapy

  • Inadequate control or intolerance to somatostatin receptor ligands (SRLs) and dopamine agonists

• Monotherapy: For biochemical control when tumour growth is not a concern

• Combination therapy: With SRLs when tumour size control is needed in addition to IGF-1 normalization

Dosage and Administration

• Route: Subcutaneous injection only

• Initiation: Loading dose of 40 mg once

• Maintenance: Start at 10 mg once daily

• Titration:

  • Increase in increments of 5 mg/day

  • Interval between dose adjustments: Minimum 4–6 weeks

  • Guided strictly by age- and sex-adjusted IGF-1 levels

• Maximum daily dose: As per product labelling (usually 30 mg/day)

• Preparation:

  • Lyophilised powder for injection; reconstitute with supplied diluent

  • Gently swirl to mix; do not shake

  • Use a fresh needle for injection after reconstitution

• Injection sites: Rotate between abdomen, thigh, upper arm, and buttock to prevent local reactions and lipodystrophy

• Storage:

  • Refrigerate at 2–8°C

  • Protect from light

  • Follow product-specific stability allowances for temporary room-temperature storage

Monitoring

• Efficacy:

  • IGF-1 at baseline, every 4–6 weeks during titration, and periodically once stable (e.g., every 3–6 months)

• Hepatic Safety:

  • ALT, AST, total bilirubin at baseline

  • Monthly for first 6 months

  • Quarterly for the next 6 months

  • Twice yearly thereafter or as clinically indicated

• Tumour Surveillance:

  • Pituitary MRI at baseline

  • Repeat as per clinical judgement and tumour risk profile

  • Combine with SRL if tumour growth control is needed

• Metabolic Profile:

  • Fasting glucose or HbA1c

  • Lipid profile as indicated, especially in patients switching from SRLs

• Clinical:

  • Symptom tracking: Soft-tissue swelling, arthropathy, hyperhidrosis, headaches, sleep apnoea

  • Quality of life assessments when available

Contraindications

• Hypersensitivity to pegvisomant or any component of the formulation

• Active, unexplained elevations in liver enzymes until the cause is identified and addressed

Precautions

• Hepatic Impairment: Use with caution; increase frequency of liver monitoring

• Tumour Growth Risk:

  • Pegvisomant does not suppress pituitary tumour GH secretion

  • Continue regular imaging and clinical assessments

  • Use combination with SRL in cases of macroadenoma with growth risk

• Diabetes Mellitus:

  • IGF-1 normalization may improve insulin sensitivity

  • Reassess and adjust antidiabetic therapy to prevent hypoglycaemia

• Pregnancy/Lactation:

  • Limited human data; use only if benefits outweigh potential risks

  • Seek specialist maternal–fetal consultation

• Paediatric Use: Not indicated for growth disorders in children

• Immunogenicity: Anti-drug antibodies may develop (usually non-neutralizing); investigate loss of response

• Assay Interference: Pegvisomant affects some GH immunoassays—never use GH values for treatment decisions

Adverse Effects

• Very Common / Common:

  • Injection site reactions: Pain, erythema, swelling, pruritus

  • Lipodystrophy at injection site (lipoatrophy/lipohypertrophy)

  • Arthralgia, myalgia

  • Headache, fatigue

  • Nausea, diarrhoea

• Laboratory Abnormalities:

  • Elevated ALT, AST

  • Hyperbilirubinaemia

• Less Common / Rare:

  • Hypersensitivity reactions: Rash, urticaria, angioedema

  • Peripheral oedema

  • Carpal tunnel syndrome

  • Pancreatitis

  • Intracranial hypertension (rare)

• Tumour Dynamics: Isolated reports of adenoma growth—generally associated with discontinuation of SRL or inadequate imaging surveillance

Drug Interactions

• Somatostatin Analogues:

  • Can reduce pegvisomant clearance

  • Dose adjustment may be required when used in combination

• Oral Oestrogens:

  • May reduce IGF-1 response

  • Consider dose adjustment or alternative estrogen routes

• Antidiabetic Agents:

  • Improved insulin sensitivity may require reduction in insulin or oral hypoglycaemic doses

• Laboratory Tests:

  • Pegvisomant interferes with some GH assays—monitor IGF-1 exclusively

Overdose

• Likely Effects:

  • Excessive GH blockade, low IGF-1

  • Symptoms: Fatigue, asthenia, possible hypoglycaemia (especially with antidiabetic therapy)

• Management:

  • Supportive care

  • Monitor IGF-1

  • Adjust or withhold doses accordingly

Patient Counselling

• Explain that the medicine blocks GH action, not its secretion; IGF-1, not GH, will be monitored

• Demonstrate correct reconstitution and self-injection technique

• Emphasise rotating injection sites to avoid local tissue changes

• Stress the importance of regular lab tests and imaging

• Advise reporting signs of liver injury immediately: Fatigue, jaundice, dark urine, pale stools, abdominal pain

• Stress adherence: Missing doses can lead to loss of disease control

• Explain storage requirements, including refrigeration and handling during travel