Schedule H

Subcutaneous (SC)

• Pegvisomant 10 mg powder for injection with diluent (vial + solvent)

• Pegvisomant 15 mg powder for injection with diluent (vial + solvent)

• Pegvisomant 20 mg powder for injection with diluent (vial + solvent)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Acromegaly

For patients with inadequate response to surgery and/or radiation therapy, or in whom these treatment modalities are not appropriate

Parameter Recommendation

Starting dose 40 mg SC as a single loading dose (administered under medical supervision)

Titration Increase by 5 mg/day increments every 4–6 weeks based on serum IGF-1 levels

Usual maintenance dose 10–20 mg SC once daily

Maximum dose 30 mg SC once daily

Clinical Notes:

• Dose adjustment guided by serum IGF-1 levels — aim to normalise IGF-1 within age-adjusted reference range

• GH levels are NOT used for dose titration (Pegvisomant is a GH receptor antagonist; GH levels may increase)

• Does NOT suppress tumour growth — concurrent somatostatin analogue or periodic MRI surveillance required for tumour control

• Administer SC injection in thigh, abdomen, or upper arm; rotate injection sites

• Allow reconstituted solution to reach room temperature before injection

Secondary Indications — Adults (Off-label, if any)

Not applicable. No established off-label indications in Indian practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable.

• Pegvisomant is NOT approved for paediatric use in India

• Safety and efficacy not established in patients below 18 years of age

Secondary Indications — Paediatric doses (Off-label, if any)

Not applicable. No documented off-label paediatric use in Indian practice.

Statement: Not recommended for use in children or adolescents under 18 years. Use only in exceptional circumstances under specialist paediatric endocrinology supervision with documented informed consent.

Severe impairment (eGFR <30) Limited data; use with caution; monitor IGF-1 and clinical response

Dialysis No specific data; use with caution under specialist supervision

Note: Pegvisomant is associated with hepatotoxicity; baseline hepatic dysfunction increases risk of transaminase elevation.

• Known hypersensitivity to Pegvisomant, latex (stopper contains latex), or any excipient

• Active liver disease or unexplained transaminase elevation >3× ULN prior to initiation

• History of anaphylaxis or angioedema related to Pegvisomant

• Hepatic dysfunction: Drug-induced hepatotoxicity reported; LFT monitoring mandatory throughout treatment

• Pituitary tumour: Does NOT control tumour growth; periodic pituitary MRI required (every 6–12 months or as clinically indicated)

• Diabetes mellitus: Pegvisomant improves insulin sensitivity; may require reduction in insulin or oral antidiabetic doses

• Concurrent somatostatin analogues: May alter Pegvisomant clearance; monitor IGF-1 levels closely if used in combination

• Lipohypertrophy: Rotate injection sites to prevent local adipose tissue changes

• Pregnancy and lactation: Not recommended

Parameter Details

Overall safety Insufficient human data; animal studies do not indicate direct harm but data limited

Recommendation Not recommended during pregnancy; use only if potential benefit clearly outweighs risk

Preferred alternatives Cabergoline (limited data but may be considered); defer treatment until post-delivery if clinically feasible

If used (specialist only) Clinical monitoring of acromegaly symptoms; IGF-1 monitoring unreliable during pregnancy

Monitoring Maternal symptoms, fetal growth surveillance via ultrasound

Parameter Details

Compatibility Not recommended — unknown if excreted in human breast milk

Excretion in milk Unknown; protein-based drug unlikely to achieve high milk levels but data lacking

Recommendation Discontinue Pegvisomant during breastfeeding or avoid breastfeeding if treatment essential

Preferred alternatives Defer therapy if possible until breastfeeding complete

Infant monitoring (if unavoidable) Growth parameters, feeding behaviour, signs of hypoglycaemia

Parameter Recommendation

Starting dose Standard loading dose (40 mg) and maintenance (10 mg/day); no specific dose reduction required

Titration Consider slower titration (every 6–8 weeks) due to potential comorbidities

Special considerations Higher risk of hepatic dysfunction; ensure baseline and periodic LFT monitoring

Additional risks Polypharmacy interactions; reduced hepatic reserve; careful assessment of injection site reactions

Interacting Drug Effect Management

Insulin Pegvisomant improves insulin sensitivity; ↑ risk of hypoglycaemia Monitor blood glucose closely; reduce insulin dose as needed (often significant reduction required)

Oral antidiabetics (Sulfonylureas, Meglitinides) ↑ Risk of hypoglycaemia Monitor glucose; anticipate need for dose reduction

Opioids (Morphine, Fentanyl) May reduce serum Pegvisomant levels (mechanism unclear) Monitor IGF-1 levels; may require Pegvisomant dose increase

Somatostatin analogues (Octreotide, Lanreotide) May reduce Pegvisomant clearance; altered drug levels Can be used together for tumour control but monitor IGF-1 closely; adjust Pegvisomant dose accordingly

Interacting Drug Effect Management

CYP3A4 inducers (Rifampicin, Phenytoin, Carbamazepine) Potential reduced Pegvisomant effectiveness (mechanism unclear) Monitor IGF-1 levels more frequently; may need dose adjustment

Hepatotoxic drugs (Methotrexate, Azathioprine, Statins, Anti-TB drugs) Additive hepatotoxicity risk Enhanced LFT monitoring; avoid combination if baseline hepatic impairment

GH or GH analogues (Somatropin) Pharmacological antagonism Avoid concurrent use — counterproductive

Corticosteroids May alter glucose metabolism Monitor glycaemic control

• Injection site reactions (pain, erythema, pruritus, bruising)

• Elevated liver enzymes (ALT, AST) — often transient

• Flu-like symptoms (myalgia, fatigue, fever)

• Headache

• Diarrhoea

• Nausea

• Dizziness

• Arthralgia

• Peripheral oedema

• Weight gain

Adverse Effect Notes

Hepatotoxicity Elevated transaminases; discontinue if ALT/AST >5× ULN or if elevation accompanied by bilirubin >2× ULN or hepatitis symptoms

Anaphylaxis / Angioedema Rare; requires immediate discontinuation and emergency management

Lipohypertrophy Chronic use at same injection site; rotate sites to prevent

Pituitary tumour enlargement Does not control tumour; progression possible — mandatory MRI surveillance

Systemic hypersensitivity reactions Urticaria, rash; may require discontinuation

During titration (every 4–6 weeks) Serum IGF-1 (primary monitoring parameter for dose adjustment); LFTs monthly for first 6 months

After stabilisation (every 3–6 months) Serum IGF-1; LFTs every 3–6 months; blood glucose in diabetics

Long-term (annually) Pituitary MRI (more frequently if symptoms suggest tumour growth); injection site examination; LFTs

Note: GH levels are NOT used for monitoring — may paradoxically increase due to receptor blockade.

• Somavert® (Pfizer) — 10 mg, 15 mg, 20 mg vials with diluent

Note: Limited availability in India; typically procured through specialty distributors, hospital pharmacies, or import channels at tertiary centres.

Note: Not listed under NLEM; prices not NPPA-controlled. High-cost orphan drug. Patient assistance programmes may be available through manufacturer. Government supply is limited — typically private procurement only.

1. IGF-1 is the monitoring parameter: Dose titration based on normalising serum IGF-1 within age-adjusted reference range. Do NOT use GH levels — they may increase due to GH receptor blockade.

1. Does NOT control tumour growth: Pegvisomant is a receptor antagonist that blocks GH action peripherally. It does NOT suppress pituitary adenoma. Concurrent somatostatin analogue therapy or periodic MRI (every 6–12 months) is essential for tumour surveillance.

1. Hepatotoxicity is a major concern: Baseline LFTs mandatory; monthly monitoring for first 6 months; discontinue if transaminases >5× ULN or if jaundice develops.

1. Improves insulin sensitivity: Patients with diabetes may experience improved glycaemic control — anticipate need to reduce insulin/oral antidiabetic doses to avoid hypoglycaemia.

1. Rotate injection sites: Lipohypertrophy at repeated injection sites is common — counsel patients on proper rotation technique (thigh, abdomen, upper arm).

1. Reserved for refractory acromegaly: Consider only after surgery/radiation failure or when somatostatin analogues provide inadequate biochemical control.

pegvisomant; Somavert; acromegaly; growth hormone antagonist; GH receptor antagonist; IGF-1 normalisation; pituitary tumour; liver monitoring; endocrinology-specialist; high-cost drug; orphan drug

RxIndia v1.0 — 01 Jun 2025

• CDSCO drug approval documentation

• Indian Pharmacopoeia

• API Textbook of Medicine (11th edition)

• Harrison's Principles of Internal Medicine (21st edition)

• Goodman & Gilman's Pharmacological Basis of Therapeutics (14th edition)

• AIIMS Endocrinology protocols

• Indian Endocrine Society — clinical practice recommendations (specialist input)

• Pfizer prescribing information (Somavert)

• Endocrine Society Clinical Practice Guidelines — Acromegaly (supportive reference)