Somatropin

Somatropin replaces or supplements endogenous growth hormone, restoring linear growth in children and metabolic and body-composition effects in adults with deficiency. The hormone acts both directly through its receptor and indirectly via IGF-1, which it strongly induces.

Mechanism of Action

• Growth hormone receptor (GHR) activation: somatropin binds the dimeric GHR expressed on hepatocytes, chondrocytes, adipocytes, and many other tissues. Ligand binding induces receptor dimerisation and recruits Janus kinase 2 (JAK2), triggering tyrosine phosphorylation of JAK2 and STAT1/3/5 transcription factors, which translocate to the nucleus and modulate target gene expression.
• IGF-1 axis: in the liver, GHR signalling upregulates production of insulin-like growth factor-1 (IGF-1), IGF-binding protein 3 (IGFBP-3), and acid-labile subunit (ALS). IGF-1 in turn acts on the IGF-1 receptor at the growth plate to drive linear growth via chondrocyte proliferation and differentiation.
• Direct effects at the growth plate: somatropin promotes differentiation of prechondrocytes and expansion of the osteoblast pool, increasing bone length.
• Metabolic effects: enhances cellular protein synthesis and nitrogen retention; stimulates lipolysis via hormone-sensitive lipase, reducing fat stores and serum LDL-C; antagonises insulin action, increasing hepatic gluconeogenesis and reducing peripheral glucose uptake (with potential for impaired glucose tolerance).
• Body composition: increases lean body mass and decreases fat mass — basis of approval in HIV-associated wasting.

Pharmacokinetics

• Absorption: subcutaneous administration at 0.024 mg/kg yields peak plasma concentrations of approximately 14–17 ng/mL at 4–5 hours.
• Volume of distribution: not fully characterised; somatropin distributes into extracellular fluid.
• Protein binding: endogenous GH complexes with growth hormone-binding protein (a soluble form of GHR) in plasma; clinical implications for dosing are minimal.
• Half-life: subcutaneous terminal half-life is several hours; IV elimination half-life ~21 minutes. Daily dosing reflects the duration of biological effect rather than plasma half-life alone.
• Metabolism: catabolised in the liver and kidney to peptides and amino acids; minimal CYP involvement (GH does modestly induce CYP1A2 and CYP3A4 activity in healthy adults).
• Clearance: mean clearance ~2.3 mL/min/kg.

Paediatric

• Growth hormone deficiency — proven or strongly suspected.
• Turner syndrome.
• Prader-Willi syndrome (with appropriate exclusion of severe obesity and respiratory impairment).
• Idiopathic short stature (in approved jurisdictions; criteria vary).
• SHOX gene haploinsufficiency.
• Small for gestational age (SGA) with failure to catch up by age 4.
• Chronic kidney disease before transplantation, to maintain growth velocity.
• Noonan syndrome (selected products and markets).

Adult

• Adult-onset growth hormone deficiency — confirmed by appropriate dynamic testing (e.g. insulin tolerance test or glucagon stimulation test), arising from pituitary disease, hypothalamic disease, surgery, radiotherapy, or trauma.
• Childhood-onset GH deficiency persisting into adulthood — typically retested in late adolescence.
• HIV-associated wasting and cachexia in patients on antiretroviral therapy (Serostim).
• Short bowel syndrome in adults receiving specialised nutritional support (Zorbtive).

• Hypersensitivity to somatropin or any excipient (including metacresol or benzyl alcohol where present).
• Active malignancy. Antitumour treatment must be complete and the tumour inactive before starting or restarting somatropin.
• Proliferative or pre-proliferative diabetic retinopathy.
• Closed epiphyses (for paediatric growth-promotion indications).
• Acute critical illness following open-heart or abdominal surgery, multiple accidental trauma, or acute respiratory failure — somatropin is associated with increased mortality in this setting.
• Prader-Willi syndrome with severe obesity, severe respiratory impairment, or untreated sleep apnoea — fatalities have been reported.

Very common (≥1/10) — adults: peripheral oedema, arthralgia, myalgia, paraesthesia.

Common (≥1/100 to <1/10): headache, carpal tunnel syndrome, hypothyroidism (often unmasking pre-existing subclinical disease), impaired fasting glucose, impaired glucose tolerance, hyperglycaemia, injection-site reactions (erythema, pain, lipoatrophy with poor site rotation), gynaecomastia, sleep apnoea exacerbation.

Uncommon (≥1/1,000 to <1/100): pseudotumour cerebri (idiopathic intracranial hypertension — present with headache, vision changes; warrants funduscopy and imaging), slipped capital femoral epiphysis in growing children, scoliosis progression, pancreatitis.

Rare (<1/1,000): new-onset type 2 diabetes mellitus, hypersensitivity reactions, antibody formation (rarely neutralising).

Mortality signal: increased mortality reported with somatropin in acutely critically ill patients; this defines a major contraindication.

• Insulin and oral antidiabetics: somatropin antagonises insulin action — antidiabetic doses may require upward adjustment.
• Glucocorticoids: cortisone-acetate and prednisone require dose review — somatropin may unmask central adrenal insufficiency, and conversely glucocorticoid replacement (where excessive) can blunt the growth response.
• Thyroid hormones: somatropin may accelerate peripheral T4-to-T3 conversion and unmask subclinical hypothyroidism; assess and treat as needed.
• Oral oestrogens: increase somatropin requirement (oestrogen reduces hepatic IGF-1 production); transdermal oestrogen does not have this effect.
• CYP450 enzymes: somatropin induces CYP1A2 and CYP3A4 activity modestly; concomitant drugs metabolised by these pathways (cyclosporin, anticonvulsants, sex steroids) may require monitoring.

Somatropin is administered by subcutaneous injection, typically once daily in the evening. Sites should be rotated to prevent lipoatrophy. Pen devices, prefilled cartridges, and vials with separate diluent are available — administration instructions are brand- and device-specific.

Paediatric Growth Hormone Deficiency

• Dose: 0.025–0.035 mg/kg/day (approximately 0.7–1.0 mg/m²/day), titrated to growth velocity and serum IGF-1 within age- and sex-appropriate reference range.

Turner Syndrome

• Dose: 0.045–0.05 mg/kg/day (approximately 1.4 mg/m²/day).

Prader-Willi Syndrome

• Dose: 0.035 mg/kg/day (approximately 1.0 mg/m²/day), maximum 2.7 mg/day. Pre-screen for severe obesity and obstructive sleep apnoea.

SGA, SHOX, Idiopathic Short Stature

• Dose: 0.035–0.067 mg/kg/day (approximately 1.0–2.0 mg/m²/day, indication-dependent).

Chronic Kidney Disease Pre-Transplant

• Dose: up to 0.05 mg/kg/day until renal transplantation.

Adult Growth Hormone Deficiency

• Starting dose: low, typically 0.15–0.30 mg/day, titrated upward over 1–2 months based on serum IGF-1, clinical response, and tolerability.
• Maintenance: typical 0.2–1.0 mg/day; women and older patients usually need lower doses; oestrogen co-administration increases requirements.

HIV-Associated Wasting (Serostim)

• Adults >55 kg: 6 mg subcutaneously every evening.
• Adults 45–55 kg: 5 mg subcutaneously every evening.
• Adults 35–45 kg: 4 mg subcutaneously every evening.
• Adults <35 kg: 0.1 mg/kg subcutaneously every evening.

Short Bowel Syndrome (Zorbtive)

• Adults: 0.1 mg/kg/day (maximum 8 mg/day) subcutaneously, for a course of up to 4 weeks; longer courses not generally recommended.

Renal and Hepatic Impairment

Reduced clearance is expected in both — titrate cautiously to clinical response and IGF-1.

Missed Dose

If the patient remembers within a few hours of the usual time, administer the dose. If close to the next scheduled dose, skip the missed dose and resume the schedule. Do not double up.

Pre-Treatment and On-Treatment Screening

Baseline assessment of thyroid function, adrenal axis, fasting glucose/HbA1c, IGF-1, fundoscopy in those with diabetes, and screening for scoliosis and sleep apnoea (especially in PWS). Repeat IGF-1 every 6–12 months and review growth velocity, glucose metabolism, and thyroid status.

Malignancy

Surveillance for tumour recurrence (in patients with prior malignancy, particularly intracranial) is essential. Hold therapy if a new neoplasm is suspected.

Prader-Willi Syndrome

Severe obesity and respiratory compromise are contraindications. Monitor weight, snoring, and respiratory status carefully; perform polysomnography in those with sleep concerns.

Diabetes and Glucose Metabolism

Somatropin is diabetogenic. Monitor fasting glucose and HbA1c regularly; adjust antidiabetic therapy as needed.

Pregnancy and Lactation

• Pregnancy: limited data — discontinue at confirmation of pregnancy unless clearly required.
• Breastfeeding: passage into breast milk uncertain; case-by-case decision.

Effect on Driving

No or negligible influence.

• Unopened pre-filled pens, cartridges, and vials: store at 2–8°C (refrigerator), protected from light. Do not freeze. Discard if accidentally frozen.
• In use (after first injection or after reconstitution): brand- and device-specific:
  • Norditropin FlexPro / NordiFlex pens: in use up to 28 days at 2–8°C; the SimpleXx and FlexPro have specific allowances for limited room-temperature use.
  • Genotropin pre-filled pen: reconstituted product 21 days at 2–8°C.
  • Saizen, Humatrope, Omnitrope, Zomacton: device- and presentation-specific; follow the leaflet.
• Always refer to the specific brand and device leaflet for in-use stability and any room-temperature excursion allowances.

Typically 2–3 years for unopened product, brand-specific. Do not use after the expiry date printed on the packaging.

Prescription required (Rx).