Introduction
Somatropin is a biosynthetic form of human growth hormone (HGH) produced using recombinant DNA technology. It is identical in structure and function to endogenous growth hormone produced by the anterior pituitary gland. Somatropin has revolutionized the treatment of growth hormone deficiency and related conditions since its introduction in the 1980s, replacing pituitary-derived human growth hormone which carried risks of Creutzfeldt-Jakob disease transmission.
Mechanism of Action
Somatropin exerts its effects by binding to growth hormone receptors located throughout the body, primarily in the liver. This binding stimulates production of insulin-like growth factor 1 (IGF-1), which mediates many of growth hormone's anabolic and growth-promoting effects. The drug promotes linear growth in children through stimulation of epiphyseal growth plates, and in adults, it maintains metabolic homeostasis by increasing protein synthesis, promoting lipolysis, reducing glucose uptake, and increasing glycogen synthesis.
Indications
FDA-approved indications include:
- Pediatric growth hormone deficiency (GHD)
- Adult growth hormone deficiency
- Turner syndrome
- Prader-Willi syndrome
- Children born small for gestational age (SGA) who fail to catch up growth by age 2-4 years
- Idiopathic short stature
- Short bowel syndrome
- HIV-associated wasting or cachexia
Dosage and Administration
Standard dosing: 0.16-0.24 mg/kg/week for pediatric GHD, divided into daily subcutaneous injections Administration: Subcutaneous injection, typically in the evening to mimic natural growth hormone secretion patterns Special populations:- Renal impairment: Dose reduction may be necessary
- Hepatic impairment: Monitor closely as IGF-1 production may be impaired
- Elderly: Start with lower doses and titrate carefully
Pharmacokinetics
Absorption: Bioavailability approximately 70-90% after subcutaneous administration Distribution: Volume of distribution approximately 0.07-0.1 L/kg Metabolism: Primarily hepatic and renal metabolism through proteolytic degradation Elimination: Half-life approximately 3-4 hours; cleared renally Onset of action: Growth effects typically observed within 3-6 months of initiationContraindications
- Active malignancy
- Diabetic retinopathy
- Acute critical illness due to complications following surgery, trauma, or acute respiratory failure
- Hypersensitivity to somatropin or any component of the formulation
- Closed epiphyses (for growth promotion indications)
- Prader-Willi syndrome with severe obesity or severe respiratory impairment
Warnings and Precautions
Boxed Warning: Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery, multiple accidental trauma, or acute respiratory failure- May reduce insulin sensitivity; monitor glucose levels
- Increased risk of secondary malignancies in patients treated during childhood
- Fluid retention may occur, potentially exacerbating conditions such as carpal tunnel syndrome
- Monitor for signs of intracranial hypertension
- Slipped capital femoral epiphysis and scoliosis progression may occur
- Pancreatitis has been reported
Drug Interactions
- Glucocorticoids: May inhibit growth-promoting effects
- Estrogen: Oral administration may reduce somatropin efficacy
- Cytochrome P450 substrates: May alter metabolism of drugs metabolized by CYP3A4
- Insulin: May require adjustment of insulin doses due to altered insulin sensitivity
Adverse Effects
Common (>10%):- Injection site reactions (redness, swelling)
- Headache
- Edema
- Arthralgia
- Myalgia
- Paresthesia
- Intracranial hypertension
- Pancreatitis
- Slipped capital femoral epiphysis
- Worsening of scoliosis
- Hypothyroidism
- Diabetes mellitus
- Malignancy recurrence
Monitoring Parameters
- Height and growth velocity (every 3-6 months in children)
- IGF-1 levels (every 6-12 months)
- Thyroid function tests (baseline and periodically)
- Fasting blood glucose and HbA1c
- Ophthalmologic examination in patients with diabetes
- Scoliosis screening in children
- Hip examinations in children with gait disturbance
Patient Education
- Proper injection technique and rotation of injection sites
- Importance of adherence to prescribed regimen
- Recognition of signs of hyperglycemia (increased thirst, urination)
- Report severe or persistent headache, visual changes, or vomiting
- Storage requirements (typically refrigerated)
- Proper disposal of needles and syringes
- Importance of regular follow-up appointments
- Not to share medication with others
References
1. Molitch ME, et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587-1609. 2. Grimberg A, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016;86(6):361-397. 3. FDA Prescribing Information: Somatropin products (Various Brands). 4. Cook DM, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children--2003 update. Endocr Pract. 2003;9(1):64-76. 5. Allen DB, et al. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. Eur J Endocrinol. 2016;174(2):P1-P9.