Introduction
Genotropin (somatropin [rDNA origin]) is a biosynthetic human growth hormone produced by recombinant DNA technology. It is identical to endogenous human growth hormone (hGH) produced by the pituitary gland, consisting of 191 amino acids with a molecular weight of 22,125 daltons. Genotropin is indicated for the treatment of growth failure due to inadequate growth hormone secretion and other medical conditions affecting growth and metabolism.
Mechanism of Action
Genotropin exerts its effects through binding to growth hormone receptors on target cells, 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 by stimulating epiphyseal growth plates, increases protein synthesis, enhances lipolysis, reduces glucose utilization, and increases mineral retention.
Indications
FDA-approved indications include:
- Pediatric growth hormone deficiency (GHD)
- Adult growth hormone deficiency
- Turner syndrome
- Prader-Willi syndrome
- Small for gestational age (SGA) with failure to catch up by age 2
- Idiopathic short stature
- Short stature homeobox-containing gene (SHOX) deficiency
- Noonan syndrome
Dosage and Administration
Pediatric GHD: 0.16-0.24 mg/kg/week divided into 6-7 daily subcutaneous injections Adult GHD: Starting dose 0.04 mg/kg/week, titrated based on clinical response and IGF-1 levels Turner syndrome: Up to 0.375 mg/kg/week divided daily Chronic renal insufficiency: Up to 0.35 mg/kg/week divided daily Administration: Subcutaneous injection in the thigh, buttocks, or abdomen with rotation of injection sites. Available in various delivery systems including Genotropin MiniQuick and Genotropin Pen. Special Populations:- Renal impairment: Dose adjustment may be necessary
- Hepatic impairment: Use with caution
- Elderly: Limited data available
Pharmacokinetics
Absorption: Bioavailability approximately 70-90% following subcutaneous administration. Peak concentrations reached 2-6 hours post-injection. Distribution: Volume of distribution approximately 0.07-0.09 L/kg. Binds to growth hormone binding protein in circulation. Metabolism: Primarily hepatic and renal metabolism through proteolytic cleavage. Elimination: Half-life 2-4 hours. Cleared primarily by the liver and kidneys.Contraindications
- Active malignancy
- Hypersensitivity to somatropin or excipients
- Active proliferative or severe non-proliferative diabetic retinopathy
- Acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma, or acute respiratory failure
- 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 or abdominal surgery, multiple accidental trauma, or acute respiratory failure. Additional Warnings:- Increased risk of neoplasia: Monitor patients with history of malignancy
- Glucose intolerance and diabetes mellitus: Monitor blood glucose regularly
- Intracranial hypertension: Funduscopic examination recommended if symptoms occur
- Fluid retention: May cause edema, arthralgia, carpal tunnel syndrome
- Slipped capital femoral epiphysis: Evaluate for limp or hip/knee pain
- Pancreatitis: Monitor for abdominal pain
- Hypothyroidism: Monitor thyroid function periodically
Drug Interactions
- Glucocorticoids: May inhibit growth response
- Estrogen: Oral administration may decrease IGF-1 response
- Cytochrome P450 substrates: Growth hormone may alter metabolism of drugs metabolized by CYP450 enzymes
- Insulin: May require dose adjustment of antidiabetic medications
Adverse Effects
Common (≥5%):- Injection site reactions
- Headache
- Edema
- Arthralgia
- Myalgia
- Paresthesia
- Hyperglycemia
- Hypothyroidism
- Intracranial hypertension
- Slipped capital femoral epiphysis
- Progression of scoliosis
- Pancreatitis
- Neoplasia
- Severe hypersensitivity reactions
Monitoring Parameters
- Height velocity every 3-6 months in children
- IGF-1 levels every 3-6 months
- Thyroid function tests annually
- Fasting blood glucose annually
- Bone age annually in children (hand/wrist radiograph)
- Funduscopic examination if symptoms suggest intracranial hypertension
- Scoliosis monitoring in at-risk patients
Patient Education
- Proper injection technique and site rotation
- Storage requirements (refrigeration at 2-8°C)
- Importance of adherence to treatment schedule
- Recognition of potential adverse effects
- Regular follow-up with healthcare provider
- Not to share needles or delivery devices
- Disposal of used needles in sharps container
- Report any severe headaches, visual changes, or limping
References
1. Genotropin [package insert]. New York, NY: Pfizer Inc; 2023. 2. Growth Hormone Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone deficiency in childhood and adolescence. J Clin Endocrinol Metab. 2000;85(11):3990-3993. 3. Molitch ME, Clemmons DR, Malozowski S, 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. 4. Allen DB, Backeljauw P, Bidlingmaier M, 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. 5. Collett-Solberg PF, Ambler G, Backeljauw PF, et al. Diagnosis, genetics, and therapy of short stature in children: a Growth Hormone Research Society international perspective. Horm Res Paediatr. 2019;92(1):1-14.