somatropin

Action and Spectrum

Actions and Spectrum

In conditions like growth hormone deficiency, growth failure, malnutrition and low body mass, somatropin mimics and restores the action of endogenous growth hormone by stimulation linear bone growth, increasing muscle and bone mass, reducing fat mass and regulating the lipid and blood glucose levels. Both directly and indirectly, somatropin mediated the effects by insulin-like growth factor-1 (IGF-1) which can elevated by growth hormone. It attaches to human growth hormone receptor (GHR) and interact and dimerize with Janus kinase 2 (JAK2). This can lead to tyrosine phosphorylation of the JAK2 and GHR. To stimulate the target gene transcription, transcription factors like signal transducer activator of transcription 3 (STAT3), STAT1 and STAT5 translocate in the nucleus and STAT pathway.

IGF-1 is produced when growth hormone binds to the receptor in the liver and cartilage. It interacts with type 1 IGF receptors to promote linear growth. The liver produces more IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS) as a result of the active growth hormone receptor signaling. These proteins bind to IGF-1 in a ternary complex to increase its half-life.

Drug Interaction

Adverse Reaction

Adverse drug reactions

Frequency Defined

<10%

Norditropin

Myalgia (15%)

Infection (non-viral) (13%)

Peripheral edema (42%)

Skeletal Pain (11%)

Leg Edema (15%)

Paraesthesia (11%)

Edema (25%)

Arthralgia (19%)

Humatrope

Edema (21.2%)

Pain (13.5%)

Paresthesia (17.3%)

Rhinitis (13.5%)

Myalgia (13.5%)

Peripheral edema (11.5%)

Arthralgia (17.3%)

1-10%

Norditropin

Bronchitis (9%)

Headache (9%)

Hypertension (8%)

Flu-like symptom (8%)

Gastroenteritis (8%)

Increased sweating (8%)

Laryngitis (6%)

Glucose tolerance abnormal (6%)

Type 2 diabetes (5%)

Humatrope

Flu syndrome (3.9%)

Surgical procedure (5.8%)

Acne (5.8%)

Hypertension (7.7%)

Joint disorder (5.8%)

Headache (7.7%)

Back pain (9.6%)

Black Box Warning

Black box warning

Somatropin is not used in diabetic retinopathy, cancer or ongoing treatment of Prader-Willi syndrome, obese patient or someone has severe breathing issues. It should not be used in severe illness because of lung complications due to recent injury, surgery or medical trauma or lung failure.

Contraindication / Caution

Contraindications/Caution

Contraindications:

Hypersensitivity to drug, benzyl alcohol

Active malignancy, acute complication due to open abdominal or heart surgery, acute respiratory failure, multiple trauma

Pediatric patient with closed epiphyses

Severe non-proliferation or active proliferation diabetic retinopathy

Pediatric patient who is obese and has Prader-Willi syndrome

Cautions:

Somatropin is used with cautions in the following situations:

• History of malignancy or intracranial tumor: It needs regular monitoring for recurrence specifically in pediatric patients with a prior history of CNS tumors.
• Diabetes mellitus or glucose intolerance: Somatropin can reduce insulin sensitivity. Blood glucose levels should be monitored, and anti-diabetic therapy may need adjustment.
• Hypothyroidism: Growth hormone therapy can worsen hypothyroidism which can blunt the growth response. Thyroid function should be monitored periodically.
• Pancreatitis: It is rare but serious. If abdominal pain occurs, pancreatitis should be considered and evaluated.
• Fluid retention: It is common in adults and may lead to peripheral edema, arthralgia or carpal tunnel syndrome.

Intracranial hypertension: Monitor for symptoms like headache, visual changes or nausea. Temporarily discontinuing therapy may be necessary.

Pregnancy / Lactation

Pregnancy warnings

AU TGA pregnancy category: B2

US FDA pregnancy category: C

Lactation:

Excreted into human milk is unknown

Pregnancy Categories:     

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.  
• Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.  
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.  
• Category N: There is no data available for the drug under this category.

Pharmacology

Pharmacology

Somatropin is used to treat the pediatric patient who has growth failure because of inadequate secretion of the endogenous growth hormone, Prader-Willi syndrome (PWS), short stature associated with Turner syndrome, idiopathic short stature (ISS), short stature born small for gestational age (SGA) and short stature homeobox-containing gene (SHOX) deficiency.

Somatropin is purified polypeptide hormone derived from recombinant DNA. It contains the same amino acid sequence as human growth hormone. Human growth hormone facilitates skeletal muscle, organ growth and linear bone and by promoting lipolysis, chondrocyte differentiation and proliferation, hepatic glucose output and protein synthesis. It stimulates the erythropoietin that can increase the red blood cell mass and give both diabetogenic and insulin-like effects.

Pharmacodynamics:

Somatotropin stimulates growth in different organs and tissues like muscle, bone, red cell mass and internal organs. It promotes the protein synthesis, nitrogen retention, collagen and chondroitin sulphate synthesis. In the end stage renal disease, growth hormones can improve the nutritional status and decreases the blood urea nitrogen. The metabolic effect of growth hormone can involve the upregulation of IGF-1 which can lead to anabolic protein phase with elevated protein synthesis, amino acid uptake and reduced protein catabolism. High dosage can lead to glucose intolerance and insulin resistance and which can increase the glucose production by glycogenolysis and gluconeogenesis from liver and kidney by reduce the glucose uptake in the adipose tissue. It stimulates the lipolysis by activating the hormone sensitive lipase in the adipose tissue and elevate the circulation of triglycerides and free fatty acid, reduces fat stores and serum level of LDL.

Pharmacokinetics:

Absorption

Humatrope

• Peak plasma level: 415 ng/mL (0.02 ng/kg dosage), 63.3 ng/mL (0.1 mg/kg intramuscular dosage), 53.2 ng/mL (0.1 mg/kg Subcutaneous dosage)

Norditropin

• SC/IM: about 63 to 90% based on the formulation and administration route
• Peak plasma level: 13.8 ng/mL (0.024 mg/kg subcutaneous dosage), 34.9 ng/mL (4 mg single dosage)
• Peak plasma level is achieved in 3 hours for 4 mg single dose.

Genotropin

• Bioavailability is 80.5%. Peak plasma level is achieved in 5.9 hours.
• Peak plasma level in adults: 17.4 ng/mL (5.3 mg/mL of dose), 23 ng/mL (0.03 mg/kg subcutaneous dosage)
• Peak plasma level in pediatric: 12.4 ng/mL (1^st injection) and 12.2 ng/mL (2^nd injection) and it is achieved at about 6 hours after the dosing.

Distribution

Volume of Distribution:

Humatrope: 0.0703 L/kg for 0.02 mg/kg dosage, 0.957 L/kg for 0.1 mg/kg intramuscular dosage, 1.55 L/kg for 0.1 mg/kg subcutaneous dosage

Genotropin: 1.3 L/kg

Omniprobe: 1.4 L/kg

Nutropin AQ and Nutropin: 50 mL/kg

Serostim, Zorbtive, Saizen: 12 L

Metabolism

It occurs in kidneys and liver.

Elimination/Excretion

It excreted through urine.

Norditropin

The half-life is 7 to 10 hours for 0.024 mg/kg subcutaneous dosage. The clearance rate is 2.3 mL/min/kg.

Genotropin

The half-life is 0.4 hr for IV administration and 3 hr SC administration. The clearance rate is 0.3 mL/min/kg.

Humatrope

The half-life is 0.363 hours (for 0.02 mg/kg dosage), 4 hours (for 0.1 mg/kg subcutaneous dosage), 3.81 hours (for 0.1 mg/kg intramuscular dosage). The clearance rate is 0.135 L/kg per hour (for 0.02 mg/kg dosage), 4.93 L/kg per hour (0.1 mg/kg subcutaneous dosage) and 3.81 L/kg per hour (0.1 mg/kg intramuscular dosage).

Adminstartion

Administration

It is administrated by subcutaneously in the abdomen, back of upper arm, thigh or buttock with the regular rotation of injection site to avoid the lipoatrophy. The solution appears colorless and clear. Do not use it is it appears cloudy or contains any precipitate. Do not administer through intravenously (IV). Do not shake the solution.

Patient Information Leaflet

Patient Information Leaflet

Generic Name: Somatropin

Pronounced: soe-ma-TROE-pin

Why do we use somatropin? 

somatropin is a growth hormone agent which is used to treat the growth failure and HIV-associated Wasting or Cachexia.

• Growth hormone deficiency (GHD): Somatropin is prescribed for the children and adults who cannot produce enough growth hormone which can lead to poor growth and other metabolic issues.
• Turner syndrome: Somatropin is used to stimulate height and growth in girls who have Turner syndrome a genetic condition that affects development.
• Small for gestational age (SGA): Somatropin is used in children who were born small and have not grown in early childhood.
• Prader-Willi syndrome: Somatropin can improve the growth and reduce the body fat in children with Prader-Willi syndrome a genetic condition linked with obesity and growth issues.
• Adult growth hormone deficiency: Adults with low growth hormone levels because of the pituitary disease, surgery or injury may use somatropin to improve muscle mass, energy level and bone health.
• HIV-associated wasting: Somatropin is used to treat severe muscle wasting in people with HIV helping them regain strength and body weight.
• Short bowel syndrome (SBS): Somatropin may be used in patients with SBS who depend on nutritional support helping improve intestinal absorption and reduce reliance on intravenous feeding.