Action and Spectrum

Actions and Spectrum: 

• mecasermin is a recombinant form of human insulin-like growth factor 1 (IGF-1) and acts as a growth hormone therapy. The mechanism of action of mecasermin is through binding to the IGF-1 receptor and activating downstream signaling pathways, including the MAPK/ERK and PI3K/Akt pathways. This leads to increased cellular proliferation and differentiation, increased protein synthesis, and decreased protein breakdown. 
• mecasermin is approved for treating growth failure in children with primary IGF-1 deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. It is also used to treat short stature associated with Turner syndrome, chronic renal insufficiency, and short stature born small for gestational age. 
• The spectrum of activity of mecasermin is limited to the indications mentioned above, as it is only used for treating growth failure associated with specific medical conditions. It is inadequate for treating growth hormone deficiency caused by other factors, such as pituitary tumors or radiation therapy, and is not used for general growth hormone supplementation or enhancement. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Tonsillar hypertrophy (15%) 

Hypoglycemia (42%)  

1-10% 

Dizziness (>5%) 

Headache (>5%) 

Lipohypertrophy (>5%) 

Arthralgia (>5%) 

Otitis media (>5%) 

Cardiac murmur (>5%) 

Convulsion (>5%) 

Thymus hypertrophy (>5%) 

Ear problems (>5%)  

<1% 

Generalized urticaria 

Dyspnea 

Alopecia, hair texture abnormal 

Anaphylaxis 

Angioedema 

Local allergic reactions at the injection site (e.g., pruritus, urticaria)  

Post-marketing reports 

generalized urticaria 

anaphylaxis 

dyspnea 

alopecia 

angioedema 

hair texture abnormal 

Black Box Warning

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• mecasermin is contraindicated in patients with a history of hypersensitivity to mecasermin or its components. It is also contraindicated in patients who have active or suspected neoplasia, as IGF-1 has been shown to stimulate the growth of some types of tumors. 
• mecasermin should not be used in patients with closed epiphyses, as it can cause premature closure of growth plates and limit the potential for further growth. It should also not be used in patients with acute critical illness, respiratory failure, or other conditions requiring rapid recovery, as mecasermin therapy is a long-term treatment that may take months or years to produce growth benefits. 
• mecasermin is not recommended for use during pregnancy or breastfeeding, as its safety in these populations has not been established. 

Caution: 

• Hypoglycemia: mecasermin can cause hypoglycemia (low blood sugar), and blood glucose levels should be monitored regularly during treatment. Dose adjustments may be necessary to prevent hypoglycemia in some patients. 
• Intracranial hypertension: mecasermin has been associated with the development of intracranial hypertension, a condition characterized by increased pressure in the skull. Patients should be monitored for signs and symptoms of intracranial hypertension, such as headache, nausea, vomiting, and visual disturbances. 
• Scoliosis: mecasermin therapy can exacerbate pre-existing scoliosis (abnormal spine curvature) in some patients. Regular monitoring of spine curvature is recommended during treatment. 
• Allergic reactions: mecasermin is a protein-based drug that can cause some patients’ allergic reactions. Signs of an allergic reaction may include rash, hives, itching, difficulty breathing, and swelling of the face or throat. Patients should be monitored closely for these symptoms during treatment. 
• Increased risk of neoplasia: As mentioned earlier, IGF-1 has been shown to stimulate the growth of some types of tumors. Patients receiving mecasermin therapy should be monitored regularly for new or worsening neoplasia development. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

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 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: 

• mecasermin is a recombinant form of human insulin-like growth factor-1 (IGF-1) and acts as a growth hormone therapy. IGF-1 is a protein hormone structurally similar to insulin and is crucial in promoting growth and development in children and adults. 

• mecasermin binds to the IGF-1 receptor, which is expressed on the surface of many different types of cells in the body. This binding activates downstream signaling pathways, including the MAPK/ERK and PI3K/Akt pathways, leading to increased cellular proliferation and differentiation, protein synthesis, and decreased protein breakdown. 

• mecasermin therapy can stimulate growth and promote catch-up growth in children with primary IGF-1 deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. In patients with other conditions associated with short statures, such as Turner syndrome or chronic renal insufficiency, mecasermin therapy can help to improve linear growth. 

Pharmacodynamics: 

• The pharmacodynamics of mecasermin are primarily related to its ability to bind to and activate the insulin-like growth factor-1 (IGF-1) receptor, leading to downstream signaling and cellular effects. 
• mecasermin therapy can stimulate growth and promote catch-up growth in children with primary IGF-1 deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.
• In patients with other conditions associated with short statures, such as Turner syndrome or chronic renal insufficiency, mecasermin therapy can help to improve linear growth. 

Pharmacokinetics: 

Absorption 

mecasermin is administered subcutaneously and is rapidly absorbed into the systemic circulation. Peak serum concentrations are typically reached within 2-4 hours after dosing.  

Distribution 

mecasermin is a protein-based drug that is extensively distributed throughout the body. The volume of distribution of mecasermin is approximately 0.14-0.28 L/kg.  

Metabolism 

mecasermin is primarily cleared by renal excretion and is not metabolized by the liver. The drug is subject to degradation by proteolytic enzymes in the body, and the resulting breakdown products are eliminated in the urine.  

Elimination and Excretion 

The elimination half-life of mecasermin is approximately 12-15 hours. The drug is primarily eliminated through renal excretion, with approximately 50-70% of the dose being excreted unchanged in the urine. 

Adminstartion

Administration: 

Subcutaneous Injection 

• Avoid hypoglycemia by giving 20 minutes before or after meals. 
• Reduce the dose if recommended doses cause hypoglycemia despite adequate food intake. 
• Avoid lipodystrophy by rotating the injection site. 

Storage 

Refrigerate unopened vials; after opening, contents are stable for 30 days 

Patient Information Leaflet

Patient information leaflet 

Generic Name: mecasermin 

Why do we use mecasermin? 

mecasermin treats growth failure in children with primary insulin-like growth factor-1 (IGF-1) deficiency or growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.

It also treats growth failure in children with other conditions associated with short statures, such as Turner syndrome or chronic renal insufficiency.