Recombinant human insulin-like growth factor I called mecasermin (Increlex) is recommended for children who have growth failure (short height) as a result of an insulin-like growth factor-1 deficit.

Mecasermin Uses:

• Primary insulin-like growth factor-1 deficiency:

  • Used to treat growth failure in children under the age of two who have a severe primary IGF-1 deficit or a growth hormone gene deletion and have produced antibodies that are neutral to GH.

Use in Adults:

Not indicated in adults (not recommended after the closure of epiphysis).

Mecasermin (Increlex) Dose in children

Mecasermin (Increlex) Dose in children with growth failure due to primary insulin-like growth factor 1 deficiency (IGFD):

• Children ≥2 years and Adolescents:

  • Subcutaneous: Initial: 0.04 to 0.08 mg/kg/dose twice a day; may increase by 0.04 mg/kg/dose, if tolerated for 7 days
  • The maximum dose is 0.12 mg/kg/dose two times a day; no studies have been done on higher doses and should not be used because of the risk of hypoglycemia.

Note: Must administer within 20 minutes of eating a meal or snack; dose should be skipped if a patient is unable to consume food. The dose should be reduced if hypoglycemia occurs despite adequate food intake; do not increase the dose to make up for ≥1 omitted dose.

Pregnancy Risk Category: C

• Patients with closed epiphysis are not recommended to use this product for growth promotion.
• It is not recommended to use during pregnancy.

Use during breastfeeding:

• Not known if mecasermin is present in breast milk.
• According to the manufacturer, there are some things you should consider when deciding whether or not to breastfeed during therapy.
  • Infant exposure is a risk
  • Breastfeeding is good for the infant
  • Treatments for the mother: Benefits

Dose in Kidney Disease:

Infants and toddlers and adolescents: The manufacturer's labelling does not mention dosage modifications, and usage has not been researched.

Dose in Liver disease:

Infants and toddlers and adolescents: The manufacturer's labelling does not mention dosage modifications, and usage has not been researched.

Common Side Effects of Mecasermin (Increlex):

• Endocrine & metabolic:

  • Hypoglycemia

• Immunologic:

  • Antibody development

• Respiratory:

  • Tonsillar hypertrophy

Less Common Side Effects of Mecasermin (Increlex):

• Cardiovascular:

  • Heart Murmur

• Central Nervous System:

  • Hypoglycemic Seizure
  • Loss Of Consciousness
  • Dizziness
  • Headache
  • Seizure
  • Intracranial Hypertension

• Endocrine & Metabolic:

  • Thymus Hypertrophy

• Gastrointestinal:

  • Vomiting

• Local:

  • Bruising At Injection Site
  • Lipotrophy At Injection Site

• Neuromuscular & Skeletal:

  • Arthralgia
  • Limb Pain

• Otic:

  • Abnormal Tympanometry
  • Fluid In Ear
  • Hypo-acusis
  • Otalgia
  • Otitis Media
  • Serous Otitis Media

• Respiratory:

  • Snoring

Frequency of side effects not defined:

• Cardiovascular:

  • Cardiomegaly
  • Heart Valve Disease

• Dermatologic:

  • Thickening Of The Soft Tissues Of The Face

• Endocrine & Metabolic:

  • Hypercholesterolemia
  • Hypertriglyceridemia
  • Increased Lactate Dehydrogenase

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Transaminase

• Neuromuscular & Skeletal:

  • Scoliosis Progression

Contraindications to Mecasermin (Increlex):

• Hypersensitivity to mecasermin and any other component of the formulation
• After epiphyseal closure
• Malignant neoplasia
• Histories of carcinoma.

Warnings and precautions

• Hypersensitivity reactions

  • Reports of hypersensitivity reactions (localized reactions to anaphylaxis in the skin) have been made. 
  • If you suspect hypersensitivity, it is best to stop taking the drug and get immediate medical attention.

• Hypoglycemia:

  • Hypoglycemic reactions may occur in small children due to inconsistent oral intake.
  • High-risk activities such as driving should be avoided within 2-3 hours of dosing, especially at the beginning of treatment.
  • Do not administer to patients who are unable or unwilling to eat. Give with a meal, or snack.

• Intracranial hypertension

  • Intracranial hypertension can be caused by growth hormone products.
  • This can lead to headaches, nausea, papilledema and/or vomiting.
  • Funduscopic examinations are recommended prior to therapy begins and again periodically thereafter.

• Hypertrophy of the lymphoid:

  • There have been cases of lymphoid hypertrophy, which can lead to complications such as snoring and sleep apnea.

• Slipped capital femoral epiphyses

  • Slippery capital femoral epiphysis is more common in patients who are deficient in growth hormone.
  • Any child with a limp, new or worsening pain in the knees or hips should be examined.

• Diabetes:

  • Avoid using this product in patients who are diabetics or have risk factors for developing glucose intolerance. Insulin sensitivity could be reduced.

• Malignancy

  • Cases of malignant neoplasms have been reported; generally observed in patients with rare genetic conditions of short stature associated with cancer risk, other cancer-predisposing conditions, and use of higher-than-recommended doses and doses that produced elevated age- and sex-matched insulin-like growth factor-1 (IGF-1) levels.
  • Patients with malignant Neoplasia or a history malignancy are not recommended to use this medication.
  • Use should be stopped if neoplasia is present

• Scoliosis:

  • In children experiencing rapid growth, scoliosis progression may occur.

Mecasermin (recombinant human insulin-like growth factor I): Drug Interaction

Monitoring parameters:

• Glucose levels
• Hypersensitivity reactions
• Facial features
• Lymphoid tissue
• Funduscopic examination 
• Growth
• New onset of a limp or complaints of hip or knee pain
• Progression of scoliosis.
• Closely monitor small children due to potentially erratic food intake.

Target treatment IGF-1 level: 0 to +2 SD score for age The dose should be decreased for adverse events and/or IGF-1 levels ≥3 SD above normal

How to administer Mecasermin (Increlex)?

Subcutaneous:

• Must administer within 20 minutes of eating a meal or snack; dose should be skipped if a patient is unable to consume food.
• For prevention of lipohypertrophy injection site should be rotated (upper arm, thigh, buttock, abdomen).
• Hypoglycemic effects may occur; high-risk activities should be avoided (driving, operating machinery) within 2 to 3 hours of dosing until a tolerated dose is established.

Mechanism of action of Mecasermin (Increlex):

• Mecasermin is a recombinant genetically generated insulin-like growth factor (IGF-1).
  It takes the place of natural IGF-1.
• The majority of endogenous IGF-1 that circulates in the systemic circulation is linked to IGFBP-3, an insulin-like growth factor-binding protein, and an acid-labile growth hormone receptor (ALS).
• By activating receptors in the liver and other organs, endogenous growth hormones (GH) promote IGF-1 production and release.
• Patients with severe IGF-1 deficiencies may not respond to GH from the liver's growth hormone receptors.
• This results in decreased endogenous IGF-1 concentrations and reduced growth (skeletal, cell and organ).
• Endogenous IGF-1 also stimulates peripheral glucose use and suppresses liver glucose production. It inhibits insulin secretion.

Protein binding:

• More than 80% bound to IGFBP-3 and a component that is acid labile (IGFBP-3 reduced with severe primary IGFD)

Metabolism:

• Metabolism occurs both in the liver and kidneys

Bioavailability:

• 100% bioavailability in healthy subjects

Half-life elimination:

• Severe primary IGFD: Almost 5.8 hours

Time to peak serum concentration:

• Two hours

International Brand Names of Mecasermin:

• Increlex

Mecasermin Brand Names in Pakistan:

No Brands Available in Pakistan.