1. Dosage
Mecasermin (Increlex) is the recombinant DNA form of human insulin-like growth factor-1 (rhIGF-1). In normal circulation, over 98% of rhIGF-1 is available in bound form to IGFBP-3, which allows IGF-1 to remain inactive until released to target tissues. This reduces the potential for adverse events associated with free levels of IGF-1. In patients with growth hormone insensitivity syndrome, the serum half-life of unbound IGF-1 is decreased, as these patients have lower rhIGFBP-3 concentrations. Patients with IGF-1 gene deletion have normal levels of rhIGFBP-3. Mecasermin is FDA-approved for use in treating growth failure in children with severe primary IGF-1 deficiency (primary IGFD) or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. Mecasermin has also been evaluated for use in short children with low IGF-1 levels; results showed improvement in height velocities following mecasermin use compared to untreated patients after one year of treatment1-3.
1.1. Pediatrics
Mecasermin is approved for use in children 2 years of age and older, but has not been studied in adults. Mecasermin should not be used in children whose bone growth plates are closed (epiphyseal closure), as linear growth is no longer possible in these patients. Additionally, mecasermin safety and efficacy have not been determined in children younger than 2 years of age. The recommended initial mecasermin dosage is 0.04 to 0.08 mg/kg twice daily subcutaneously, which can be titrated up in increments of 0.04 mg/kg, if tolerated, to a maximum dose of 0.12 mg/kg twice daily (total: 0.24 mg/kg/day). Patient profiles containing prescriptions for doses exceeding these recommendations will be reviewed1-3 .
Mecasermin should be administered with food or a snack as IGF-1 decreases hepatic glucose production and increases peripheral glucose utilization and may induce hypoglycemia. Mecasermin administration should be withheld in patients unable or unwilling to eat a meal prior to mecasermin dosing1-3.