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Chapter: Basic & Clinical Pharmacology : Hypothalamic & Pituitary Hormones

Mecasermin

A small number of children with growth failure have severe IGF-I deficiency that is not responsive to exogenous GH.

MECASERMIN

A small number of children with growth failure have severe IGF-I deficiency that is not responsive to exogenous GH. Causes include mutations in the GH receptor and in the GH receptor signaling pathway, neutralizing antibodies to GH, and IGF-I gene defects. In 2005, the FDA approved two forms of recombinant human IGF-I (rhIGF-I) for treatment of severe IGF-I deficiency that is not responsive to GH: mecasermin and mecasermin rinfabate. Mecasermin is rhIGF-I alone, while mecasermin rinfabate is a complex of recombinant human IGF-I (rhIGF-I) and recombi-nant human insulin-like growth factor-binding protein-3 (rhIGFBP-3). This binding protein significantly increases the cir-culating half-life of rhIGF-I. Normally, the great majority of the circulating IGF-I is bound to IGFBP-3, which is produced prin-cipally by the liver under the control of GH. Mecasermin rinfa-bate is not currently available in the United States. Mecasermin is administered subcutaneously twice daily at a recommended start-ing dosage of 0.04–0.08 mg/kg and increased weekly up to a maximum twice-daily dosage of 0.12 mg/kg.

The most important adverse effect observed with mecasermin is hypoglycemia. To avoid hypoglycemia, the prescribing instruc-tions require consumption of a carbohydrate-containing meal or snack 20 minutes before or after mecasermin administration. Several patients have experienced intracranial hypertension and asymptomatic elevation of liver enzymes.


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Basic & Clinical Pharmacology : Hypothalamic & Pituitary Hormones : Mecasermin |


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