Diagnostic Tools and Tests

There are diagnostic tools and tests available to determine factors that affect growth failure in patients including:

Total IGF-1 level: level of IGF-1 in body²⁵

GH Stimulation Test: measures level of GH in body; hallmark of diagnosis of GHD;²⁶ essential for distinguishing between primary and secondary IGFD; should be performed in all patients with unexplained short stature; helpful for diagnosis of severe Primary IGFD

Other diagnostic tests to consider:

IGFBP-3: used as an aid in diagnosis of short stature; normal for some patients with severe Primary IGFD and GHD; not specific²⁶

Free IGF-1: no clinical role at this time

GHBP: GH binding protein measurements are useful in patients with a suspicion of severe Primary IGFD; patients with GH receptor defects have an absence of serum GHBP³

Acid-Labile Subunit (ALS): GH-dependent²⁸; low in GHR, normal in IGF-1 gene defects; ALS deficiency is cause of IGFD

These tests and tools can guide you in the differential diagnosis of your patients with growth failure. Once your diagnostic evaluation is complete, you can determine the appropriate course of treatment.

If IGFD is determined to be primary and severe, treatment with Increlex^® may help improve your patient's growth.¹ Determination of your patient's IGF-1 level is the first step. Adequate dosages, correct frequency of dosing and monitoring your patient's compliance with the prescribed treatment regimen will improve therapeutic outcome.

Indication and Important Safety Information

INCRELEX^® (mecasermin [rDNA origin] injection) is indicated for the treatment of growth failure in children with severe primary IGF-1 deficiency, or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. Severe primary IGF-1 deficiency (IGFD) is defined by height standard deviation score ≤ -3.0 and basal IGF-1 standard deviation score ≤ -3.0 and normal or elevated growth hormone (GH). Severe Primary IGFD includes classical and other forms of growth hormone insensitivity. Patients with Primary IGFD may have mutations in the GH receptor (GHR), post-GHR signaling pathway including the IGF-1 gene. They are not GH deficient, and therefore, they cannot be expected to respond adequately to exogenous GH treatment.

INCRELEX is not intended for use in subjects with secondary forms of IGF-1 deficiency, such as GH deficiency, malnutrition, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory steroids. Thyroid and nutritional deficiencies should be corrected before initiating INCRELEX treatment.

Limitations of use: INCRELEX is not a substitute to GH for approved GH indications.

INCRELEX is contraindicated in the presence of active or suspected malignancy, and therapy should be discontinued if evidence of malignancy develops. INCRELEX should not be used by patients who are allergic to mecasermin (rhIGF-1) or any of the inactive ingredients in INCRELEX, or who have experienced a severe hypersensitivity to INCRELEX [see Warnings and Precautions and Adverse Reactions]. Intravenous administration of INCRELEX is contraindicated. INCRELEX should not be used for growth promotion in patients with closed epiphyses.

INCRELEX has insulin-like hypoglycemic effects and should be administered 20 minutes before or after a meal or snack. Hypersensitivity and allergic reactions have been reported, including a low number of cases indicative of anaphylaxis requiring hospitalization. Intracranial hypertension has occurred in patients treated with INCRELEX. Funduscopic examination is recommended at the initiation of and periodically during the course of therapy. Patients should have periodic examinations to rule out potential complications from tonsillar/adenoidal hypertrophy and receive appropriate treatment if necessary. Children with onset of limp or hip/knee pain should be evaluated for possible slipped capital femoral epiphysis. Monitor any child with scoliosis for progression of the spine curve.

In clinical studies of 71 pediatric subjects with severe Primary IGFD representing 274 patient-years of treatment, no subjects discontinued due to adverse events. Hypoglycemia was reported by 30 subjects (42%) at least once during their course of therapy with INCRELEX. Most cases of hypoglycemia were mild or moderate in severity. Five subjects had severe hypoglycemia (requiring assistance and treatment) on one or more occasion and four subjects experienced hypoglycemic seizures/loss of consciousness on one or more occasion. Symptomatic hypoglycemia was generally avoided when a meal or snack was consumed either shortly (i.e., 20 minutes) before or after the administration of INCRELEX. Tonsillar hypertrophy was noted in 11 (15%) subjects in the first 1 to 2 years of therapy with lesser tonsillar growth in subsequent years. Intracranial hypertension occurred in three subjects. In two subjects the events resolved without interruption of INCRELEX treatment. INCRELEX treatment was discontinued in the third subject and resumed later at a lower dose without recurrence.

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