PRECAUTIONS
5.1 Hypoglycemia 5.2 Hypersensitivity and Allergic Reactions, including Anaphylaxis 5.3 Intracranial Hypertension 5.4 Lymphoid Tissue Hypertrophy 5.5 Slipped Capital Femoral Epiphysis 5.6 Progression of Preexisting Scoliosis 5.7 Benzyl Alcohol 6 ADVERSE REACTIONS
6.1 Clinical Trial Experience 6.2 Immunogenicity 6.3 Post-Marketing Experience 8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Renal Impairment 8.7 Hepatic Impairment 10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES
14.1 Effects of INCRELEX® Treatment in Children with Severe Primary Insulin-like Growth Factor-1 Deficiency (Primary IGFD) 16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescribing information are not listed. Close
1 INDICATIONS AND USAGE
1.1 Severe Primary IGF-1 Deficiency (Primary IGFD)INCRELEX® (mecasermin [rDNA origin] injection) is indicated for the treatment of:
growth failure in children with severe primary IGF-1 deficiency.
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.
2 DOSAGE AND ADMINISTRATION
2.1 DosagePreprandial glucose monitoring is recommended at treatment initiation and until a well-tolerated dose is established. If frequent symptoms of hypoglycemia or severe hypoglycemia occur, preprandial glucose monitoring should continue. The dosage of INCRELEX® should be individualized for each patient. The recommended starting dose of INCRELEX® is 0.04 to 0.08 mg/kg (40 to 80 micrograms/kg) twice daily by subcutaneous injection. If well-tolerated for at least one week, the dose may be increased by 0.04 mg/kg per dose, to the maximum dose of 0.12 mg/kg given twice daily. Doses greater than 0.12 mg/kg given twice daily have not been eva luated in children with Primary IGFD and, due to potential hypoglycemic effects, should not be used. If hypoglycemia occurs with recommended doses despite adequate food intake, the dose should be reduced. INCRELEX® should be administered shortly before or after (± 20 minutes) a meal or snack. If the patient is unable to eat shortly before or after a dose for any reason, that dose of INCRELEX® should be withheld. Subsequent doses of INCRE |
