Safety Profile of Increlex^® (mecasermin [rDNA origin] injection)

Increlex is the only FDA-approved medicine for the long-term treatment of 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.¹

In the years of clinical research and trials conducted to gain FDA approval of Increlex, no subject withdrew from any study due to adverse events.¹ However, it is important to consider certain adverse reactions and treatment precautions. Treatment with Increlex should be directed by physicians who are experienced in the diagnosis and management of patients with growth disorders.

For a complete list of adverse reactions and treatment precautions click here

Contraindications and Warnings

Increlex should not be used for growth promotion in patients with:¹

• Closed epiphyses
• Active or suspected neoplasia
• Allergies to mecasermin (IGF-1) or any of the other inactive ingredients in Increlex

Intravenous administration of Increlex is contraindicated.¹ Increlex contains benzyl alcohol; if sensitivity occurs, treatment with Increlex should be discontinued.¹

Precautions

• Increlex has not been studied in children less than 2 years of age or in adults¹
• Slipped capital femoral epiphysis and progression of scoliosis can occur in patients who experience rapid growth¹
• As with any exogenous protein administration, local or systemic allergic reactions may occur¹

Adverse Reactions

Hypoglycemia

Hypoglycemia was the most common adverse event reported for 30 subjects (42%); 14 (47%) of whom had prior history.¹ Five subjects had severe hypoglycemia requiring assistance and treatment on one or more occasion and 4 of these subjects had seizures.¹ The frequency of hypoglycemia was highest in the first month of treatment. Hypoglycemic episodes were more frequent in younger children but were generally avoided when a meal or snack was consumed shortly before or after administration of Increlex.¹

Getting to know your patients and understanding their history can help you determine whether or not pre-prandial glucose monitoring is necessary. If hypoglycemia occurs with recommended doses, despite adequate food intake, the dose should be reduced.¹

Tonsillar hypertrophy

Tonsillar hypertrophy was noted in 11 (15%) subjects in the first 1 to 2 years of therapy with lesser tonsillar growth in subsequent years.¹

Examine your patient's tonsils, pharynx, and adenoids. Be sure to inquire about snoring, difficulty swallowing and sleep apnea during treatment as these issues may be due to tonsillar hypertrophy.

Intracranial hypertension

Intracranial hypertension occurred in three subjects.¹ For two of the three subjects, the events resolved without interruption of Increlex treatment.¹ One subject discontinued and resumed later at a lower dose without recurrence.¹ Funduscopic examination is recommended at the initiation and periodically during the course of Increlex therapy to rule out presence of papilledema.¹

Lipohypertrophy at injection sites

Lipohypertrophy was noted in 24 subjects (32%)⁷ and was associated with lack of proper rotation of injection sites.^7,30 This resolved when injections were properly rotated.⁷ It was most pronounced in 3 subjects who had the poorest overall growth response.³⁰

Increlex injection sites should be rotated to a different site with each injection.¹ Educating your patients and caregivers about the importance of rotating the injection sites ultimately will benefit everyone.

Observational Data is Growing through the Registry

Ipsen is committed to the ongoing collection of long-term data and has established the Increlex Growth Forum Database (IGFD); a patient registry program monitoring the long-term safety and efficacy of Increlex. It allows physicians to register and enter information regarding their experiences with Increlex on a real-time basis. Over 650 patients are enrolled and this number will continue to grow.²⁹ For more information or to contact a Clinical Registry Liaison, click here.

Indication and Important Safety Information ¹

INCRELEX^® (mecasermin [rDNA origin] injection) is indicated for the long-term treatment of 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. Severe Primary 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 patients with mutations in the GH receptor (GHR), post-GHR signaling pathway, and IGF-1 gene defects; 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.

INCRELEX is not a substitute for GH treatment.

INCRELEX should not be used for growth promotion in patients with closed epiphyses. INCRELEX is contraindicated in the presence of active or suspected neoplasia, and therapy should be discontinued if evidence of neoplasia develops. Intravenous administration of INCRELEX is contraindicated. INCRELEX should not be used by patients who are allergic to mecasermin (IGF-1) or any of the inactive ingredients in INCRELEX.

INCRELEX contains benzyl alcohol as a preservative, which has been associated with neurologic toxicity in neonates.

INCRELEX has not been studied in patients under 2 years old.

Slipped capital femoral epiphysis and progression of scoliosis can occur in patients who experience rapid growth.

Local or systemic allergic reactions may occur.

In clinical studies of 71 subjects with severe Primary IGFD treated for a mean duration of 3.9 years and representing 274 subject-years, no subjects withdrew from any clinical study because of adverse events.

Hypoglycemia was reported by 30 subjects (42%) at least once during their course of therapy. Of the 30 subjects reporting hypoglycemia, 14 (47%) had a history of hypoglycemia prior to treatment. Most cases 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. The frequency of hypoglycemia was highest in the first month of treatment, and episodes were more frequent in younger children. Hypoglycemia was generally avoided when a meal or snack was consumed either shortly before or shortly after administration.

Tonsillar hypertrophy was noted in 11 subjects (15%) 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.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

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