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HIGHLIGHTS OF PRESCRIBING INFORMATION |
These highlights do not include all the information needed to use INCRELEX® safely and effectively. See full prescribing information for INCRELEX®.
INCRELEX® (mecasermin [rDNA origin] injection]
Initial U.S. Approval: 2005
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RECENT MAJOR CHANGES
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Contraindications, Known Hypersensitivity (4.2) |
02/2011 |
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Warnings and Precautions, Hypersensitivity and Allergic Reactions, including Anaphylaxis (5.2) |
02/2011 |
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INDICATIONS AND USAGE
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INCRELEX® (mecasermin [rDNA origin] injection) is indicated for:
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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. (1.1)
Limitations of use: INCRELEX® is not a substitute to GH for approved GH indications.
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DOSAGE AND ADMINISTRATION
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INCRELEX® should be administered subcutaneously. (2.2)
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Injection sites should be rotated to avoid lipohypertrophy. (2.2)
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Recommended starting dose: 0.04 to 0.08 mg/kg (40 to 80 micrograms/kg) twice daily. 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. (2.1)
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DOSAGE FORMS AND STRENGTHS
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INCRELEX® is a sterile solution supplied in a multiple dose glass vial at a concentration of 10 mg per mL (40 mg per vial). (3)
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CONTRAINDICATIONS
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Active or Suspected Neoplasia (4.1)
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Known Hypersensitivity to mecasermin (4.2)
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Intravenous Administration (4.3)
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Closed Epiphyses (4.4)
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WARNINGS AND PRECAUTIONS
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INCRELEX® should be administered shortly before or after a meal or snack, because it has insulin-like hypoglycemic effects. (5.1)
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Hypersensitivity and Allergic Reactions, including Anaphylaxis: A low number of cases indicative of anaphylaxis requiring hospitalization have been reported. Parents and patients should be informed that such reactions are possible and that if a systemic allergic reaction occurs, treatment should be interrupted and prompt medical attention should be sought. (5.2)
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Intracranial Hypertension: Funduscopic examination is recommended at the initiation and periodically during the course of INCRELEX® therapy. (5.3)
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Lymphoid Tissue Hypertrophy (tonsillar/adenoidal hypertrophy): Patients should have periodic examinations to rule out potential complications and receive appropriate treatment if necessary. (5.4)
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Slipped Capital Femoral Epiphysis (SCFE): eva luate any child with onset of a limp or hip/knee pain for possible SCFE. (5.5)
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Progression of Scoliosis: Monitor any child with scoliosis for progression of the spine curve. (5.6)
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ADVERSE REACTIONS
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Common INCRELEX®-related adverse reactions in clinical trials include: hypoglycemia (5.1, 6.2), local and systemic hypersensitivity (5.2, 6.2, 6.3), tonsillar hypertrophy (5.4, 6.2)
To report SUSPECTED ADVERSE REACTIONS, contact Tercica at 1-866-837-2422 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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USE IN SPECIFIC POPULATIONS
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Pregnancy: Based on animal data, INCRELEX® may cause fetal harm. (8.1)
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Pediatric Use: Safety and effectiveness has not been established in children less than 2 years of age. (8.4)
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See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling |
Revised: 02/2011 |
Back to Highlights and Tabs
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FULL PRESCRIBING INFORMATION: CONTENTS* |
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1 INDICATIONS AND USAGE
1.1 Severe Primary IGF-1 Deficiency (Primary IGFD)
2 DOSAGE AND ADMINISTRATION
2.1 Dosage
2.2 Administration
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
4.1 Active or Suspected Neoplasia
4.2 Known Hypersensitivity
4.3 Intravenous Administration
4.4 Closed Epiphyses
5 WARNINGS AND 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 Most Serious and/or Most Frequently Observed Adverse Reactions:
6.2 Clinical Trial Experience
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
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FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Severe Primary IGF-1 Deficiency (Primary IGFD)
INCRELEX® (mecasermin [rDNA origin] injection) is indicated for the treatment of:
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growth failure in children with severe primary IGF-1 deficiency.
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growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.
Severe Primary IGF-1 deficiency (IGFD) is defined by:
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height standard deviation score ≤ –3.0 and
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basal IGF-1 standard deviation score ≤ –3.0 and
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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 Dosage
Preprandial 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 INCRELEX® should never be increased to make up for one or more omitted dose.
2.2 Administration
INCRELEX® is administered by subcutaneous injection.
INCRELEX® injection sites should be rotated to a different site (upper arm, thigh, buttock or abdomen) with each injection to avoid lipohypertrophy.
INCRELEX® should be administered using sterile disposable syringes and needles. The syringes should be of small enough volume so that the prescribed dose can be withdrawn from the vial with accuracy.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
3 DOSAGE FORMS AND STRENGTHS
INCRELEX® is a sterile solution available at a concentration of 10 mg per mL (40 mg per vial).
4 CONTRAINDICATIONS
4.1 Active or Suspected Neoplasia
INCRELEX® is contraindicated in the presence of active or suspected malignancy, and therapy should be discontinued if evidence of malignancy develops.
4.2 Known Hypersensitivity
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 (5.2) and Adverse Reactions (6.2)]
4.3 Intravenous Administration
Intravenous administration of INCRELEX® is contraindicated.
4.4 Closed Epiphyses
INCRELEX® should not be used for growth promotion in patients with closed epiphyses.
5 WARNINGS AND PRECAUTIONS
5.1 Hypoglycemia
Because INCRELEX® has insulin-like hypoglycemic effects it should be administered shortly before or after (± 20 minutes) a meal or snack. Glucose monitoring and INCRELEX® dose titration are recommended until a well tolerated dose is established (see Dosage 2.1) and subsequently as medically indicated. Special attention should be paid to small children because their oral intake may not be consistent. Patients should avoid engaging in any high-risk activities (e.g., driving, etc.) within 2 to 3 hours after dosing, particularly during the initiation of INCRELEX® treatment until tolerability and a stable dose have been established [see Adverse Reactions (6.1)]. INCRELEX® should not be administered when the meal or snack is omitted. The dose of INCRELEX® should never be increased to make up for one or more omitted doses.
5.2 Hypersensitivity and Allergic Reactions, including Anaphylaxis
Allergic reactions to INCRELEX® have been reported post-marketing. They range from localized (injection site) reactions to systemic reactions, including anaphylaxis requiring hospitalization. Parents and patients should be informed that such reactions are possible and that if a systemic allergic reaction occurs treatment should be interrupte
