Included as part of the "PRECAUTIONS" Section
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 AND ADMINISTRATION] 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]. 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
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 interrupted and prompt medical attention should be
sought. [see CONTRAINDICATIONS and ADVERSE REACTIONS]
Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or
vomiting have occurred in patients treated with INCRELEX. IH-associated signs and symptoms
resolved after interruption of dosing. Funduscopic examination is recommended at the initiation
and periodically during the course of INCRELEX therapy. [see ADVERSE REACTIONS].
Lymphoid Tissue Hypertrophy
Lymphoid tissue (e.g., tonsillar and adenoidal) hypertrophy associated with complications, such
as snoring, sleep apnea, and chronic middle-ear effusions have been reported with the use of
INCRELEX. Patients should have periodic examinations to rule out such potential
complications and receive appropriate treatment if necessary [see ADVERSE REACTIONS].
Slipped Capital Femoral Epiphysis
Slipped capital femoral epiphysis can occur in patients who experience rapid growth. Any
pediatric patient with the onset of a limp or complaints of hip or knee pain during INCRELEX
therapy should be carefully evaluated.
Progression Of Preexisting Scoliosis
Progression of scoliosis may occur in patients who experience rapid growth. Because
INCRELEX increases growth rate, patients with a history of scoliosis who are treated with
INCRELEX should be monitored for progression of scoliosis.
Benzyl alcohol, a component of this product, has been associated with serious adverse
events and death, particularly in pediatric patients. The “gasping syndrome,”
(characterized by central nervous system depression, metabolic acidosis, gasping
respirations, and high levels of benzyl alcohol and its metabolites found in the blood and
urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and
low-birth weight neonates. Additional symptoms may include gradual neurological
deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin
breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular
collapse. Practitioners administering this and other medications containing benzyl
alcohol should consider the combined daily metabolic load of benzyl alcohol from all
Patient Counseling Information
Patients and/or their parents should be instructed in the proper administration of INCRELEX.
INCRELEX should be given shortly before or after (20 minutes on either side of) a meal or
snack. 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. INCRELEX
therapy should be initiated at a low dose and the dose should be increased only if no
hypoglycemia episodes have occurred after at least 7 days of dosing. If severe hypoglycemia or
persistent hypoglycemia occurs on treatment despite adequate food intake, INCRELEX dose
reduction should be considered. Providers should educate patients and caregivers on how to
recognize the signs and symptoms of hypoglycemia.
Providers should educate patients and caregivers on the identification of signs and symptoms of
serious allergic reactions to INCRELEX and the need to seek prompt medical contact should
such a reaction occur. They should be informed that if an allergic reaction occurs, INCRELEX
treatment should be discontinued.
Patients and/or parents should be thoroughly instructed in the importance of proper needle
disposal. A puncture-resistant container should be used for the disposal of used needles and/or
syringes (consistent with applicable state requirements). Needles and syringes must not be
Carcinogenesis, Mutagenesis, Impairment Of Fertility
INCRELEX was tumorigenic in rats in a study using doses of 0, 0.25, 1,
4, and 10 mg/kg/day by subcutaneous injection for up to 2 years. The incidence of
adrenal medullary hyperplasia and pheochromocytoma increased in male rats given ≥1
mg/kg/day (below clinical exposure at the maximum recommended human dose [MRHD]
based on AUC) and in female rats at all dose levels (below clinical exposure at the
MRHD based on AUC). The incidence of keratoacanthoma in the skin increased in male
rats given 4 and 10 mg/kg/day (approximately the clinical exposure at the MRHD based
on AUC). The incidence of mammary gland carcinoma in male rats increased in animals
treated with 10 mg/kg/day (3 times the MRHD based on AUC). Only doses that exceeded
the maximum tolerated dose (MTD) (based on excess mortality secondary to IGF-1
induced hypoglycemia) caused skin and mammary tumors.
INCRELEX was not clastogenic in the in vitro chromosome aberration
assay and the in vivo mouse micronucleus assay.
Impairment Of Fertility
INCRELEX had no effects on fertility in rats using intravenous
doses 0.25, 1, and 4 mg/kg/day (up to 3 times the clinical exposure at the MRHD based
Use In Specific Populations
There are no available data on INCRELEX use in pregnant women. Exposure to
INCRELEX during pregnancy is unlikely because the drug is not indicated for use after
epiphyseal closure. In animal reproduction studies, there were no observed embryo-fetal
development abnormalities with intravenous administration of INCRELEX to pregnant
rats and rabbits during fetal organogenesis given at exposures up to 11 and 3 times the
maximum recommended human dose (MRHD) of 0.24 mg/kg/day based on body surface
area (BSA), respectively (see Data).
The estimated background risk of birth defects and miscarriage for the indicated
population is unknown. In the U.S. general population, the estimated background risk of
major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-
Studies to assess embryo-fetal toxicity evaluated the effects of INCRELEX during
organogenesis in Sprague Dawley rats given 1, 4, and 16 mg/kg/day and in New Zealand
White rabbits given 0.125, 0.5, and 2 mg/kg/day, administered intravenously. There were
no observed embryo-fetal developmental abnormalities in rats given up to 16 mg/kg/day
(11 times the MRHD based on BSA comparison). In the rabbit study, the NOAEL for
fetal toxicity was 0.5 mg/kg/day (approximately equivalent to the MRHD based on BSA)
due to an increase in fetal death at 2 mg/kg. INCRELEX displayed no teratogenicity or
maternal toxicity in rabbits given up to 2 mg/kg (3 times the MRHD based on BSA).
There is no information available on the presence of mecasermin in human or animal
milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk
production. The developmental and health benefits of breastfeeding should be considered
along with the mother’s clinical need for INCRELEX and any potential adverse effects
on the breast-fed child from INCRELEX or from the underlying maternal condition.
Safety and effectiveness in pediatric patients below the age of 2 years of age have not been
The safety and effectiveness of INCRELEX in patients aged 65 and over has not been
No Studies have been conducted in Primary IGFD children or adult subjects with renal
impairment [see CLINICAL PHARMACOLOGY].
No studies have been conducted in Primary IGFD children or adult subjects with hepatic
impairment [see CLINICAL PHARMACOLOGY].