Included as part of the PRECAUTIONS section.

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) 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 doses.

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

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting have occurred in patients treated with INCRELEX®, similar to patients treated with therapeutic doses of growth hormone. 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 may 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

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 sources.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

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 ( ≥ 1 times the clinical exposure with the maximum recommended human dose [MRHD] based on AUC) and in female rats at all dose levels ( ≥ 30% of the clinical exposure with the MRHD based on AUC). The incidence of keratoacanthoma in the skin increased in male rats given 4 and 10 mg/kg/day ( ≥ 4 times the MRHD). The incidence of mammary gland carcinoma in male rats increased in animals treated with 10 mg/kg/day (7 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.

Mutagenesis

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/day (up to 4 times the clinical exposure with the MRHD based on AUC.)

Use In Specific Populations

Pregnancy

Pregnancy Category C

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 (20 times the maximum recommended human dose [MRHD] based on body surface area [BSA] comparison). In the rabbit study, the NOAEL for fetal toxicity was 0.5 mg/kg (2 times 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 (8 times the MRHD based on BSA).

The effects of INCRELEX® on an unborn child have not been studied. Therefore, there is insufficient medical information to determine whether there are significant risks to a fetus.

Nursing Mothers

Excretion of INCRELEX® in human milk has not been studied. As many drugs are excreted in human milk, caution should be exercised when INCRELEX® is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 2 years of age have not been established.

Geriatric Use

The safety and effectiveness of INCRELEX® in patients aged 65 and over has not been established.

Renal Impairment

No Studies have been conducted in Primary IGFD children or adult subjects with renal impairment [see CLINICAL PHARMACOLOGY].

Hepatic Impairment

No studies have been conducted in Primary IGFD children or adult subjects with hepatic impairment [see CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 9/21/2012
This monograph has been modified to include the generic and brand name in many instances.