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

If sensitivity to INCRELEX occurs, treatment should be discontinued.

General. Treatment with INCRELEX should be directed by physicians who are experienced in the diagnosis and management of patients with growth disorders.

INCRELEX has not been studied in children less than 2 years of age or in adults.

INCRELEX should be administered shortly before or after a meal or snack, because it has insulin-like hypoglycemic effects. 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 2-3 hours after dosing, particularly at the initiation of INCRELEX treatment, until a well-tolerated dose of INCRELEX has been established.

Lymphoid tissue (e.g., tonsillar) 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.

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting have been reported in patients treated with INCRELEX, as they have been reported with therapeutic growth hormone administration. 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.

Slipped capital femoral epiphysis and progression of scoliosis can occur in patients who experience rapid growth. These conditions and other symptoms and signs known to be associated with GH treatment in general should be monitored during INCRELEX treatment.

As with any exogenous protein administration, local or systemic allergic reactions may occur. Parents and patients should be informed that such reactions are possible and that if an allergic reaction occurs, treatment should be interrupted and prompt medical attention should be sought.

Geriatric Use. The safety and effectiveness of INCRELEX in patients aged 65 and over has not been evaluated in clinical studies.

Carcinogenesis, mutagenesis, impairment of fertility

INCRELEX was administered subcutaneously to Sprague Dawley rats at doses of 0, 0.25, 1, 4, and 10 mg/kg/day for up to 2 years. An increased incidence of adrenal medullary hyperplasia and pheochromocytoma was observed in male rats at doses of 1 mg/kg/day and above (≥ 1 times the clinical exposure with the maximum recommended human dose [MRHD] based on AUC) and female rats at all dose levels (≥ 0.3 times the clinical exposure with the MRHD based on AUC). An increased incidence of keratoacanthoma in the skin was observed in male rats at doses of 4 and 10 mg/kg/day (≥ 4 times the MRHD) and in female rats treated with 10 mg/kg/day (7 times the MRHD based on AUC). An increased incidence of mammary gland carcinoma in both male and female rats was observed in animals treated with 10 mg/kg/day (7 times the MRHD based on AUC). Based on excess mortality secondary to IGF-1 induced hypoglycemia, these skin and mammary tumor findings were only observed at doses that exceeded the maximum tolerated dose (MTD).

Mutagenesis: INCRELEX was not clastogenic in the in vitro chromosome aberration assay and the in vivo mouse micronucleus assay.

Impairment of fertility: INCRELEX was administered intravenously to rats at doses of 0.25, 1, and 4 mg/day to conduct the fertility study. No effects on fertility were observed in male or female rats treated with doses up to 4 mg/kg/day (4 times the clinical exposure with the MRHD based on AUC.)

Pregnancy Category C. Embryo-fetal toxicity studies were conducted in Sprague Dawley rats with doses of 1, 4, and 16 mg/kg/day, and in New Zealand White rabbits with doses of 0.125, 0.5, and 2 mg/kg/day administered intravenously. No embryo-fetal developmental abnormalities were observed in rats with doses up to 16 mg/kg/day (20 times the MRHD based on body surface area [BSA] comparison). In the rabbit study, the NOAEL for maternal toxicity was 2 mg/kg (8 times the MRHD based on BSA) and the NOAEL for fetal toxicity was 0.5 mg/kg (2 times the MRHD based on BSA). INCRELEX displayed no teratogenicity at doses 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. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when INCRELEX is administered to a nursing woman.

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