"The U.S. Food and Drug Administration today approved Dotarem (gadoterate meglumine) for use in magnetic resonance imaging (MRI) of the brain, spine and associated tissues of patients ages 2 years and older.
Dotarem is a gadolinium-based"...
- Patient Information:
Details with Side Effects
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 (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 sources.
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 reused.
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 ( ≥ 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.
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 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.
Excretion of INCRELEX® in human milk has not been studied. Caution should be exercised when INCRELEX® is administered to a nursing woman.
Safety and effectiveness in pediatric patients below the age of 2 years of age have not been established.
The safety and effectiveness of INCRELEX® in patients aged 65 and over has not been established.
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].
Last reviewed on RxList: 6/16/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Increlex Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.