Omniscan Warnings, Precautions, Pregnancy, Nursing, Abuse - Gadodiamide

Omniscan Warnings, Precautions, Pregnancy, Nursing, Abuse - Gadodiamide

WARNINGS

Deoxygenated sickle erythrocytes have been shown in in vitro studies to align perpendicular to a magnetic field which may result in vaso-occlusive complications in vivo. The enhancement of magnetic moment by paramagnetic contrast agents may possibly potentiate sickle erythrocyte alignment. OMNISCAN has not been studied in patients with sickle cell anemia and other hemoglobinopathies.

Patients with other hemolytic anemias have not been adequately evaluated following administration of OMNISCAN to exclude the possibility of increased hemolysis.

Patients with history of allergy or drug reaction should be observed for several hours after drug administration.

Some paramagnetic contrast agents may impair the visualization of existing lesions which are seen on the unenhanced, noncontrast MRI. This may be due to effects of the paramagnetic contrast agent, imaging parameters, misregistration, etc. CAUTION SHOULD BE EXERCISED WHEN A CONTRAST ENHANCED INTERPRETATION IS MADE IN THE ABSENCE OF ACOMPANION UNENHANCED MRI.

OMNISCAN is cleared from the body by glomerular filtration. Significant hepatobiliary enteric pathway excretion has not been demonstrated. Dose adjustments in renal or hepatic impairment have not been studied. Caution should be exercised in patients with impaired renal insufficiency with or without hepatic impairment. For elimination of OMNISCAN in pediatric patients, see the Pediatric Use section. The possibility of a reaction, including serious, life threatening, fatal, anaphylactoid or cardiovascular reactions or other idiosyncratic reactions should always beconsidered especially in those patients with a known clinical hypersensitivity, a history of asthma, or other allergic respiratory disorders (see ADVERSE REACTIONS).

Repeat procedures: Sequential use during the same diagnostic session has been studied in adult central nervous system use only. Data for sequential injections during the same session or repeated injections for monitoring in other indications are not available. If the physician determines repeat dosing is required in non-CNS use in adults or in CNS pediatric administration, in patients with normal renal function the time interval between repeat doses should be at least 7 hours to allow for normal clearance of the drug from the body (see Pharmacokinetics section).

OMNISCAN should be drawn into the syringe and used immediately. If nondisposable equipment is used, scrupulous care should be taken to prevent residual contamination with traces of cleansing agents. Diagnostic procedures involving the use of contrast agents should be conducted under supervision of a physician with the prerequisite training and a thorough knowledge of the procedure to be performed.

INFORMATION FOR PATIENTS

Patients receiving OMNISCAN should be instructed to: 1. Inform their physician if they are pregnant or breast feeding. 2. Inform their physician if they have anemia or diseases that affect red blood cells.

3. Inform their physician if they have a history of renal or hepatic disease, seizure, asthma or allergic respiratory disorders, or hemoglobinopathies.

Long-term animal studies have not been performed to evaluate the carcinogenic potential of gadodiamide. The results of the following genotoxicity assays were negative: bacterial reverse mutation assay, CHO/HGPRT forward mutation assay, CHO chromosome aberration assay, and the in vivo mouse micronucleus assay at intravenous doses up to 27 mmol/kg. Impairment of male or female fertility was not observed in rats after intravenous administration three times per week at 1.0 mmol/kg, the maximum dose tested.

OMNISCAN has been shown to have an adverse effect on embryo-fetal development in rabbits that is observed as an increased incidence of flexed appendages and skeletal malformations at dosages as low as 0.5 mmol/kg/day for 13 days during gestation (approximately 2 times the maximum human cumulative dose of 0.3 mmol/kg based on a mmol/kg comparison or 0.6 times the human dose based on a mmol/m² comparison). Skeletal malformations may be due to maternal toxicity since the body weight of the dams was significantly reduced in response to OMNISCAN administration during pregnancy. In rat studies, fetal abnormalities were not observed at doses up to 2.5 mmol/kg/day for 10 days during gestation (8 times the maximum human cumulative dose, or 1.3 times the human dose on a mg/m² comparison); however, maternal toxicity was not achieved in these studies and a definitive conclusion about teratogenicity in rats at doses above 2.5 mmol/kg/day cannot be made at this time. Adequate and well controlled studies in pregnant women have not been conducted. OMNISCAN should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

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 OMNISCAN is administered to a nursing woman.

The safety and efficacy of OMNISCAN at a single dose of 0.05 to 0.1 mmol/kg have been established in the pediatric population over 2 years of age. The safety and efficacy for doses greater than 0.1 mmol/kg and the clinical benefit of repeated procedures have not been studied in pediatric patients. The use of OMNISCAN in these age groups is supported by evidence from adequate and well controlled studies of OMNISCAN in adults, a pediatric study of the MR imaging of the central nervous system and additional safety data obtained in the literature. Pharmacokinetics of OMNISCAN have not been studied in the pediatric population. Literature reports that the glomerular filtration rate of neonates and infants is much less than that of adults. The pharmacokinetics volume of distribution is different as well. The effect of these differences on the elimination and dosing regimen in pediatric patients under 2 years of age has not been studied. Whether the dose administered or optimal imaging times should be adjusted has not been studied.

However, in the 173 pediatric patients in the central nervous system study with OMNISCAN (see the CLINICAL PHARMACOLOGY: CLINICAL TRIALS section) and the 144 pediatric patients in the literature, the adverse events were similar to those reported in adults.

Of the total number of patients in clinical studies of OMNISCAN, 19.3 percent were 65 to 80, while 1.2 percent were over 80. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose selection for an elderly patient should be cautious usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.