Included as part of the PRECAUTIONS section.
Not For Intrathecal Use
Inadvertent intrathecal use of
OMNISCAN has occurred and caused convulsions, coma, sensory and motor
Nephrogenic Systemic Fibrosis
agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among
patients with impaired elimination of the drugs. Avoid use of GBCAs among these
patients unless the diagnostic information is essential and not available with
non-contrast enhanced MRI or other modalities. The GBCA-associated NSF risk
appears highest for patients with chronic, severe kidney disease (GFR < 30
mL/min/1.73m²) as well as patients with acute kidney injury. Do not
administer OMNISCAN to these patients. The risk appears lower for patients with
chronic, moderate kidney disease (GFR 30-59 mL/min/1.73m²) and
little, if any, for patients with chronic, mild kidney disease (GFR 60-89
mL/min/1.73m²). NSF may result in fatal or debilitating fibrosis
affecting the skin, muscle and internal organs. Report any diagnosis of NSF
following OMNISCAN administration to GE Healthcare (1-800-6540118) or FDA
(1-800-FDA-1088 or www.fda.gov/medwatch).
Screen patients for acute kidney injury and other
conditions that may reduce renal function. Features of acute kidney injury
consist of rapid (over hours to days) and usually reversible decrease in kidney
function, commonly in the setting of surgery, severe infection, injury or
drug-induced kidney toxicity. Serum creatinine levels and estimated GFR may not
reliably assess renal function in the setting of acute kidney injury. For
patients at risk for chronically reduced renal function (e.g., age > 60
years, diabetes mellitus or chronic hypertension), estimate the GFR through
Among the factors that may increase the risk for NSF are
repeated or higher than recommended doses of a GBCA and the degree of renal
impairment at the time of exposure. Record the specific GBCA and the dose
administered to a patient. When administering OMNISCAN, do not exceed the
recommended dose and allow a sufficient period of time for elimination of the
drug prior to any readministration [see BOXED WARNING, CONTRAINDICATIONS,
CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION].
Anaphylactoid and anaphylactic reactions, with
cardiovascular, respiratory and/or cutaneous manifestations, resulting in death
have occurred. Personnel trained in resuscitation techniques and resuscitation
equipment should be present prior to OMNISCAN administration. If a
hypersensitivity reaction occurs, stop OMNISCAN Injection and immediately begin
appropriate therapy. Observe patients closely, particularly those with a
history of drug reactions, asthma, allergy or other hypersensitivity disorders,
during and up to several hours after OMNISCAN Injection.
Acute Renal Failure
In patients with renal insufficiency, acute renal failure
requiring dialysis or worsening renal function have occurred, mostly within 48
hours of OMNISCAN Injection. The risk of renal failure may increase with
increasing dose of gadolinium contrast. Use the lowest necessary dose of
contrast and evaluate renal function in patients with renal insufficiency.
Acute renal failure was observed in < 1% of patients in OMNISCAN clinical
studies [see ADVERSE REACTIONS]. OMNISCAN is cleared by glomerular
filtration. Hemodialysis also enhances OMNISCAN clearance [see Use in
Impaired Visualization Of Lesions Detectable With Non-contrast
Paramagnetic contrast agents such as OMNISCAN might
impair the visualization of lesions which are seen on the non-contrast MRI.
This may be due to effects of the paramagnetic contrast agent, or imaging
parameters. Exercise caution when OMNISCAN MRI scans are interpreted in the
absence of a companion non-contrast MRI.
Laboratory Test Findings
Asymptomatic, transitory changes in serum iron have been
observed. The clinical significance is unknown.
OMNISCAN interferes with serum calcium measurements with
some colorimetric (complexometric) methods commonly used in hospitals,
resulting in serum calcium concentrations lower than the true values. In
patients with normal renal function, this effect lasts for 12-24 hours. In
patients with decreased renal function, the interference with calcium
measurements is expected to last during the prolonged elimination of OMNISCAN.
After patients receive OMNISCAN, careful attention should be used in selecting
the type of method used to measure calcium.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long term animal studies have not been performed to
evaluate the carcinogenic potential of gadodiamide. The results of the
following genotoxicity assays were negative: in vitro bacterial reverse
mutation assay, in vitro Chinese Hamster Ovary (CHO)/Hypoxanthine Guanine
Phosphoribosyl Transferase (HGPT) forward mutation assay, in vitro CHO chromosome
aberration assay, and the in vivo mouse micronucleus assay at intravenous doses
of 27 mmol/kg (approximately 7 times the maximum human dose based on a body
surface area comparison). Impairment of male or female fertility was not
observed in rats after intravenous administration three times per week at the
maximum dose tested of 1.0 mmol/kg (approximately 0.5 times the maximum human
dose based on a body surface area comparison).
Use In Specific Populations
Pregnancy Category C
OMNISCAN has been shown to have an adverse effect on
embryo-fetal development in rabbits at dosages as low as 0.5 mmol/kg/day for 13
days during gestation (approximately 0.6 times the human dose based on a body
surface area comparison). These adverse effects are observed as an increased
incidence of flexed appendages and skeletal malformations which may be due to
maternal toxicity since the body weight of the dams was 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
(1.3 times the maximum human dose based on a body surface area 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. 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, exercise caution when
administering OMNISCAN 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 pediatric patients over 2 years of
age based on adequate and well controlled studies of OMNISCAN in adults, a
pediatric CNS imaging study, and safety data in the scientific literature.
However, the safety and efficacy of doses greater than 0.1 mmol/kg and of
repeated doses have not been studied in pediatric patients.
Pharmacokinetics of OMNISCAN have not been studied in
pediatrics. The glomerular filtration rate of neonates and infants is much
lower than that of adults. The pharmacokinetics volume of distribution is also
different. Therefore, the optimal dosing regimen and imaging times in patients
under 2 years of age have not been established.
In clinical studies of OMNISCAN, 243 patients were
between 65 and 80 years of age while 15 were over 80. No overall differences in
safety or effectiveness were observed between these patients and younger
patients. Other reported clinical experience has not identified differences in
response between the elderly and younger patients, but greater sensitivity in
the elderly cannot be ruled out. In general, dose selection for an elderly
patient should be cautious, reflecting the greater frequency of decreased
hepatic, renal or cardiac function, and of concomitant disease or other drug
therapy. OMNISCAN is excreted by the kidney, and the risk of toxic reactions to
OMNISCAN is greater in patients with impaired renal function [see WARNINGS
AND PRECAUTIONS]. Because elderly patients are more likely to have
decreased renal function, select dose carefully and assess eGFR by laboratory
testing before OMNISCAN use.
Dose adjustments in renal or hepatic impairment have not
been studied. Caution should be exercised in patients with impaired renal
insufficiency [see WARNINGS AND PRECAUTIONS].