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Gadodiamide (Systemic)


VA CLASSIFICATION
Primary: DX900

Commonly used brand name(s): Omniscan.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Diagnostic aid, paramagnetic (brain disorders; spine disorders)—
Note: Gadodiamide is a nonionic paramagnetic contrast agent {01}.



Indications

Accepted

Brain imaging, magnetic resonance—Gadodiamide is indicated to provide contrast enhancement during magnetic resonance imaging (MRI) and thus facilitate visualization of intracranial lesions with abnormal vascularity or those suspected of causing an abnormality in the blood-brain barrier. {01} {04} {05} {06}

Spinal lesions imaging, magnetic resonance—Gadodiamide is indicated to provide contrast enhancement during MRI and thus facilitate visualization of lesions in the spine and associated tissues. {01} {03} {04} {05} {06}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    591.68 {07}


Osmolality
    789 mOsmol per kg of water. {01}


pH
    5.5 to 7.0 {01}

Mechanism of action/Effect:

Based on the behavior of protons when placed in a strong magnetic field, which is interpreted and transformed into images by magnetic resonance (MR) instruments. Paramagnetic agents have unpaired electrons that generate a magnetic field about 700 times larger than the proton's field, thus disturbing the proton's local magnetic field. When the local magnetic field around a proton is disturbed, its relaxation process is altered. MR images are based on proton density and proton relaxation dynamics. MR instruments can record 2 different relaxation processes, the T1 (spin-lattice or longitudinal relaxation time) and the T2 (spin-spin or transverse relaxation time). In magnetic resonance imaging (MRI), visualization of normal and pathological brain tissue depends in part on variations in the radiofrequency signal intensity that occur with changes in proton density, alteration of the T1, and variation in the T2. When placed in a magnetic field, gadodiamide shortens both the T1 and the T2 relaxation times in tissues where it accumulates. At clinical doses, gadodiamide primarily affects the T1 relaxation time, thus producing an increase in signal intensity. Gadodiamide does not cross the intact blood-brain barrier; therefore, it does not accumulate in normal brain tissue or in central nervous system (CNS) lesions that have not caused an abnormal blood-brain barrier (e.g., cysts, mature post-operative scars). Abnormal vascularity or disruption of the blood-brain barrier allows accumulation of gadodiamide in lesions such as neoplasms, abscesses, and subacute infarcts. {01} {02}

Half-life:

Distribution—3.7±2.7 minutes (mean). {01}

Elimination—77.8±16 minutes (mean). {01}

Elimination:
    Renal (approximately 96% of dose excreted within 24 hours). {01}


Precautions to Consider

Carcinogenicity

Animal studies to evaluate the carcinogenic potential of gadodiamide have not been performed. {01}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies with gadodiamide have not been done in humans. Also, although there is no evidence that the magnetic and electric fields associated with MRI have an effect on human development, in vitro studies and theoretical predictions raise concern regarding the risk of exposure of the developing embryo and fetus to MR. More studies are needed to establish the safety of MRI in pregnant patients.

Studies in rabbits showed that gadodiamide at doses 5 times the maximum recommended human dose increased the incidence of skeletal and visceral abnormalities in the offspring. {01}

FDA Pregnancy Category C. {01}

Breast-feeding

It is not known whether gadodiamide is distributed into breast milk. {01}

Pediatrics

Appropriate studies on the relationship of age to the effects of gadodiamide have not been performed in the pediatric population. However, pediatrics-specific problems that would limit the usefulness of this agent in children are not expected.


Geriatrics


Appropriate studies on the relationship of age to the effects of gadodiamide have not been performed in the geriatric population. However, clinical trials conducted to date, which included older patients, have not demonstrated geriatrics-specific problems that would limit the usefulness of this agent in the elderly. {06}

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Allergies or asthma, history of    (increased risk of idiosyncratic response {01})


Anemia, hemolytic    (although this effect has not been specifically reported for gadodiamide, the use of gadopentetate dimeglumine, another paramagnetic contrast agent, has been associated with an increased risk of hemolysis; until more conclusive evidence is available, caution is recommended {01})


» Renal function impairment, severe    (excretion of gadodiamide may be impaired {01})


» Sensitivity to gadodiamide
Sickle cell disease    (in in vitro studies, deoxygenated sickle erythrocytes have been shown to align perpendicular to a magnetic field, which may result in vascular occlusion in vivo ; however, more studies are needed to establish extent of risk {01})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent or rare
    
Pseudo-allergic reaction (itching, watery eyes; skin rash or hives; swelling of face; thickening of tongue; wheezing, tightness in chest, or troubled breathing{01}{08})



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Dizziness
    
headache
    
nausea{01}{08}

Incidence less frequent or rare
    
Changes in taste
    
chest pains
    
CNS effects (anxiety; confusion; convulsions)
    
diarrhea
    
dryness of mouth
    
pain at injection site
    
vasodilation (unusual warmth and flushing of skin{01})





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, MRI Contrast Agents (Diagnostic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Action in the body: Accumulates in brain and spinal lesions creating a local magnetic field; visualization of lesions possible with MR instruments

Before having this test
»   Conditions affecting use, especially:
Sensitivity to gadodiamide
Other medical problems, especially allergies or asthma (history of) or severe renal function impairment

Preparation for this test
Special preparatory instructions may apply; patient should inquire in advance


Side/adverse effects
Signs of possible side effects, especially pseudo-allergic reaction


General Dosing Information
The manufacturer's package insert or other appropriate literature should be consulted for specific techniques and procedures for the administration of gadodiamide.

During and for at least 30 to 60 minutes after injection of gadodiamide, the patient should be observed for possible severe reactions. Competent personnel and emergency facilities should be available during this period. {01}

Imaging procedures should be completed within 1 hour of injection of gadodiamide. {01}


Parenteral Dosage Forms

GADODIAMIDE INJECTION

Usual adult and adolescent dose
Brain and spinal lesions imaging, magnetic resonance
Intravenous, by direct injection (at a rate >60 mL per minute), 0.2 mL (0.1 mmol) per kg of body weight. {01}


Note: To insure complete injection of gadodiamide, a 5-mL flush using 0.9% sodium chloride injection should be administered following injection of gadodiamide. {01}
If repeat examinations are required, an interval of time should elapse between injections to allow for normal clearance of gadodiamide. {01}


Usual adult prescribing limits
Up to a total dose of 5.74 grams (20 mL). {01}

Usual pediatric dose
Brain and spinal lesions imaging, magnetic resonance
Dosage must be individualized by physician.


Note: Doses based on 0.2 mL (0.1 mmol) of gadodiamide per kg of body weight have been used in pediatric patients. {08}


Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—


287 mg (0.5 mmol) per mL of gadodiamide (Rx) [Omniscan (12 mg of caldiamide sodium per mL)]

Canada—


287 mg (0.5 mmol) per mL of gadodiamide (Rx) [Omniscan]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), in a light-resistant container, unless otherwise specified by manufacturer. Protect from freezing. {01}



Revised: 08/30/1994



References
  1. Omniscan package insert (Sanofi Winthrop—US), Rev 12/92.
  1. Wolf GL. Magnetic resonance imaging and the future of cardiac imaging. Am J Cardiol 1989; 64: 60E-63E.
  1. Greco A. Gadodiamide injection: nonionic gadolinium chelate for MR imaging of the brain and spine—phase II-III clinical trial. Radiology 1990; 176(2): 451-6.
  1. Kaplan GD, Aisen AM, Aravapalli SR. Preliminary clinical trial of gadodiamide injection: a new nonionic gadolinium contrast agent for MR imaging. J Magn Reson Imaging 1991; 1(1): 57-62.
  1. Myhr G, Rinck PA, Brseth A. Gadodiamide injection and gadopentetate dimeglumine. A double-blind study in MR imaging of the CNS. Acta Radiol 1992; 33(5): 405-9.
  1. Sze G, Brant-Zawadzki M, Haughton VM, et al. Multicenter study of gadodiamide as a contrast agent in MR imaging of the brain and spine. Radiology 1991; 181(3): 693-9.
  1. Fleeger CA, editor. USAN 1993. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1993: 293.
  1. Reviewers' responses to monograph revision of 03/01/93.

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