Gadopentetate (Systemic)



INN:

Gadopentetic Acid

VA CLASSIFICATION
Primary: DX900

Commonly used brand name(s): Magnevist.

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

Not commercially available in Canada.



Category:


Diagnostic aid, paramagnetic (brain disorders; spine disorders; breast disease; cardiac disease; liver disorders; musculoskeletal disease; uterus disorders)—
Note: Gadopentetate meglumine is an ionic paramagnetic agent. {29}



Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Brain imaging, magnetic resonance—Gadopentetate dimeglumine is indicated in adults and children 2 years of age and older to provide contrast enhancement during magnetic resonance imaging (MRI) of intracranial lesions with abnormal vascularity or those suspected of causing an abnormality in the blood-brain barrier. Gadopentetate-enhanced MRI helps in the diagnosis and characterization of neoplastic disease, acoustic neuroma, subacute infarction, inflammatory disease, certain vascular abnormalities, and certain demyelinating abnormalities (e.g., multiple sclerosis). {01} {02} {07} {08} {09} {14} {21} {24} {30} {41} {42}
—Gadopentetate dimeglumine is used in magnetic resonance (MR) studies to help differentiate changes that occur secondary to brain tumor resection (e.g., encephalomalacia, gliosis) or to postoperative irradiation or chemotherapy (e.g., edema, ischemia, demyelination, necrosis) from changes that represent residual or recurrent tumors, to accurately assess treatment results. {06}
—MRI with gadopentetate dimeglumine is particularly useful in patients with normal unenhanced studies who have central nervous system (CNS) symptoms, in patients with CNS tumors that are difficult to separate from surrounding edema, and in patients who have undergone surgery, to differentiate recurrence of the lesions from postoperative changes. {21}
—In patients with suspected meningitis, gadopentetate-enhanced MRI may be particularly useful in defining the active inflammatory process of the meninges and focal lesions. {09}

Spinal lesions imaging, magnetic resonance—Gadopentetate dimeglumine is indicated in adults and children 2 years of age and older to provide contrast enhancement and facilitate visualization of lesions in the spine and associated tissues. {01} {04}
—Gadopentetate dimeglumine provides enhanced contrast of epidural abscesses, which makes it possible to differentiate them from adjacent compressed thecal sac; it facilitates the diagnosis of disk space infection and osteomyelitis; it helps localize portions of paraspinal masses most likely to yield a positive percutaneous biopsy; and it helps distinguish active spinal infections from those that have responded adequately to antibiotic therapy. {20}
—MRI with gadopentetate dimeglumine may be useful in differentiating postoperative epidural fibrosis (scar tissue) from recurrent disk herniation in patients with symptoms of failed back surgery syndrome, to avoid unnecessary, and possibly damaging, reoperation if scar tissue is the cause. {17}

Body imaging, magnetic resonance—Gadopentetate dimeglumine is indicated in adults to improve lesion contrast during MR body imaging (excluding the heart) in the evaluation of suspected hepatic lesions, endometrial or cervical carcinomas or pelvic masses, breast lesions (suspected or known), and musculoskeletal lesions. {11} {33} {34} {35} {36} {37} {38} {39} {40}
—MRI of the breast is also used in patients with postoperative scarring and silicon implants to exclude or demonstrate malignancy, especially in patients with uncertain mammographic and/or clinical findings. {15}

[Cardiac imaging, magnetic resonance]—Gadopentetate-enhanced MRI is used in the evaluation of patients with great vessel disease (e.g., aortic aneurysm, aortic dissection, congenital abnormalities, vena cava obstruction); in patients with ischemic cardiac disease to examine the heart for regions of wall thinning and intracardiac thrombus, to assess chamber size, myocardial mass, wall motion, and wall thickening, and to detect regions of acute infarction; and in patients with congenital heart disease to evaluate malrotations of the heart and for post-surgery assessment. {19} {28} Also, gadopentetate-enhanced MRI helps in the assessment of coronary artery reperfusion after thrombolysis. {26}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    938.01

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. MR images are based primarily on proton density and proton relaxation dynamics. MR instruments are sensitive to two different relaxation processes, the T1 (spin-lattice or longitudinal relaxation time) and T2 (spin-spin or transverse relaxation time). Paramagnetic agents contain one or more unpaired electrons that enhance the T1 and T2 relaxation rates of protons in their molecular environment. The proton relaxation effect (PRE) of an unpaired electron is 700 times stronger than that of a proton itself. {42} In MRI, visualization of normal and pathological brain tissue depends in part on variations in the radio frequency signal intensity that occur with changes in proton density, alteration of the T1, and variation in T2. When placed in a magnetic field, gadopentetate dimeglumine shortens the T1 and T2 relaxation times in tissues where it accumulates. In the central nervous system (CNS), gadopentetate dimeglumine enhances visualization of normal tissues that lack a blood-brain barrier, such as the pituitary gland and the meninges. Gadopentetate dimeglumine does not cross the intact blood-brain barrier; therefore, it does not accumulate in normal brain tissue or in 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 gadopentetate dimeglumine in lesions such as neoplasms, abscesses, and subacute infarcts. Outside the CNS, gadopentetate dimeglumine rapidly reaches equilibrium in the interstitial compartment and enhances signal in all tissues as a function of delivery and size of the interstitial compartment. {01} {02} {11} {14} {19} {21} {29} {31} {42}

Distribution:

Rapidly cleared from blood after intravenous administration and distributed in extracellular space. {29}

Half-life:

Elimination—1.6±0.13 hours (mean). {01}

Elimination:
    Renal, by passive filtration (approximately 83% of dose excreted within 6 hours). {01} {30}


Precautions to Consider

Carcinogenicity/Mutagenicity

Long-term animal studies to evaluate carcinogenic or mutagenic potential of gadopentetate dimeglumine have not been performed. {01}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done. 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 to MR to the developing embryo and fetus. More studies are needed to establish the safety of MRI in pregnant patients. {03}

Studies in rats with gadopentetate dimeglumine at doses 2.5 times, and in rabbits at doses 7.5 and 12.5 times, the human dose have shown that this agent causes slight retardation in development.

FDA Pregnancy Category C. {01} {33}

Breast-feeding

Problems in humans have not been documented. Since gadopentetate is distributed in small amounts into breast milk, temporary discontinuation of breast-feeding should be considered for at least 24 hours following its administration. {01} {31} {32}

Pediatrics

Appropriate studies have not been performed in children up to 2 years of age. In older children, pediatrics-specific problems that would limit the usefulness of this agent are not expected. {01} {06} {12} {21}


Geriatrics


Appropriate studies on the relationship of age to the effects of gadopentetate dimeglumine have not been performed in the geriatric population. However, clinical trials, which included older patients, were conducted and geriatrics-specific problems that would limit the usefulness of this medication in the elderly are not expected. {04}


Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Bilirubin and
Iron    (serum concentrations may be transiently increased {01} {04})


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
» Anemia, hemolytic    (possible risk of increased hemolysis {01})


Epilepsy    (gadopentetate dimeglumine may precipitate seizure {01})


Hypotension    (may be exacerbated {01})


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


» Sensitivity to gadopentetate dimeglumine


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 {01} {13} {25} {31}
    
Convulsions
    
pseudo-allergic reaction (skin rash or hives; wheezing, tightness in chest, or troubled breathing)
    
severe hypotension (unusual tiredness or weakness)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Coldness at injection site —2.8%
    
dizziness —less than 2%
    
headache —5.5%
    
nausea —2.5%{01}{25}{33}

Incidence less frequent or rare
    
Agitation
    
dryness of mouth
    
fever
    
increased salivation
    
pain and/or burning sensation at injection site
    
ringing or buzzing in ears
    
stomach pain
    
vasodilation (unusual warmth and flushing of skin)
    
vomiting
    
weakness or tiredness





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 gadopentetate dimeglumine





Breast-feeding—Distributed in small amounts into breast milk; temporary discontinuation of breast-feeding should be considered
Other medical problems, especially hemolytic anemia 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 convulsions, pseudo-allergic reaction, or severe hypotension


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

Imaging procedures of the CNS should be completed within 1 hour of injection of gadopentetate. {01} Maximal lesion-liver contrast occurs within the first few minutes after administration of gadopentetate dimeglumine; thus liver scans should be obtained immediately after contrast administration and, preferably, with rapid image acquisition sequences. {11} {31}

Gadopentetate dimeglumine injection, although hypertonic as compared to plasma (6.8 times the osmolality of plasma), is subject to rapid hemodilution. {01} {42}


Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.


GADOPENTETATE DIMEGLUMINE INJECTION

Usual adult and adolescent dose
Brain and spinal lesions imaging, magnetic resonance {01} ; Body imaging, magnetic resonance; and [Cardiac imaging, magnetic resonance] {26}
Intravenous, 93.8 mg (0.1 mmol [0.2 mL]) per kg of body weight, administered at a rate not to exceed 10 mL per minute. {11} {33}


Note: Injection rates that exceed 10 mL per minute have been associated with nausea. {01}
To insure complete injection of gadopentetate, a 5-mL normal saline flush should be administered following injection of gadopentetate. {01}
If repeat examinations are required, an interval of time should elapse between injections to allow for normal clearance of gadopentetate. {01}


Usual adult prescribing limits
Up to a total dose of 9.38 grams (20 mL). {01}

Usual pediatric dose
Brain and spinal lesions imaging, magnetic resonance {01} {33}
Children up to 2 years of age: Safety and efficacy have not been established.

Children 2 years of age and older: See Usual adult and adolescent dose . {01}

Body imaging, magnetic resonance
Dosage has not been established. {33}


Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—


469.01 mg (0.5 mmol) per mL (Rx) [Magnevist (meglumine 0.39 mg) (diethylenetriamine pentaacetic acid 0.15 mg)]

Canada—
Not commercially available.

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.



Revised: 08/19/1994



References
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  1. National Institutes of Health Panel Issues Report. Consensus Development Conference: Magnetic resonance imaging 1987; Vol 6 No 14.
  1. Goldstein HA, Kashanian FK, Blumetti RF, et al. Safety assessment of gadopentetate dimeglumine in U.S. clinical trials. Radiology 1990 Jan; 174(1): 17-23.
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