Magnevist

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Magnevist

Classes

MRI Agents

Administration

 
NOTE: Hypersensitivity reactions may occur. Epinephrine, antihistamines, and corticosteroids should be on hand for immediate treatment.

Injectable Administration

Visually inspect solution for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored or if particulate matter is present. Do not use if container has been damaged or protective seal broken.

Intravenous Administration

The imaging procedure should be completed within 1 hour of injection of gadopentetate dimeglumine.
Usual safety rules customary for magnetic resonance imaging (e.g., exclusion of cardiac pacemakers and ferromagnetic implants) must be observed.
Administer as single intravenous injection. The rate of administration should not exceed 10 mL per 15 seconds.
To ensure complete injection of the contrast medium, the injection should be followed by a 5 mL normal saline flush.
Data for repeat injections are not available. If, in the clinical judgment of the physician, sequential or repeat examinations are required, a suitable interval of time between administrations should be observed to allow for normal clearance of the drug from the body.
When gadopentetate dimeglumine is to be injected using a plastic disposable syringe, the contrast medium should be drawn into the syringe and used immediately.
The product contains no antimicrobial preservatives. Discard all unused product. Discard any unused portion in accordance with regulations dealing with the disposal of such materials.
When using the 100 mL Pharmacy Bulk Package, the contents should be used within 12 hours after the initial puncture. After 12 hours, any unused portion should be discarded.
If nondisposable equipment is used, scrupulous care should be taken to prevent residual contamination with traces of cleansing agents.

Adverse Reactions
Severe

seizures / Delayed / 0-1.0
thrombosis / Delayed / 0-1.0
skin necrosis / Early / 0-1.0
tissue necrosis / Early / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
renal failure (unspecified) / Delayed / Incidence not known
nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) / Delayed / Incidence not known
coma / Early / Incidence not known
erythema multiforme / Delayed / Incidence not known
laryngospasm / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
laryngeal edema / Rapid / Incidence not known
cyanosis / Early / Incidence not known
bronchospasm / Rapid / Incidence not known
cardiac arrest / Early / Incidence not known
pulmonary edema / Early / Incidence not known
respiratory arrest / Rapid / Incidence not known

Moderate

hypotension / Rapid / 0-1.0
conjunctivitis / Delayed / 0-1.0
nystagmus / Delayed / 0-1.0
urinary incontinence / Early / Incidence not known
phlebitis / Rapid / Incidence not known
dyspnea / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
peripheral vasodilation / Rapid / Incidence not known
hypertension / Early / Incidence not known

Mild

headache / Early / 4.8-4.8
nausea / Early / 2.7-2.7
injection site reaction / Rapid / 2.3-2.3
anxiety / Delayed / 0-1.0
drowsiness / Early / 0-1.0
agitation / Early / 0-1.0
dizziness / Early / 1.0-1.0
paresthesias / Delayed / 0-1.0
fever / Early / 0-1.0
vomiting / Early / 0-1.0
abdominal pain / Early / 0-1.0
diarrhea / Early / 0-1.0
dysgeusia / Early / 0-1.0
hypersalivation / Early / 0-1.0
dental pain / Delayed / 0-1.0
hyperhidrosis / Delayed / 0-1.0
rash / Early / 0-1.0
urticaria / Rapid / 0-1.0
pruritus / Rapid / 0-1.0
rhinitis / Early / 0-1.0
throat irritation / Early / 0-1.0
sneezing / Early / 0-1.0
diplopia / Early / 0-1.0
lacrimation / Early / 0-1.0
otalgia / Early / 0-1.0
ocular pain / Early / 0-1.0
xerostomia / Early / 0-1.0
ocular irritation / Rapid / 0-1.0
back pain / Delayed / 0-1.0
fatigue / Early / 0-1.0
asthenia / Delayed / 0-1.0
urinary urgency / Early / Incidence not known
tremor / Early / Incidence not known
arthralgia / Delayed / Incidence not known
shivering / Rapid / Incidence not known
chills / Rapid / Incidence not known
cough / Delayed / Incidence not known
syncope / Early / Incidence not known
pallor / Early / Incidence not known
parosmia / Delayed / Incidence not known

Boxed Warning
Diabetes mellitus, dialysis, geriatric, hypertension, nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy), renal disease, renal failure, renal impairment

Gadopentetate (Magnevist) is contraindicated in patients with renal failure, acute kidney injury, and in patients with chronic, severe renal disease (GFR < 30 mL/min/1.73 m2). Serious adverse reactions, including nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) (NSF/NFD), have been reported in patients with renal impairment after receiving gadopentetate. Although rare, NSF may result in fatal or debilitating systemic fibrosis affecting the internal organs, muscle, and skin. Patients at highest risk for NSF after receiving gadopentetate are those with impaired elimination of the drug, including those with acute renal insufficiency of any severity due to hepato-renal syndrome or liver transplant in the perioperative period. Avoid use of gadopentetate in patients with impaired drug elimination unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF has not been reported in patients with normal kidney function, but use of higher than recommended doses or repeated administration may increase the risk for NSF. Re-administration should occur only after a sufficient period of time has passed for elimination of the agent from the body. Gadopentetate is removed by hemodialysis. For patients receiving hemodialysis, it may be prudent to dialyze patients after receiving the contrast agents, although a relationship between dialysis and prevention of NSF has not been determined. Of note, hemodialysis is the preferred method of dialysis as continuous ambulatory peritoneal dialysis does not appear to be as effective in eliminating gadolinium-containing contrast media. All patients should be screened for evidence of renal dysfunction by obtaining a medical history and/or laboratory results prior to the administration of gadolinium-based contrast agents. Acute kidney injury occurs commonly after surgery, severe infection, injury, or drug-induced kidney toxicity. In patients with acute kidney injury, serum creatinine concentrations and estimated GFR may not reliably assess renal function; therefore, obtaining a medical history in these patients is of utmost importance. For patients at risk of chronic renal disease (e.g., patients with hypertension, diabetes mellitus, or geriatric patients [> 60 years of age]), estimate the GFR through laboratory testing. Tell patients about the signs and symptoms of NSF/NFD. Report possible cases of NSF to the FDA through the FDA Medwatch program.

Common Brand Names

Magnevist

Dea Class

Rx

Description

Paramagnetic, gadolinium-containing contrast agent used to enhance MRI of intracranial, spinal, head, neck, and body lesions with abnormal vascularity.
Nephrogenic systemic fibrosis (NSF) may occur in those with renal insufficiency.
Screening of renal function prior to administration is recommended.

Dosage And Indications
For use as contrast enhancement in magnetic resonance imaging (MRI) to visualize lesions with abnormal vascularity within the central nervous system (brain, spine, and associated tissues), head, neck, and body (excluding the heart). Intravenous dosage Adults, including the Geriatric

0.2 mL/kg (0.1 mmol/kg) given intravenously at a rate not to exceed 10 mL per 15 seconds. Doses in excess of 26 mL, for patients > 130 kg (or 286 pounds) has not been studied. Data for repeat injections are not available; however, if in the clinical judgment of the physician, sequential or repeat examinations are required, a suitable interval of time between administrations should be observed to allow for normal clearance of the drug from the body. In studies of CNS MRI, no difference in safety, imaging, or diagnosis was found between 0.1 mmol/kg and 0.3 mmol/kg.

Adolescents and Children >= 2 years of age

0.2 mL/kg (0.1 mmol/kg) given intravenously at a rate not to exceed 10 mL per 15 seconds.

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. However, patients are advised to inform their provider of any liver disease prior to receiving gadopentetate.

Renal Impairment

GFR >= 30 mL/min/1.73 m2: No dosage adjustments are recommended; do not exceed recommended dose and allow sufficient time for elimination prior to any repeat administration. For patients at higher risk for renal side effects of contrast use.; avoid use unless the diagnostic information is essential and not available with non-contrast MRI or other modalities.
 
GFR < 30 mL/min/1.73 m2: Contraindicated. Includes patients with chronic severe kidney disease and acute kidney injury.
 
Intermittent hemodialysis
Gadopentetate is removed from the body by hemodialysis.

Drug Interactions

There are no drug interactions associated with Gadopentetate products.

How Supplied

Magnevist Intravenous Inj Sol: 1mL, 469.01mg

Maximum Dosage
Adults

0.2 mL/kg (0.1 mmol/kg) IV.

Geriatric

0.2 mL/kg (0.1 mmol/kg) IV.

Adolescents

0.2 mL/kg (0.1 mmol/kg) IV.

Children

>= 2 years: 0.2 mL/kg (0.1 mmol/kg) IV.
< 2 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Gadopentetate dimeglumine, a paramagnetic agent, is used to enhance lesion detection and characterization during magnetic resonance imaging (MRI). In magnetic resonance, the visualization of normal or pathological tissue depends on changes in the radiofrequency signal intensity that occur with: differences in proton density; differences of the spin-lattice or longitudinal relaxation time (T1); and differences in the spin-spin or transverse relaxation time (T2). Gadopentetate dimeglumine causes increased signal intensity by developing a magnetic moment when placed in a magnetic field. This magnetic moment enhances the relaxation rates of water protons, thereby shortening T1 and T2 in target tissues. When administered at recommended doses, the effects are primarily observed in the T1 relaxation time. Disruption of the blood-brain barrier or abnormal vascularity allows accumulation of the diagnostic agent in lesions such as neoplasms, abscesses, and subacute infarcts.

Pharmacokinetics

Gadopentetate dimeglumine injection is administered intravenously. The extent of protein binding and blood cell partitioning of gadopentetate dimeglumine is not known; the volume of distribution (266 +/- 43 mL/kg) is equal to that of extracellular water.
 
Gadopentetate dimeglumine is exclusively eliminated in the urine with (reported as mean +/- SD) 83 +/- 14% of the dose excreted within 6 hours, and 91 +/- 13% excreted within 24 hours post-injection. There was no detectable biotransformation or decomposition of gadopentetate dimeglumine. The mean elimination half-life (reported as mean +/- SD) was 1.6 +/- 0.13 hours. The urinary and plasma clearance rates (1.76 +/- 0.39 mL/min/kg and 1.94 +/- 0.28 mL/min/kg, respectively) of gadopentetate dimeglumine are essentially identical, indicating no alteration in elimination kinetics on passage through the kidneys and that the drug is essentially cleared through the kidney; furthermore, clearance is similar to that of substances which are subject to glomerular filtration.

Intravenous Route

Human pharmacokinetic studies show that in normal subjects intravenously administered gadopentetate dimeglumine conforms to a two compartment open model with a mean distribution half-life (reported as mean +/- SD) of about 0.2 +/- 0.13 hours. Upon injection, the meglumine salt is completely dissociated from the gadopentetate dimeglumine complex.

Pregnancy And Lactation
Pregnancy

Use gadopentetate dimeglumine during pregnancy only if imaging is essential and cannot be delayed. Gadolinium-based contrast agents (GBCAs) cross the placenta and result in fetal exposure and gadolinium retention. Pregnant women may be at greater risk for gadolinium retention. Data on the association between GBCAs and adverse fetal outcomes in human pregnancy are limited and inconclusive. In animal studies, retarded fetal development was observed following intravenous administration of gadopentetate dimeglumine to pregnant rats for 10 days at 2-times the human dose (based on body surface area) and when administered to pregnant rabbits for 13 days at 2.4-times the human dose. No congenital anomalies were noted in rats or rabbits. The American College of Radiology (ACR) manual on contrast media states that the drug crosses the human placenta when administered in clinical doses; however, the risk to the fetus is unknown. Therefore, the ACR advises against its routine use in pregnant women; the drug should only be administered during pregnancy if absolutely necessary and only after informed consent is obtained. The Guidelines for Computed Tomography and Magnetic Resonance Imaging in Pregnancy and Lactation states that because of the potential for fetal toxicity, the drug should only be used during pregnancy if deemed absolutely essential.

Gadopentetate dimeglumine is excreted in human milk. An analysis of 18 lactating women receiving 0.1 mmol/kg found 0.001% to 0.04% of the administered gadolinium was excreted into breast milk within 24 hours; for a 70-kg woman, this correlates to less than 3 micromoles of gadolinium. There is no information on the effects of gadopentetate dimeglumine on the breast-fed infant or milk production. Consider the benefits of breast-feeding along with the mother's clinical need for gadopentetate dimeglumine and any potential adverse effects on the breast-fed infant from gadopentetate dimeglumine or the underlying maternal condition. Previous American Academy of Pediatrics (AAP) recommendations considered gadolinium-based contrast agents (GBCAs) compatible with breast-feeding. Additionally, the Guidelines for Computed Tomography and Magnetic Resonance Imaging Use During Pregnancy and Lactation and the American College of Radiology (ACR) manual on contrast media state that lactating women receiving GBCAs can continue to breast-feed without interruption. The reasoning for this recommendation is based on estimates of limited systemic exposure in the breast-fed infant and reviews that conclude maternally administered drug poses no risk to the nursing infant.