Gadoterate meglumine is a macrocyclic ionic paramagnetic contrast agent indicated for use during magnetic resonance imaging (MRI) of the brain, spine, and associated tissues in adults and pediatric patients (including neonates). When administered prior to imaging, gadoterate meglumine provides enhanced visualization and detection of areas with disruptions in the blood brain barrier or abnormal vascularity. Nephrogenic systemic fibrosis (NSF) may develop after use of gadoterate meglumine, and other gadolinium-based contrast agents (GBCAs), in patients with impaired elimination of the drugs. GBCA-induced NSF may result in fatal or debilitating fibrosis affecting the skin, muscle, and internal organs. Patients at highest risk include those with acute renal injury and chronic, severe renal impairment (glomerular filtration rate less than 30 mL/minute/1.73 m2); a black boxed warning has been issued regarding use of these agents in patients with renal insufficiency.
Approval was based on the results of a clinical trial involving 364 adults and 38 pediatric patients with known or suspected central nervous system (CNS) lesions. Patients underwent a baseline MRI examination, followed by administration of the assigned contrast agent (either 0.1 mmol/kg of gadoterate meglumine or gadopentetate dimeglumine) and a post-contrast MRI examination. The pre- and post-contrast images were interpreted by 3 blinded readers for contrast enhancement, border delineation, and internal morphology. When compared against pre-contrast images, gadoterate meglumine provided statistically significant improvement for all 3 visualization components; visualization scores with gadopentetate dimeglumine were similar to those for gadoterate meglumine. Similar results were observed in a 2nd study in which the MRI images were reread in 150 adults with known CNS lesions who participated in the initial study. Finally, a 3rd study evaluated use of gadoterate meglumine in 28 pediatric patients younger than 2 years of age who were referred for contrast MRI of the CNS. Data from this study supported extrapolation of CNS efficacy findings from adults and older children.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Hypersensitivity reactions may occur. Before administration, assess all patients for previous reactions to contrast media. Trained personnel and therapies used to treat hypersensitivity reactions (epinephrine, antihistamines, and corticosteroids) should be readily available. During and after administration, observe patient for signs and symptoms of hypersensitivity reactions.
Route-Specific Administration
Injectable Administration
-Visually inspect for particulate matter and discoloration prior to administration. The solution is clear and colorless to yellow. Do not use if particulate matter is present or if container appears damaged.
-Do not mix with other drugs.
-Perform the magnetic resonance imaging (MRI) immediately after the bolus injection.
Intravenous Administration
Glass Vials
-Aseptically draw up the contrast medium into a disposable syringe and use immediately.
Prefilled Glass or Plastic Syringe
-Holding the syringe barrel firmly, screw the threaded tip of the plunger rod clockwise into the cartridge plunger.
--For the glass prefilled syringe: Push forward a few millimeters to break any friction between the cartridge plunger and the syringe barrel.
-For the plastic prefilled syringe: After screwing the push rod into the syringe cartridge plunger, turn the push rod clockwise an additional half turn, so the cartridge plunger rotates freely.
-Holding the syringe vertically, aseptically remove the rubber cap from the tip of the syringe and attach either a sterile disposable needle or compatible needless luer lock tubing set. If using a needle, hold the syringe vertically and push the plunger forward until all air is evacuated and fluid appears at the needle tip. If using a needleless luer lock tubing set, check the connection between the syringe and tubing as the fluid flows.
-Storage: Product contains no antimicrobial preservatives. Discard any unused product.
Pharmacy Bulk Packaging
-Do not use bulk packaging for direct IV administration. Contents must be transferred to empty sterile syringes in an aseptic work area (i.e., laminar flow hood using aseptic technique and suitable transfer device).
-Bulk packaging may only be penetrated once. Do not remove from aseptic work area after container closure is punctured.
-Use each individual dose promptly after withdrawal from the pharmacy bulk packaging.
-Storage: Use the contents of the bulk packaging within 24 hours after the initial puncture.
Bolus Injection
-Ensure catheter and venous patency before the injection. Extravasation may result in tissue irritation.
-Administer as a single IV bolus injection at a rate of 2 mL/second for adults and 1 to 2 mL/second for pediatric patients.
-Follow the bolus injection with a normal saline flush to ensure administration of the total dose.
Cases of nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) (NSF/NFD) have been reported following administration of gadolinium-based contrast agents (GBCAs) in patients with moderate to severe renal impairment; however, this reaction has not been definitively associated with the use of gadoterate meglumine as a single agent. In fact, an association of any one specific GBCA with the development of NSF/NFD is not always identified; most reports have involved the use of gadodiamide (Omniscan), gadopentetate dimeglumine (Magnevist), and gadoversetamide (OptiMARK). In one retrospective study of 370 patients with severe renal insufficiency, the estimated risk for NSF/NFD was 4%. In a report by the CDC, a case-control study from a single hospital found that the risk of NSF/NFD is higher in patients undergoing peritoneal dialysis compared to hemodialysis (estimated 4.6 cases/100 peritoneal dialysis patients vs. 0.61 cases/100 hemodialysis patients). The mechanism of NSF/NFD in patients receiving GBCAs is unknown; however, dissociation of gadolinium from its chelating agent after intravenous injection is hypothesized. The free gadolinium ion then binds to anions such as phosphate, resulting in an insoluble precipitate that deposits in various tissues, and a fibrotic reaction ensues. NFD is characterized by burning, itching, swelling, scaling, tightening, and hardening of the skin, red or dark patches on the skin, stiffness in joints, resulting in trouble moving, straightening or bending the arms, legs or feet; muscle weakness, pain in hip bones or ribs. NSF involves fibrosis of organs (e.g., heart, liver, lungs) and can lead to death. Diagnosis of NSF/NFD is confirmed by skin biopsy. Patients at risk for NSF due to exposure to GBCAs include certain patients with renal insufficiency and those receiving repeated or higher than recommended doses. Although efficacy of hemodialysis for the prevention of NSF/NFD is unknown, healthcare providers may consider prompt initiation of a hemodialysis session after administration of GBCAs to aid in the elimination of the agent from the body for those patients already receiving hemodialysis. Hemodialysis is preferred to peritoneal dialysis as available data indicate that continuous ambulatory peritoneal dialysis may not be as efficient as hemodialysis in eliminating GBCAs. Treatment options for NSF/NFD are minimal; patients should be enrolled in physical therapy programs. Limited data in support of plasmapheresis or photopheresis are promising.
Acute renal failure (unspecified) has developed after administration of gadolinium-based contrast agents (GBCAs) to patients with pre-existing chronic renal insufficiencies. The risk for acute renal injury appears to be dose-related; therefore, use of the lowest dose necessary for adequate imaging is recommended. During clinical trials, less than 0.2% of gadoterate meglumine recipients experienced elevations in serum creatinine. Monitor renal function in patients receiving GBCAs.
Anaphylactoid reactions, characterized by cardiovascular, respiratory, and cutaneous symptoms, have been associated with the use of all gadolinium-based contrast agents (GBCAs), including gadoterate meglumine. Most cases develop within minutes of drug administration and resolve with urgent medical treatment; however, fatalities have been reported in some patients who experienced circulatory collapse. Some of the symptoms associated with these reactions may include cardiac arrest, respiratory arrest, cyanosis, pharyngeal edema, laryngospasm, bronchospasm, angioedema, conjunctivitis, ocular hyperemia, eyelid edema or blepharitis, increased lacrimation, hyperhidrosis, and urticaria. Observe patients for these symptoms, both during and after administration of gadoterate meglumine.
Injection site reaction (i.e., pain, burning, inflammation, pruritus, swelling, and feeling of warmth or coldness) was reported in up to 0.4% of gadoterate meglumine recipients during clinical trials. Other adverse events reported in less than 0.2% of patients and possibly associated with the administration of the drug included rash (unspecified), pain in extremity, and extravasation. To avoid extravasation and potential tissue irritation, the FDA-approved product labeling recommends ensuring catheter and venous patency prior to administering gadoterate meglumine.
Headache (0.4% adults; 1.1% pediatric patients) was among the most frequently reported adverse events during gadoterate meglumine clinical trials. Other adverse events observed in less than 0.2% of drug recipients included asthenia, fatigue, somnolence or drowsiness, anxiety, dizziness, and paresthesias. Nervous system disorders reported during postmarketing use of the drug include coma, convulsions or seizures, parosmia, syncope, presyncope, and tremor. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
Nausea (0.6%), vomiting (less than 0.2%), dysgeusia (less than 0.2%), and oropharyngeal discomfort (less than 0.2%) were experienced by recipients of gadoterate meglumine during clinical trials. Cases of diarrhea and hypersalivation were noted during postmarketing use of the drug. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
Less than 0.2% of patients administered gadoterate meglumine during clinical trials experienced palpitations and episodes of hypotension and hypertension. Cardiovascular adverse events reported during postmarketing use of the drug include bradycardia, sinus tachycardia, and arrhythmia exacerbation. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
Complaints of malaise, fever, muscle contracture, and muscle weakness were reported during postmarketing use of gadoterate meglumine. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
Diagnostic procedures that involve use of contrast agents, such as gadoterate meglumine, should be carried out under direction of a physician with the prerequisite training and a thorough knowledge of the procedure to be performed. As with any paramagnetic contrast agent, use of gadoterate meglumine during contrast enhanced magnetic resonance imaging (MRI) could impair visualization of lesions seen on non-contrast MRI. Caution must be used when a contrast-enhanced MRI is interpreted without a companion non-contrast MRI. In addition, gadolinium deposits may remain in patients' bodies for months to years after gadolinium-based contrast agent (GBCA) receipt. Bone has been identified as the main reservoir, retaining the highest concentration of gadolinium (nanomoles per gram of tissue) for the longest duration of time. Other organs which retain lesser amounts of gadolinium include the brain, skin, kidney, liver, and spleen. The consequences of gadolinium retention in the brain have not been established; however, retention in the skin and kidney has been associated with pathologic clinical consequences in patients with impaired renal function. There are rare reports of pathologic skin changes in patients with normal renal function. Other patients who may be at higher risk for gadolinium retention include patients requiring multiple lifetime doses, pregnant women, pediatric patients, and patients with inflammatory conditions. Limit repeated GBCA imaging studies, particularly closely spaced MRI studies, but do not defer or avoid necessary GBCA MRI scans. When choosing a GBCA, consider the retention characteristics of each agent. In general, linear GBCAs result in more retention and retention for longer periods of time than do macrocyclic GBCAs. More specifically, at equivalent doses, use of gadodiamide or gadoversetamide results in higher gadolinium concentrations remaining in the body than gadoxetate disodium, gadopentetate dimeglumine, or gadobenate dimeglumine. Gadolinium concentrations in the body are lowest after administration of gadoterate meglumine, gadobutrol, and gadoteridol. Instruct patients to inform their health care professional about all medical conditions, including if pregnant or thinking about becoming pregnant, dates and numbers of any previous gadolinium-enhanced MRIs, and history of kidney problems.
Administration to patients with a history of clinically important hypersensitivity reactions to gadoterate meglumine is contraindicated. The drug has been associated with serious, and sometimes fatal, anaphylactoid/anaphylactic reactions involving cardiovascular, respiratory, and/or cutaneous manifestations. In most cases, these reactions developed within minutes of drug administration and resolved with emergency treatment. Prior to administration, assess hypersensitivity risk factors in all potential drug recipients. Patients at increased risk include those with a history of radiopaque contrast media hypersensitivity, asthma, atopy (including hay fever, food allergies, and drug allergies) or other allergic disorders. The manufacturer recommends appropriate facilities (trained personnel and therapies) be available for coping with the emergency treatment of severe reactions, and patients be closely observed for signs and symptoms of a hypersensitivity reaction during and following drug administration. One group of authors recommends taking similar precautions to those that are taken in patients who have previously reacted to iodinated radiopaque contrast media that require subsequent doses. First, the necessity of contrast enhancement during MRI should be determined. If it is determined that contrast enhancement outweighs any potential risk, the intensity of a previous reaction (to either iodinated or gadolinium-based contrast media) should guide precautionary measures. If the previous reaction to contrast media was mild or nonallergic, use of a different or low-osmolar (i.e., gadoteridol or gadodiamide) agent is recommended. If the previous reaction to contrast media was moderate or severe, premedication with steroids (e.g., in adults, prednisone 50 mg PO or equivalent 13, 7, and 1 hour prior to the exam) and antihistamines (e.g., adult dose diphenhydramine 50 mg IM/PO one hour prior to the exam) along with the use of a different or low-osmolar contrast agent is recommended.
Serious adverse reactions, including nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) (NSF/NFD), have been reported in patients with renal impairment after receiving gadolinium-based contrast agents (GBCAs), such as gadoterate meglumine. NSF may result in fatal or debilitating systemic fibrosis affecting the internal organs, muscle, and skin. Patients at highest risk for NSF are those with chronic, severe renal disease or renal failure (glomerular filtration rate [GFR] less than 30 mL/minute/1.73 m2) and patients with acute renal injury. Avoid use of GBCAs in patients with impaired drug elimination unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. Use of higher than recommended doses or repeated administration may increase the risk for NSF; therefore, administer the lowest dose necessary for adequate imaging and, if needed, only repeat the dose after a sufficient period of time has passed for elimination of the agent from the body. Gadoterate meglumine 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 GBCAs. All patients should be screened for evidence of renal dysfunction by obtaining a medical history or laboratory results prior to the administration of GBCAs. Acute renal injury occurs commonly after surgery, severe infection, injury, or drug-induced renal toxicity. In patients with acute renal 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 or older]), estimate the GFR through laboratory testing. Counsel patients on the signs and symptoms of NSF/NFD. Report possible cases of NSF to the FDA through the FDA MedWatch program at 800-FDA-1088 and to the manufacturer at 877-729-6679. In contrast, guidelines suggest kidney function screening is optional for American College of Radiology (ACR) group II GBCAs, which includes gadoterate meglumine, given risk of NSF is very low comparatively; the risk of NSF is very low for a standard dose (0.1 mmol/kg) of group II GBCA, even in patients with eGFR less than 30 mL/minute/1.73 m2. Do not withhold or delay group II GBCA in patients with kidney disease if harm would result from not proceeding with an indicated contrast-enhanced MRI. If multiple urgent group II GBCA doses are indicated, do not delay subsequent dose(s) for NSF concerns. If not urgent, delaying the subsequent dose(s) for more than 24 hours or performing intercurrent dialysis can promote GBCA clearance. In general, do not initiate or alter dialysis based on group II GBCA administration. These recommendations are not altered by patients receiving concomitant nephrotoxic medications, chemotherapy, or contrast-enhanced CT.
Ensure the patency and integrity of the intravenous line prior to administering gadoterate meglumine. Furthermore, appropriate surveillance of the dosing limb for development of local injection site reactions is recommended. Take care to avoid extravasation as tissue irritation may occur.
Deoxygenated sickle erythrocytes have been shown in vitro to align perpendicular to a magnetic field which may result in vaso-occlusive complications in vivo. The enhancement of magnetic moment by gadolinium-based contrast agents (GBCAs), such as gadoterate meglumine, may possibly potentiate sickle erythrocyte alignment. Although the use of gadoterate meglumine in patients with sickle cell disease and other hemoglobinopathies has not been studied, the American College of Radiology (ACR) manual on contrast media considers any special risk to sickle cell patients from administration of GBCAs to be extremely low; no restrictions for use of GBCAs are recommended by the ACR.
Gadoterate meglumine is for intravenous use only. Intrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious adverse reactions including death, coma, encephalopathy, and seizures. Safety and effectiveness of gadoterate meglumine have not been established with intrathecal use.
Use gadoterate meglumine 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, no adverse effects on embryo fetal development were observed after intravenous administration of gadoterate meglumine to pregnant rats at 3-, 7-, and 16-times the recommended human dose (based on body surface) or when administered to pregnant rabbits at 3- and 10-times the recommended human dose. The American College of Radiology (ACR) manual on contrast media acknowledges that a standard gadolinium-based contrast agent (GBCA) crosses the primate placenta; however, the risk to the human 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.
There are no data on the presence of gadoterate meglumine in human milk, the effects on the breast-fed infant, or the effects on milk production. Limited data demonstrates that breast-feeding after administration of another gadolinium-based contrast agent (GBCA) to the mother would result in the infant receiving an oral dose of 0.01% to 0.04% of the maternal dose. Gastrointestinal absorption of a GBCA is limited. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for gadoterate meglumine and any potential adverse effects on the breast-fed infant from gadoterate meglumine or the underlying maternal condition. Previous American Academy of Pediatrics (AAP) recommendations considered 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.
For use as a contrast enhancement in magnetic resonance imaging (MRI) to detect and visualize areas of the brain, spine, and associated tissues with disruption of the blood brain barrier and/or abnormal vascularity:
Intravenous dosage:
Adults: 0.2 mL/kg (0.1 mmol/kg) administered as a single IV bolus injection at a rate of 2 mL/second. 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. Cumulative doses up to 0.3 mmol/kg have been administered to patients and healthy volunteers without increased adverse events. The FDA-approved product labeling provides weight-adjusted dose volumes as follows: 30 kg: 6 mL; 40 kg: 8 mL; 50 kg: 10 mL; 60 kg: 12 mL; 70 kg: 14 mL; 80 kg: 16 mL; 90 kg: 18 mL; 100 kg: 20 mL; 110 kg: 22 mL; 120 kg: 24 mL; 130 kg: 26 mL; 140 kg: 28 mL; 150 kg: 30 mL.
Infants, Children, Adolescents: 0.2 mL/kg (0.1 mmol/kg) administered as a single IV bolus injection at a rate of 1 to 2 mL/second. 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. Cumulative doses up to 0.3 mmol/kg have been administered to patients and healthy volunteers without increased adverse events. The FDA-approved product labeling provides weight-adjusted dose volumes as follows: 2.5 kg: 0.5 mL; 5 kg: 1 mL; 10 kg: 2 mL; 20 kg: 4 mL; 30 kg: 6 mL; 40 kg: 8 mL; 50 kg: 10 mL; 60 kg: 12 mL; 70 kg: 14 mL; 80 kg: 16 mL; 90 kg: 18 mL; 100 kg: 20 mL; 110 kg: 22 mL; 120 kg: 24 mL; 130 kg: 26 mL; 140 kg: 28 mL; 150 kg: 30 mL.
Neonates: 0.2 mL/kg (0.1 mmol/kg) administered as a single IV bolus injection at a rate of 1 to 2 mL/second. 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. Cumulative doses up to 0.3 mmol/kg have been administered to patients and healthy volunteers without increased adverse events. The FDA-approved product labeling provides weight-adjusted dose volumes as follows: 2.5 kg: 0.5 mL; 5 kg: 1 mL.
Maximum Dosage Limits:
-Adults
0.2 mL/kg (0.1 mmol/kg) IV single dose.
-Geriatric
0.2 mL/kg (0.1 mmol/kg) IV single dose.
-Adolescents
0.2 mL/kg (0.1 mmol/kg) IV single dose.
-Children
0.2 mL/kg (0.1 mmol/kg) IV single dose.
-Infants
0.2 mL/kg (0.1 mmol/kg) IV single dose.
-Neonates
Term Neonates: 0.2 mL/kg (0.1 mmol/kg) IV single dose.
Premature Neonates: Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
No dosage adjustments are recommended; do not exceed recommended dose and allow sufficient time for elimination prior to any repeat administration. The manufacturer recommends caution in patients with chronic, severe renal disease (GFR < 30 mL/min/1.73 m2) and in patients with acute kidney injury; these patients are at highest risk for renal side effects of contrast use. Avoid use in these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities.
Intermittent hemodialysis
Gadoterate meglumine is removed from the body by hemodialysis. For patients receiving hemodialysis, consider initiating a hemodialysis session after drug administration in order to enhance clearance of the contrast agent.
*non-FDA-approved indication
There are no drug interactions associated with Gadoterate meglumine products.
Gadoterate meglumine, a paramagnetic agent, is used to enhance lesion detection and characterization during magnetic resonance imaging (MRI). In MRI, 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). Gadoterate meglumine 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 infarcts.
Gadoterate meglumine is administered intravenously. At steady state, the volume of distribution is approximately equivalent to extracellular water at 179 +/- 25 mL/kg in females and 211 +/- 35 mL/kg in males. No protein binding has been observed in vitro, and gadoterate meglumine is not known to be metabolized. The mean elimination half-life is approximately 1.5 hours in females and 2 to 2.5 hours in males. Elimination occurs primarily via the kidneys, with 72.9 +/- 17% and 85.4 +/- 9.7% of a single 0.1 mmol/kg dose excreted in the urine within 48 hours, in females and males, respectively. Within the studied dosage ranges (0.1 to 0.3 mmol/kg), the kinetics of the contrast agents appear to be linear.
Affected cytochrome P450 isoenzymes: None
-Route-Specific Pharmacokinetics
Intravenous Route
After intravenous administration in normal subjects, the pharmacokinetics of gadoterate meglumine conform to a one-compartment open-model.
-Special Populations
Renal Impairment
The pharmacokinetics of gadoterate meglumine were observed in 8 patients with impaired renal function. Data from these patients were stratified based on renal function, either moderate renal impairment (CrCl 30 to 60 mL/minute) or severe renal impairment (CrCl 10 to 30 mL/minute). The data was then compared against data from healthy volunteers. The results of this study found total clearance of gadolinium was reduced as a function of the degree of renal impairment, with plasma clearance decreasing from 0.1 +/- 0.01 L/hour/kg in healthy volunteers to 0.036 +/- 0.007 L/hour/kg in moderate impairment patients and 0.012 +/- 0.001 L/hour/kg in severe impairment. Elimination half-lives were prolonged from 1.6 +/- 0.2 hours in healthy volunteers, to 5.1 +/- 1 hours in moderate impairment, and 13.9 +/- 1.2 hours in severe renal impairment. An evaluation of the mean cumulative urinary excretion of total gadolinium found healthy volunteers excreted 93.3 +/- 4.7% in 24 hours, moderate impairment patients excreted 76.9 +/- 4.5% in 48 hours, and severe impairment patients excreted 68.4 +/- 3.5% in 72 hours. Renal impairment did not alter the volume of distribution.
Pediatrics
In a pharmacokinetic study, the body weight adjusted clearance of gadoterate meglumine in pediatric subjects aged less than 2 years (n = 45) was similar to that observed in healthy adults. Subjects were administered a single 2 mL/kg intravenous dose, and gadoterate concentrations were obtained up to 8 hours after drug administration.