Gadoteridol is a nonionic, paramagnetic contrast agent indicated for magnetic resonance imaging (MRI) of the central nervous system (CNS) to visualize lesions with abnormal vascularity in adults and pediatric patients, including term neonates. In adults, gadoteridol is also indicated for use during MRI to visualize lesions in the extracranial or extraspinal tissues of the head and neck. Approval was based on the results of clinical trials in adults with an indication for head and neck extracranial or extraspinal MRI and pediatric patients with an indication for brain or spine MRI. In adult trials, gadoteridol-enhanced MRI imaging was used in 75% to 82% of the scans and provided additional diagnostic information in 45% to 48% of the scans; diagnosis was changed in 8% to 25% of the scans. In the pediatric trial, gadoteridol enhanced 60% of the MRI scans and provided additional diagnostic information in 30% to 95% of the scans. Like all gadolinium-based contrast agents (GBCAs), gadoteridol carries a black box warning for nephrogenic systemic fibrosis (NSF). NSF is a serious condition that may result in fatal or debilitating fibrosis of the skin, muscle, and internal organs. The propensity to cause NSF differs among available GBCAs; most unconfounded cases have been reported with gadodiamide, gadopentetate dimeglumine, and gadoversetamide.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Hypersensitivity reactions may occur. Prior to 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. Observe patient for signs and symptoms of hypersensitivity reactions during and for up to 2 hours after administration.
Route-Specific Administration
Injectable Administration
-Visually inspect for particulate matter and discoloration prior to administration. Solution is clear and colorless to slightly yellow. Do not use if discolored or if particulate matter is present.
-Concurrent medications or parenteral nutrition should not be physically mixed with contrast agents and should not be administered in the same intravenous line because of the potential for chemical incompatibility.
-Complete imaging within 1 hour of the first injection.
Intravenous Administration
Single-dose Vials
-Draw gadoteridol into the syringe immediately before use. Do not pierce the rubber stopper more than once. Discard any unused vial contents.
-Storage: Do not freeze. Should freezing of the vial occur, allow the vial to stand at room temperature for a minimum of 60 minutes. The frozen solution within the vial should return to clear and colorless to slightly yellow. Ensure all solids have dissolved prior to administering solution from a previously frozen vial. Discard vial if solids persist.
Prefilled Syringes
-Screw threaded tip of plunger rod clockwise into the cartridge plunger and push forward a few millimeters to break any friction.
-Holding the syringe erect, unscrew the plastic tip cap and attach a sterile, disposable needle or tubing with compatible luer lock.
-While still holding the syringe erect, push plunger until all air is evacuated and fluid appears at the tip of the needle or the tubing is filled.
-Storage: Do not freeze. Discard prefilled syringes if they have been frozen. Properly discard the syringe and any unused solution in accordance with regulations.
Bulk Vials
-Prior to entering the vial, remove the seal and cleanse the rubber closure with a suitable antiseptic agent.
-The container closure may be penetrated only one time, utilizing a suitable transfer device or dispensing set that allows measured dispensing of the contents.
-Once the pharmacy bulk package is punctured, it should not be removed from the aseptic work area during the entire period of use.
-Withdrawal of container contents should be accomplished without delay. A maximum time of 8 hours from initial closure entry is permitted to complete fluid transfer operations.
-Any unused contents must be discarded by 8 hours after initial puncture of the bulk package.
-Once drawn into syringe, administer transferred agent promptly for single-dose administration.
Intravenous Injection
-Administer intravenously as bolus injection at a rate of more than 60 mL/minute.
-Follow the injection with a 5 mL normal saline flush to ensure complete dose is administered.
Intravenous Infusion
-Administer intravenously as rapid infusion at a rate of 10 to 60 mL/minute.
-Follow the injection with a 5 mL normal saline flush to ensure complete dose is administered.
Nausea (1.4%) and dysgeusia (0.9%) were the most commonly noted GI adverse events associated with gadoteridol during clinical trials. Other gastrointestinal adverse events experienced by less than 0.4% of patients receiving gadoteridol included abdominal pain or discomfort, diarrhea, vomiting, decreased appetite (anorexia), dry mouth or xerostomia, swollen or itching tongue, gingival pain, and gingivitis.
Cardiovascular adverse events experienced by less than 0.4% of patients receiving gadoteridol during clinical trials included chest discomfort or chest pain (unspecified), angina pectoris, palpitations, AV block (first degree), sinus tachycardia, hypotension, peripheral coldness, vascular rupture, peripheral vasodilation, and vasospasm. Bradycardia and hypertension have been reported with gadoteridol in postmarketing surveillance.
Headache (0.7%) and dizziness (0.4%) were the most common neurologic adverse events reported by patients receiving gadoteridol during clinical trials. Other neurologic adverse events reported by less than 0.4% of patients included anxiety, mental status changes, formication, hypoesthesia, hypokinesia, lethargy, loss of consciousness, migraine, paresthesias, seizures, and syncope. Coma, vasovagal reaction, and tremor have been reported with gadoteridol in postmarketing surveillance.
Dermatologic adverse events experienced by less than 0.4% of patients receiving gadoteridol during clinical trials included rash, morbilliform or maculopapular rash, pruritus, and diaphoresis.
Respiratory adverse events reported in less than 0.4% of patients receiving gadoteridol during clinical trials included dyspnea, rhinitis, dry throat, nasal discomfort, and throat irritation. Pulmonary edema and respiratory arrest were reported with gadoteridol in postmarketing surveillance.
Tinnitus and ear discomfort (otalgia) were reported in less than 0.4% of patients receiving gadoteridol during clinical trials.
Anaphylactoid reactions (characterized by cardiovascular, respiratory, and cutaneous symptoms) have been reported in patients receiving gadoteridol during clinical trials; in rare cases, the anaphylactoid reaction resulted in death. Hypersensitivity/anaphylactoid reactions have included cardiac arrest, bronchospasm, laryngospasm, cyanosis, pharyngeal edema, facial edema, angioedema, cough, sneezing, hyperhidrosis, and urticaria. In most cases, initial symptoms occurred within minutes of gadoteridol administration and resolved with prompt emergency treatment. Observe patients for signs and symptoms of a hypersensitivity reaction during and for up to 2 hours after gadoteridol administration. If a hypersensitivity reaction occurs, discontinue gadoteridol and immediately begin appropriate therapy. Other general adverse events observed in less than 0.4% of patients included fever, flushing, and an injection site reaction (including pain, erythema, cold, and warmth at the injection site).
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, an association of any 1 specific GBCA with the development of NSF/NFD is not always identified; most reports have involved the use of gadodiamide, gadopentetate dimeglumine, and gadoversetamide. In 1 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) requiring dialysis has developed after administration of gadolinium-based contrast agents (GBCAs) in patients with preexisting chronic renal insufficiency. The risk for acute kidney injury appears to be dose-related; therefore, use the lowest dose necessary for adequate imaging.
Hypoglycemia was reported in less than 0.4% of patients receiving gadoteridol during clinical trials.
Asthenia, back pain, and musculoskeletal stiffness were reported in less than 0.4% of patients receiving gadoteridol during clinical trials. Fatigue, pain syndromes, and heterogenous clusters of symptoms in the neurological and musculoskeletal systems have been reported with gadoteridol in postmarketing surveillance.
Ocular pruritus and increased lacrimation have been reported in less than 0.4% of patients receiving gadoteridol during clinical trials. Conjunctivitis and eyelid edema (ocular inflammation) have also been reported with gadoteridol as part of hypersensitivity/anaphylactoid reactions.
Elevated hepatic enzymes were reported in less than 0.4% of patients receiving gadoteridol during clinical trials. Other laboratory abnormalities reported in less than 0.4% of patients were increased chloride or hyperchloremia, decreased blood urea, and decreased hemoglobin.
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 gadoteridol. 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. Gadoteridol 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 [more than 60 years of age]), 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 800-257-5181. In contrast, guidelines suggest kidney function screening is optional for American College of Radiology (ACR) group II GBCAs, which includes gadoteridol, 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.
Diagnostic procedures that involve use of contrast agents, such as gadoteridol, 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 gadoteridol 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.
Gadoteridol is contraindicated in patients with known allergic or hypersensitivity reactions to gadoteridol. The drug has been associated with serious, and sometimes fatal, anaphylactic reactions involving cardiovascular, respiratory, and cutaneous manifestations. In most cases, initial symptoms occurred within minutes of gadoteridol administration and resolved with prompt emergency treatment. Prior to administration, assess hypersensitivity risk factors in all potential drug recipients. According to the American College of Radiology (ACR), the risk of adverse reactions is approximately 8-times higher in patients with a previous gadolinium-based radiopaque contrast media hypersensitivity reaction; the subsequent reactions have the potential to be more severe than the first. Other individuals at increased risk include those with a history of asthma, atopy (including hay fever, food allergies, and drug allergies), or other allergic disorders. Appropriate facilities (trained personnel and therapies) should be available for coping with the emergency treatment of severe reactions, and patients should be closely observed for signs and symptoms of a hypersensitivity reaction during and for up to 2 hours after gadoteridol administration. If a hypersensitivity reaction occurs, immediately discontinue gadoteridol treatment and institute appropriate measures. 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., prednisone or equivalent given 13, 7, and 1 hour prior to the exam; adult dose 50 mg PO) and antihistamines (e.g., diphenhydramine given 1 hour prior to the exam; adult dose 50 mg IV/IM/PO) along with the use of a different or low-osmolar contrast agent is recommended.
Gadoteridol 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 gadoteridol have not been established with intrathecal use.
Use gadoteridol 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 rabbits given gadoteridol 6 mmol/kg/day (19 times the maximum recommended human dose) for 13 days during gestation, increased incidences of spontaneous abortion and early delivery were observed. The incidence of postimplantation loss was doubled in rats after the administration of gadoteridol 10 mmol/kg/day (16-times the maximum recommended human dose) for 12 days during gestation. 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; GBCA 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 state 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 gadoteridol in human milk, the effects on the breastfed infant, or the effects on milk production. However, published data on other GBCAs indicate that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk and there is limited GBCA gastrointestinal absorption in the breastfed infant. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for gadoteridol and any potential adverse effects on the breastfed infant from gadoteridol or from the underlying maternal condition. Previous American Academy of Pediatrics (AAP) recommendations considered GBCAs as 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 with magnetic resonance imaging (MRI) to enhance visualization of lesions with abnormal vascularity within the central nervous system (CNS) or extracranial/extraspinal tissues of the head and neck:
-for visualization of lesions within the CNS:
Intravenous dosage:
Adults: 0.2 mL/kg (0.1 mmol/kg) IV as a single dose. In patients with normal renal function suspected of having poorly enhanced lesions on negative or equivocal scans, additional 0.4 mL/kg (0.2 mmol/kg) IV may be given up to 30 minutes after the first dose.
Infans, Children, and Adolescents: 0.2 mL/kg (0.1 mmol/kg) IV as a single dose. The safety and efficacy of higher doses and sequential and/or repeat procedures have not been studied.
Term Neonates: 0.2 mL/kg (0.1 mmol/kg) IV as a single dose. The safety and efficacy of higher doses and sequential and/or repeat procedures have not been studied.
-for visualization of lesions in extracranial/extraspinal tissues of the head and neck:
Intravenous dosage:
Adults: 0.2 mL/kg (0.1 mmol/kg) IV as a single dose.
Maximum Dosage Limits:
-Adults
0.4 mL/kg (0.2 mmol/kg) IV single dose.
-Geriatric
0.4 mL/kg (0.2 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
0.2 mL/kg (0.1 mmol/kg) IV single dose.
Patients with Hepatic Impairment Dosing
Dose adjustments in hepatic impairment have not been studied; use caution.
Patients with Renal Impairment Dosing
Dose adjustments in renal impairment have not been studied; use caution. Do not exceed the recommended dose and allow sufficient time for elimination prior to any repeat administration. Avoid use in patients with chronic, severe renal disease (GFR less than 30 mL/minute/1.73 m2) and in patients with acute kidney injury unless the diagnostic information is essential and not available with noncontrast imaging or other modalities; these patients are at highest risk for nephrogenic systemic fibrosis.
Intermittent hemodialysis
Gadoteridol 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 Gadoteridol products.
Gadoteridol, 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). Gadoteridol 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.
Gadoteridol is administered intravenously. Gadoteridol is rapidly distributed in the extracellular space. The mean plasma distribution volume for non-renally impaired adults is 0.205 +/- 0.025 L/kg. The volume of distribution is approximately equivalent to extracellular water at 204 +/- 58 mL/kg. It is unknown if protein binding of gadoteridol occurs in vivo. Following GBCA administration, gadolinium is present for months or years in brain, bone, skin, and other organs. It is unknown if the drug undergoes metabolism or is degraded in vivo. Gadoteridol is eliminated unchanged via the kidneys. Renal and plasma clearance rates (1.41 +/- 0.33 mL/minute/kg and 1.5 +/- 0.35 mL/minute/kg, respectively) are essentially identical, indicating the drug is renally cleared with no alteration in elimination kinetics on passage through the kidneys. Within 24 hours, 94.4 +/- 4.8% of the dose is excreted in the urine. The mean elimination half-life is approximately 1.57 +/- 0.08 hours.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
After intravenous administration in normal subjects, the pharmacokinetics of gadoteridol conform to a 2-compartment open model.
-Special Populations
Renal Impairment
In patients with impaired renal function, the serum half-life of gadoteridol is prolonged. After intravenous injection of 0.1 mmol/kg, the elimination half-life of gadoteridol was 10.65 +/- 0.06 hours in mild to moderately impaired patients (creatinine clearance 30 to 60 mL/minute) and 9.10 +/- 0.26 hours in severely impaired patients not on dialysis (creatinine clearance 10 to 30 mL/minute). The mean serum clearance of gadoteridol in patients with normal renal function was 116.14 +/- 26.77 mL/minute, compared to 37.2 +/- 16.4 mL/minute in patients with mild to moderate renal impairment and 16.0 +/- 3.0 mL/minute in patients with severe renal impairment. In patients with moderately and severely impaired renal function, approximately 97% and 76% of the administered dose was recovered in the urine within 7 days and 14 days, respectively. Gadoteridol is removed from the body by hemodialysis; 72% of gadoteridol is removed from the body after the first dialysis, 91% after the second dialysis, and 98% after the third dialysis session.
Pediatrics
A population pharmacokinetic analysis incorporated data from 28 pediatric subjects between 5 years and 15 years of age. The pediatric subjects received a single intravenous dose of 0.1 mmol/kg of gadoteridol. From population PK model, the mean Cmax was 0.66 +/- 0.21 mmol/L in pediatric subjects 2 years to 6 years of age, 0.58 +/- 0.06 mmol/L in pediatric subjects 6 years to 12 years of age, and 0.68 +/- 0.12 mmol/L in adolescent subjects older than 12 years. The mean AUC was 0.74 +/- 0.20 mmol/L x hour in pediatric subjects 2 years to 6 years of age, 0.74 +/- 0.09 mmol/L x hour in pediatric subjects 6 years to 12 years of age, and 0.98 +/- 0.09 mmol/L x hour in adolescent subjects older than 12 years of age. The mean distribution half-life was 0.14 +/- 0.04 hours in pediatric subjects 2 years to 6 years of age, 0.18 +/- 0.07 hours in pediatric subjects 6 years to 12 years of age, and 0.20 +/- 0.07 hours in adolescent subjects older than 12 years of age. The mean elimination half-life was 1.32 +/- 0.006 hours in pediatric subjects 2 years to 6 years, 1.32 +/- 0.07 hours in pediatric subjects 6 years to 12 years of age, and 1.61 +/- 0.19 hours in adolescent subjects older than 12 years of age. There was no significant gender-related difference in the pharmacokinetic parameters in the pediatric patients. Over 80% of the dose was recovered in the urine for pediatric subjects after 10 hours. Pharmacokinetic simulations indicate similar half-life, AUC, and Cmax values for gadoteridol in pediatric subjects less than 2 years of age when compared to those reported for adults; no age-based dose adjustment is necessary for this pediatric population.
Geriatric
The clearance of gadoteridol was slightly lower in 7 elderly subjects receiving 0.1 (n = 3) and 0.3 mmol/kg (n = 4) doses as compared to non-elderly subjects.
Gender Differences
Gender has no clinically relevant effect on the pharmacokinetics of gadoteridol.