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Prohance
Classes
MRI Agents
Administration
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.
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.
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.
Adverse Reactions
AV block / Early / 0-0.4
seizures / Delayed / 0-0.4
bradycardia / Rapid / Incidence not known
coma / Early / Incidence not known
respiratory arrest / Rapid / Incidence not known
pulmonary edema / Early / Incidence not known
cyanosis / Early / Incidence not known
laryngospasm / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
cardiac arrest / Early / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
chest pain (unspecified) / Early / 0-0.4
palpitations / Early / 0-0.4
angina / Early / 0-0.4
hypotension / Rapid / 0-0.4
sinus tachycardia / Rapid / 0-0.4
peripheral vasodilation / Rapid / 0-0.4
formication / Early / 0-0.4
migraine / Early / 0-0.4
dyspnea / Early / 0-0.4
hypoglycemia / Early / 0-0.4
hyperchloremia / Delayed / 0-0.4
elevated hepatic enzymes / Delayed / 0-0.4
hypertension / Early / Incidence not known
erythema / Early / Incidence not known
edema / Delayed / Incidence not known
ocular inflammation / Early / Incidence not known
nausea / Early / 1.4-1.4
dysgeusia / Early / 0.9-0.9
headache / Early / 0.7-0.7
vomiting / Early / 0-0.4
diarrhea / Early / 0-0.4
xerostomia / Early / 0-0.4
abdominal pain / Early / 0-0.4
anorexia / Delayed / 0-0.4
paresthesias / Delayed / 0-0.4
syncope / Early / 0-0.4
dizziness / Early / 0.4-0.4
lethargy / Early / 0-0.4
hypoesthesia / Delayed / 0-0.4
anxiety / Delayed / 0-0.4
maculopapular rash / Early / 0-0.4
pruritus / Rapid / 0-0.4
rash / Early / 0-0.4
throat irritation / Early / 0-0.4
rhinitis / Early / 0-0.4
otalgia / Early / 0-0.4
tinnitus / Delayed / 0-0.4
fever / Early / 0-0.4
flushing / Rapid / 0-0.4
injection site reaction / Rapid / 0-0.4
back pain / Delayed / 0-0.4
asthenia / Delayed / 0-0.4
lacrimation / Early / 0-0.4
ocular pruritus / Rapid / 0-0.4
gingivitis / Delayed / Incidence not known
tremor / Early / Incidence not known
diaphoresis / Early / Incidence not known
sneezing / Early / Incidence not known
cough / Delayed / Incidence not known
hyperhidrosis / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
fatigue / Early / Incidence not known
Boxed Warning
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.
Common Brand Names
Prohance
Dea Class
Rx
Description
Nonionic, paramagnetic contrast agent
Used for magnetic resonance imaging (MRI) to visualize CNS lesions with abnormal vascularity in adults and pediatric patients, including term neonates, and to visualize extracranial or extraspinal lesions in the head and neck in adults
May be associated with nephrogenic systemic fibrosis
Dosage And Indications
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.
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.
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.
0.2 mL/kg (0.1 mmol/kg) IV as a single dose.
Dosing Considerations
Dose adjustments in hepatic impairment have not been studied; use caution.
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.
Drug Interactions
There are no drug interactions associated with Gadoteridol products.
How Supplied
Prohance Intravenous Inj Sol: 1mL, 279.3mg
Maximum Dosage
0.4 mL/kg (0.2 mmol/kg) IV single dose.
0.4 mL/kg (0.2 mmol/kg) IV single dose.
0.2 mL/kg (0.1 mmol/kg) IV single dose.
0.2 mL/kg (0.1 mmol/kg) IV single dose.
0.2 mL/kg (0.1 mmol/kg) IV single dose.
0.2 mL/kg (0.1 mmol/kg) IV single dose.
Mechanism Of Action
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.
Pharmacokinetics
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
After intravenous administration in normal subjects, the pharmacokinetics of gadoteridol conform to a 2-compartment open model.
Pregnancy And Lactation
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.