Optimark

MRI Agents

 
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 several hours after administration.

Visually inspect for particulate matter and discoloration prior to administration. Solution is clear, colorless to slightly yellow. Do not use if discolored or if particulate matter is present.
Do not mix with other drugs. Do not administer other medications in the same intravenous line.

For single dose vials: Using aseptic technique, draw solution into a sterile syringe. Administer immediately after opening.
For pharmacy bulk packages: In a suitable environment, such as a laminar flow hood, penetrate the container closure of the pharmacy bulk package with an appropriate transfer device. Once the container closure is punctured, it should not be removed from the aseptic work area. Using aseptic technique, transfer the contents of the pharmacy bulk package into syringes without delay. A maximum duration of 24 hours from initial closure entry is allowed to complete the transfer process; discard any unused solution 24 hours after initial puncture.
Ensure catheter and venous patency prior to the injection. Extravasation may result in tissue irritation.
Administer as a single, intravenous bolus injection at a rate of 1—2 mL/second.
To ensure administration of the total dose, follow the bolus injection with 5 mL of 0.9% Sodium Chloride Injection flush.
Preform the imaging within 1 hour of the bolus injection.
Usual safety rules customary for magnetic resonance procedures must be observed.
The product contains no antimicrobial preservatives. Discard any unused product.

oliguria / Early / 0-1.0
erythema multiforme / Delayed / 0-1.0
arrhythmia exacerbation / Early / 0-1.0
nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
laryngeal edema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
seizures / Delayed / Incidence not known

peripheral vasodilation / Rapid / 6.4-6.4
phlebitis / Rapid / 0-1.0
dysphagia / Delayed / 0-1.0
confusion / Early / 0-1.0
hypertonia / Delayed / 0-1.0
constipation / Delayed / 0-1.0
sinus tachycardia / Rapid / 0-1.0
hypertension / Early / 0-1.0
edema / Delayed / 0-1.0
chest pain (unspecified) / Early / 0-1.0
palpitations / Early / 0-1.0
hypotension / Rapid / 0-1.0
dysphonia / Delayed / 0-1.0
dyspnea / Early / 0-1.0
hypercalcemia / Delayed / 0-1.0

headache / Early / 9.4-9.4
dysgeusia / Early / 6.2-6.2
dizziness / Early / 3.7-3.7
nausea / Early / 3.2-3.2
paresthesias / Delayed / 2.2-2.2
diarrhea / Early / 1.9-1.9
abdominal pain / Early / 1.8-1.8
injection site reaction / Rapid / 1.5-1.5
rhinitis / Early / 1.5-1.5
asthenia / Delayed / 1.5-1.5
dyspepsia / Early / 1.2-1.2
back pain / Delayed / 1.2-1.2
fever / Early / 0-1.0
urticaria / Rapid / 0-1.0
hyperhidrosis / Delayed / 0-1.0
pruritus / Rapid / 0-1.0
rash / Early / 0-1.0
anxiety / Delayed / 0-1.0
vertigo / Early / 0-1.0
diplopia / Early / 0-1.0
tremor / Early / 0-1.0
agitation / Early / 0-1.0
drowsiness / Early / 0-1.0
tinnitus / Delayed / 0-1.0
parosmia / Delayed / 0-1.0
hypersalivation / Early / 0-1.0
anorexia / Delayed / 0-1.0
polydipsia / Early / 0-1.0
eructation / Early / 0-1.0
xerostomia / Early / 0-1.0
vomiting / Early / 0-1.0
syncope / Early / 0-1.0
pallor / Early / 0-1.0
pharyngitis / Delayed / 0-1.0
cough / Delayed / 0-1.0
sinusitis / Delayed / 0-1.0
muscle cramps / Delayed / 0-1.0
pelvic pain / Delayed / 0-1.0
arthralgia / Delayed / 0-1.0
myalgia / Early / 0-1.0
malaise / Early / 0-1.0

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 gadoversetamide. 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] < 30 mL/min/1.73m2) 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. Gadoversetamide 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 and/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]), 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—778—7898.

Optimark

Rx

Gadolinium-based paramagnetic contrast agent
For use during magnetic resonance imaging of the central nervous system or liver
May be associated with nephrogenic systemic fibrosis

0.2 mL/kg (0.1 mmol/kg) administered as a single IV bolus injection at a rate of 1 to 2 mL/second. Complete imaging within 1 hour of the injection. The manufacturer provides weight-based dose volumes as follow: 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.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

No dosage adjustments are recommended. 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 < 30 mL/min/1.73m2) and in patients with acute kidney injury unless the diagnostic information is essential and not available with non-contrast imaging or other modalities; these patients are at highest risk for nephrogenic systemic fibrosis.
Intermittent hemodialysis
Gadoversetamide 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.

Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.

Optimark Intravenous Inj Sol: 1mL, 330.9mg

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

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

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Gadoversetamide, a paramagnetic agent, is used to enhance lesion detection and characterization during magnetic resonance imaging (MRI). In magnetic resonance, the visualization of normal and 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). Gadoversetamide 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 the extravascular spaces of lesions.

Gadoversetamide is administered intravenously. Following administration, the drug conforms to a two-compartment open-model. At steady state, the volume of distribution is roughly equivalent to that of extracellular body water at 0.162 +/- 0.025 L/kg. No protein binding has been observed in vitro, and gadoversetamide does not appear to cross the intact blood-brain barrier; however, disruptions in the barrier or abnormal vascularity allows for drug accumulation in the extravascular spaces of lesions. Gadoversetamide is not metabolized. Elimination occurs primarily through the kidneys via glomerular filtration. The mean elimination half-life is 103.6 +/- 19.5 minutes; at 24 hours post-dose, approximately 95% of the administered dose is excreted in the urine. Following repeated administration, gadolinium deposits may remain for months to years in bone, liver, skin, brain, and other organs. Deposition may be greater following administration of gadoversetamide and other linear gadolinium-based contrast agents (GBCAs) than with macrocyclic GBCAs. The clinical significance of gadolinium retention in the body is unknown.
Affected cytochrome P450 isoenzymes: none

Within the studied dosage range (0.1 to 0.7 mmol/kg), the pharmacokinetic parameters of gadoversetamide appears to be linear.

Use gadoversetamide 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, gadoversetamide was associated with adverse fetal effects at doses equivalent to the recommended human dose (RHD) based on body surface area. In rats, reduced neonatal weights were observed with maternally administered doses of 1-time the RHD for 5 weeks, and fetal toxicities (i.e., abnormal liver lobation, delayed sternebrae ossification, delayed behavioral development) were observed with maternal doses of 10-times the RHD. The drug was also associated with forelimb flexures and cardiovascular changes (i.e., malformed thoracic arteries, septal defect, abnormal ventricle) in fetuses of female rabbits administered 1- to 4-times the RHD. 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 GBCA 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.

Radiolabeled gadoversetamide was excreted in the milk of lactating rats after a single intravenous dose of 0.1 mmol/kg. FDA-approved labeling recommends that women discontinue breast-feeding and discard breast milk for up to 72 hours after gadoversetamide administration. However, 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.