Drugs Details

Drugs Info of OptiMARK
Drugs Details
  • Drugs Type  : FDA
  • Date : 26th Feb 2015 05:30 am
  • Brand Name : OptiMARK
  • Generic Name : gadoversetamide) Injection
Descriptions

OptiMARK (gadoversetamide) injection is a nonionic gadolinium chelate of diethylenetriamine pentaacetic acid bismethoxyethylamide (gadoversetamide), for intravenous injection.

OptiMARK injection is provided as a sterile, preservative-free, nonpyrogenic, clear, and colorless to pale yellow, aqueous solution of gadoversetamide. Each mL of OptiMARK contains 330.9 mg of gadoversetamide (0.5 millimole), 28.4 mg of calcium versetamide sodium (0.05 millimole), 0.7 mg calcium chloride dihydrate (0.005 millimole), and water for injection. Sodium hydroxide and/or hydrochloric acid may have been added for pH adjustment.

Gadoversetamide is designated chemically as [8, 11-bis(carboxymethyl)-14-[2-[(2-methoxyethyl)amino]-2-oxoethyl ]-6-oxo-2-oxa-5, 8,1 1, 14-tetraazahexadec an-16-oato(3-)] gadolinium with a formula weight of 661.77 g/mol and empirical formula of C20H34N5O10Gd. The structural formula of gadoversetamide in aqueous solution is:

 

OPTIMARK (gadoversetamide) Structural Formula Illustration

OptiMARK has a pH of 5.5 to 7.5. Pertinent physiochemical data are provided below (Table 4).

Table 4 : Physiochemical Properties of OptiMARK

Osmolality (mOsmol/kg water) @ 37°C 1110
Viscosity (cP) @ 20°C 3.1
@ 37°C 2.0
Density (g/mL) @ 25°C 1.160

 

OptiMARK has an osmolality of approximately 3.9 times that of plasma (285 mOsm/kg water) and is hypertonic under conditions of use.

What are the possible side effects of gadoversetamide (OptiMARK)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • urinating less than usual or not at all;
  • drowsiness, confusion, mood changes, increased thirst, loss of appetite;
  • swelling, weight gain, feeling short of breath; or
  • fast, uneven heart rate.

Less serious side effects may include:

  • headache, dizziness;
  • nausea, diarrhea;
  • flushing...

Read All Potential Side Effects and See Pictures of OptiMARK »


This monograph has been modified to include the generic and brand name in many instances.

Indications

MRI Of Central Nervous System (CNS)

OptiMARK is indicated for use with magnetic resonance imaging (MRI) in patients with abnormal blood-brain barrier or abnormal vascularity of the brain, spine and associated tissues.

MRI of Liver

OptiMARK is indicated for use with MRI to provide contrast enhancement and facilitate visualization of lesions with abnormal vascularity in the liver of patients who are highly suspect for liver structural abnormalities on computed tomography.

Dosage Administration

Dosing Guidelines

  • Administer OptiMARK as a bolus peripheral intravenous injection at a dose of 0.2 mL/kg (0.1 mmol/kg) and at a rate of 1 to 2 mL/sec delivered by manual or by power injection (see Table 1).
  • Use sterile technique to withdraw and administer OptiMARK.
  • Follow injection with a 5 mL normal saline flush to ensure complete administration of the contrast.
  • Discard unused portions of the drug.

Table 1 : Dosage Chart for OptiMARK Injection

Body Weight Kilograms (kg) 0.1 mmol/kg Volume (mL)
40 8
50 10
60 12
70 14
80 16
90 18
100 20
110 22
120 24
130 26
140 28
150 30

Drug Handling

  • Visually inspect OptiMARK for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored or particulate matter is present.
  • Do not mix OptiMARK with other medications or parenteral nutrition and do not administer OptiMARK in the same intravenous line as other medications because of the potential for chemical incompatibility.

Imaging

  • Complete the imaging procedure within 1 hour of the injection of OptiMARK.
  • Paramagnetic contrast agents may impair the visualization of lesions seen on non-contrast MRI. Interpret OptiMARK MR images with companion non-contrast MR images [see CLINICAL PHARMACOLOGY].
 

How Supplied

Dosage Forms And Strengths

OptiMARK is supplied as a clear, colorless to slightly yellow solution for injection containing 330.9 mg gadoversetamide per mL (equivalent to 0.5 mmol/mL).

Storage And Handling

OptiMARK is a clear, colorless to slightly yellow solution containing 330.9 mg/mL (equivalent to 0.5 mmol/mL) of gadoversetamide for injection. OptiMARK is supplied in 10 mL vials containing 5 mL or 10 mL of solution and is also provided in 20 mL vials containing 15 mL or 20 mL of solution. Each single dose vial is rubber stoppered with an aluminum seal and the contents are sterile. OptiMARK is supplied in 10 mL, 15 mL, 20 mL or 30 mL syringes containing 10 mL, 15 mL, 20 mL or 30 mL of solution respectively. Each syringe is sealed with rubber closures and the contents are sterile. Vials and syringes are contained in shipping cartons with the following configurations:

5 mL in glass vials in cartons of 10 vials
(NDC Code 0019-1177-02)

10 mL in glass vials in cartons of 10 vials
(NDC Code 0019-1177-04)

15 mL in glass vials in cartons of 10 vials
(NDC Code 0019-1177-06)

20 mL in glass vials in cartons of 10 vials
(NDC Code 0019-1177-08)

10 mL in plastic syringes in cartons of 10 syringes
(NDC Code 0019-1177-11)

15 mL in plastic syringes in cartons of 10 syringes
(NDC Code 0019-1177-16)

20 mL in plastic syringes in cartons of 10 syringes
(NDC Code 0019-1177-21)

30 mL in plastic syringes in cartons of 10 syringes
(NDC Code 0019-1177-31)

Storage

OptiMARK should be stored at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature] and protected from light and freezing. OptiMARK may be stored at 37°C for up to one month in a contrast media warmer utilizing circulating warm air. For periods longer than one month, store at 20°C to 25°C (68°F to 77°F).

Manufactured and Distributed by: Mallinckrodt Inc. St. Louis, MO 63042 U.S.A. Issued 11/14


This monograph has been modified to include the generic and brand name in many instances.

Side Effects

The following adverse reactions are discussed in greater detail in other sections of the prescribing information:

  • Nephrogenic systemic fibrosis [see CONTRAINDICATIONS, BOXED WARNING and WARNINGS AND PRECAUTIONS]
  • Hypersensitivity reactions [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The adverse reactions described in this section were observed in a total of 1,309 subjects (24 healthy volunteers and 1,285 patients in clinical trials). Patients ranged in age from 12 to 85 years (mean age of 50 years) and 680 subjects (52%) were men. The ethnic distribution was 84% White, 9% Black, 3% Asian, and 4% other.

Overall, 460 subjects (35%) reported at least one adverse reaction. Most adverse reactions were mild or moderate in severity. The most commonly noted adverse reactions were: injection associated discomfort (26%), headache (9.4%), vasodilatation (6.4%), taste perversion (6.2%), dizziness (3.7%), nausea (3.2%), and paresthesia (2.2%). Table 2 lists adverse reactions reported in 1% or greater of patients.

Table 2 : Adverse Reactions Experienced by ≥ 1% of Patients

Body System or Event OptiMARK
(N = 1309)
Injection associated discomfort 26.4%
Headache 9.4%
Vasodilatation 6.4%
Taste Perversion 6.2%
Dizziness 3.7%
Nausea 3.2%
Paresthesia 2.2%
Diarrhea 1.9%
Pain Abdomen 1.8%
Asthenia 1.5%
Injection Site Reaction 1.5%
Rhinitis 1.5%
Dyspepsia 1.2%
Pain Back 1.2%
Pain 1.0%

The following adverse reactions occurred in less than 1% of the patients:

Body as a W hole: allergic reaction, facial edema, fever, malaise, neck rigidity, neck pain, pelvic pain, increased sweating

Cardiovascular: arrhythmia, chest pain, hypertension, hypotension, pallor, palpitation, syncope, tachycardia, vasospasm

Digestive: anorexia, constipation, dry mouth, dysphagia, eructation, increased salivation, thirst, vomiting

Metabolic and Nutritional: increased creatinine, edema, hypercalcemia

Musculoskeletal: arthralgia, leg cramps, myalgia, spasm

Nervous System: agitation, anxiety, confusion, diplopia, dystonia, hypertonia, hypesthesia, somnolence, tremor, vertigo

Respiratory System: cough, dyspnea, laryngismus, pharyngitis, sinusitis, voice alteration

Skin and Appendages: erythema multiforme, pruritus, rash, thrombophlebitis, urticaria

Special Senses: parosmia, tinnitus

Urogenital: oliguria

Post-marketing Experience

The following adverse reactions have been identified during post-approval use of OptiMARK. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to OptiMARK.

  • Nephrogenic Systemic Fibrosis (NSF)
  • Hypersensitivity reactions including bronchospasm and laryngeal/pharyngeal edema
  • Seizures

Read the OptiMARK (gadoversetamide injection) Side Effects Center for a complete guide to possible side effects

Interactions

Drug interactions with other contrast agents and other drugs have not been studied.
This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Nephrogenic Systemic Fibrosis (NSF)

Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs among these patients unless the diagnostic information is essential and not available with non-contrast enhanced MRI or other modalities. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease (GFR < 30 mL/min/1.73m²) as well as patients with acute kidney injury. Do not administer OptiMARK to these patients. The risk appears lower for patients with chronic, moderate kidney disease (GFR 30 to 59 mL/min/1.73m²) and little, if any, for patients with chronic, mild kidney disease (GFR 60 to 89 mL/min/1.73m²). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Report any diagnosis of NSF following OptiMARK administration to Mallinckrodt Inc. (1-800-778-7898) or FDA (1-800-FDA-1088 or www.fda.gov/medwatch).

Screen patients for acute kidney injury and other conditions that may reduce renal function. Features of acute kidney injury consist of rapid (over hours to days) and usually reversible decrease in kidney function, commonly in the setting of surgery, severe infection, injury, or drug-induced kidney toxicity. Serum creatinine levels and estimated GFR may not reliably assess renal function in the setting of acute kidney injury. For patients at risk for chronic kidney disease (e.g., age > 60 years, diabetes mellitus or chronic hypertension), estimate the GFR through laboratory testing.

Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a GBCA and the degree of renal impairment at the time of exposure. Record the specific GBCA and the dose administered to a patient. When administering OptiMARK, do not exceed the recommended dose and allow a sufficient period of time for elimination of the drug prior to any re-administration [see DOSAGE AND ADMINISTRATION].

Acute Kidney Injury (AKI)

In patients with chronically reduced renal function, acute kidney injury requiring dialysis has occurred with the use of GBCAs. The risk of acute kidney injury may increase with increasing dose of the contrast agent; administer the lowest dose necessary for adequate imaging.

Hypersensitivity Reactions

Severe hypersensitivity reactions including anaphylaxis have been observed with administration of gadolinium products including OptiMARK. Before administering OptiMARK ensure the availability of resuscitation equipment and personnel trained in resuscitation techniques. Patients with a history of allergy, drug reactions or other hypersensitivity-like disorders may be at greater risk and should be closely observed during the procedure and for several hours after drug administration. If a reaction occurs, stop OptiMARK and immediately begin appropriate therapy including resuscitation.

Interference With Laboratory Testing

Interference by OptiMARK in the measurements of serum iron, copper and zinc has been observed. OptiMARK causes interference in the measurement of serum calcium using the ortho-cresophthalin complexone (OCP) colorimetric method. In the presence of OptiMARK, OCP produces an erroneous, low value for serum calcium. The magnitude of this artifact is proportional to the concentration of OptiMARK in the blood, and accurate values can be obtained approximately 90 minutes following injection. In patients with renal insufficiency, clearance of OptiMARK is slowed and the interference with calcium determination by OCP is prolonged. Neither the arsenazo III dye system nor the inductively coupled plasma mass spectroscopy methods for calcium assay are affected by OptiMARK.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of gadoversetamide. The results of the following genotoxicity assays were negative: Salmonella/E. Coli reverse mutation (Ames) assay, mouse lymphoma mutagenesis assay, and the in vivo mammalian micronucleus assay. The in vitro CHO chromosome aberration assay without metabolic activation was positive.

Gadoversetamide administered to rats in a fertility study was shown to have irreversible reduction and degeneration of spermatocytes in testes and epididymides, and impaired male fertility following intravenous doses of 2.0 mmol/kg/day (4 times the human dose based on body surface area) for 7 weeks. These effects were not observed at dose of 0.5 mmol/kg/day (1 times the human dose based on body surface area).

In a separate 28-day repeat dose study in rats, gadoversetamide was shown to have irreversible reduction of male reproductive organ weights, degeneration of the germinal epithelium of the testes, presence of germ cells in the epididymides, and reduced sperm count following daily intravenous doses of 3.0 mmol/kg/day (6 times the human dose based on body surface area). These effects were not observed at 0.6 mmol/kg/day (1 times the human dose based on surface area). These effects were not observed in similar studies conducted in dogs.

In a single dose study in rats, gadoversetamide did not produce adverse effects on the male reproductive system 24 hours and 14 days after intravenous administration of 0.5 to 15 mmol/kg (1 to 25 times the human dose based on body surface area).

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. OptiMARK should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Gadoversetamide administered to rats reduced neonatal weights from birth through weaning at maternal doses of 0.5 mmol/kg/day (1 times the human dose based on body surface area) for 5 weeks (including gestation) and paternal doses of 0.5 mmol/kg/day for 12 weeks. This effect was not observed at 0.1 mmol/kg (0.2 times the human dose based on body surface area). Maternal toxicity was not observed at any dose.

Gadoversetamide injection caused a reduced mean fetal weight, abnormal liver lobation, delayed ossification of sternebrae, and delayed behavioral development (startle reflex and air righting reflex) in fetuses from female rats dosed with 4.9 mmol/kg/day (10 times the human dose based on body surface area) on days 7 through 17 of gestation. These effects were not observed at 0.7 mmol/kg/day (1 times the human dose based on body surface area). Maternal toxicity was observed at 4.9 mmol/kg/day.

Gadoversetamide injection caused forelimb flexures and cardiovascular changes in fetuses from female rabbits dosed with 0.4 and 1.6 mmol/kg/day (respectively, 1 and 4 times the human dose based on body surface area) on gestation days 6 through 18. The cardiovascular changes were malformed thoracic arteries, a septal defect, and abnormal ventricle. These effects were not observed at 0.1 mmol/kg/day (0.3 times the human dose based on body surface area). Maternal toxicity was not observed at any dose.

Nursing Mothers

Radiolabeled gadoversetamide (153Gd) was excreted in the milk of lactating rats receiving a single intravenous dose of 0.1 mmol/kg. Women should discontinue nursing and discard breast milk up to 72 hours after OptiMARK administration [see CLINICAL PHARMACOLOGY].

Pediatric Use

The safety and effectiveness of OptiMARK in pediatric patients have not been established. Pediatric patients may be particularly vulnerable to adverse GBCA reactions due to renal immaturity or unrecognized renal insufficiency.

Geriatric Use

Since gadoversetamide is cleared from the body by glomerular filtration, the risk of adverse reactions may be greater in patients with impaired renal function (GFR ≥ 30 and < 90 mL/min/1.73m²). Due to the risk for NSF, estimate the GFR through laboratory testing for patients > 60 years of age [see WARNINGS AND PRECAUTIONS].

Renal Impairment

A single intravenous dose of 0.1 mmol/kg of OptiMARK was administered to 28 patients (17 men and 11 women) with impaired renal function (mean serum creatinine of 2.4 mg/dL). Sixteen patients had concurrent central nervous system or liver pathology. Renal impairment was shown to delay the elimination of gadoversetamide (see Table 3). The mean cumulative urinary excretion of gadoversetamide at 72 hours was approximately 93.5% for renally impaired patients and 95.8% for subjects with normal renal function. Dose adjustments in renal impairment have not been studied. OptiMARK has been shown to be removed from the body by hemodialysis [see CLINICAL PHARMACOLOGY].

Hepatic Impairment

A single intravenous dose of 0.1 mmol/kg of OptiMARK was administered to 4 patients (2 men and 2 women) with impaired hepatic function. Hepatically impaired patients with normal renal function had plasma kinetics similar to normal subjects (see Table 3).

Table 3 : Elimination Profiles of Normal, Renally Impaired and Hepatically Impaired Men and Women (mean ± SD)

Population Elimination t½ (hours)
Men
(N = 52)
Women
(N = 48)
Healthy Volunteers 1.73 ± 0.31 (N = 8) 1.73 ± 0.40 (N = 4)
Normal Patients 1.90 ± 0.50 (N = 25) 1.94 ± 0.57 (N = 31)
Renally Impaired 8.74 ± 5.14 (N = 17) 6.91 ± 2.46 (N = 11)
Hepatically Impaired 2.09 ± 0.03 (N = 2) 2.35 ± 1.09 (N = 2)


This monograph has been modified to include the generic and brand name in many instances.

OverDose

Clinical consequences of overdosage with OptiMARK have not been reported. Treatment of overdose is directed toward supporting vital functions and prompt institution of symptomatic therapy. OptiMARK has been shown to be dialyzable [see CLINICAL PHARMACOLOGY].

ContrainDications

OptiMARK is contraindicated in patients with:

  • chronic, severe kidney disease (glomerular filtration rate, GFR < 30 mL/min/1.73m²)
  • acute kidney injury
  • known hypersensitivity reactions to gadolinium, versetamide or any of the inert ingredients.


This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism Of Action

Gadoversetamide is a paramagnetic agent that develops a magnetic moment when placed in a magnetic field. The relatively large magnetic moment can enhance the relaxation rates of water protons in its vicinity, leading to an increase in signal intensity (brightness) of tissues.

Pharmacodynamics

In MRI, visualization of normal and pathological brain, spinal and hepatic tissue depends in part on variations in the radiofrequency signal intensity that occurs with: 1) changes in proton density; 2) alterations of the spin-lattice or longitudinal relaxation time (T1); and 3) variation of the spin-spin or transverse relaxation time (T2). When placed in a magnetic field, gadoversetamide decreases T1 and T2 relaxation times in tissues where it accumulates. At the recommended dose, the effect is primarily on T1 relaxation time, and produces an increase in signal intensity (brightness).

Pharmacokinetics

The pharmacokinetics of intravenously administered gadoversetamide in normal subjects conforms to a two-compartment open-model with mean distribution and elimination half-lives (reported as mean ± SD) of about 13.3 ± 6.8 and 103.6 ± 19.5 minutes.

Distribution

Gadoversetamide does not undergo protein binding in vitro. In pregnant and lactating rats which received 153Gd-labeled gadoversetamide, radioactivity was detected in the placenta, fetus, and maternal milk. The volume of distribution at steady state of gadoversetamide in normal subjects is 162 ± 25 mL/kg, roughly equivalent to that of extracellular water.

Gadoversetamide does not cross the intact blood-brain barrier, and, therefore, does not accumulate in the normal brain or in lesions that may have a normal blood-brain barrier. However, disruption of the blood-brain barrier or abnormal vascularity allows accumulation of gadoversetamide in the extravascular spaces of lesions. The pharmacokinetic parameters of gadoversetamide in various lesions are not known.

Metabolism

Gadoversetamide is not metabolized.

Elimination Gadoversetamide (0.1 mmol/kg) is eliminated primarily in the urine with 95.5 ± 17.4% (mean ± SD) of the administered dose eliminated by 24 hours. Animal data demonstrated that insignificant levels of 153Gd-labeled gadoversetamide are eliminated via the feces. In experimentally induced anephria in the rat, hepatobiliary excretion did not significantly compensate for the absence of urinary elimination. The renal and plasma clearance rates of gadoversetamide in normal subjects are similar (69 ± 15.4 and 72 ± 16.3 mL/hr/kg, respectively) indicating that the drug is cleared through the kidneys via glomerular filtration. Within the studied dose range (0.1 to 0.7 mmol/kg), the kinetics of gadoversetamide appear to be linear. Gadoversetamide is removed from the body by hemodialysis. Approximately 98% of the administered dose (0.1 mmol/kg) was cleared from the circulation over the three dialysis sessions that occurred 2 hours, 48 hours, and 120 hours after injection. After each of three dialysis sessions, respectively, 70%, 93%, and 98% of the administered dose was cleared from the plasma. The mean dialysis clearance of gadoversetamide was 93.2 ± 17.1 mL/min, or 48% of the creatinine clearance (194 ± 18.6 mL/min), using a high flux PMMA membrane.

Clinical Studies

OptiMARK was evaluated in 4 controlled clinical trials (two liver and two CNS studies). Out of 461 patients who received OptiMARK, there were 252 men and 209 women with a mean age of 49 years (range 12 to 82 years); 83% were Caucasian, 9% Black, 3% Asian, and 5% other racial or ethnic groups. The trials were designed to compare combined non-contrast and OptiMARK 0.1 mmol/kg contrast MR images to non-contrast MR images, based on pre-specified imaging characteristics (endpoints).

In the two CNS studies, MR images were analyzed from 262 patients who were highly suspect for CNS disorders and received OptiMARK. Pre-contrast and pre-plus-post-contrast (combined) images were independently evaluated by three blinded readers (each reader examined approximately 1/3 of the images). The images were evaluated by the blinded readers for the following endpoints using a scale from 1 to 10: the level of conspicuity of all lesions, the ability to delineate lesion borders from parenchyma/structures, the number of lesions, and the confidence in the number of lesions. As shown in Table 5, the first row of each endpoint group represents the difference in the mean score of the combined pre-and post-contrast MRI from the mean score of the pre-contrast MRI alone. Also, the table shows the number of patients whose paired MRI images were better, worse or the same as the pre-contrast MRI. Results from the contrast image alone were not evaluated. In Table 5 for these endpoints, when read in combination with the non-contrast images, OptiMARK provided a statistically significant improvement over baseline. In addition to these measures, the images were evaluated for the blinded reader's confidence in the diagnosis. Although improvement over baseline was noted, the diagnosis was not rigorously confirmed.

Table 5 :Results of MRI Central Nervous System Studies with 0.1 mmol/kg OptiMARK

Endpoints Study A Study B
OptiMARK
N = 132†
OptiMARK
N = 129
Conspicuity: Difference of Meansa 0.39* 0.66*
  Worse 24 (18%) 24 (19%)
  Same 69 (52%) 52 (40%)
  Better 39 (30%) 53 (41%)
Border Delineation: Difference of Means 0.70* 0.86*
  Worse 23 (17%) 25 (19%)
  Same 55 (42%) 51 (40%)
  Better 54 (41%) 53 (41%)
Number of Lesions: Difference of Means    
  Pre 1.8 3.0
  Pairb 2.0◊ 3.3*
  Worse 9 (7%) 16 (12%)
  Same 101 (77%) 86 (67%)
  Better 22 (16%) 27 (21%)
Confidence in Number of Lesions: Difference of Means 0.11* 0.56*
  Worse 19 (14%) 18 (14%)
  Same 86 (65%) 60 (47%)
  Better 27 (20%) 51 (40%)
a Difference of means = (Side-by-side pre-and post-OptiMARK mean) -(pre-mean)
b Pair = Side-by-side pre-and post-OptiMARK
* Statistically significant for both the median (Wilcoxon test) and mean (paired t test)
◊ Statistically significant for median (Wilcoxon test)
† 1 patient was excluded from this analysis because a non-contrast image was not obtained for that patient

In the two liver studies, MR images were analyzed from 199 patients with a suspected liver abnormality on a contrast CT who received OptiMARK. Patients had both pre-contrast and post-contrast MRI scans covering the entire liver. In each study, the images were read by 3 blinded readers (each reader examined approximately 1/3 of the images). Using a scale of 1 to 10, the images were evaluated by the blinded readers for the level of conspicuity of all lesions, the ability to delineate lesion borders from parenchyma/structures, the number of lesions and confidence in the number of lesions. The results are shown in Table 6. The first row of each endpoint group represents the difference in the mean score of the combined pre-and post-contrast MRI from the mean score of the pre-contrast MRI alone. Also, the table shows the number of patients whose paired MRI images were better, worse or the same as the pre-contrast MRI. Results from the contrast image alone were not evaluated. As shown in Table 6 for these endpoints, when read in combination with the non-contrast image, OptiMARK provided a statistically significant improvement over non-contrast images. In addition to these measures, the images were evaluated for the blinded reader's confidence in the diagnosis. Although improvement over baseline was noted, the trial was not designed to rigorously confirm the diagnosis.

Table 6 : Results of MRI Liver Studies with 0.1 mmol/kg OptiMARK

Endpoints Study C Study D
OptiMARK
N = 99
OptiMARK
N = 100
Conspicuity:    
Difference of Meansa 0.77 0.75
  Worse 21 (21%) 14 (14%)
  Same 37 (37%) 50 (50%)
  Better 41 (41%) 36 (36%)
Border Delineation:    
Difference of Means 0.77 0.69
  Worse 21 (21%) 15 (15%)
  Same 38 (38%) 45 (45%)
  Better 40 (40%) 40 (40%)
Number of Lesions: Difference of Means    
  Pre 2.4 3.5
  Pairb 3.0 3.8t
  Worse 13 (13%) 16 (16%)
  Same 50 (51%) 58 (58%)
  Better 36 (36%) 26 (26%)
Confidence in Number of Lesions: Difference    
  of Means 1.6 1.0
  Worse 39 (39%) 38 (38%)
  Same 2 (2%) 8 (8%)
  Better 58 (59%) 54 (54%)
a Difference of means = (Side-by-side pre-and post-OptiMARK mean) -(pre-mean)
b Pair = Side-by-side pre-and post-OptiMARK
* Statistically significant for both the median (Wilcoxon test) and mean (paired t test)
† Borderline statistical significance in paired t test

A subsequent study of 140 normal volunteers evaluated the safety of OptiMARK 0.1 mmol/kg delivered by power injector. Imaging results were not studied. The normal volunteers were randomized to receive OptiMARK injected manually, or OptiMARK or saline injected at 3 different power injector rates. At 2 mL/sec, the adverse event rates were comparable in the OptiMARK and saline controls when delivered manually and by power injector. In these small sample sizes, there was a trend towards increasing adverse events with increasing rates of power injection. Patients with abnormal vascularity were not evaluated. The safety and efficacy of power injector rates higher than 2 mL/sec has not been established.


This monograph has been modified to include the generic and brand name in many instances.

Patient Information

Nephrogenic Systemic Fibrosis

Instruct patients to inform their physician if they:

  • have a history of kidney disease
  • have recently received a GBCA

GBCAs increase the risk for NSF in patients with impaired elimination of the drugs. To counsel patients at risk for NSF:

  • describe the clinical manifestations of NSF
  • describe procedures to screen for the detection of renal impairment

Instruct the patients to contact their physician if they develop signs or symptoms of NSF following OptiMARK administration, such as burning, itching, swelling, scaling, hardening and tightening of the skin; red or dark patches on the skin; stiffness in joints with trouble moving, bending or straightening the arms, hands, legs or feet; pain in the hip bones or ribs; or muscle weakness.

Other

Instruct patients to inform their physician if they:

  • are pregnant or breast feeding
  • have a history of renal disease or heart disease, seizure, asthma or allergic respiratory diseases


This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

No Information Available!

Consumer Overview Side Effect

No Information Available!

Consumer Overview Missed Dose

No Information Available!

Patient Detailed Side Effect

Brand Names: OptiMARK

Generic Name: gadoversetamide (Pronunciation: GAD oh ver SET a mide)

  • What is gadoversetamide (OptiMARK)?
  • What are the possible side effects of gadoversetamide (OptiMARK)?
  • What is the most important information I should know about gadoversetamide (OptiMARK)?
  • What should I discuss with my healthcare provider before taking gadoversetamide (OptiMARK)?
  • How should I take gadoversetamide (OptiMARK)?
  • What happens if I miss a dose (OptiMARK)?
  • What happens if I overdose (OptiMARK)?
  • What should I avoid while taking gadoversetamide (OptiMARK)?
  • What other drugs will affect gadoversetamide (OptiMARK)?
  • Where can I get more information?

What is gadoversetamide (OptiMARK)?

Gadoversetamide is a contrast agent. It is used in combination with magnetic resonance imagining (MRI) to allow blood vessels, organs, and other non-bony tissues to be seen more clearly on the MRI.

Gadoversetamide is used to help diagnose certain disorders of the brain and spine (central nervous system), or the liver.

Gadoversetamide may also be used for purposes not listed in this medication guide.

What are the possible side effects of gadoversetamide (OptiMARK)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • urinating less than usual or not at all;
  • drowsiness, confusion, mood changes, increased thirst, loss of appetite;
  • swelling, weight gain, feeling short of breath; or
  • fast, uneven heart rate.

Less serious side effects may include:

  • headache, dizziness;
  • nausea, diarrhea;
  • flushing (warmth, redness, or tingly feeling);
  • unusual or unpleasant taste in your mouth;
  • numbness, burning pain, or tingling in your hands or feet; or
  • cold feeling, warmth, pain, bruising, swelling, or burning where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the OptiMARK (gadoversetamide injection) Side Effects Center for a complete guide to possible side effects

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What is the most important information I should know about gadoversetamide (OptiMARK)?

Gadoversetamide can cause a life-threatening condition in people with advanced kidney disease. The symptoms of this condition include:

  • burning, itching, swelling, scaling, and tightening or hardening of your skin;
  • muscle weakness;
  • joint stiffness in your arms, hands, legs, or feet;
  • deep bone pain in your ribs or your hips;
  • trouble moving; or
  • skin redness or discoloration.

Before receiving this medication, tell your doctor if you have kidney disease or if you are on dialysis. You may not be able to receive gadoversetamide. Also tell your doctor if you have recently received any contrast agents similar to gadoversetamide.

Also tell your doctor if you have diabetes, high blood pressure, liver disease (or liver transplant), anemia or other red blood cell disorder, a heart rhythm disorder, a personal or family history of Long QT Syndrome, asthma or allergies, a history of seizures, if you are over 60 years old, if you have ever had a reaction to a contrast agent, or if you have recently had an injury, surgery, or severe infection.

Your doctor or other healthcare provider may want to watch you for a short time after your test is over. This is to make sure you do not have any unwanted side effects or delayed reactions.

Side Effects Centers
  • OptiMARK

Patient Detailed How Take

What should I discuss with my healthcare provider before taking gadoversetamide (OptiMARK)?

Gadoversetamide can cause a life-threatening condition in people with advanced kidney disease. The symptoms of this condition include:

  • burning, itching, swelling, scaling, and tightening or hardening of your skin;
  • muscle weakness;
  • joint stiffness in your arms, hands, legs, or feet;
  • deep bone pain in your ribs or your hips;
  • trouble moving; or
  • skin redness or discoloration.

Before receiving this medication, tell your doctor if you have kidney disease or if you are on dialysis. You may not be able to receive gadoversetamide. Also tell your doctor if you have recently received any contrast agents similar to gadoversetamide.

To make sure you can safely receive this medication, tell your doctor if you have any of these other conditions:

  • diabetes;
  • high blood pressure;
  • liver disease (or liver transplant);
  • a heart rhythm disorder;
  • anemia or other red blood cell disorder;
  • a history of seizures (convulsions);
  • a personal or family history of Long QT Syndrome;
  • asthma, hay fever, or a history of food or drug allergies;
  • if you are over 60 years old;
  • if you have ever had any type of reaction to a contrast agent; or
  • if you have recently had an injury, surgery, or severe infection.

FDA pregnancy category C. It is not known whether gadoversetamide will harm an unborn baby. Before you receive this medication, tell your doctor if you are pregnant.

It is not known whether gadoversetamide passes into breast milk or if it could harm a nursing baby. Do not breast-feed for at least 72 hours after receiving gadoversetamide. If you use a breast pump during this time, throw out any milk you collect. Do not feed it to your baby.

How should I take gadoversetamide (OptiMARK)?

Gadoversetamide is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting during your MRI.

Your doctor or other healthcare provider may want to watch you for a short time after your test is over. This is to make sure you do not have any unwanted side effects or delayed reactions.

Gadoversetamide can cause you to have unusual results with certain medical tests for 12 to 24 hours after your MRI. Tell any doctor who treats you that you have received gadoversetamide.

Side Effects Centers
  • OptiMARK

Patient Detailed Avoid Taking

What happens if I miss a dose (OptiMARK)?

Since gadoversetamide is used only during your MRI, you will not be on a dosing schedule.

What happens if I overdose (OptiMARK)?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid while taking gadoversetamide (OptiMARK)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

What other drugs will affect gadoversetamide (OptiMARK)?

This medication can harm the kidneys in certain people, and this effect may be increased if you also use other medicines harmful to the kidneys. Before you receive gadoversetamide, tell your doctor about all other medications you use. Many other drugs (including some over-the-counter medicines) can be harmful to the kidneys.

There may be other drugs that can affect gadoversetamide. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about gadoversetamide.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 1.01. Revision date: 8/13/2012.

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