Data from FDA - Curated by Marshall Pearce - Last updated 22 December 2016

Indication(s)

1 INDICATIONS AND USAGE Optimark is a gadolinium-based paramagnetic contrast agent for diagnostic magnetic resonance imaging (MRI) indicated for intravenous use: In patients with abnormal blood-brain barrier or abnormal vascularity of the brain, spine and associated tissues (1) To provide contrast enhancement and facilitate visualization of lesions with abnormal vascularity in the liver in patients who are highly suspect for liver structural abnormalities on computed tomography (1) 1.1 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. 1.2 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.

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Advisory information

contraindications
4 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. Chronic, severe kidney disease (glomerular filtration rate, GFR <30 mL/min/1.73m2), acute kidney injury (4) Prior hypersensitivity reactions to gadolinium, versetamide or any of the inert ingredients (4)
Adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the prescribing information: Nephrogenic Systemic Fibrosis [see Contraindications (4), Boxed Warning and Warnings and Precautions (5.1)] Hypersensitivity reactions [see Contraindications (4) and Warnings and Precautions (5.3)] Most common adverse reactions (incidence >2%) are: headache, vasodilatation, taste perversion, dizziness, nausea and paresthesia. (6) To report SUSPECTED ADVERSE REACTIONS contact Liebel- Flarsheim Company LLC at 1-855-266-5037 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 Whole: 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 6.2 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

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Bolus peripheral intravenous injection at a dose of 0.2 mL/kg (0.1 mmol/kg) (2) Follow injection with a 5 mL normal saline flush. (2) Complete imaging procedure within 1 hour of injection. (2) 2.1 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 2.2 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. 2.3 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 (12.2)].
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 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. 8.3 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 (12.3)]. 8.4 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. 8.5 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 (5.1)]. 8.6 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 (12.3)]. 8.7 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 t1/2 (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)
Pregnancy and lactation
8.3 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 (12.3)].

Interactions

7 DRUG INTERACTIONS Drug interactions with other contrast agents and other drugs have not been studied.

More information

Category Value
Authorisation number NDA020937
Agency product number RLM74T3Z9D
Orphan designation No
Product NDC 0019-1177
Date Last Revised 12-09-2016
Type HUMAN PRESCRIPTION DRUG
Storage and handling 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).
Marketing authorisation holder Liebel-Flarsheim Company LLC
Warnings WARNING: NEPHROGENIC SYSTEMIC FIBROSIS Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Do not administer Optimark to patients with: chronic, severe kidney disease (GFR <30 mL/min/1.73m2), or acute kidney injury [see Contraindications (4)]. Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g. age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. Do not exceed the recommended Optimark dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration [see Warnings and Precautions (5.1)]. WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF) See full prescribing information for complete boxed warning. Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs (5.1). Do not administer Optimark to patients with: chronic, severe kidney disease (GFR <30 mL/min/1.73m2), or acute kidney injury (4). Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g. age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing (5.1).