gadoterate meglumine (Dotarem)
Classes: Gadolinium-Containing Contrast Agents; Diagnostic Imaging Agents
Dosing and uses of Dotarem (gadoterate meglumine)
Adult dosage forms and strengths
IV solution
- 0.5 mmol/mL (contains 376.9 mg/mL gadoterate meglumine)
MRI Contrast
Gadolinium-based contrast agent for use in MRI of the brain, spine, and associated tissues to detect and visualize areas with disruption of the blood brain barrier and/or abnormal vascularity
0.2 mL/kg (0.1 mmol/kg) IV bolus infused at rate of 2 mL/second
Pediatric dosage forms and strengths
IV solution
- 0.5 mmol/mL (contains 376.9 mg/mL gadoterate meglumine)
MRI Contrast
Gadolinium-based contrast agent for use in MRI of the brain, spine, and associated tissues to detect and visualize areas with disruption of the blood brain barrier and/or abnormal vascularity
<2 years: Safety and efficacy not established
≥2 years: 0.2 mL/kg (0.1 mmol/kg) IV bolus infused at rate of 1-2 mL/second
Dotarem (gadoterate meglumine) adverse (side) effects
1-10%
Headache (1.5% pediatric)
<1%
Nausea (0.6%)
Headache (0.5% adult)
Injection site pain (0.4%)
Injection site coldness (0.2%)
Burning sensation (0.2%)
Feeling cold (<0.2%)
Rash (<0.2%)
Somnolence (<0.2%)
Fatigue (<0.2%)
Dizziness (<0.2%)
Vomiting (<0.2%)
Pruritus (<0.2%)
Paresthesia (<0.2%)
Dysgeusia (<0.2%)
Pain in extremity (<0.2%)
Anxiety (<0.2%)
Hypertension (<0.2%)
Palpitations (<0.2%)
Oropharyngeal discomfort (<0.2%)
Serum creatinine increased (<0.2%)
Injection site reactions, including site inflammation, extravasation, pruritus, and warmth (<0.2%)
Postmarketing Reports
Cardiac disorders: Bradycardia, tachycardia, arrhythmia
Nervous system disorders: Coma, convulsion, syncope, presyncope, parosmia, tremor
Musculoskeletal and connective tissue disorders: Muscle contracture, muscle weakness
Gastrointestinal disorders: Diarrhea, salivary hypersecretion
General disorders and administration site conditions: Malaise, fever
Skin and subcutaneous tissue disorders: Nephrogenic systemic fibrosis
Vascular disorders: Superficial phlebitis
Warnings
Black box warnings
Gadolinium-based contrast agents (GBCAs) increase risk of nephrogenic systemic fibrosis (NSF) among patients with impaired elimination
Avoid use in these patients unless the diagnostic information is essential and not available with noncontrasted MRI or other modalities
NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs
Risk of NSF highest with chronic, severe kidney disease (ie, GFR <30 mL/min/1.73 m2) or acute kidney injury
Screen for acute kidney injury and other conditions that may reduce renal function; for patients at risk for chronically reduced renal function (eg, age >60 years, hypertension, diabetes), estimate GFR through laboratory testing
For patients at highest risk for NSF, do not exceed recommended dose and allow sufficient period of time for elimination of the drug before readministration
Contraindications
Hypersensitivity
Cautions
Gadolinium-based contrast agents increase the risk for NSF among patient with impaired elimination (see Black box warnings)
Anaphylactic and anaphylactoid reactions reported and may involve cardiovascular, respiratory, and/or cutaneous manifestations, including reports of patients experiencing cardiovascular collapse and death
Acute kidney injury requiring dialysis has occurred in patients with chronically reduced renal function
Brain deposits
- 7/28/2015: FDA is investigating the risk of brain deposits following repeated use of gadolinium-based contrast agents (GBCAs) for MRI
- Recent publications in the medical literature have reported that deposits of GBCAs remain in the brains of some patients who undergo ≥4 contrast MRI scans, long after the last administration
- It is unknown whether these gadolinium deposits are harmful or can lead to adverse health effects
- Early data in rat studies show that linear GBCAs are more prone to dissociation into free gadolinium and demonstrate greater brain deposition than macrocyclic GBCAs, which are less prone to dissociation
Pregnancy and lactation
Pregnancy category: C
Lactation: 0.01-0.04% of maternal gadolinium dose is excreted in human breast milk; absorption of gadolinium via GI tract is poor
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Dotarem (gadoterate meglumine)
Mechanism of action
In MRI, visualization of normal and pathological tissue depends in part on variations in the radiofrequency signal intensity that occurs with differing proton density and longitudinal/transverse relaxation times; gadolinium contrast agents lead to distinct shortening of proton relaxation times in plasma and may improve tissue visualization
Gadoterate does not cross the intact blood-brain barrier (BBB) and, therefore, does not enhance normal brain or lesions that have a normal blood-brain barrier (eg, cysts, mature postoperative scars); however, disruption of the BBB or abnormal vascularity allows distribution of gadoterate in brain lesions such as neoplasms, abscesses, and infarcts
Distribution
Protein bound: None
Vd: 179 mL/kg (females); 211 mL/kg (males)
Metabolism
Not known to be metabolized
Elimination
Half-life: 1.4 hr (females); 2 hr (males); 5.1 hr (moderate renal impairment; 13.9 hr (severe renal impairment)
Renal clearance: 1.27 mL/min/kg (females); 1.74 mL/min/kg (males)
Excretion: urine (72.9-85.5% females; 85.4-92% males)
Administration
IV Incompatibilities
Do not mix with other drugs or parenteral nutrition
IV Preparation
Visually inspect vials/syringes for particulate matter
Do not use if solution contains particulates or container appears damaged
Solution should appear clear, colorless to yellow
When injected using plastic disposable syringes, the contrast medium should be drawn into the syringe and used immediately
Discard unused portion
IV Administration
Ensure catheter and venous patency before injection to avoid tissue extravasation
Adults: Infuse IV bolus at rate of 2 mL/second
Pediatrics (≥2 years): Infuse IV bolus at rate of 1-2 mL/second
To ensure complete injection, follow with saline flush
Contrast MRI can begin immediately following injection
Administer only where trained personnel and therapies are promptly available for hypersensitivity reactions, including resuscitation
Monitoring
- Before administration, assess all patients for history of reaction to contrast media, bronchial asthma, and/or allergic disorders – these patients have an increased risk of hypersensitivity to GBCAs
- During and following administration, observe for signs/symptoms of hypersensitivity
Storage
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
Prefilled syringes must not be frozen; frozen syringes should be discarded
Should solidification occur in the vial because of exposure to the cold, bring to room temperature before use
If vial allowed to stand at room temperature for a minimum of 90 minutes, gadoterate meglumine should return to a clear, colorless to yellow solution; if solids persist, discard viaL