gadoterate meglumine (Dotarem)

Dosing and uses of Dotarem (gadoterate meglumine)

• Adult
• Pediatric

 

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