gadoterate meglumine (Rx)

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%)

Asthenia

Paraesthesia (<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, hypotension

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

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

Gadolinium retention

• Gadolinium is retained for months or years in several organs
• Highest concentrations (nanomoles per gram of tissue) have been identified in the bone, followed by other organs (eg, brain, skin, kidney, liver, and spleen)
• Duration of retention also varies by tissue and is longest in bone
• Patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions are at higher risk of gadolinium retention

• Brain deposits

  • FDA investigated the risk of brain deposits following repeated use of GBCAs for MRI in 2015
  • 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
  • As of 2017, the FDA review had not identified adverse health effects from gadolinium retained in the brain after the use of GBCAs MRI; all GBCAs may be associated with some gadolinium retention in the brain and other body tissues
  • 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

GBCAs cross the placenta and result in fetal exposure and gadolinium retention

Human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive

Estimated background risk of major birth defects and miscarriage for the indicated population is unknown

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes

Lactation

Estimated infant exposure is 0.001%-0.04% of the maternal dose

Unknown whether the effects of the drug on the breastfed infant or the effects of the drug on milk production

Developmental and health benefits of breastfeeding should be considered together with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant or from underlying maternal condition

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.

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)

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