gadoversetamide (Rx)

1-10%

Headache (9.4%)

Vasodilation (6.4%)

Dizziness (3.7%)

Nausea (3.2%)

Paresthesia (2.2%)

Diarrhea (1.9%)

Abdominal pain (1.8%)

Rhinitis (2%)

Injection site reaction (2%)

Back pain (1%)

Dyspepsia (1%)

<1%

Seizures

Amblyopia

Anorexia

Cough

Diplopia

Dry skin

Dystonia

Flatulence

Hyponatremia

Neck pain

Pallor

Parosmia

Rash

Seizure

Postmarketing Reports

Seizures

Nephrogenic systemic fibrosis

Hypersensitivity reactions including bronchospasm and laryngeal/pharyngeal edema

Contraindications

Severe hypersensitivity reactions including anaphylaxis reported

Acute kidney disease or chronic, severe kidney disease (ie, GFR<30 mL/min/1.73m²); use associated with increased risk for nephrogenic systemic fibrosis (NSF)

Cautions

Screen all patients for renal dysfunction

Acute renal failure has occurred in patients with pre-existing renal insufficiency; use the lowest necessary dose and evaluate renal function

Nephrogenic systemic fibrosis (NSF) reported in patients with impaired elimination; higher than recommended dosing or repeat dosing appears to increase the risk

Anaphylactoid and other serious hypersensitivity reactions including fatal reactions reported, particularly in patients with history of allergy or drug reactions; monitor patients closely for need of emergency cardiorespiratory support

Thrombotic syndromes, anemia, hepatic/renal impairment, hemoglobinopathies (sickle cell anemia)

Risk of hypotension

Caution with hepatic impairment

History of grand mal seizure

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

Nonionic gadolinium contrast agent; paramagnetic ion that develops a magnetic moment when placed in magnetic field that can disrupt water protons in the vicinity leading to an increase in signal intensity (brightness) of tissues

Pharmacokinetics

Half-Life: 103.6 minutes (elimination)

Vd: 162 mL/kg

Excretion: Urine (96%)

Hemodialysis: 98% removed by hemodialysis over 3 sessions within 120 hr