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gadobutrol (Gadavist)

 

Classes: Gadolinium-Containing Contrast Agents; Contrast Media, Nonionic/ High Osmolality

Dosing and uses of Gadavist (gadobutrol)

 

Adult dosage forms and strengths

Injectable solution

  • 1mmol/mL (ie, 604.72mg/mL)

 

MRI Contrast

0.1 mmol/kg (0.1 mL/kg) IV bolus

CNS and BBB

  • Indicated to detect and visualize areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity of the central nervous system
  • Infuse at rate 2 mL/second
  • Flush IV cannula with 0.9% NaCl after injection

Breast

  • Indicated for use with MRI to assess the presence and extent of malignant breast disease
  • Flush IV cannula with 0.9% NaCl after injection

Magnetic resonance angiography

  • Indicated for use in magnetic resonance angiography (MRA) to evaluate known or suspected supra-aortic or renal artery disease
  • Infuse at rate 1.5 mL/second
  • Flush IV cannula with 30 mL of 0.9% NaCl after injection

 

Renal Impairment

Prior to administration, screen all patients for renal dysfunction by obtaining a history and/or laboratory tests (see Black box warnings)

No dosage adjustment is recommended for patients with renal impairment

Removed by hemodialysis

 

Pediatric dosage forms and strengths

Injectable solution

  • 1mmol/mL (ie, 604.72mg/mL)

 

MRI Contrast

0.1 mmol/kg (0.1 mL/kg) IV bolus

Flush IV cannula with 0.9% NaCl after injection

CNS and BBB

  • Indicated to detect and visualize areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity of the central nervous system in adult and pediatric patients (including term neonates)
  • Infuse at rate 2 mL/second

Magnetic resonance angiography

  • Indicated for use in magnetic resonance angiography (MRA) in adult and pediatric patients (including term neonates) to evaluate known or suspected supra-aortic or renal artery disease
  • Infuse at rate 1.5 mL/second

 

Renal Impairment

Prior to administration, screen all patients for renal dysfunction by obtaining a history and/or laboratory tests (see Black box warnings)

No dosage adjustment is recommended for patients with renal impairment

Removed by hemodialysis

 

Geriatric dosage forms and strengths

In clinical studies, 1377 patients were 65 years of age or older, while 104 patients were 80 years of age or older

No overall differences in safety or effectiveness were observed between elderly and younger individuals, and other reported clinical experience has not identified differences in responses between the elderly and younger patients

In general, use in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy

 

Gadavist (gadobutrol) adverse (side) effects

1-10%

Headache (1.5%)

Nausea (1.2%)

 

<1%

Injection site reactions

Dysgeusia

Feeling hot

Dizziness

Vomiting

Rash

Pruritus

Erythema

Dyspnea

Paresthesia

 

Postmarketing Reports

Cardiac arrest

Nephrogenic systemic fibrosis

Hypersensitivity/anaphylactoid reactions

 

Warnings

Black box warnings

Nephrogenic systemic fibrosis (NSF)

  • Gadolinium-based contrast agents (GBCAs) increase the risk for 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
  • For patients at highest NSF risk, do not exceed the recommended dose and allow a sufficient period of time for elimination of the drug from the body prior to any readministration
  • Risk appears highest among patients with:
    • Chronic, severe kidney disease (GFR <30 mL/min/1.73 m²), or
    • Acute kidney injury
  • Monitoring
    • Screen for acute kidney injury and other conditions that may reduce renal function
    • Screen for risk of chronically reduced renal function (eg, aged >60 yr, hypertension, diabetes)
    • Estimate glomerular filtration rate (GFR) through laboratory testing

 

Contraindications

Hypersensitivity; most hypersensitivity reactions to occur within 30 minutes after administration; delayed reactions can occur up to several days after administration

 

Cautions

History of allergy, renal insufficiency, or drug reaction

Asthma, allergic disorder, hypersensitivity

Risk of nephrogenic systemic fibrosis (NSF) with severe renal impairment

Screen patients for kidney disease before use and monitor renal function afterward; nephrogenic systemic fibrosis (NSF) associated with use of gadolinium contrast media in patients with kidney disease; do not exceed recommended dose

In patients with chronic renal impairment, acute kidney injury sometimes requiring dialysis reported with the use of some gadolinium-based contrast agents; do not exceed recommended dose, the risk of acute kidney injury may increase with higher than recommended doses

Extravasation precautions; ensure catheter and venous patency before injection; avoid IM injection

Caution in patients with seizure disorders

In sickle cell anemia, sickling leading to vaso-occlusion reported

Local tissue damage/reactions may occur with extravasation

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; unknown if gadobutrol crosses the human placenta, other gadolinium-based contrast agents (GBCAs) do cross the placenta in humans and result in fetal exposure; limited published human data on exposure to other GBCAs during pregnancy did not show adverse effects in exposed neonates

Based on animal data, may cause fetal harm

Lactation: unknown whether distributed in breast milk, caution advised; limited case reports on use of GBCAs in nursing mothers indicate that 0.01-0.04% of the maternal gadolinium dose is excreted in human breast milk

 

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 Gadavist (gadobutrol)

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; gadobutrol leads to distinct shortening of proton relaxation times in plasma and may improve tissue visualization

 

Pharmacokinetics

Half-Life: 1.5-2 hr

Distribution: Rapidly distributed in extracellular space

Peak Plasma Concentration: 0.59 mmol/L (2 minutes after injection); 0.3 mmol/L (60 minutes after injection)  

Metabolism: None

Excretion: Urine (<90% within 12 hr); feces (minimal)

Clearance: 1.1-1.7 mL/(min•kg)