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)