When is Clariscan (gadobutrol) appropriate for MRI, and what are its dosing, contraindications, and safety precautions regarding renal impairment, NSF risk, allergic reactions, breastfeeding, and pediatric use?

Clariscan (Gadobutrol) for MRI: Indications, Dosing, and Safety

Indications

Clariscan (gadobutrol) is FDA-approved for contrast-enhanced MRI of the CNS, breast, cardiac perfusion/late enhancement, and MRA of supra-aortic or renal vessels in adults and pediatric patients including term neonates. 1

• CNS imaging: Detects areas with disrupted blood-brain barrier and/or abnormal vascularity 1
• Breast MRI: Assesses presence and extent of malignant breast disease in adults 1
• Cardiac MRI: Evaluates myocardial perfusion (stress/rest) and late gadolinium enhancement in adults with known or suspected coronary artery disease 1
• MRA: Evaluates supra-aortic or renal artery disease 1

Dosing

The standard dose is 0.1 mmol/kg (0.2 mL/kg) body weight administered as a single intravenous bolus injection. 1

• No dose adjustment is required for pediatric patients, elderly patients, or patients with renal impairment 1
• In real-world practice, the mean dose used is 0.13 mmol/kg, with nervous system imaging typically using ≥0.1 mmol/kg and musculoskeletal/pediatric imaging often using ≤0.1 mmol/kg 2
• Use the lowest diagnostic dose in all patients, particularly those with severe renal impairment 3

Nephrogenic Systemic Fibrosis (NSF) Risk

Gadobutrol is a Group II macrocyclic gadolinium-based contrast agent with an extremely low NSF risk, even in patients with severe renal impairment. 3

Risk Stratification by Renal Function

• eGFR ≥30 mL/min/1.73m²: No NSF risk; proceed without restriction 3, 4
• eGFR <30 mL/min/1.73m²: Risk remains extremely low (upper bound 95% CI: 0.1-0.5%) 3, 4
• Dialysis patients: Upper bound 95% CI of 0.2% (1 in 500 exposed) 3, 4

Evidence Base

• In a systematic review of 4,931 Group II GBCM administrations to patients with stage 4-5 CKD, zero NSF cases occurred 3, 4
• In the GRIP study of 908 patients with moderate to severe renal impairment (including 284 with severe impairment), no NSF cases developed over 2 years of follow-up 5
• Few if any unconfounded NSF cases have been associated with Group II agents like gadobutrol 3

Renal Impairment Management

Do not withhold or delay gadobutrol when clinically indicated, even in patients with severe renal impairment (eGFR <30 mL/min/1.73m²), as the potential harm from delayed diagnosis outweighs the minimal NSF risk. 3, 4

Pre-Screening Recommendations

• Kidney function screening is optional before Group II GBCM administration 3, 4
• Screen all patients for renal dysfunction by obtaining history and/or laboratory tests 1
• When screening is performed in patients with risk factors, measure eGFR using appropriate equations 3

Dialysis Considerations

Do not initiate, accelerate, or alter established dialysis schedules solely because gadobutrol was administered. 3, 4

• For patients already on dialysis, timing gadobutrol before a regularly scheduled session is reasonable but not mandatory 4
• Hemodialysis removes gadobutrol from the body, but prophylactic dialysis has never been proven to reduce NSF risk in randomized trials 4
• In a study of 1,461 Gd-MRI examinations in 1,129 ESRD patients, no NSF cases occurred regardless of dialysis timing or frequency 6
• The risks of additional dialysis sessions outweigh the theoretical benefit 3, 4

Allergic Reactions

Gadobutrol has a very low incidence of allergic reactions, with anaphylaxis occurring in approximately 1:100,000 administrations. 3

• Side effects are generally mild and include headache 3
• In a real-world study of 1,376 patients, only 14 adverse events occurred in 10 subjects, all of mild severity 2
• The rate of serious allergic reactions is less than 0.01% 3

Pregnancy and Breastfeeding

Pregnancy

Gadobutrol is not recommended in pregnancy unless absolutely necessary. 3

• Embryolethality occurred in animal studies at doses 8-12 times the human dose 1
• Gadolinium persists in offspring tissues for months after maternal exposure in animal studies 1

Breastfeeding

Breastfeeding can continue after gadobutrol administration; the amount excreted in breast milk is minimal (0.01-0.04% of maternal dose) and gastrointestinal absorption by the infant is poor. 1

• In lactating rats, only 0.01% of administered radioactivity transferred to pups via milk within 3 hours 1
• Approximately 5% of orally administered dose is absorbed from the infant's gastrointestinal tract 1
• The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need 1

Pediatric Use

Gadobutrol is safe and effective in pediatric patients including term neonates, with no dose adjustment required. 1

Safety Profile

• No case of NSF associated with gadobutrol or any other GBCA has been identified in pediatric patients ages 6 years and younger 1
• The frequency, type, and severity of adverse reactions in pediatric patients are similar to adults 1
• Zero unconfounded NSF cases have been reported in children who received Group II agents 4
• Only 23 NSF cases total have been reported in children ≥6 years (1997-2012), and the majority involved Group I linear agents, not Group II agents like gadobutrol 4

Renal Function Considerations

• Normal eGFR is approximately 30 mL/min/1.73m² at birth and increases to mature levels around 1 year of age 1
• Clearance of gadobutrol is similar in pediatric patients and adults, including those younger than 2 years 1
• Clinical studies have been conducted in neonates with eGFR as low as 31 mL/min/1.73m² (age 2-7 days) without safety concerns 1
• Pediatric kidney function should be assessed with pediatric-specific equations (Bedside Schwartz or CKiD) rather than adult eGFR formulas 4

Screening in Healthy Children

Routine laboratory testing is not required before administering gadobutrol to a healthy pediatric patient without renal risk factors. 7

• Kidney function screening prior to Group II GBCM is optional in pediatric patients 7
• Screening should be considered only when specific renal risk factors are present (known CKD or AKI) 7

Contraindications and Precautions

Absolute Contraindications

• History of severe hypersensitivity reaction to gadobutrol 1

Relative Contraindications and Cautions

• Severe renal impairment requires careful risk-benefit assessment, but gadobutrol should not be withheld if clinically indicated 3, 4
• Acute kidney injury of any severity 3
• Perioperative liver transplantation period 3
• Preterm neonates (safety not established) 1

Key Clinical Pitfalls to Avoid

• Do not reflexively order pre-contrast laboratory work in patients without renal risk factors 7, 4
• Do not use Group I linear gadolinium agents (gadopentetate, gadodiamide, gadoversetamide) in any patient, especially those with renal impairment 3, 8
• Do not initiate or alter dialysis schedules based solely on gadobutrol administration 3, 4
• Do not delay clinically indicated imaging in patients with severe renal impairment due to theoretical NSF concerns with Group II agents 3, 4
• Do not administer repeat doses within 7 days unless clinically urgent; if not urgent, allow >24 hours between doses 3, 4
• Do not use adult eGFR formulas for pediatric patients 4

Documentation Recommendations

• If screening is omitted in a healthy patient, document that no clinical renal risk factors were identified 7
• If screening is performed, record the specific indication (e.g., CKD, AKI) 7
• Ensure the radiology department uses Group II (macrocyclic) agents rather than older Group I (linear) agents 7