Author: Endrikat J, Schwenke C, Prince MR (biho/ktg)

Source: Clin Radiol. 2015;70(7):743-51.

Last Updated: June 11, 2015

Gadobutrol shows good safety profile in elderly patients

A meta-analysis of internationally relevant clinical studies, pharmacovigilance and post-marketing data confirms a good safety profile of the macrocyclic contrast agent gadobutrol in MRI examinations. Patients older than 65 years did not show a higher incidence of adverse drug reactions compared to younger patients.

Gadobutrol (Gadavist®, Bayer Healthcare) plays a central role in dynamic MR imaging. Available data confirm the excellent safety profile of the contrast agent. However, the worldwide ever-increasing number of elderly patients deserves distinct attention. Patients over 65 years tend to take several medications and may be more susceptible to adverse drug events than younger patients.
Jan Endrikat, Saarland University Hospital and Bayer HealthCare Pharmaceuticals, Carsten Schwenke, Statistical Consulting, Germany, and Martin R. Prince, Weill Cornell Medical College, NY, USA, analyzed three separate databases for the safety of gadobutrol in patients over 65 years and patients between 18 and 64 years.


The authors compared adverse drug reactions (ADR) across a number of clinical studies, postmarketing study data and pharmacovigilance reports in the two different age groups. They also calculated the odds ratio (OR) to depict the risk that an ADR will occur in the respective study population.
Three databases were part of the meta-analysis:

1. Clinical study data
38 prospective, international, multi-center phase II, III and IV trials between 1992 and 2013, sponsored by Bayer Healthcare.

2. Post-marketing surveillance (PMS) data
ADR from six prospective, international, multi-center PMS studies were recorded.

3. Pharmacovigilance reports
Bayer’s pharmocovigilance safety database was screened for all available ADRs between 1999 and February 26th, 2013.


1. Clinical study data from 5608 patients were available, 1697 patients were older than 65, 3911 were between 18 and 64 years old. The reported number of ADRs was lower in the elderly patients (2.7% vs. 3.8%), and the odds ratio (OR)=0.7 revealed a lower risk factor for ADRs in this group.

2. PMS studies included data of 14,064 patients, with 4400 elderly patients and 9664 between 18 and 64. Reported ADRs accounted for 0.30% in the elderly population and 0.53% in the younger group. An OR of 0.56 abnormally favored the elderly. Subanalysis revealed that former allergic diseases seem to be a cofactor; an adjusted OR value was 0.71.

3. Pharmacovigilance reports included ADRs of 2031 patients in the analysis, with 330 >65 years and 1701

Serious ADRs could only be statistically measured in the PMS reports. However, their incidence was below 0.005% in both age groups.

Dosing of gadobutrol was similar for both age groups. Median dose was 0.10 mmol/kg body weight (b.w.), but doses ranged from 0.01 to 0.51 mmol/kg b.w..

The observed ADRs were similar in all databases. With one exception, occurrence rates were very low and did not serve for statistical comparison. Only nausea showed a slightly higher rate in the younger patient group, though not statistically significant (0.2% vs. 0.16%).


An analysis of clinical and pharmacovigilance data of gadobutrol confirmed the good safety of the contrast agent for MRI. Elderly patients even showed a slightly lower risk of reacting to the contrast agent than younger people.

Original Article: Gadobutrol for contrast-enhanced magnetic resonance imaging in elderly patients: review of the safety profile from clinical trial, post-marketing surveillance, and pharmacovigilance data.