Primovist^® in the Elderly

Gadoxetate disodium shows a good safety profile in patients older than 65 years.

The hepatospecific contrast agent gadoxetate disodium (Primovist^®) has an excellent safety profile. However, the worldwide ever-increasing number of elderly patients deserves distinct attention. Patients over 65 years tend to take several medications and are more fragile than younger patients, which may make them more susceptible to adverse drug events.

Jan Endrikat, Saarland University Hospital and Bayer AG, Germany, and colleagues analyzed two separate datasets for the safety of Primovist^® in patients over 65 years and patients between 18 and 64 years.

Method

The authors compared adverse drug reactions (ADR) across a number of clinical studies phase II-III and from pharmacovigilance reports in the two different age groups.

Two databases were part of the meta-analysis:

1. Clinical study data: Four prospective phase II (n=580) and eight prospective phase III (n=1409) trials between 1994 and 2015, conducted in Europe, the USA, China and Japan, sponsored by Bayer AG.

2. Pharmacovigilance reports: Bayer’s pharmacovigilance safety database was screened for all available ADRs between 25/3/2004 and 31/12/2015. The total application rate was 3.5 million.

Results

1. Clinical study data: Of the 1989 patients, 675 patients were older than 65, and 1314 were between 18 and 64 years old. The reported number of ADRs was almost similar in the elderly patients (n=23, 3.4%) and the younger patient group (n=58, 4.4%).

The majority of observed ADRs was similar in both groups and comprised gastrointestinal disorders, general disorders and administration site conditions as well as nervous system disorders. Only nausea showed a slightly higher rate in the younger patient group, though not statistically significant (0.9% vs. 0.3%). No serious ADRs were reported.

2. Pharmacovigilance reports included 1.7 million elderly patients, while younger adults accounted for 1.8 million. ADRs of 793 patients were reported, with 354 >65 years and 439 between 18-64 years. Accordingly, the total percentage of ADRs was significantly lower in the elderly (0.021%) compared to the young (0.024%).

Serious ADRs occurred in 166 elderly patients (0.010%) and 139 adults (0.008%).
33 deaths occurred among the elderly, as assumed to be due to the higher cancer morbidity. Only for two patients, a relationship to gadoxetate disodium administration could not be excluded.

The observed ADRs were similar in both groups and comprised hypersensitivity/immune disorders, gastrointestinal disorders and respiratory disorders as most frequent ADRs.

Conclusion

An analysis of clinical and pharmacovigilance data of Primovist^® in the elderly confirmed the good safety profile of the contrast agent for MRI. Pharmacovigilance data even showed a slightly lower risk of reacting to the contrast agent for elderly patients than for patients between 18 and 64 years. The fact that this is not confirmed in the clinical trial results could be due to the relatively low number of clinical trial patients, but also to the underreporting of delayed and mild UAEs in the real world.

Original Article:Safety profile of gadoxetate disodium in elderly patients (≥65 years).