The Food and Drug Administration on Sept. 9 required manufacturers of five gadolinium contrast agents to strengthen boxed warnings on their products to minimize the risk of nephrogenic systemic fibrosis in some patients with kidney dysfunction.
Three of the agents – Magnevist (gadopentetate dimeglumine), Omniscan (gadodiamide), and Optimark (gadoversetamide) – are now contraindicated in patients with acute kidney injury (AKI) or chronic, severe kidney disease. Severe kidney disease is marked by a glomerular filtration rate of less than 30 mL/min/1.73m2.
In addition, the revised labeling recommends that healthcare professionals screen all patients being considered for any gadolinium-based contrast agent (GBCA) for AKI or chronic, severe kidney disease. GBCAs also should be avoided in patients suspected or known to have impaired drug elimination unless the diagnostic information obtained is essential and cannot be acquired without the use of a contrast agent.
It’s been known since at least 2006 that patients with AKI or chronic, severe kidney disease are at increased risk of developing nephrogenic systemic fibrosis (NSF). In 2007 the FDA issued its first boxed warning about the risk of NSF associated with GBCA use. That warning stated only that healthcare professionals should be aware of the possibility that some patients might develop NSF. The new warning adds the absolute contraindication for the use of the three agents in patients with AKI and chronic, severe kidney disease.
The earlier boxed warning appears to have had the effect of reducing the incidence of NSF, according to one FDA official. Late last year, at a joint meeting of the FDA’s Cardiovascular and Renal Drugs and Drug Safety and Risk Management advisory committees, Dr. James Kaiser of the agency’s office of surveillance and epidemiology noted that in 2006 there were 194 cases of NSF associated with GBCAs. That number decreased to 128 cases in 2007, 55 in 2008, and 6 in 2009 (through September).
While three GBCAs had been associated with numerous cases of NSF, the other two – MultiHance (gadobenate dimeglumine) and ProHance (gadoteridol) ‑ have not. As of September 2009, a total of 382 reports of NSF had been associated with Omniscan (GE HealthCare), 195 with Magnevist (Bayer HealthCare), 35 with OptiMARK (Covidien), 1 with MultiHance (Bracco Diagnostics), and 0 with ProHance (Bracco Diagnostics). At last year’s meeting a majority of advisory committee members recommended that Omniscan and OptiMARK be contraindicated in patients with serious kidney dysfunction. There was less agreement on whether Magnevist should also be contraindicated.