MRI contrast reaction leads to one agent per patient policy

May 4, 1994

Total number of adverse reactions remains lowAn adverse reaction to MRI contrast agent ProHance has prompteda change in the University of Nebraska Medical Center's policyon MRI contrast administration. Candidates for repeat contrast-enhancedMRI

Total number of adverse reactions remains low

An adverse reaction to MRI contrast agent ProHance has prompteda change in the University of Nebraska Medical Center's policyon MRI contrast administration. Candidates for repeat contrast-enhancedMRI studies at the university now receive only gadolinium chelatessimilar in structure to the agent injected in the initial examination.

The policy change was instituted following an anaphylactoidreaction to Squibb Diagnostics' ProHance (gadoteridol) in a patientwho had previously received Berlex's Magnevist (gadopentate dimeglumine)with no adverse reaction.

"If we have a patient who has had Magnevist, we won'tinject ProHance," said Dr. Robert J. Witte, an assistantprofessor of neuroradiology and nuclear medicine at the university."We will inject that person again with Magnevist."

Similarly, patients who have previously received ProHance withoutincident will be injected with it again on subsequent examinations,Witte said.

Though more data will be needed to adequately explain the phenomenon,Witte hypothesized that structural differences between the twoagents stimulated an immunogenic reaction. Antibodies formed followinginjection of Magnevist, which is linear, may have reacted negativelyto subsequent injection of ProHance, which is macrocyclic.

"There have not been enough of these reactions to reallyget a handle on what's going on, but it certainly raises the possibilityof sensitization," said Witte, who described the incidentin the March issue of the American Journal of Neuroradiology.

The third commercially available MRI contrast agent, Omniscan(gadodiamide), raises more questions regarding compatibility withother agents. Because Omniscan and Magnevist are both linear instructure, Witte hypothesized that administration of one wouldnot preclude subsequent injection of the other. Similarly, hesaid he would hesitate to use Omniscan in patients previouslygiven ProHance.

Further investigation to explain the event is under way atSquibb Diagnostics. Data from unrelated in-house research, however,suggest that the University of Nebraska experience may be an isolatedcase.

Squibb researchers tested the benefits of triple-dose ProHancein about 1000 patients whose MRI findings were equivocal followinga single dose of Magnevist, said Dr. Adeoye Olukotun, Squibb'svice president of medical affairs.

Though the sequence of contrast agent administrations was similarto that in the University of Nebraska case, Olukotun said no seriousreactions were noted in the triple-dose study, which has not yetbeen published.

"That a patient would react to one agent and not anotherin the same class is most unlikely," Olukotun said.

There were questions raised about the safety of ProHance followingthe product's late 1992 entry into what had been a single-agentmarket (SCAN 4/21/93). Several serious cases of adverse reactionsto ProHance were reported shortly after its launch. The numberof reported adverse reactions following ProHance injection hasdropped off in the last year, however.

About 600 adverse reactions have been reported to Squibb outof several hundred thousand doses administered, according to Dr.Mark J. Carvlin, Squibb's senior market manager for magnetic resonanceproducts. This figure compares favorably with a 3% incidence ratefound in postmarketing clinical trials, Carvlin said.

"All of the gadolinium agents have really demonstratedan enviable record of safety compared with other types of agents,"Carvlin said.