FDA panelendorses new CNS contrast agent able 2detect blood-brain barrier disruption

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This may assist in knowing whether it is possible to give agents which normally do not cross the blood-brain barrier and to prevent those of them which can be harmful to the brain from being given when they shouldn't be.

There will be a black box warning as they are unsure whether the dosage of the agent (higher than most gadolinium-based contrast agents) will be more likely to cause a potential side effect, one which usually only occurs in those with impaired kidney function. That effect, NSF, causes deposits and tightening of the skin and joints and can be, rarely, fatal.


FDA Panel Endorses CNS Contrast Agent



WASHINGTON -- An FDA panel has voted unanimously to recommend approval of a new contrast agent for MRI scans of the central nervous system.

The Peripheral and Central Nervous System Drugs Advisory Committee voted 16-0 that gadobutrol, made by Bayer, is safe and effective enough to be used with diagnostic magnetic resonance imaging to "detect areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system."

The FDA does not have to follow the advice of its advisory committees, but it usually does. If the agency decides to approve gadobutrol, it would join five other gadolinium-based contrast agents (GBCAs) currently on the market for a CNS indication.

In briefing documents released earlier in the week, FDA reviewers were concerned that gadobutrol's unique strength and dosing might lead to overdose. Gadobutrol is twice as strong as the other drugs, at just half the volume in each injection.

FDA staff reviewers expressed concern that physicians might mistakenly assume all six GBCAs have the same strength and administer gadobutrol at the same dose as they do the other drugs.

Reviewers were also concerned about the potential for a rare but serious disease called nephrogenic systemic fibrosis (NSF) which is seen with high doses of other GBCAs. NSF is primarily a skin disorder, but can affect the joints, eyes, and internal organs, potentially fatally.

The advisory panel didn't seem to share the reviewers' safety concerns and voted 15-1 against placing gadobutrol in a higher-risk category than the other approved agents.

"The safety and efficacy is at least as good as the approved agents, and possibly better," said panelist James Tatum, MD, a radiology and nuclear medicine physician at Hunter Holmes McGuire Medical Center in Richmond, Va.

Gadobutrol was first approved in Europe in 1998. Since then, Bayer has reported three cases of overdose, but none resulted in NSF. Bayer also provided the FDA with 10 postmarketing reports of NSF following gadobutrol administration, but in most of those cases, another GBCA had also been administered, making it difficult to determine whether gadobutrol was the cause.

In September, the FDA required makers of three of the five available GBCAs to add new warnings to their labels about the risk for NSF in some patients with kidney dysfunction. That requirement came following an FDA review that revealed those three agents carried a higher risk of developing the condition in patients with kidney disease than other GBCAs.

Bayer proposed adding the same boxed warning to gadobutrol.