Guerbet Announces US Labeling Changes for Optimark

Guerbet LLC, a subsidiary of Guerbet Group, takes note of the recommendations issued March 10, 2017, by the European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) on gadolinium-based contrast agents (GBCAs).

Guerbet concurs with the PRAC recommendations and does not intend to request a reexamination. In the United States, Guerbet markets Optimark (gadoversetamide) injection and Dotarem (gadoterate meglumine) injection. Optimark is a product belonging to the class of linear GBCAs, a class of agents the PRAC has identified as having "a structure more likely to release gadolinium." Dotarem is a product belonging to the class of macrocyclic GBCAs, which the PRAC specifies has a "much lower propensity to release gadolinium."

In March 2016, the EMA initiated a review of the risk of gadolinium deposition in brain tissue following the repeated use of GBCAs in patients undergoing MRI scans. After a nearly yearlong, in-depth review, the PRAC has identified linear agents as more likely to release gadolinium and has recommended the suspension of the following four linear agents from the market:

• MultiHance (gadobenic acid);
• Optimark (gadoversetamide);
• Magnevist (gadopentetic acid); and
• Omniscan (gadodiamide).

Although the PRAC recommendations do not apply to the US market, the company requested a labeling change in the United States for Optimark (gadoversetamide) injection. The FDA approved Guerbet's request at the end of August 2016, and the change is currently reflected in the Optimark Prescribing Information. This change is included in the Pharmacokinetics section of the Prescribing Information and notes: "Increased signal intensity on noncontrast T1-weighted images within the brain, mainly the globus pallidus and the dentate nucleus, has been observed after multiple administrations of linear (ionic and nonionic) GBCAs contrast agents due to gadolinium deposition."

The Prescribing Information further notes that following repeated GBCA administration gadolinium deposits may be present for months or years in bone, liver, skin, brain, and other organs. Deposition depends on multiple factors and may be greater following administration of linear GBCAs than following administration of macrocyclic GBCAs. The clinical significance of gadolinium retention in the body and brain is otherwise unknown.

Optimark (gadoversetamide) injection will continue to be available for clinical use in the approved indications. This position will be reconsidered once regulatory authorities provide the final decision.

Source: Guerbet LLC