Dec 27, 2017   SOURCE: PR NewsWire

Gadolinium-based contrast agents: update from Guerbet LLC on U.S. Food and Drug Administration (FDA) requirements

PRINCETON, N.J., Dec. 27, 2017 /PRNewswire/ -- Guerbet LLC takes note of the drug safety communication(1) issued on December 19, 2017 by the U.S. Food and Drug Administration (FDA), regarding gadolinium-based contrast agents (GBCAs) and the retention of gadolinium in the body.

The FDA is requiring a new class warning and other safety measures for all gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI).

The FDA notes that following administration of all GBCAs, gadolinium retention can be found in patients' bodies, including the brain, for months to years. However, gadolinium retention has not been directly linked to adverse health effects in patients with normal kidney function, and FDA concluded that the benefit of all approved GBCAs continues to outweigh any potential risks.

As noted in the communication, FDA explains that there are two types of GBCAs based on their chemical structures: linear and macrocyclic. Linear GBCAs result in more retention, and retention for a longer period of time than macrocyclic GBCAs. FDA adds that gadolinium levels in the body are lowest after administration of macrocyclic agents such as Dotarem® (gadoterate meglumine).

"Health care professionals should consider the retention characteristics of each agent when choosing a GBCA for patients who may be at higher risk for gadolinium retention...These patients include those requiring multiple lifetime doses, pregnant women, children, and patients with inflammatory conditions. Minimize repeated GBCA imaging studies when possible, particularly closely spaced MRI studies. However, do not avoid or defer necessary GBCA MRI scans."(1)

In addition to labeling changes, the FDA is requiring the development of a new patient Medication Guide to provide educational information that every patient will be asked to read before receiving a GBCA. Guerbet is currently working with the FDA to develop a guide, which is considered part of the product labeling and therefore must go through FDA regulatory review and approval prior to release to the public.

Magnetic resonance imaging (MRI) is a widely used diagnostic procedure which is critical to patient health. Contrast-enhanced MRI exams are necessary to give physicians a sharper, more accurate picture of tissue than would otherwise be available to them.

Guerbet will continue to work with FDA to implement the required labeling changes, including the Medication Guide, and will continue to work with all Health Authorities to further understand the mechanisms and consequences of gadolinium deposition in tissue.

(1)Drug safety communication on the FDA website: https://www.fda.gov/Drugs/DrugSafety/ucm589213.htm

About Guerbet
Guerbet is a pioneer in the contrast-agent field, with more than 90 years' experience, and is a leader in medical imaging worldwide. It offers a comprehensive range of pharmaceutical products, medical devices and services for x-ray scans, magnetic resonance imaging (MRI) and interventional radiology and theranostics (IRT), to improve the diagnosis and treatment of patients. With 7% of revenue dedicated to R&D and more than 200 employees distributed amongst its three centers in France and the United States, Guerbet is a substantial investor in research and innovation. Guerbet (GBT) is listed on Euronext Paris (segment B - mid caps) and generated EUR776 million in revenue in 2016. For more information about Guerbet, visit www.guerbet.com

Important Safety Information for Dotarem® (gadoterate meglumine)


    WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF)

    Gadolinium-based contrast agents (GBCAs) increase the risk for NSF
     among patients with impaired elimination of the drugs. Avoid use of
     GBCAs in these patients unless the diagnostic information is
     essential and not available with non-contrasted MRI or other
     modalities. NSF may result in fatal or debilitating fibrosis
     affecting the skin, muscle and internal organs.

     The risk for NSF appears highest among patients with: 

    Chronic,
      severe kidney disease (GFR < 30 mL/min/1.73m(2)), or 
    Acute
      kidney injury.
    Screen patients for acute kidney injury and other
      conditions that may reduce renal function. For patients at risk for
      chronically reduced renal function (e.g. age > 60 years,
      hypertension, diabetes), estimate the glomerular filtration rate
      (GFR) through laboratory testing. 
    For patients at highest risk for
      NSF, do not exceed the recommended DOTAREM dose and allow a
      sufficient period of time for elimination of the drug from the body
      prior to any re-administration.
     --------------------------------------------------------------------

Indications and Usage
DOTAREM(®) (gadoterate meglumine) injection is a prescription gadolinium-based contrast agent indicated for intravenous use with magnetic resonance imaging (MRI) in brain (intracranial), spine and associated tissues in adult and pediatric patients (including term neonates) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity.

Contraindications
History of clinically important hypersensitivity reactions to DOTAREM.

Warnings and Precautions

    --  Anaphylactic and anaphylactoid reactions have been reported with
        DOTAREM, involving cardiovascular, respiratory, and/or cutaneous
        manifestations. Some patients experienced circulatory collapse and died.
        In most cases, initial symptoms occurred within minutes of DOTAREM
        administration and resolved with prompt emergency treatment.
    --  Before DOTAREM administration, assess all patients for any history of a
        reaction to contrast media, bronchial asthma and/or allergic disorders.
        These patients may have an increased risk for a hypersensitivity
        reaction to DOTAREM.
    --  Administer DOTAREM only in situations where trained personnel and
        therapies are promptly available for the treatment of hypersensitivity
        reactions, including personnel trained in resuscitation.
    --  In patients with chronically reduced renal function, acute kidney injury
        requiring dialysis has occurred with the use of GBCAs. The risk of acute
        kidney injury may increase with increasing dose of the contrast agent;
        administer the lowest dose necessary for adequate imaging.
    --  Ensure catheter and venous patency before the injection of DOTAREM.
        Extravasation into tissues during DOTAREM administration may result in
        tissue irritation.

Adverse Reactions

    --  The most common adverse reactions associated with DOTAREM in clinical
        trials were nausea, headache, injection site pain, injection site
        coldness and rash.
    --  Serious adverse reactions in the Postmarketing experience have been
        reported with DOTAREM. These serious adverse reactions include but are
        not limited to: arrhythmia, cardiac arrest, respiratory arrest,
        pharyngeal edema, laryngospasm, bronchospasm, coma and convulsion.

Use in Specific Populations

    --  Pregnancy: There are no available data with DOTAREM use in pregnant
        women to inform a drug-associated risk of adverse developmental
        outcomes. While it is unknown if gadoterate crosses the placenta, other
        GBCAs have been shown to cross the human placenta and result in fetal
        exposure.  Advise pregnant women of the potential risk of fetal exposure
        to GBCAs.
    --  Lactation: There are no data on the presence of gadoterate in human
        milk, the effects on the breastfed infant, or the effects on milk
        production. However, published lactation data on other GBCAs indicate
        that 0.01 to 0.04% of the maternal gadolinium dose is present in breast
        milk.
    --  Pediatric Use: The safety and efficacy of DOTAREM at a single dose of
        0.1 mmol/kg has been established in pediatric patients from birth (term
        neonates >= 37 weeks gestational age) to 17 years of age based on
        clinical data. The safety of DOTAREM has not been established in preterm
        neonates. No cases of NSF associated with DOTAREM or any other GBCA have
        been identified in pediatric patients age 6 years and younger.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch or call 1-800-FDA-1088.

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SOURCE Guerbet LLC