ELUCIREM™ (gadopiclenol) injection Important Safety Information
WARNING: RISK ASSOCIATED WITH INTRATHECAL USE and NEPHROGENIC SYSTEMIC FIBROSIS (NSF)
Risk Associated with Intrathecal Use
lntrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious adverse reactions including death, coma, encephalopathy, and seizures.
ELUCIREM is not approved for intrathecal use.
Nephrogenic Systemic Fibrosis
GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of ELUCIREM 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 andinternal organs.
The risk for NSF appears highest among patients with:
- Chronic, severe kidney disease (GFR <30 mVmin/1.73m2), 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 (for example, age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing.
For patients at highest risk for NSF, do not exceed the recommended ELUCIREM dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration.
Breast MR is a critical tool in the early detection, diagnosis and treatment planning of breast cancer. It offers superior sensitivity over traditional screening methods in identifying tumors to help accurately determine the extent of malignancies, guide biopsies and surgical interventions, and evaluate treatment success.1 Choosing the appropriate gadolinium-based contrast agent (GBCA) in MR imaging is essential to enhancing lesion visibility and improving diagnostic accuracy, while managing the potential risks of gadolinium retention.
Dr Pinker-Domenig discussed using Elucirem ™ (gadopiclenol) injection for breast MR, particularly in challenging cases where conventional imaging, such as mammography and ultrasound, fall short.
Elucirem is a highly stable macrocyclic GBCA that requires only half the gadolinium dose of conventional, nonspecific GBCAs, addressing practitioners’ concerns about gadolinium exposure.2,3 The administration of a GBCA improves the contrast between lesions and surrounding tissues by accelerating the relaxation of protons through interaction with gadolinium atoms.4 Gadopiclenol delivers twice as much interaction as other GBCAs, resulting in the highest relaxivity among nonspecific GBCAs.4
Elucirem™ is indicated for use in adults and children aged 2 years and older, for contrast-enhanced magnetic resonance imaging (MRI). The product is used to detect and visualize lesions with abnormal vascularity in the central nervous system (brain, spine and associated tissues) and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system).8
“In screening and staging breast cancer, we need to see the lesions well and that can be done with less gadolinium, and we can keep the dose and patient exposure as low as possible,” she said.
Enhancing Diagnostic Precision With Gadopiclenol
Dr Pinker-Domenig explains that breast MR is the most sensitive imaging modality for detecting breast cancer, with studies reporting nearly 75% to 100% sensitivity for cancerous tumors.5 Unlike conventional screening methods, such as mammography and ultrasound, the sensitivity of breast MR is independent of breast density.
Breast MR is particularly useful in staging lesions and determining if they’re unifocal (a single tumor in one area of the breast), multifocal (multiple tumors within the same quadrant of the breast), or multicentric (multiple tumors in different quadrants of the breast), she said. MR can also effectively screen high-risk patients, as its high sensitivity and specificity help minimize unnecessary biopsies while detecting cancers at early, treatable stages.5
“Breast MR is the most accurate imaging modality for staging of lesioning extent, and it can detect noninvasive breast cancers“ she said. “It also provides crucial information about lesion size, allowing for tailored surgical planning and improved patient outcomes.”
Using a GBCA in breast MR imaging is critical to accurately visualizing abnormal breast tissue.6
“We want to use high-relaxivity GBCA, ideally at the lowest dose possible, that still gives us a good image quality,” said Dr Pinker-Domenig. “This is where gadopiclenol comes in because it’s a macrocyclic agent with a very high relaxivity. We can lower the dose of gadolinium while achieving the same imaging results.”
Breast MR with a GBCA improves neoadjuvant chemotherapy monitoring in large and small tumors, including triple-negative and HER2-positive cancers, to optimize surgical candidacy and outcomes, she said.
GBCAs support both morphological and kinetic assessments in MR interpretation, which are critical to guiding biopsy decisions and treatment strategies.6 Morphological descriptors such as shape, margin, and internal enhancement characteristics help differentiate benign from malignant lesions, while kinetic assessments focus on contrast enhancement patterns, such as wash-in and wash-out curves, to provide additional clues about lesion behavior and further refine diagnostic certainty.6
“Gadopiclenol visualizes neovascularity, which is crucial for identifying even the smallest cancers early, and mitigates concerns about gadolinium retention,” she explained.
Clinical Utility of Gadopiclenol in Breast MRI
In the webinar noted above, Dr Pinker-Domenig presented several case studies showcasing the clinical utility of breast MR with gadopiclenol, including the case of a 34-year-old woman with the BRCA2 gene, which indicated her high risk for breast cancer. MR subtraction imaging clearly visualized a small lesion, which prompted clinicians to perform an MR-guided biopsy.
“MR revealed a small, enhancing lesion not visible on other modalities, underscoring its role in high-risk patient management,” she said. “In this case, it clearly solidified what needed to be done next.”
View this Breast MRI Case
Dr Pinker-Domenig stressed the importance of providing an accurate surgical roadmap of the pathology. Contrast-enhanced MRI can help stage a metaplastic carcinoma, a rare, aggressive form of breast cancer that often presents as invasive ductal carcinoma, a common cancer with a high survival rate.7 Accurate visualization with gadopiclenol-enhanced MRI can help with disease management and treatment plans.
“In these patients, we really need to know what’s going on to give them the best surgical planning,” she said. “We want the surgical roadmap to be as perfect as possible because it reduces re-excision rates. The surgeon will know if they have to take out more tissue and can include a bigger area in the surgical field.”
As breast imaging evolves, Dr Pinker-Domenig stressed the importance of balancing diagnostic efficacy with patient safety, advocating for judicious use of contrast agents to minimize gadolinium exposure.
References
- Gombos, E. C., Jagadeesan, J., Richman, D. M., & Kacher, D. F. (2015, November). Magnetic resonance imaging-guided breast interventions: Role in biopsy targeting and lumpectomies. Magnetic resonance imaging clinics of North America. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621771/
- Loevner LA, Kolumban B, Hutóczki G, et al. Efficacy and safety of gadopiclenol for contrast-enhanced MRI of the central nervous system: the PICTURE randomized clinical trial. Invest Radiol. 2023;58(5):307-313. doi:10.1097/RLI.0000000000000944
- 4Robic C, Port M, Rousseaux O, et al. Physicochemical and pharmacokinetic profiles of gadopiclenol: a new macrocyclic gadolinium chelate with high T1 relaxivity. Invest Radiol. 2019;54(8):475-484. doi:10.1097/RLI.0000000000000563
- Breast Mri Indications. UCLA Health. (n.d.-b). https://www.uclahealth.org/departments/radiology/education/breast-imaging-teaching-resources/birads/breast-mri-indications. Accessed July 19, 2024.
- Gunduru, M. (2023, August 28). Breast magnetic resonance imaging. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK539727/. Accessed July 19, 2024.
- Çelik, H., Başara Akın, I., Durak, M. G., & Balcı, P. (2023, January 31). Multimodality imaging and histopathology of Metaplastic Breast Cancer. Diagnostic and interventional radiology (Ankara, Turkey). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679585/
- Elucirem™ (gadopiclenol) injection [Package Insert]. Princeton, NJ. 5/2024 https://www.guerbet.com/media/12ini2kl/elucirem-uspi-5-2024-clean-version.pdf
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ELUCIREM™ (gadopiclenol) injection Important Safety Information
WARNING: RISK ASSOCIATED WITH INTRATHECAL USE and NEPHROGENIC SYSTEMIC FIBROSIS (NSF)
Risk Associated with Intrathecal Use
lntrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious adverse reactions including death, coma, encephalopathy, and seizures.
ELUCIREM is not approved for intrathecal use.
Nephrogenic Systemic Fibrosis
GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of ELUCIREM 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 andinternal organs.
The risk for NSF appears highest among patients with:
- Chronic, severe kidney disease (GFR <30 mVmin/1.73m2), 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 (for example, age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing.
For patients at highest risk for NSF, do not exceed the recommended ELUCIREM dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration.
Indications and Usage
ELUCIREM™ gadopiclenol) injection is indicated in adult and pediatric patients aged 2 years and older for use with magnetic resonance imaging (MRI) to detect and visualize lesions with abnormal vascularity in the central nervous system (brain, spine, and associated tissues), and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletalsystem).
Contraindications
Contraindicated in patients with history of hypersensitivity reactions to ELUCIREM.
Warnings and Precautions
- Risk Associated with Intrathecal Use: lntrathecal administration of GBCAs can cause serious adverse reactions including death, coma, encephalopathy, and seizures. The safety and effectiveness of ELUCIREM have not been established with intrathecal use. ELUCIREM is not approved for intrathecal use.
- Nephrogenic Systemic Fibrosis: GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of ELUCIREM among these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities.
- Hypersensitivity Reactions: With GBCAs, serious hypersensitivity reactions have occurred. Before ELUCIREM 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 ELUCIREM.
- Gadolinium Retention: Gadolinium is retained for months or years in several organs. The highest concentrations have been identified in the bone, followed by other organs (e.g. brain, skin, kidney, liver, and spleen). While clinical consequences of gadolinium retention have not been established in patients with normal renal function, certain patients might be at higher risk. These include patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions. Minimize repetitive GBCA imaging studies, particularly closely spaced studies when possible.
- Acute Kidney Injury: 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.
- Extravasation and Injection Site Reactions: Injection site reactions such as injection site pain have been reported in the clinical studies with ELUCIREM. Extravasation during ELUCIREM administration may result in tissue irritation. Ensure catheter and venous patency before the injection of ELUCIREM.
- Interference with Visualization of Lesions Visible with Non-Contrast MRI: As with any GBCA, ELUCIREM may impair the visualization of lesions seen on non-contrast MRI.
Adverse Reactions:
In clinical trials, the most frequent adverse reactions that occurred in > 0.2% of patients who received ELUCIREM included: injection site pain, headache, nausea, injection site warmth, injection site coldness, dizziness, and localized swelling.
Postmarketing Experience: Acute pancreatitis with onset within 48 hours after GBCA administration.
Use in Specific Populations
- Pregnancy: GBCAs cross the human placenta and result in fetal exposure and gadolinium retention. There are no available data on ELUCIREM use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
- Lactation: There are no data on the presence of ELUCIREM 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 excreted in breast milk.
- Pediatric Use: The safety and effectiveness of ELUCIREM have not been established in pediatric patients younger than 2 years of age.
- Geriatric Use: This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.
- Renal Impairment: In patients with renal impairment, the exposure of gadopiclenol is increased compared to patients with normal renal function. This may increase the risk of adverse reactions such as NSF. No dose adjustment of ELUCIREM is recommended for patients with renal impairment.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. Please see the full Prescribing Information, including the Medication Guide, for additional important safety information.GU06240107
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