Elucirem Prescribing Information
Intrathecal 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
The risk for NSF appears highest among patients with:
- Chronic, severe kidney disease (GFR < 30 mL/min/1.73 m2), or
- Acute kidney injury.
GBCAs increase the risk for nephrogenic systemic fibrosis (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. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease (GFR <30 mL/min/1.73 m2) as well as patients with acute kidney injury. The risk appears lower for patients with chronic, moderate kidney disease (GFR 30-59 mL/min/1.73 m2) and little, if any, for patients with chronic, mild kidney disease (GFR 60-89 mL/min/1.73 m2). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle, and internal organs. Report any diagnosis of NSF following ELUCIREM administration to Guerbet LLC (1-877-729-6679) or FDA (1-800-FDA-1088 or www.fda.gov/medwatch).
Screen patients for acute kidney injury and other conditions that may reduce renal function. Features of acute kidney injury consist of rapid (over hours to days) and usually reversible decrease in kidney function, commonly in the setting of surgery, severe infection, injury or drug-induced kidney toxicity. Serum creatinine levels and estimated GFR may not reliably assess renal function in the setting of acute kidney injury. For patients at risk for chronically reduced renal function (e.g., age >60 years, diabetes mellitus or chronic hypertension), estimate the GFR through laboratory testing.
Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a GBCA and the degree of renal impairment at the time of exposure. Record the specific GBCA and the dose administered to a patient. 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 prior to re-administration. For patients receiving hemodialysis, physicians may consider the prompt initiation of hemodialysis following the administration of a GBCA in order to enhance the contrast agent’s elimination
ELUCIREMTM 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),
- the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system).
Injection: ELUCIREM is a clear, colorless to yellow aqueous solution at a concentration of 0.5 mmol/mL of gadopiclenol available as:
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ELUCIREM is contraindicated in patients with history of hypersensitivity reactions to ELUCIREM.
GBCAs increase the risk for nephrogenic systemic fibrosis (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. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease (GFR <30 mL/min/1.73 m2) as well as patients with acute kidney injury. The risk appears lower for patients with chronic, moderate kidney disease (GFR 30-59 mL/min/1.73 m2) and little, if any, for patients with chronic, mild kidney disease (GFR 60-89 mL/min/1.73 m2). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle, and internal organs. Report any diagnosis of NSF following ELUCIREM administration to Guerbet LLC (1-877-729-6679) or FDA (1-800-FDA-1088 or www.fda.gov/medwatch).
Screen patients for acute kidney injury and other conditions that may reduce renal function. Features of acute kidney injury consist of rapid (over hours to days) and usually reversible decrease in kidney function, commonly in the setting of surgery, severe infection, injury or drug-induced kidney toxicity. Serum creatinine levels and estimated GFR may not reliably assess renal function in the setting of acute kidney injury. For patients at risk for chronically reduced renal function (e.g., age >60 years, diabetes mellitus or chronic hypertension), estimate the GFR through laboratory testing.
Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a GBCA and the degree of renal impairment at the time of exposure. Record the specific GBCA and the dose administered to a patient. 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 prior to re-administration. For patients receiving hemodialysis, physicians may consider the prompt initiation of hemodialysis following the administration of a GBCA in order to enhance the contrast agent’s elimination
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 nephrogenic systemic fibrosis (NSF). Avoid use of GBCAs among these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities. No dose adjustment of ELUCIREM is recommended for patients with renal impairment. ELUCIREM can be removed from the body by hemodialysis
The Cmaxand AUCinfof gadopiclenol increased proportionally over a dosage range from 0.025 mmol/kg to 0.3 mmol/kg (0.5 times to 6 times the recommended dosage). At the recommended dose, the mean (CV%) Cmaxand AUCinfwere 525 (13%) µg/mL and 569 (18%) µg·h/mL, respectively.
After intravenous administration of ELUCIREM, gadopiclenol is distributed in the extracellular fluids.
The mean (CV%) volume of distribution of gadopiclenol at steady state is 13 (13%) L.
Protein binding of gadopiclenol is ≤ 1.8% at clinically relevant concentrations.
Following GBCA administration, gadolinium is present for months or years in brain, bone, skin, and other organs
The mean (CV%) elimination half-life (t1/2) of gadopiclenol is 1.5 (14%) hour.
The mean (CV%) total body clearance (CL) and renal clearance (CLr) of gadopiclenol are 100 (9.5%) mL/min and 81 (35%) mL/min, respectively.
Gadopiclenol is not metabolized.
Gadopiclenol is mainly eliminated through the kidneys by glomerular filtration. Approximately 98% of the dose was recovered in urine within 48 hours after administration.
No clinically significant differences in the pharmacokinetics of gadopiclenol were observed based on sex.
The pharmacokinetics of gadopiclenol for pediatric patients (2 to 17 years of age) were within range to those of adults (> 18 years of age)
The pharmacokinetic parameters (median [range]) of gadopiclenol in pediatric patients are presented in Table 4.
2-6 years | 7-11 years | 12-17 years | >18 years | |
Cl (L/h/kg) | 0.12 [0.05; 0.28] | 0.10 [0.04; 0.24] | 0.08 [0.04; 0.20] | 0.08 [0.05; 0.14] |
t1/2(h) | 1.29 [0.69; 3.38] | 1.48 [0.83; 3.20] | 1.77 [1.00; 3.57] | 1.82 [0.93; 3.68] |
AUCinf(ng.h/L) | 403 [169; 964] | 478 [183; 1077] | 582 [267; 1291] | 590 [353; 937] |
C20 (µg/mL) | 236 [136; 387] | 260 [151; 401] | 286 [155; 441] | 296 [166; 485] |
aAt the recommended dosage
The pharmacokinetic parameters (mean (%CV)) of gadopiclenol in patients with renal impairment are presented in Table 5.
Normal (eGFR ≥ 90 mL/min) | Mild (eGFR 60 to < 90 mL/min) | Moderate (eGFR 30 to < 60 mL/min) | Severe (eGFR 15 to < 30 mL/min) | |
AUCinf(µg·h/mL) | 1113 (24%) | 1711 (31%) | 2759 (28%) | 9671 (18%) |
CLr(mL/min) | 96 (10%) | 76 (23%) | 44 (25%) | 14 (26%) |
t1/2(h) | 1.9 | 3.3 | 3.8 | 11.7 |
aFollowing administration of a single gadopiclenol 0.1 mmol/kg dose (2 times the recommended dosage).
beGFR: estimate of GFR based on an estimation equation and expressed in mL/min. To convert mL/min/1.73 m2to mL/min, multiply by the individual’s BSA and divide by 1.73.
In patients with mild or moderate renal impairment, more than 90% of the administered ELUCIREM was recovered in urine within 48 hours. In patients with severely impaired renal function about 84% of the administered ELUCIREM was recovered in urine within 5 days.
In patients with eGFR < 15 mL/min, hemodialysis effectively removed gadopiclenol from plasma as the percentage of decrease in blood concentrations was 95 to 98% at the end of the first hemodialysis session and 100% after the third hemodialysis session
The following additional adverse reactions have been identified during postmarketing use of ELUCIREM or other GBCAs. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.