BRIEF SUMMARY

GADOPICLENOL- (Sept 2022)

Indn- To detect and visulize lesions together with MRI with abnormal vasularity in central nervous system in certors of the body.    

Comp-  Injection: 0.5 mmol/mL of gadopiclenol in single-dose vials, single-dose prefilled syringes, and pharmacy bulk packages 0.1 mL/kg) administered intravenously at approximately 2 mL/sec.

The recommended dose for adult and pediatric patients aged 2 years and older is 0.05 mmol/kg actual body weight (equivalent to 0.1 mL/kg) administered intravenously at approximately 2 mL/sec. 

ADR- Most common adverse reactions (incidence >0.2%) in patients who received  are injection site pain, headache, nausea, injection site warmth and coldness, dizziness, and localized swelling.

CI- Nephrogenic Systemic Fibrosis has occurred in patients with impaired elimination of GBCAs. Higher than recommended dosing or repeat dosing appear to increase the risk.

• Hypersensitivity Reactions: Serious hypersensitivity reactions have occurred with GBCAs. Monitor patients closely for need of emergency cardiorespiratory support.

Pat inform-

Nephrogenic Systemic Fibrosis- Inform the patient that ELUCIREM may increase the risk for NSF among patients with impaired elimination of the drugs and that NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs.

 Instruct the patients to contact their physician if they develop signs or symptoms of NSF following administration, such as burning, itching, swelling, scaling, hardening and tightening of the skin; red or dark patches on the skin; stiffness in joints with trouble moving, bending or straightening the arms, hands, legs or feet; pain in the hip bones or ribs; or muscle weakness.

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U.S.  APPROVED DRUGS SURING 2022                                        

Serial No 23

Name-        LUCIREME                

Active Ingredient -   Gadopiclenol 

Pharmacological Classification- To detect and visulize lesions together with MRI with abnormal vasularity in central nervous system in certors of the body.                                                                                                                                

Date of Approval-         9/21/2022          

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                        ELUCIREMTM safely and effectively.                                                                            See full prescribing information for ELUCIREM. ELUCIREMTM (gadopiclenol) injection, for intravenous use

Initial U.S. Approval: 2022

WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF) -                                         See full prescribing information for complete boxed warning

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

. • The risk for NSF appears highest among patients with: 2  Chronic, severe kidney disease (GFR <30 mL/min/1.73 m ), 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.

INDICATIONS AND USAGE-

 ELUCIREM is a gadolinium-based contrast agent 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).

ADVERSE REACTIONS-

 Most common adverse reactions (incidence >0.2%) in patients who received ELUCIREM are injection site pain, headache, nausea, injection site warmth and coldness, dizziness, and localized swelling.

CONTRAINDICATIONS-

 History of hypersensitivity reactions to ELUCIREM

WARNINGS AND PRECAUTIONS-

 • Nephrogenic Systemic Fibrosis has occurred in patients with impaired elimination of GBCAs. Higher than recommended dosing or repeat dosing appear to increase the risk.

 • Hypersensitivity Reactions: Serious hypersensitivity reactions have occurred with GBCAs. Monitor patients closely for need of emergency cardiorespiratory support.

 • Gadolinium Retention: Gadolinium is retained for months or years in brain, bone, and other organs.

DOSAGE AND ADMINISTRATION-

 • The recommended dose for adult and pediatric patients aged 2 years and older is 0.05 mmol/kg actual body weight (equivalent to 0.1 mL/kg) administered intravenously at approximately 2 mL/sec. 

DOSAGE FORMS AND STRENGTHS-

 Injection: 0.5 mmol/mL of gadopiclenol in single-dose vials, single-dose prefilled syringes, and pharmacy bulk packages 0.1 mL/kg) administered intravenously at approximately 2 mL/sec. 

PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Nephrogenic Systemic Fibrosis-                                                                               Inform the patient that ELUCIREM may increase the risk for NSF among patients with impaired elimination of the drugs and that NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs.

 Instruct the patients to contact their physician if they develop signs or symptoms of NSF following ELUCIREM administration, such as burning, itching, swelling, scaling, hardening and tightening of the skin; red or dark patches on the skin; stiffness in joints with trouble moving, bending or straightening the arms, hands, legs or feet; pain in the hip bones or ribs; or muscle weakness.

Gadolinium Retention-                                                                                               Advise patients that gadolinium is retained for months or years in brain, bone, skin, and other organs following ELUCIREM administration even in patients with normal renal function. The clinical consequences of retention are unknown.

Retention depends on multiple factors and is greater following administration of linear GBCAs than following administration of macrocyclic GBCAs .

Injection Site Reactions-                                                                                               Inform the patient that ELUCIREM may cause reactions along the venous injection site, such as mild and transient burning or pain or feeling of warmth or coldness at the injection site

 Pregnancy-                                                                                                                      Advise pregnant women of the potential risk of fetal exposure to ELUCIREM.

Manufactured by Liebel-Flarsheim Company LLC, 8800 Durant Road, Raleigh, North Carolina (NC) 27616-3104, USA Distributed by Guerbet LLC 214 Carnegie Center, Suite 300, Princeton, NJ 08540, USA 16 Reference ID: 5047757

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                               Gadopiclenol is a paramagnetic molecule (macrocyclic non-ionic complex of gadolinium) that develops a magnetic moment when placed in a magnetic field.

2. Pharmacodynamics-                                                                                                   In MRI, visualization of normal and pathological tissue depends in part on variations in the radiofrequency signal intensity that occur with: • differences in proton density • differences of the spin-lattice or longitudinal relaxation times (T1) • differences in the spin-spin or transverse relaxation time (T2).

Cardiac Electrophysiology-                                                                                            At 6 times the recommended dosage in adult patients, gadopiclenol does not prolong the QT interval to any clinically relevant extent.

3. Pharmacokinetics-                                                                                                   The Cmax and AUCinf of 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%) Cmax and AUCinf were 525 (13%) µg/mL and 569 (18%) µg·h/mL, respectively.

Distribution-                                                                                                                      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.

Elimination-                                                                                                                   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.

Metabolism-                                                                                                              Gadopiclenol is not metabolized.

Excretion-                                                                                                                 Gadopiclenol is mainly eliminated through the kidneys by glomerular filtration. Approximately 98% of the dose was recovered in urine within 48 hours after administration.

Specific Populations-                                                                                                    No clinically significant differences in the pharmacokinetics of gadopiclenol were observed based on sex.

Pediatric Patients-                                                                                                               The pharmacokinetics of gadopiclenol for pediatric patients (2 to 17 years of age) were within range to those of adults (> 18 years of age).

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-                                                                               There are no available data on ELUCIREM use in pregnant women to evaluate for a drugassociated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. GBCAs cross the human placenta and result in fetal exposure and gadolinium retention.

The 6 Reference ID: 5047757 available human data on GBCA exposure during pregnancy and adverse fetal outcomes are limited and inconclusive (see Data). In animal reproduction studies, there were no adverse developmental effects observed in rats or rabbits with intravenous administration of ELUCIREM during orga nogenesis

 Because of the potential risks of gadolinium to the fetus, use ELUCIREM only if imaging is essential during pregnancy and cannot be delayed.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20% respectively.

2. Lactation Risk Summary-                                                                                       There are no data on the presence of gadopiclenol 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. Additionally, there is limited GBCA gastrointestinal absorption in the breast-fed infant. Gadopiclenol is present in rat milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk .

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ELUCIREM and any potential adverse effects on the breastfed infant from ELUCIREM or from the underlying maternal condition.

3.Pediatric Use-                                                                                                            The safety and effectiveness of ELUCIREM for use with MRI to detect and visualize lesions with abnormal vascularity in the CNS (brain, spine, and associated tissues), and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system) have been established in pediatric patients aged 2 years and older.

Use of ELUCIREM in this age group is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data from an open-label, uncontrolled, multicenter, single dose study of ELUCIREM (0.05 mmol/kg) in 80 pediatric patients aged 2 to 17 years. The 80 patients consisted of 60 patients who underwent a CNS MRI and 20 patients who underwent a body MRI

 The safety and effectiveness of ELUCIREM have not been established in pediatric patients younger than 2 years of age.

4.Geriatric Use-                                                                                                               Of the total number of ELUCIREM-treated patients in clinical studies, 270 (26%) patients were 65 years of age and over, while 62 (6%) patients were 75 years of age and over. No overall differences in safety or efficacy were observed between these subjects and younger subjects. 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.

Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function

5.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 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.

 OVERDOSAGE -                                                                                                     Among subjects who received a single 0.3 mmol/kg intravenous dose of gadopiclenol (6 times the recommended dose of ELUCIREM), headache and nausea were the most frequently reported adverse reactions. Gadopiclenol can be removed from the body by hemodialysis