Dosing & Uses
Dosage Forms & Strengths
IV solution, single-dose vials
- 1.5 mmol/3mL (0.5 mmol/mL)
- 3.75 mmol/7.5mL (0.5 mmol/mL)
- 5 mmol/10mL (0.5 mmol/mL)
- 7.5 mmol/15mL (0.5 mmol/mL)
IV solution, single-dose prefilled syringes
- 3.75 mmol/7.5mL (0.5 mmol/mL)
- 5 mmol/10mL (0.5 mmol/mL)
- 7.5 mmol/15mL (0.5 mmol/mL)
IV solution, pharmacy bulk package
- 15 mmol/30mL (0.5 mmol/mL)
- 25 mmol/50mL (0.5 mmol/mL)
- 50 mmol/100mL (0.5 mmol/mL)
MRI Contrast
Indicated 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 musculoskeletal system)
0.05 mmol/kg actual body weight (0.1 mL/kg) IV bolus infused ~2 mL/second
Dosage Modifications
Renal impairment
- Exposure increased in patients with renal impairment compared with normal renal function
- Avoid gadolinium-based contrast agents (GBCAs) among these patients unless diagnostic information is essential and not available with non-contrast MRI or other modalities
- No dose adjustment recommended
- Can be removed from body by hemodialysis
Hepatic impairment
- No hepatic elimination
Dosage Forms & Strengths
IV solution, single-dose vials
- 1.5 mmol/3mL (0.5 mmol/mL)
- 3.75 mmol/7.5mL (0.5 mmol/mL)
- 5 mmol/10mL (0.5 mmol/mL)
- 7.5 mmol/15mL (0.5 mmol/mL)
IV solution, single-dose prefilled syringes
- 3.75 mmol/7.5mL (0.5 mmol/mL)
- 5 mmol/10mL (0.5 mmol/mL)
- 7.5 mmol/15mL (0.5 mmol/mL)
IV solution, pharmacy bulk package
- 15 mmol/30mL (0.5 mmol/mL)
- 25 mmol/50mL (0.5 mmol/mL)
- 50 mmol/100mL (0.5 mmol/mL)
MRI Contrast
Indicated for use with magnetic resonance imaging (MRI) in patients aged ≥2 years 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)
<2 years: Safety and efficacy not established
≥2 years: 0.05 mmol/kg actual body weight (0.1 mL/kg) IV bolus infused ~2 mL/second
Dosage Modifications
Renal impairment
- Exposure increased in patients with renal impairment compared with normal renal function
- Avoid gadolinium-based contrast agents (GBCAs) among these patients unless diagnostic information is essential and not available with non-contrast MRI or other modalities
- No dose adjustment recommended
- Can be removed from body by hemodialysis
Hepatic impairment
- No hepatic elimination
Adverse Effects
<1%
Injection site pain (0.7%)
Headache (0.7%)
Nausea (0.4%)
Injection site warmth (0.4%)
Injection site coldness (0.3%)
Dizziness (0.3%)
Localized swelling (0.3%)
≤0.2%
- Maculopapular rash
- Vomiting
- Worsened renal impairment
- Feeling hot
- Pyrexia
- Oral paresthesia
- Dysgeusia
- Diarrhea
- Pruritus
- Allergic dermatitis
- Erythema
- Injection site paresthesia
- Cystatin C increase
- Blood creatinine increased
Warnings
Black Box Warnings
Nephrogenic systemic fibrosis (NSF)
- Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired drug elimination
- Avoid use in these patients unless diagnostic information is essential and not available with noncontrast MRI or other modalities
- NSF may result in fatal or debilitating fibrosis affecting skin, muscle, and internal organs
- Risk of NSF highest with chronic, severe kidney disease (ie, GFR <30 mL/min/1.73 m2) or acute kidney injury
- Screen for acute kidney injury and other conditions that may reduce renal function; for patients at risk for chronically reduced renal function (eg, age >60 years, hypertension, diabetes), estimate GFR through laboratory testing
- For patients at highest risk for NSF, do not exceed recommended dose and allow sufficient time for drug elimination before readministration
Contraindications
History of hypersensitivity reactions to gadopiclenol
Cautions
Gadolinium-based contrast agents increase risk for NSF among patient with impaired drug elimination (see Black Box Warnings)
Anaphylactic and anaphylactoid reactions reported and may involve cardiovascular, respiratory, and/or cutaneous manifestations, including reports of patients experiencing cardiovascular collapse and death
Acute kidney injury requiring dialysis has occurred in patients with chronically reduced renal function; serum creatinine levels and estimated GFR may not reliably assess renal function in setting of acute kidney injury
Injection site extravasation reported
GBCAs may impair visualization of lesions seen on noncontrast MRI; caution when MRI scans interpreted without a companion noncontrast MRI scan
Nephrogenic systemic fibrosis (NSF)
- Gadolinium-based contrast agents increase risk for NSF among patient with impaired drug elimination (see Black Box Warnings)
- Report any diagnosis of NSF following administration to Guerbet LLC (1-877-729-6679) or FDA (1-800-FDA-1088 or www.fda.gov/medwatch)
- For patients receiving hemodialysis, physicians may consider prompt initiation of hemodialysis following administration of a GBCA in order to enhance contrast agent’s elimination; the usefulness of hemodialysis in prevention of NSF is unknown
Gadolinium retention
- Gadolinium is retained for months or years in several organs
- Highest concentrations (nanomoles per gram of tissue) have been identified in bone, followed by other organs (eg, brain, skin, kidney, liver, and spleen)
- Duration of retention also varies by tissue and is longest in bone
- Patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions are at higher risk of gadolinium retention
- Consequences of gadolinium retention in the brain have not been established
- Pathologic and clinical consequences of GBCA administration and retention in skin and other organs have been established in patients with impaired renal function
- Rare reports of pathologic skin changes in patients with normal renal function
Pregnancy & Lactation
Pregnancy
GBCAs cross the placenta and result in fetal exposure and gadolinium retention
Human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive
Lactation
Estimated infant exposure is 0.01%-0.04% of the maternal dose
Data are not available regarding presence of gadopiclenol in human milk, effects on breastfed infants, or effects on milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Paramagnetic molecule (macrocyclic non-ionic complex of gadolinium) that develops a magnetic moment when placed in a magnetic field
The magnetic moment alters relaxation rates of water protons in its vicinity in the body, leading to an increase in signal intensity (brightness) of tissues
The extent to which a contrast agent can affect the relaxation rate of tissue water (1/T1 or 1/T2) is termed relaxivity (r1 or r2)
Gadopiclenol relaxivity is 12.8, which is 2-3 times that of other GBCAs; thereby, a lower dose can be administered
Absorption
Peak plasma concentration: 525 mcg/mL
AUC
- 2-6 years: 403 mcg⋅h/mL
- 7-11 years: 478 mcg⋅h/mL
- 12-17 years: 582 mcg⋅h/mL
- Adults: 569 mcg⋅h/mL
Distribution
Protein bound: ≤1.8%
Vd: 13 L
Following administration, gadolinium is present for months or years in brain, bone, skin, and other organs
Metabolism
Not metabolized
Elimination
Total body clearance: 100 mL/min
Renal clearance: 81 mL/min
Excretion: Urine 98%
Half-life
- eGFR >≥0 mL/min: 1.5-1.9 hr
- eGFR 60 to <90 mL/min: 3.3 hr
- eGFR 30 to <60 mL/min: 3.8 hr
- eGFR 15 to <30 mL/min: 11.7 hr
Half-life (pediatrics)
- 2-6 years: 1.29 hr
- 7-11 years: 1.48 hr
- 12-17 years: 1.77 hr
Clearance
- eGFR ≥90 mL/min: 96 mL/min
- eGFR 60 to <90 mL/min: 96 mL/min
- eGFR 30 to <60 mL/min: 44 mL/min
- eGFR 15 to <30 mL/min: 14 mL/min
Clearance (pediatrics)
- 2-6 years: 0.12 L/hr/kg
- 7-11 years: 0.1 L/hr/kg
- 12-17 years: 0.08 L/hr/kg
Administration
IV Incompatibilities
Do not mix with other drugs or parenteral nutrition
IV Preparation
Visually inspect for particulate matter and discoloration; do not use if solution contains particulates or container appears damaged
Solution should appear clear, colorless to yellow
Prime IV line before use with 0.9% NaCl to ensure patency
Single-dose vial
- Do not pierce rubber stopper more than once
- Aseptically draw up into a disposable syringe and use immediately
- If solidification occurs in vial because of exposure to cold, bring vial to room temperature before use and inspect that solution is clear, colorless to yellow without any particulate matter and discoloration
- Discard unused portion
Prefilled syringe
- Remove tip cap of syringe, screw plunger rod and use immediately
- All luer connections should be gently hand tightened without over tightening, to ensure secure connections and to prevent damage to device
- Prefilled syringes must not be frozen; discard if frozen
- Discard unused portion
Bulk package
- Do not use pharmacy bulk package for direct infusion
- Bulk package is used with appropriate transfer device for filling empty sterile syringes
- Perform transfer from bulk package in aseptic work area (ie, laminar flow hood), using aseptic technique and suitable transfer device for filling empty syringes
- Penetrate closure only one time; once container closure punctured, do not remove bulk package from aseptic work area
- Use each individual dose promptly following withdrawal from bulk package
- Use bulk pack contents within 24 hr at room temperature after initial puncture
- If solidification occurs in vial because of exposure to cold, bring vial to room temperature before use and inspect that solution is clear, colorless to yellow without any particulate matter and discoloration
IV Administration
Before 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 this drug
Administer IV at rate of ~2 mL/second
Flush IV line with 0.9% NaCl after administration
Contrast MRI can immediately following injection
Administer in facility where trained personnel and therapies are promptly available for treatment of hypersensitivity reactions, including personnel trained in resuscitation
During and following administration, observe patients for signs and symptoms of hypersensitivity reactions
Storage
Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)
Do not freeze prefilled syringes
Images
Formulary
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