GADAVIST Injection Prescribing Information (Vials and Syringes)
GADAVIST Injection Prescribing Information (Pharmacy Bulk Package)
GADAVIST™ (gadobutrol) injection
Frequently asked questions about GADAVIST™
- What is the indication for GADAVIST?
- What is the recommended dose in adults and children (2 years of age and older) and how should GADAVIST be administered?
- How does the volume administered of GADAVIST compare to 0.5 molar GBCAs?
- How many GADAVIST-enhanced procedures have been performed worldwide since launch?
- What is the relaxivity of GADAVIST and other gadolinium-based contrast agents approved for CNS imaging?
- What are the structural classes of Gd-chelate complexes?
- Which gadolinium-based contrast agents approved for CNS imaging are linear and which are macrocyclic?
- What are the warnings and precautions for GADAVIST?
- What is the safety profile of GADAVIST from clinical trials?
- How does the FDA classify GADAVIST in terms of renal impairment and risk?
What is the indication for GADAVIST?
GADAVIST is a gadolinium-based contrast agent indicated for intravenous use in diagnostic magnetic resonance imaging (MRI) in adults and children (2 years of age and older) to detect and visualize areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity of the central nervous system.
What is the recommended dose in adults and children (2 years of age and older), and how should GADAVIST be administered?
The recommended dose of GADAVIST is 0.1 mL/kg body weight (0.1 mmol/kg).
- Visually inspect GADAVIST for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored, if particulate matter is present or if the container appears damaged.
- Administer GADAVIST as an intravenous bolus injection, manually or by power injector, at a flow rate of approximately 2 mL/second. Flush the intravenous cannula with physiological saline solution after the injection.
How does the volume administered of GADAVIST compare to 0.5 molar GBCAs?
GADAVIST is formulated at a higher concentration (1 mmol/mL) compared to certain other gadolinium based contrast agents, resulting in a lower volume of administration.
How many GADAVIST-enhanced procedures have been performed worldwide since launch?
There have been over 6 million GADAVIST-enhanced procedures worldwide since its launch in Switzerland in 1998.
What is the relaxivity of GADAVIST and other gadolinium-based contrast agents approved for CNS imaging?
What are the structural classes of Gd-chelate complexes?
There are two structural classes of Gd-chelate complexes: macrocyclic and linear. The GADAVIST macrocyclic chelate binds the Gd3+ ion in a cage. The molecular structures of both Gd-chelate complexes are shown below:
Which gadolinium-based contrast agents approved for CNS imaging are linear and which are macrocyclic?
The structures of GBCA approved for CNS imaging are as following:
What are the warnings and precautions for GADAVIST?
Nephrogenic Systemic Fibrosis. GADAVIST has a boxed warning for 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 among these patients unless the diagnostic information is essential and not available with non-contrast enhanced MRI or other modalities. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease (GFR <30 mL/min/1.73m2) as well as patients with acute kidney injury. The risk appears lower for patients with chronic, moderate kidney disease (GFR 30–59 mL/min/1.73m2) and little, if any, for patients with chronic, mild kidney disease (GFR 60–89 mL/min/1.73m2). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Report any diagnosis of NSF following GADAVIST administration to Bayer Healthcare (1-888-842-2937) 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 (for example, 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 anddegree 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 GADAVIST 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. The usefulness of hemodialysis in the prevention of NSF is unknown [see Clinical Pharmacology (12) and Dosage and Administration (2)].
Hypersensitivity Reactions
Anaphylactoid and anaphylactic reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following GADAVIST administration [see Adverse Reactions (6)].
- Before GADAVIST 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 GADAVIST.
- Administer GADAVIST only in situations where trained personnel and therapies are promptly available for treatment of hypersensitivity reactions, including personnel trained in resuscitation.
Most hypersensitivity reactions to GADAVIST have occurred within half an hour after administration. Delayed reactions can occur up to several days after administration. Observe patients for signs and symptoms of hypersensitivity reactions during and following GADAVIST administration.
Extravasation and Injection Site Reactions
Ensure catheter and venus patency before the injection of GADAVIST. Extravasation into tissues during GADAVIST administration may result in moderate irritation. Avoid intramuscular administration of GADAVIST [see Nonclinical Toxicology (13.2)].
What is the safety profile of GADAVIST from clinical trials?
In 34 clinical trials of 4,549 patients worldwide, GADAVIST established the following safety profile:
- Adverse reactions that occurred with a frequency of <0.1% in subjects who received GADAVIST include: hypersensitivity/anaphylactoid reactions (hypotension, urticarial, flushing, pallor), loss of consciousness, convulsion, parosmia, tachycardia, palpitation, dry mouth, malaise and feeling cold.
How does the FDA classify GADAVIST based on renal impairment and risk of nephrogenic
systemic fibrosis?
The table below details the FDA’s classification of GADAVIST based on renal impairment and risk:
INDICATIONS and IMPORTANT SAFETY INFORMATION
GADAVIST (gadobutrol) Injection
INDICATIONS AND USAGE
Gadavist® (gadobutrol) injection is a gadolinium-based contrast agent indicated for intravenous use in diagnostic magnetic resonance imaging (MRI) in adults and children (2 years of age and older) to detect and visualize areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity of the central nervous system.
IMPORTANT SAFETY INFORMATION
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/1.73m2), 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 Gadavist dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration [see Warnings and Precautions].
- The possibility of serious or life-threatening hypersensitivity, anaphylactic or anaphylactoid reactions associated with cardiovascular, respiratory, or cutaneous manifestations, including death, should always be considered.
- The most frequent adverse reactions associated with Gadavist in clinical studies were headache, nausea, injection site reaction, dysgeusia and feeling hot.
Please see full prescribing information.
EOVIST (gadoxetate disodium) Injection
INDICATIONS AND USAGE
Eovist® (gadoxetate disodium) Injection is a gadolinium-based contrast agent indicated for intravenous use in T1-weighted magnetic resonance imaging (MRI) of the liver to detect and characterize lesions in adults with known or suspected focal liver disease.
IMPORTANT SAFETY INFORMATION
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/1.73m2), 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 Eovist dose and allow a sufficient period of time for elimination of the drug from the body prior to re-administration (see WARNINGS AND PRECAUTIONS).
- The possibility of life-threatening anaphylactoid/hypersensitivity reactions with cardiovascular, respiratory and/or cutaneous manifestations should always be considered.
- The most frequent (≥0.5%) adverse reactions associated with the use of Eovist are nausea, headache, feeling hot, dizziness, and back pain.
Please see full prescribing information.
MAGNEVIST (gadopentetate dimeglumine) Injection
INDICATIONS AND USAGE
Central Nervous System: Magnevist® (gadopentetate dimeglumine) Injection is indicated for use with magnetic resonance imaging (MRI) in adults and pediatric patients (2 years of age and older) to visualize lesions with abnormal vascularity in the brain (intracranial lesions), spine and associated tissues. Magnevist has been shown to facilitate visualization of intracranial lesions including but not limited to tumors.
Extracranial/Extraspinal Tissues: Magnevist is indicated for use with MRI in adults and pediatric patients (2 years of age and older) to facilitate the visualization of lesions with abnormal vascularity in the head and neck.
Body: Magnevist is indicated for use with MRI in adults and pediatric patients (2 years of age and older) to facilitate the visualization of lesions with abnormal vascularity in the body (excluding the heart).
IMPORTANT SAFETY INFORMATION
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.
- Do not administer Magnevist to patients with:
- chronic, severe kidney disease (GFR < 30 mL/min/1.73m2), or
- acute kidney injury (see CONTRAINDICATIONS)
- 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.
Do not exceed the recommended Magnevist dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration (see WARNINGS AND PRECAUTIONS).
- Magnevist is contraindicated in patients with chronic, severe kidney disease (glomerular filtration rate, GFR < 30 mL/min/1.73m2), or acute kidney injury.
- The possibility of serious or life-threatening hypersensitivity, anaphylactic or anaphylactoid reactions associated with cardiovascular, respiratory, or cutaneous manifestations, including death, should always be considered.
- Caution should be exercised in patients with renal impairment due to the possibility of further deterioration in renal function.
- Cases of phlebitis and thrombophlebitis have been reported; assessment of the dosed limb for the development of injection site reactions is recommended.
- In clinical trials, the most frequently reported adverse reactions included headache, nausea, injection site coldness/localized coldness and dizziness.
Please see full prescribing information.
ULTRAVIST® (iopromide) Injection
INDICATIONS AND USAGE
Ultravist® (iopromide) Injection is an iodinated contrast agent indicated for:
Intra-arterial Procedures*: 300 mg I/mL for cerebral arteriography and peripheral arteriography; 370 mg I/mL for coronary arteriography and left ventriculography, visceral angiography, and aortography.
Intravenous Procedures*: 240 mg I/mL for peripheral venography; 300 mg I/mL for excretory urography; 300 mg I/mL and 370 mg I/mL for contrast Computed Tomography (CT) of the head and body (intrathoracic, intraabdominal and retroperitoneal regions) for the evaluation of neoplastic and non-neoplastic lesions. The usefulness of contrast enhancement for the investigation of the retrobulbar space and of low grade or infiltrative glioma has not been demonstrated.
* For information on the concentrations and doses for the Pediatric Population [see Dosage and Administration (2.3) and Use in Specific Populations (8.4) in the full prescribing information].
IMPORTANT SAFETY INFORMATION
WARNING: NOT FOR INTRATHECAL USE
Inadvertent intrathecal administration may cause death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema.
CONTRAINDICATIONS
Ultravist Injection is contraindicated for intrathecal use.
Preparatory dehydration (e.g. prolonged fasting and the administration of a laxative before Ultravist Injection) is contraindicated in pediatric patients because of risk of renal failure.
SELECTED WARNINGS AND PRECAUTIONS
- Life-threatening or fatal anaphylactoid reactions may occur during or after Ultravist administration, particularly in patients with allergic disorders.
- Acute kidney injury, including renal failure, may occur after intravascular administration of Ultravist. Risk factors include: pre-existing renal insufficiency, dehydration, diabetes mellitus, congestive heart failure, advanced vascular disease, elderly age, concomitant use of nephrotoxic or diuretic medications, multiple myeloma/paraproteinemia, repetitive and/or large doses of Ultravist. Use the lowest necessary dose of Ultravist in patients with renal impairment. Adequately hydrate patients prior to and following Ultravist administration.
- Hemodynamic disturbances including shock and cardiac arrest may occur during or shortly after administration of Ultravist.
- Angiography may be associated with local and distal organ damage, ischemia, thromboembolism and organ failure. In angiographic procedures, consider the possibility of dislodging plaques or damaging or perforating the vessel wall. The physicochemical properties of the contrast agent, the dose and the speed of injection can influence the reactions.
- Extravasation of Ultravist may cause tissue necrosis and/or compartment syndrome, particularly in patients with severe arterial or venous disease.
- Thyroid storm has occurred after the intravascular use of iodinated contrast agents in patients with hyperthyroidism, or with autonomously functioning thyroid nodule. Evaluate the risk in such patients before use of any iodinated contrast agent.
- Administer iodinated contrast agents with extreme caution in patients with known or suspected pheochromocytoma. Inject the minimal amount of contrast necessary.
- Contrast agents may promote sickling in individuals who are homozygous for sickle cell disease when administered intravascularly.
MOST COMMON ADVERSE REACTIONS
Most common adverse reactions (>1%) are headache, nausea, injection site and infusion site reactions, vasodilatation, vomiting, back pain, urinary urgency, chest pain, pain, dysgeusia, and abnormal vision.
Please see full prescribing information.
