Usage
Gadobutrol is a gadolinium-based contrast agent (GBCA) used in magnetic resonance imaging (MRI). It’s prescribed to enhance the visualization of internal organs and tissues, particularly in the following scenarios:
- Central Nervous System (CNS): Detecting and visualizing areas with a disrupted blood-brain barrier (BBB) and/or abnormal vascularity in the brain and spine. This aids in the diagnosis of conditions like tumors, inflammation, and infections.
- Breast: Assessing the presence and extent of malignant breast disease.
- Supra-aortic and Renal Arteries: Evaluating known or suspected arterial disease in these regions.
- Myocardial Perfusion: Assessing blood flow to the heart muscle (myocardium) and identifying areas of damaged heart tissue, particularly in patients with known or suspected coronary artery disease.
Pharmacological Classification: Contrast Agent (MRI)
Mechanism of Action: Gadobutrol shortens the T1 relaxation time of water protons within body tissues. This increases the signal intensity on T1-weighted MRI images, creating a brighter appearance in areas where the contrast agent accumulates, leading to improved tissue differentiation and visualization of abnormalities.
Alternate Names
- Generic Name: Gadobutrol
- Other Names: Gadoteric acid, Butrol
- Brand Name: Gadavist
How It Works
Pharmacodynamics: Gadobutrol exerts its effect by shortening the T1 relaxation time of water protons in tissues. This leads to increased signal intensity on T1-weighted MRI images. It does not have any direct pharmacological effect on the body.
Pharmacokinetics:
- Absorption: Administered intravenously, therefore 100% bioavailable. Peak plasma concentration is reached within minutes of administration.
- Distribution: Distributed rapidly into the extracellular space. Does not cross the intact blood-brain barrier.
- Metabolism: Not metabolized.
- Elimination: Excreted primarily unchanged via the kidneys through glomerular filtration. A small amount may be eliminated through the feces. Elimination half-life is approximately 1.5 to 2 hours in patients with normal renal function.
Mode of Action: Gadobutrol contains the paramagnetic gadolinium ion, which interacts with surrounding water molecules. This interaction shortens the T1 relaxation time of the protons in these water molecules, ultimately resulting in enhanced signal intensity on MRI images.
Receptor Binding, Enzyme Inhibition, Neurotransmitter Modulation: Gadobutrol does not bind to receptors, inhibit enzymes, or modulate neurotransmitters.
Dosage
Standard Dosage
Adults:
0.1 mmol/kg body weight (equivalent to 0.1 mL/kg of a 1.0 M solution) administered as an intravenous bolus injection at a rate of approximately 2 mL/second. For certain indications, like CNS imaging, a minimum dose of 0.075 mmol/kg may be used. In cases where a lesion is suspected despite an unremarkable initial MRI, a second injection of up to 0.2 ml/kg body weight may be administered within 30 minutes of the first injection. For breast MRI, a maximum total dose of 0.3 mmol/kg may be administered.
Children:
0.1 mmol/kg body weight (equivalent to 0.1 mL/kg of a 1.0 M solution) administered as an intravenous bolus injection. This dosage applies to children of all ages, including term neonates. The infusion rate for CNS imaging and BBB disruption evaluation should be approximately 2 mL/second. For magnetic resonance angiography (MRA), a rate of approximately 1.5 mL/second is recommended.
Special Cases:
- Elderly Patients: No dose adjustment is typically necessary. However, caution should be exercised due to the potential for reduced renal function.
- Patients with Renal Impairment: No dose adjustment is recommended, but caution is warranted. Gadobutrol is cleared by hemodialysis.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary as gadobutrol is primarily renally excreted.
- Patients with Comorbid Conditions: Evaluate patient-specific factors, such as cardiovascular disease or diabetes, which may increase the risk of complications.
Clinical Use Cases
The standard dose (0.1 mmol/kg) applies to various clinical settings, including intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations. However, renal function should always be assessed beforehand. Cardiac MRI may use a modified protocol.
Dosage Adjustments
No routine dosage adjustments are recommended for specific medical settings or emergency situations outside the guidelines provided above. Patient-specific factors like renal dysfunction or comorbid conditions should be considered when determining the suitability and safety of Gadobutrol administration.
Side Effects
Common Side Effects:
- Headache
- Nausea
- Injection site reactions (pain, burning, coldness)
- Dysgeusia (altered taste)
- Feeling hot or cold
Rare but Serious Side Effects:
- Nephrogenic Systemic Fibrosis (NSF) in patients with severe renal impairment
- Hypersensitivity/anaphylactoid reactions (ranging from mild skin reactions to severe cardiovascular and respiratory compromise, including anaphylactic shock and death).
- Cardiac arrest
Long-Term Effects:
Gadolinium deposition may occur in various tissues, including the brain. The long-term effects of gadolinium retention are not fully understood, but current evidence suggests no significant adverse effects in patients with normal renal function.
Adverse Drug Reactions (ADR):
Any hypersensitivity reaction should be considered a serious ADR and requires immediate medical intervention. NSF, although rare, is also a serious ADR.
Contraindications
- Known hypersensitivity to gadobutrol or any component of the formulation.
Drug Interactions
No clinically significant drug interactions have been reported. However, as a precaution, it is generally recommended not to mix Gadobutrol with other drugs in the same syringe or IV line.
Pregnancy and Breastfeeding
- Pregnancy: Gadobutrol crosses the placenta. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies showed adverse effects at high doses.
- Breastfeeding: Gadobutrol is excreted in breast milk in small amounts. While no adverse effects are anticipated in infants due to limited absorption, the decision to continue or discontinue breastfeeding should be made in consultation with the physician and the mother. Consider temporarily withholding breastfeeding for 24 hours after administration.
Drug Profile Summary
- Mechanism of Action: Shortens T1 relaxation time of water protons, enhancing MRI signal intensity.
- Side Effects: Headache, nausea, injection site reactions, dysgeusia, feeling hot/cold. Rarely: NSF, hypersensitivity reactions, cardiac arrest.
- Contraindications: Hypersensitivity to gadobutrol.
- Drug Interactions: None known.
- Pregnancy & Breastfeeding: Use with caution. Discuss risks and benefits with the patient.
- Dosage: 0.1 mmol/kg IV.
- Monitoring Parameters: Renal function, signs of hypersensitivity, signs/symptoms of NSF.
Popular Combinations
Gadobutrol is typically used alone. In cardiac MRI, it might be used in conjunction with pharmacologic stress agents, but these should be administered through a separate IV line in the contralateral arm.
Precautions
- General Precautions: Evaluate renal function prior to administration. Be prepared to manage hypersensitivity reactions.
- Specific Populations: Assess risk/benefit carefully in pregnant/breastfeeding women. No dose adjustments necessary for children or elderly, but consider age-related physiological changes and potential for renal impairment.
- Lifestyle Considerations: No specific lifestyle considerations are associated with Gadobutrol administration.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Gadobutrol?
A: The standard dose is 0.1 mmol/kg (0.1 mL/kg) administered as an IV bolus injection. For children, including term neonates, the same dose is recommended.
Q2: What are the common side effects of Gadobutrol?
A: Common side effects include headache, nausea, injection site reactions (pain, burning, coldness), dysgeusia, and feeling hot or cold.
Q3: What are the contraindications for Gadobutrol?
A: The primary contraindication is a known hypersensitivity to gadobutrol or any component of the formulation.
Q4: How is Gadobutrol eliminated from the body?
A: Gadobutrol is primarily eliminated unchanged through the kidneys via glomerular filtration.
Q5: Can Gadobutrol be used in patients with renal impairment?
A: While no dose adjustment is routinely recommended, caution should be exercised in patients with renal impairment. Gadobutrol can be removed by hemodialysis.
Q6: Can Gadobutrol be used in pregnant or breastfeeding women?
A: It should only be used if essential and the benefits outweigh the risks. Discuss the risks and benefits with the patient. For breastfeeding women, consider temporarily withholding breastfeeding for 24 hours after administration.
Q7: Are there any known drug interactions with Gadobutrol?
A: No clinically significant drug interactions have been established. However, avoid mixing Gadobutrol with other drugs in the same syringe or IV line.
A: NSF is a rare but serious condition characterized by fibrosis of the skin and internal organs. It has been associated with the use of GBCAs, including Gadobutrol, particularly in patients with severe renal impairment.
Q9: What monitoring parameters are important after Gadobutrol administration?
A: Monitor renal function, observe for any signs of hypersensitivity reaction, and conduct short- and long-term monitoring for signs and symptoms of NSF.
Q10: Can Gadobutrol be used in children?
A: Yes, the recommended dose for children of all ages, including neonates, is the same as for adults: 0.1 mmol/kg.
