gadobutrol
Injection · Intravenous
Uses
Gadobutrol Injection is indicated for: Magnetic resonance imaging (MRI) of the central nervous system (CNS) to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity in adult and pediatric patients including term neonates MRI of the breast to assess the presence and extent of malignant breast disease in adult patients Magnetic resonance angiography (MRA) to evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients including term neonates Cardiac MRI (CMRI) to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD) Gadobutrol Injection is a gadolinium-based contrast agent indicated for use with magnetic resonance imaging (MRI): To detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system in adult and pediatric patients, including term neonates To assess the presence and extent of malignant breast disease in adult patients To evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients including term neonates To assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD). ( 1 ).
Dosage and administration
Recommended dose for adults and pediatric patients, including term neonates, is 0.1 mmol/kg actual body weight (equivalent to 0.1 mL/kg) administered by intravenous bolus injection. ( 2.1 , 2.2 ) See Full Prescribing Information for administration, imaging, and handling.( 2.2 , 2.3 ) 2.1 Recommended Dose The recommended dose of Gadobutrol Injection for adult and pediatric patients, including term neonates, is 0.1 mmol/kg actual body weight (equivalent to 0.1 mL/kg) administered intravenously. For CMRI, the dose is divided into two separate, equal injections [see Dosage and Administration (2.2) ] . Refer to Table 1 for volumes to be administered for example body weights. Table 1: Volume of Gadobutrol Injection for Example Body Weights Body Weight (kg) Volume to be Administered (mL) 2.5 0.25 5 0.5 10 1 15 1.5 20 2 25 2.5 30 3 35 3.5 40 4 45 4.5 50 5 60 6 70 7 80 8 90 9 100 10 110 11 120 12 130 13 140 14 2.2 Administration and Imaging Instructions General Gadobutrol Injection is formulated at a higher concentration (1 mmol/mL) compared to certain other gadolinium-based contrast agents, resulting in a lower volume of administration [see Dosage and Administration (2.1) ] . Gadobutrol Injection is for intravenous use only and must not be administered intrathecally [see Warnings and Precautions (5.1) ] . Use aseptic technique when preparing and administering Gadobutrol Injection. Visually inspect Gadobutrol Injection 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. If solidification occurs due to cold exposure, bring Gadobutrol Injection to room temperature before use and inspect to ensure that the solution is clear and colorless to pale yellow. Do not mix Gadobutrol Injection with other medications and do not administer Gadobutrol Injection in the same intravenous line simultaneously with other medications. MRI of the CNS in Adult and Pediatric Patients Including Term Neonates Administer Gadobutrol Injection as an intravenous injection, manually or by power injector, at a flow rate of approximately 2 mL/sec. Follow Gadobutrol Injection with a flush of 0.9% Sodium Chloride Injection to ensure complete administration of the contrast. Post contrast MRI can commence immediately following contrast administration. MRI of the Breast in Adults Administer Gadobutrol Injection as an intravenous bolus by power injector, followed by a flush of 0.9% Sodium Chloride Injection to ensure complete administration of the contrast. Start image acquisition following Gadobutrol Injection administration and then repeat sequentially to determine peak intensity and wash-out. MR Angiography in Adult and Pediatric Patients Including Term Neonates Image acquisition should coincide with peak arterial concentration, which varies among patients. For adults, administer Gadobutrol Injection as an intravenous injection by power injector, at a flow rate of approximately 1.5 mL/sec, followed by a 30 mL flush of 0.9% Sodium Chloride Injection at the same rate to ensure complete administration of the contrast. For pediatric patients including term neonates, administer Gadobutrol Injection as an intravenous injection by power injector or manually, followed by a flush of 0.9% Sodium Chloride Injection to ensure complete administration of the contrast. Cardiac MRI in Adults Administer Gadobutrol Injection through a separate intravenous line in the contralateral arm if concomitantly providing a continuous infusion of a pharmacologic stress agent. Administer Gadobutrol Injection as two separate bolus injections: 0.05 mmol/kg actual body weight (equivalent to 0.05 mL/kg) at peak pharmacologic stress followed by 0.05 mmol/kg (equivalent to 0.05 mL/kg) at rest. Administer Gadobutrol Injection via a power injector at a flow rate of approximately 4 mL/sec and follow each injection with a 20 mL flush of 0.9% Sodium Chloride Injection at the same flow rate. 2.3 Directions for Use of Single-Dose Containers Single-Dose Vials Draw Gadobutrol Injection into the syringe immediately before use. Pierce the rubber stopper only once. Discard any unused vial contents.
Dosage forms and strengths
Injection: 1 mmol/mL of gadobutrol as a clear and colorless to pale yellow solution available in the following strengths: Strength Package Type 7.5 mmol/7.5 mL (1 mmol/mL) 10 mmol/10 mL (1 mmol/mL) 15 mmol/15 mL (1 mmol/mL) Single-Dose Vial Injection: 1 mmol/mL of gadobutrol available in single-dose vial ( 3 )
Contraindications
Gadobutrol Injection is contraindicated in patients with history of severe hypersensitivity reactions to Gadobutrol Injection [see Warnings and Precautions (5.3) ] . History of severe hypersensitivity reaction to Gadobutrol Injection ( 4 )
Warnings and precautions
• Hypersensitivity Reactions:Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, have occurred. Monitor patients closely during and after administration of Gadobutrol Injection. ( 5.3 )
• Acute Respiratory Distress Syndrome: For patients demonstrating respiratory distress after administration, assess oxygen requirement and monitor for worsening respiratory function. ( 5.4 )
• Gadolinium Retention: Gadolinium is retained for months or years in brain, bone, and other organs. ( 5.5 ) 5.1 Risk Associated with Intrathecal Use Intrathecal administration of GBCAs can cause serious adverse reactions including death, coma, encephalopathy, and seizures. The safety and effectiveness of Gadobutrol Injection have not been established with intrathecal use. Gadobutrol Injection is not approved for intrathecal use [see Dosage and Administration (2.2) ] . 5.2 Nephrogenic Systemic Fibrosis GBCAs increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of Gadobutrol Injection 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/1.73m 2 ) as well as patients with acute kidney injury. The risk appears lower for patients with chronic, moderate kidney disease (GFR 30 to 59 mL/min/1.73m 2 ) and little, if any, for patients with chronic, mild kidney disease (GFR 60 to 89 mL/min/1.73m 2 ). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Report any diagnosis of NSF following Gadobutrol Injection administration to Zydus Pharmaceuticals (USA) Inc. (1-877-993-8779) 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 and 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 Gadobutrol Injection dose and allow a sufficient period of time for elimination of the drug prior to re-administration. For patients receiving hemodialysis, consider the prompt initiation of hemodialysis following the administration of a GBCA in order to enhance the contrast agent’s elimination [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . The usefulness of hemodialysis in the prevention of NSF is unknown. 5.3 Hypersensitivity Reactions Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, have occurred following Gadobutrol Injection administration [see Adverse Reactions (6.1 , 6.2) ] . There have been reports of life-threatening and fatal outcomes from these adverse reactions. Most hypersensitivity reactions to Gadobutrol Injection have occurred within half an hour after administration. Delayed reactions can occur up to several days after administration. Before Gadobutrol Injection 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 Gadobutrol Injection. Gadobutrol Injection is contraindicated in patients with history of hypersensitivity reactions to Gadobutrol Injection [see Contraindications (4) ] . Administer Gadobutrol Injection only in situations where trained personnel and therapies are promptly available for the treatment of hypersensitivity reactions, including personnel trained in resuscitation. Observe patients for signs and symptoms of hypersensitivity reactions during and following Gadobutrol Injection administration. 5.4 Acute Respiratory Distress Syndrome Acute respiratory distress syndrome (ARDS) has been reported in patients administered Gadobutrol Injection and may be characterized by severe hypoxemia requiring oxygen support and mechanical ventilation. These manifestations may resemble an immediate hypersensitivity reaction with onset of respiratory distress within <30 minutes to 24 hours after Gadobutrol Injection administration. For patients demonstrating respiratory distress after Gadobutrol Injection administration, assess oxygen requirement and monitor for worsening respiratory function. 5.5 Gadolinium Retention Gadolinium is retained for months or years in several organs. The highest concentrations (nanomoles per gram of tissue) have been identified in the bone, followed by other organs (for example, brain, skin, kidney, liver, and spleen). The duration of retention also varies by tissue and is longest in bone. Linear GBCAs cause more retention than macrocyclic GBCAs. At equivalent doses, gadolinium retention varies among the linear agents with gadodiamide causing greater retention than other linear agents such as gadoxetate disodium and gadobenate dimeglumine. Retention is lowest and similar among the macrocyclic GBCAs such as gadoterate meglumine, gadobutrol, gadoteridol, and gadopiclenol. Consequences of gadolinium retention in the brain have not been established.
Side effects
The following clinically significant adverse reactions are discussed elsewhere in labeling: Nephrogenic Systemic Fibrosis [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Contraindications (4) and Warnings and Precautions (5.3) ] Acute Respiratory Distress Syndrome [see Warnings and Precautions (5.4) ] Most common adverse reactions (incidence ≥ 0.5%) are headache, nausea, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of Gadobutrol Injection was evaluated in 7,713 subjects (including 184 pediatric population, ages 0 to 17 years) who received Gadobutrol Injection in clinical trials. Approximately 52% of the subjects were male and the racial and ethnic distribution was 62% White, 28% Asian, 5% Hispanic or Latino, 2.5% Black or African American, and 2.5% other ethnic groups. The average age was 56 years (range from 1 week to 93 years). Table 2 lists adverse reactions that occurred in ≥ 0.1% subjects who received Gadobutrol Injection. Table 2: Adverse Reactions Reported in ≥0.1% Subjects who Received Gadobutrol Injection in Clinical Trials Adverse Reaction Gadobutrol Injection n=7,713 Rate (%) Headache 1.7 Nausea 1.2 Dizziness 0.5 Dysgeusia 0.4 Feeling Hot 0.4 Injection site reactions 0.4 Vomiting 0.4 Rash (includes generalized, macular, papular, pruritic) 0.3 Erythema 0.2 Paresthesia 0.2 Pruritus (includes generalized) 0.2 Dyspnea 0.1 Urticaria 0.1 Adverse reactions that occurred with a frequency of < 0.1% in subjects who received Gadobutrol Injection include: hypersensitivity/anaphylactic reaction, loss of consciousness, convulsion, parosmia, tachycardia, palpitation, dry mouth, malaise and feeling cold. Adverse Reactions in Pediatric Patients The frequency, type, and severity of adverse reactions observed in pediatric patients from the clinical studies were similar to adverse reactions in adults [see Use in Specific Populations (8.4) ] . 6.2 Postmarketing Experience The following additional adverse reactions have been identified during postmarketing use of Gadobutrol Injection or other GBCAs. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac Disorders: Cardiac arrest Gastrointestinal Disorders: Acute pancreatitis with onset within 48 hours after GBCA administration General Disorders and Administration Site Conditions: Fatigue, asthenia, pain syndromes, and heterogeneous clusters of symptoms in the neurological, cutaneous, and musculoskeletal systems with variable onset and duration after GBCA administration [see Warnings and Precautions (5.5) ] Immune System Disorders: Hypersensitivity reactions (anaphylactic shock, circulatory collapse, respiratory arrest, bronchospasm, cyanosis, oropharyngeal swelling, laryngeal edema, blood pressure increased, chest pain, angioedema, conjunctivitis, hyperhidrosis, cough, sneezing, burning sensation, and pallor). Renal Disorders: Nephrogenic systemic fibrosis Respiratory, Thoracic, and Mediastinal Disorders: Acute respiratory distress syndrome, pulmonary edema Skin Disorders: Gadolinium associated plaques
Use in specific populations
Pregnancy: Use only if imaging is essential during pregnancy and cannot be delayed. ( 8.1 ) 8.1 Pregnancy Risk Summary GBCAs cross the placenta and result in fetal exposure. In human placental imaging studies, contrast was visualized in the placenta and fetal tissues after maternal GBCA administration. Based on animal studies, use of GBCAs during pregnancy may result in fetal gadolinium retention. Published epidemiological studies on the association between GBCAs and adverse fetal outcomes have reported inconsistent findings and have important methodological limitations (see Data ) . In animal reproduction studies, although teratogenicity was not observed, embryolethality was observed in monkeys, rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 times and above the recommended human dose. Retardation of embryonal development was observed in rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 and 12 times, respectively, the recommended human dose (see Data ) . Because of the potential risks of gadolinium to the fetus, use Gadobutrol Injection only if imaging is essential during pregnancy and cannot be delayed. The background risk of major birth defects and miscarriage for the indicated population is 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 is 15% to 20%, respectively. Data Human Data Available data regarding exposure to GBCAs during pregnancy from published epidemiological studies are not sufficient to assess the risk of adverse fetal and neonatal effects that may be associated with GBCAs. A retrospective cohort study of over 1.4 million pregnancies in Ontario, Canada, comparing pregnant women who had a GBCA MRI to pregnant women who did not have an MRI, reported a higher occurrence of stillbirths and neonatal deaths in the group receiving GBCA MRI. Limitations of this study include a lack of comparison with non- contrast MRI and lack of information about the maternal indication for MRI. Another retrospective cohort study of over 11 million pregnancies in the Medicaid database found no increased risk of fetal or neonatal death or Neonatal Intensive Care Unit admission when comparing pregnancies exposed to GBCA MRI versus non-contrast MRI. These two retrospective observational studies assessed a limited number of potential pregnancy outcomes and did not evaluate the full spectrum of potential fetal risk. Animal Data Gadolinium Retention GBCAs administered to pregnant non-human primates (0.1 mmol/kg on gestational days 85 and 135) result in measurable gadolinium concentration in the offspring in bone, brain, skin, liver, kidney, and spleen for at least 7 months. GBCAs administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one month postnatal age. Reproductive Toxicology Embryolethality was observed when gadobutrol was administered intravenously to monkeys during organogenesis at doses 8 times the recommended single human dose (based on body surface area); gadobutrol was not maternally toxic or teratogenic at this dose. Embryolethality and retardation of embryonal development also occurred in pregnant rats receiving maternally toxic doses of gadobutrol (≥ 7.5 mmol/kg body weight; equivalent to 12 times the human dose based on body surface area) and in pregnant rabbits (≥ 2.5 mmol/kg body weight; equivalent to 8 times the recommended human dose based on body surface area). In rabbits, this finding occurred without evidence of pronounced maternal toxicity and with minimal placental transfer (0.01% of the administered dose detected in the fetuses). Because pregnant animals received repeated daily doses of Gadobutrol Injection, their overall exposure was significantly higher than that achieved with the standard single dose administered to humans. 8.2 Lactation Risk Summary There are no data on the presence of gadobutrol 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 present in breast milk and there is limited GBCA gastrointestinal absorption in the breast-fed infant. Gadobutrol is present in rat milk (see Data ) . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Gadobutrol Injection and any potential adverse effects on the breastfed infant from Gadobutrol Injection or from the underlying maternal condition. Data In lactating rats receiving 0.5 mmol/kg of intravenous [ 153 Gd]-gadobutrol, 0.01% of the total administered radioactivity was transferred to the pup via maternal milk within 3 hours after administration, and the gastrointestinal absorption is poor (approximately 5% of the dose orally administered was excreted in the urine). 8.4 Pediatric Use The safety and effectiveness of Gadobutrol Injection have been established in pediatric patients, including term neonates, for use with MRI to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the CNS and for use in MRA to evaluate known or suspected supra-aortic or renal artery disease. Use of Gadobutrol Injection for these indications is supported by adequate and well-controlled studies in adults and by additional imaging, pharmacokinetic, and safety data from two studies (i.e., Trials 1 and 2) in a total of 182 pediatric patients aged less than 18 years, including term neonates, with CNS and non-CNS lesions.
Pregnancy
8.1 Pregnancy Risk Summary GBCAs cross the placenta and result in fetal exposure. In human placental imaging studies, contrast was visualized in the placenta and fetal tissues after maternal GBCA administration. Based on animal studies, use of GBCAs during pregnancy may result in fetal gadolinium retention. Published epidemiological studies on the association between GBCAs and adverse fetal outcomes have reported inconsistent findings and have important methodological limitations (see Data ) . In animal reproduction studies, although teratogenicity was not observed, embryolethality was observed in monkeys, rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 times and above the recommended human dose. Retardation of embryonal development was observed in rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 and 12 times, respectively, the recommended human dose (see Data ) . Because of the potential risks of gadolinium to the fetus, use Gadobutrol Injection only if imaging is essential during pregnancy and cannot be delayed. The background risk of major birth defects and miscarriage for the indicated population is 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 is 15% to 20%, respectively. Data Human Data Available data regarding exposure to GBCAs during pregnancy from published epidemiological studies are not sufficient to assess the risk of adverse fetal and neonatal effects that may be associated with GBCAs. A retrospective cohort study of over 1.4 million pregnancies in Ontario, Canada, comparing pregnant women who had a GBCA MRI to pregnant women who did not have an MRI, reported a higher occurrence of stillbirths and neonatal deaths in the group receiving GBCA MRI. Limitations of this study include a lack of comparison with non- contrast MRI and lack of information about the maternal indication for MRI. Another retrospective cohort study of over 11 million pregnancies in the Medicaid database found no increased risk of fetal or neonatal death or Neonatal Intensive Care Unit admission when comparing pregnancies exposed to GBCA MRI versus non-contrast MRI. These two retrospective observational studies assessed a limited number of potential pregnancy outcomes and did not evaluate the full spectrum of potential fetal risk. Animal Data Gadolinium Retention GBCAs administered to pregnant non-human primates (0.1 mmol/kg on gestational days 85 and 135) result in measurable gadolinium concentration in the offspring in bone, brain, skin, liver, kidney, and spleen for at least 7 months. GBCAs administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one month postnatal age. Reproductive Toxicology Embryolethality was observed when gadobutrol was administered intravenously to monkeys during organogenesis at doses 8 times the recommended single human dose (based on body surface area); gadobutrol was not maternally toxic or teratogenic at this dose. Embryolethality and retardation of embryonal development also occurred in pregnant rats receiving maternally toxic doses of gadobutrol (≥ 7.5 mmol/kg body weight; equivalent to 12 times the human dose based on body surface area) and in pregnant rabbits (≥ 2.5 mmol/kg body weight; equivalent to 8 times the recommended human dose based on body surface area). In rabbits, this finding occurred without evidence of pronounced maternal toxicity and with minimal placental transfer (0.01% of the administered dose detected in the fetuses). Because pregnant animals received repeated daily doses of Gadobutrol Injection, their overall exposure was significantly higher than that achieved with the standard single dose administered to humans.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of Gadobutrol Injection have been established in pediatric patients, including term neonates, for use with MRI to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the CNS and for use in MRA to evaluate known or suspected supra-aortic or renal artery disease. Use of Gadobutrol Injection for these indications is supported by adequate and well-controlled studies in adults and by additional imaging, pharmacokinetic, and safety data from two studies (i.e., Trials 1 and 2) in a total of 182 pediatric patients aged less than 18 years, including term neonates, with CNS and non-CNS lesions. Trial 1 included 138 patients aged 2 to less than 18 years and Trial 2 included 44 patients aged less than 2 years [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14.1 , 14.3 )] . The safety and effectiveness of Gadobutrol Injection have not been established in preterm neonates for any indication or in pediatric patients of any age for use with MRI to assess the presence and extent of malignant breast disease, or for use in CMRI to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in patients with known or suspected coronary artery disease (CAD).
Geriatric use
8.5 Geriatric Use In clinical studies of Gadobutrol Injection, 1,377 patients were 65 years of age and over, while 104 patients were 80 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences between the elderly and younger patients. This drug is known to be 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 [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6) ] .
Overdosage
In the event of an overdose with Gadobutrol Injection, the substance can be removed by hemodialysis [see Clinical Pharmacology (12.3) ] . For additional overdose management recommendations, consider contacting the Poison Help line at 1-800-222-1222 or consulting a medical toxicologist.
Description
Gadobutrol Injection is a paramagnetic macrocyclic gadolinium-based contrast agent for intravenous use. The chemical name for gadobutrol is 10–[(1SR,2RS)–2,3–dihydroxy–1–hydroxymethylpropyl]–1,4,7,10–tetraazacyclododecane–1,4,7–triacetic acid, gadolinium complex. Gadobutrol is a water-soluble, hydrophilic compound with a partition coefficient between n-butanol and buffer at pH 7.6 of 0.006,and has a molecular formula of C 18 H 31 GdN 4 O 9 and a molecular weight of 604.72.The structural formula of gadobutrol is: Gadobutrol Injection is a sterile, clear, colorless to pale yellow solution. Each mL contains 604.72 mg (1 mmol) of gadobutrol (containing 1 mmol of gadolinium) and the following inactive ingredients: 0.513 mg of calcobutrol sodium, 1.211 mg of trometamol, hydrochloric acid (for pH adjustment), and water for injection. Gadobutrol Injection contains no preservatives. The main physicochemical properties of Gadobutrol Injection are listed in Table 3. Table 3: Physicochemical Properties of Gadobutrol Injection Parameter Value Density (g/mL at 37°C) 1.3 Osmolarity at 37°C (mOsm/L solution) 1117 Osmolality at 37°C (mOsm/kg H 2 O) 1603 Viscosity at 37°C (mPa·s) 4.96 pH 6.6 to 8 The thermodynamic stability constants for gadobutrol (log Ktherm and log Kcond at pH 7.4) are 21.8 and 15.3, respectively. Structural Formula
Mechanism of action
12.1 Mechanism of Action Gadobutrol is a paramagnetic molecule (macrocyclic non-ionic complex of gadolinium) that develops a magnetic moment when placed in a magnetic field. The magnetic moment alters the relaxation rates of water protons in its vicinity in the body, leading to an increase in signal intensity (brightness) of tissues.
How supplied
How Supplied Gadobutrol Injection is supplied at a concentration of 1 mmol/mL of gadobutrol as a clear and colorless to pale yellow solution available in the following strengths: NDC 42337-005-02: 7.5 mmol/7.5 mL (1 mmol/mL) single-dose vials (42337-005-01) rubber stoppered in cartons of 10. NDC 42337-006-02: 10 mmol/10 mL (1 mmol/mL) single-dose vials (42337-006-01) rubber stoppered in cartons of 10. NDC 42337-007-02: 15 mmol/15 mL (1 mmol/mL) single-dose vials (42337-007-01) rubber stoppered in cartons of 10. Storage and Handling Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. If solidification occurs due to cold exposure, bring Gadobutrol Injection to room temperature before use and inspect to ensure that the solution is clear and colorless to pale yellow.
Storage
Storage and Handling Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. If solidification occurs due to cold exposure, bring Gadobutrol Injection to room temperature before use and inspect to ensure that the solution is clear and colorless to pale yellow.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Nephrogenic Systemic Fibrosis Inform the patient that Gadobutrol Injection may increase the risk of NSF among patients with impaired elimination of the drug 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 Gadobutrol Injection 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. [see Warnings and Precautions (5.2) ] . Acute Respiratory Distress Syndrome Advise patients that acute respiratory distress syndrome (ARDS) has occurred with Gadobutrol Injection. Inform patients on the symptoms of the observed ARDS cases, and instruct patients to inform their healthcare provider if they experience these symptoms [see Warnings and Precautions (5.4) ] . Gadolinium Retention Advise patients that gadolinium is retained for months or years in brain, bone, skin, and other organs following Gadobutrol Injection 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. [see Warnings and Precautions (5.5) ] . Pregnancy Advise pregnant women of the potential risk of fetal exposure to Gadobutrol Injection [see Use in Specific Populations (8.1) ] .
Label text from the FDA structured product label by Viwit Pharmaceutical Co., Ltd. (revised Jul 23, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Gadobutrol in 15 products
gadobutrol NDC products (15)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 65219-281 | Gadobutrol 604.72 mg/mL Injection | Fresenius Kabi USA, LLC | ANDA |
| 65219-287 | Gadobutrol 604.72 mg/mL Injection | Fresenius Kabi USA, LLC | ANDA |
| 65219-289 | Gadobutrol 604.72 mg/mL Injection | Fresenius Kabi USA, LLC | ANDA |
| 70436-212 | Gadobutrol 604.72 mg/mL Injection | Slate Run Pharmaceuticals, LLC | ANDA |
| 70436-213 | Gadobutrol 604.72 mg/mL Injection | Slate Run Pharmaceuticals, LLC | ANDA |
| 70436-214 | Gadobutrol 604.72 mg/mL Injection | Slate Run Pharmaceuticals, LLC | ANDA |
| 70436-216 | Gadobutrol 604.72 mg/mL Injection | Slate Run Pharmaceuticals, LLC | ANDA |
| 70436-217 | Gadobutrol 604.72 mg/mL Injection | Slate Run Pharmaceuticals, LLC | ANDA |
| 70436-218 | Gadobutrol 604.72 mg/mL Injection | Slate Run Pharmaceuticals, LLC | ANDA |
| 42337-005 | Gadobutrol 604.72 mg/mL Injection | Viwit Pharmaceutical Co., Ltd. | ANDA |
| 42337-006 | Gadobutrol 604.72 mg/mL Injection | Viwit Pharmaceutical Co., Ltd. | ANDA |
| 42337-007 | Gadobutrol 604.72 mg/mL Injection | Viwit Pharmaceutical Co., Ltd. | ANDA |
| 70710-2064 | Gadobutrol 604.72 mg/mL Injection | Zydus Pharmaceuticals USA Inc. | ANDA |
| 70710-2065 | Gadobutrol 604.72 mg/mL Injection | Zydus Pharmaceuticals USA Inc. | ANDA |
| 70710-2066 | Gadobutrol 604.72 mg/mL Injection | Zydus Pharmaceuticals USA Inc. | ANDA |
Frequently asked questions
What is gadobutrol used for?
Gadobutrol Injection is indicated for: Magnetic resonance imaging (MRI) of the central nervous system (CNS) to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity in adult and pediatric patients including term neonates MRI of the breast to assess the presence and extent of malignant breast disease in adult patients Magnetic resonance angiography (MRA) to…
What are the side effects of gadobutrol?
The following clinically significant adverse reactions are discussed elsewhere in labeling: Nephrogenic Systemic Fibrosis [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Contraindications (4) and Warnings and Precautions (5.3) ] Acute Respiratory Distress Syndrome [see Warnings and Precautions (5.4) ] Most common adverse reactions (incidence ≥ 0.5%) are headache, nausea, and… See the full label for the complete list.
Who makes gadobutrol?
gadobutrol is listed by 4 labelers in the FDA NDC directory, including Fresenius Kabi USA, LLC, Slate Run Pharmaceuticals, LLC, Viwit Pharmaceutical Co., Ltd., Zydus Pharmaceuticals USA Inc..