gadobutrol 604.72 mg/mL Injection
🆔 Identity & classification
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🩺 Clinical
- Gadobutrol is a contrast agent — a special liquid injected into your vein just before the MRI scan. It contains a metal called gadolinium that responds to the MRI's magnetic field...
- What exactly is gadobutrol and why do I need it for my MRI?
- Most people feel little to nothing, or a brief cool or flushing sensation as the injection goes in. The most common side effects are headache, nausea, dizziness, and occasionally a...
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UNII PO5286589K
A synthetic compound used as a preservative and antimicrobial agent in medicines. It helps prevent bacterial and fungal growth, extending the product's shelf life and maintaining stability.
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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UNII 023C2WHX2V
Tromethamine is a chemical buffer that helps maintain the proper acidity level in liquid medicines. It neutralizes acids and stabilizes the solution so the medication remains effective and safe throughout its shelf life.
3 inactive ingredients listed in the exact product block matched to this NDC.
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| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Gadobutrol 604.72 mg/mL 65219-0287-30 | Fresenius | 10 bottles | — | — | FDA listed | — |
| gadobutrol 604.72 mg/mL 70436-0217-80 | Slate | 1 vial | — | AP | FDA listed | — |
| Gadavist 604.72 mg/mL 50419-0325-14 | Bayer | 5 bottles | — | AP | Discontinued | — |
| gadobutrol 604.72 mg/mL 70436-0214-54 | Slate | 20 vials | — | AP | FDA listed | — |
| gadobutrol 604.72 mg/mL 70436-0213-82 | Slate | 10 vials | — | AP | FDA listed | — |
| gadobutrol 604.72 mg/mLthis 70436-0218-84 | Slate | 3 vials | — | AP | FDA listed | — |
| gadobutrol 604.72 mg/mL 70436-0212-54 | Slate | 20 vials | — | AP | FDA listed | — |
| Gadobutrol 604.72 mg/mL 65219-0289-65 | Fresenius | 10 bottles | — | — | FDA listed | — |
| gadobutrol 604.72 mg/mL 70436-0216-81 | Slate | 5 vials | — | AP | FDA listed | — |
| Gadobutrol 604.72 mg/mL 65219-0281-02 | Fresenius | 3 vials | — | — | FDA listed | — |
| gadobutrol 604.72 mg/mL 42337-0007-02 | Viwit | 10 vials | — | AP | FDA listed | — |
| gadobutrol 604.72 mg/mL 70710-2066-06 | Zydus | 10 vials | — | AP | FDA listed | — |
| gadobutrol 604.72 mg/mL 42337-0005-02 | Viwit | 10 vials | — | AP | FDA listed | — |
| gadobutrol 604.72 mg/mL 70710-2064-06 | Zydus | 10 vials | — | AP | FDA listed | — |
| gadobutrol 604.72 mg/mL 70710-2065-06 | Zydus | 10 vials | — | AP | FDA listed | — |
| gadobutrol 604.72 mg/mL 42337-0006-02 | Viwit | 10 vials | — | AP | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 70436-0218-84 You're viewing this | 3 VIAL, SINGLE-DOSE in 1 CARTON (70436-218-84) / 2 mL in 1 VIAL, SINGLE-DOSE (70436-218-30) | 2025-04-16 | Active |
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: RISK ASSOCIATED WITH INTRATHECAL USE and NEPHROGENIC SYSTEMIC FIBROSIS Risk Associated with Intrathecal Use Intrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious adverse reactions including death, coma, encephalopathy, and seizures. Gadobutrol injection is not approved for intrathecal use [see Warnings and Precautions ( 5.1 )] . 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 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/1.73m 2 ), 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 gadobutrol injection 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 ( 5.2 )] .
WARNING: RISK ASSOCIATED WITH INTRATHECAL USE and NEPHROGENIC SYSTEMIC FIBROSIS See full prescribing information for complete boxed warning. Intrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious adverse reactions including death, coma, encephalopathy, and seizures. Gadobutrol injection is not approved for intrathecal use ( 5.1 ) GBCAs increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs.
Avoid use of gadobutrol injection 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: Chronic, severe kidney disease (GFR <30 mL/min/1.73m 2 ), 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. ( 5.2 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE 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 ( 1.1 ) To assess the presence and extent of malignant breast disease in adult patients ( 1.2 ) To evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients, including term neonates ( 1.3 ) To assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD) ( 1.4 )
1.1Magnetic Resonance Imaging (MRI) of the Central Nervous System (CNS) Gadobutrol injection is indicated for use with magnetic resonance imaging (MRI) in adult and pediatric patients, including term neonates to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system.
1.2MRI of the Breast Gadobutrol injection is indicated for use with MRI in adult patients to assess the presence and extent of malignant breast disease.
1.3Magnetic Resonance Angiography (MRA) Gadobutrol injection is indicated for use in magnetic resonance angiography (MRA) in adult and pediatric patients, including term neonates, to evaluate known or suspected supra-aortic or renal artery disease.
1.4Cardiac MRI Gadobutrol injection is indicated for use in cardiac MRI (CMRI) to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD).
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended dose for adults and pediatric patients (including term neonates) is 0.1 mL/kg body weight ( 2.1 ) Administer as an intravenous bolus injection ( 2.2 ) Follow injection with a normal saline flush ( 2.2 )
2.1Recommended Dose The recommended dose of gadobutrol injection for adult and pediatric patients (including term neonates) is 0.1 mL/kg body weight (0.1 mmol/kg). Refer to Table 1 to determine the volume to be administered. Table 1: Volume of Gadobutrol Injection by Body Weight for Cardiac MRI, the dose is divided into 2 separate, equal injections 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
2.2Administration Guidelines 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. Use Table 1 to determine the volume to be administered. Use sterile technique when preparing and administering gadobutrol injection.
MRI of the Central Nervous System Administer gadobutrol injection as an intravenous injection, manually or by power injector, at a flow rate of approximately 2 mL/second. Follow gadobutrol injection with a normal saline flush to ensure complete administration of the contrast. Post contrast MRI can commence immediately following contrast administration.
MRI of the Breast Administer gadobutrol injection as an intravenous bolus by power injector, followed by a normal saline flush to ensure complete administration of the contrast. Start image acquisition following contrast administration and then repeat sequentially to determine peak intensity and wash-out. MR Angiography Image acquisition should coincide with peak arterial concentration, which varies among patients.
Adults Administer gadobutrol injection by power injector, at a flow rate of approximately 1.5 mL/second, followed by a 30 mL normal saline flush at the same rate to ensure complete administration of the contrast. Pediatric patients Administer gadobutrol injection by power injector or manually, followed by a normal saline flush to ensure complete administration of the contrast. Cardiac MRI 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 (2) separate bolus injections: 0.05 mL/kg (0.05 mmol/kg) body weight at peak pharmacologic stress followed by 0.05 mL/kg (0.05 mmol/kg) body weight at rest. Administer gadobutrol injection via a power injector at a flow rate of approximately 4 mL/second and follow each injection with a normal saline flush of 20 mL at the same flow rate.
2.3Drug Handling 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. Do not mix gadobutrol injection with other medications and do not administer gadobutrol injection in the same intravenous line simultaneously with other medications because of the potential for chemical incompatibility.
Vials Draw gadobutrol injection into the syringe immediately before use. Do not pierce the rubber stopper more than once. Discard any unused vial contents.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Gadobutrol injection is a sterile, clear, and colorless to pale yellow solution for injection containing 604.72 mg gadobutrol per mL (equivalent to 1 mmol gadobutrol/mL) supplied in single-dose vials. Gadobutrol injection contains 604.72 mg gadobutrol/mL (equivalent to 1 mmol gadobutrol/mL) and is available in vials ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Gadobutrol injection is contraindicated in patients with history of severe hypersensitivity reactions to gadobutrol injection. History of severe hypersensitivity reaction to gadobutrol injection ( 4 )
⚠️ Warnings and Cautions ▾
5 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 )
5.1Risk 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 )] .
5.2Nephrogenic 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 Slate Run Pharmaceuticals, LLC at 1-888-341-9214 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 [see Clinical Pharmacology ( 12.3 )] .
5.3Hypersensitivity Reactions Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following gadobutrol injection administration [see Adverse Reactions ( 6 )] . 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.
Administer gadobutrol injection only in situations where trained personnel and therapies are promptly available for the treatmen…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in labeling: Nephrogenic Systemic Fibrosis (NSF) [see Boxed Warning and 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 )] .
Gadolinium Retention [see Warnings and Precautions ( 5.5 )]. Most common adverse reactions (incidence ≥0.5%) are headache, nausea, and dizziness ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Slate Run Pharmaceuticals, LLC at 1-888-341-9214 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 adverse reactions described in this section reflect gadobutrol injection exposure in 7,713 subjects (including 184 pediatric patients, ages 0 to 17 years) with the majority receiving the recommended dose. Approximately 52% of the subjects were male and the ethnic distribution was 62% Caucasian, 28% Asian, 5% Hispanic, 2.5% Black, and 2.5% patients of other ethnic groups.
The average age was 56 years (range from 1 week to 93 years). Overall, approximately 4% of subjects reported one or more adverse reactions during a follow-up period that ranged from 24 hours to 7 days after gadobutrol injection administration. Adverse reactions associated with the use of gadobutrol injection were usually mild to moderate in severity and transient in nature.
Table 2 lists adverse reactions that occurred in ≥0.1% subjects who received gadobutrol injection. Table 2: Adverse Reactions Reaction Rate (%) n=7713 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
0.1Adverse 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.
6.2Postmarketing Experience The following additional adverse reactions have been reported 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 arrest Nephrogenic Systemic Fibrosis (NSF) 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).
Respiratory, Thoracic, and Mediastinal Disorders: Acute respiratory distress syndrome, pulmonary edema General Disorders and Administration Site Conditions: Adverse reactions with variable onset and duration have been reported after GBCA administration. These include fatigue, asthenia, pain syndromes, and heterogeneous clusters of symptoms in the neurological, cutaneous, and musculoskeletal systems. Skin: Gadolinium associated plaques Gastrointestinal Disorders: Acute pancreatitis with onset within 48 hours after GBCA administration
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Use only if imaging is essential during pregnancy and cannot be delayed. ( 8.1 )
8.1Pregnancy Risk Summary GBCAs cross the placenta and result in fetal exposure and gadolinium retention. The human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive (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 estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
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 Contrast enhancement is visualized in the placenta and fetal tissues after maternal GBCA administration. Cohort studies and case reports on exposure to GBCAs during pregnancy have not reported a clear association between GBCAs and adverse effects in the exposed neonates.
However, a retrospective cohort study, 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. Overall, these data preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of GBCAs in pregnancy.
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.
8.2Lactation 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 breastfe…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary GBCAs cross the placenta and result in fetal exposure and gadolinium retention. The human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive (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 estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
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 Contrast enhancement is visualized in the placenta and fetal tissues after maternal GBCA administration. Cohort studies and case reports on exposure to GBCAs during pregnancy have not reported a clear association between GBCAs and adverse effects in the exposed neonates.
However, a retrospective cohort study, 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. Overall, these data preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of GBCAs in pregnancy.
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 ▾
8.4Pediatric 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 central nervous system and for use in MRA to evaluate known or suspected supra-aortic or renal artery disease. Use of gadobutrol injection in these indications is supported by adequate and well-controlled studies in adults and supportive imaging data in two studies in 135 patients 2 to less than 18 years of age and 44 patients less than 2 years of age with CNS and non-CNS lesions, and pharmacokinetic data in 130 patients 2 to less than 18 years of age and 43 patients less than 2 years of age, including term neonates [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.1 )] .
The frequency, type, and severity of adverse reactions in pediatric patients were similar to adverse reactions in adults [see Adverse Reactions ( 6.1 )] . No dose adjustment according to age is necessary in pediatric patients [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14.1 )] . 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).
NSF Risk No case of NSF associated with gadobutrol injection or any other GBCA has been identified in pediatric patients ages 6 years and younger. Pharmacokinetic studies suggest that clearance of gadobutrol injection is similar in pediatric patients and adults, including pediatric patients age younger than 2 years. No increased risk factor for NSF has been identified in juvenile animal studies of gadobutrol.
Normal estimated GFR (eGFR) is around 30 mL/min/1.73m 2 at birth and increases to mature levels around 1 year of age, reflecting growth in both glomerular function and relative body surface area. Clinical studies in pediatric patients younger than 1 year of age have been conducted in patients with the following minimum eGFR: 31 mL/min/1.73m 2 (age 2 to 7 days), 38 mL/min/1.73m 2 (age 8 to 28 days), 62 mL/min/1.73m 2 (age 1 to 6 months), and 83 mL/min/1.73m 2 (age 6 to 12 months). Juvenile Animal Data Single and repeat-dose toxicity studies in neonatal and juvenile rats did not reveal findings suggestive of a specific risk for use in pediatric patients including term neonates and infants.
🧓 Geriatric Use ▾
8.5Geriatric 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 in responses between the elderly and younger patients. In general, use of gadobutrol injection in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy.
No dose adjustment according to age is necessary in this population.
🆘 Overdosage ▾
10 OVERDOSAGE The maximum dose of gadobutrol injection tested in healthy volunteers, 1.5 mL/kg body weight (1.5 mmol/kg; 15 times the recommended dose), was tolerated in a manner similar to lower doses. Gadobutrol injection can be removed by hemodialysis [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )].
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action In MRI, visualization of normal and pathological tissue depends in part on variations in the radiofrequency signal intensity that occurs with: Differences in proton density Differences of the spin-lattice or longitudinal relaxation times (T 1 ) Differences in the spin-spin or transverse relaxation time (T 2 ) When placed in a magnetic field, gadobutrol injection shortens the T 1 and T 2 relaxation times. The extent of decrease of T 1 and T 2 relaxation times, and therefore the amount of signal enhancement obtained from gadobutrol injection, is based upon several factors including the concentration of gadobutrol injection in the tissue, the field strength of the MRI system, and the relative ratio of the longitudinal and transverse relaxation times.
At the recommended dose, the T 1 shortening effect is observed with greatest sensitivity in T 1 -weighted magnetic resonance sequences. In T 2 *-weighted sequences the induction of local magnetic field inhomogeneities by the large magnetic moment of gadolinium and at high concentrations (during bolus injection) leads to a signal decrease.
12.2Pharmacodynamics Gadobutrol injection leads to distinct shortening of the relaxation times even in low concentrations. At pH 7, 37°C and
1.5T, the relaxivity (r 1 ) - determined from the influence on the relaxation times (T 1 ) of protons in plasma - is
5.2L/(mmol·sec) and the relaxivity (r 2 ) - determined from the influence on the relaxation times (T 2 ) - is
6.1L/(mmol·sec). These relaxivities display only slight dependence on the strength of the magnetic field. The T 1 shortening effect of paramagnetic contrast agents is dependent on concentration and r 1 relaxivity (see Table 3). This may improve tissue visualization. Table 3: Relaxivity (r 1 ) of Gadolinium Chelates at 1.5T Gadolinium-Chelate r 1 (L·mmol -1 ·s -1 ) Gadobenate
6.3 Gadobutrol
5.2 Gadodiamide
4.3 Gadofosveset 16 Gadopentetate
4.1 Gadoterate
3.6 Gadoteridol
4.1 Gadoversetamide
4.7Gadoxetate 6.9 r 1 relaxivity in plasma at 37°C Compared to 0.5 molar gadolinium-based contrast agents, the higher concentration of gadobutrol injection results in half the volume of administration and a more compact contrast bolus injection. At the site of imaging, the relative height and width of the time intensity curve for gadobutrol injection varies as a function of imaging location and multiple patient, injection, and device-specific factors. Gadobutrol injection is a water-soluble, hydrophilic compound with a partition coefficient between n-butanol and buffer at pH 7.6 of about 0.006.
12.3Pharmacokinetics Distribution After intravenous administration, gadobutrol is rapidly distributed in the extracellular space. After a gadobutrol dose of 0.1 mmol/kg body weight, an average level of 0.59 mmol gadobutrol/L was measured in plasma 2 minutes after the injection and 0.3 mmol gadobutrol/L 60 minutes after the injection. Gadobutrol does not display any particular protein binding.
Following GBCA administration, gadolinium is present for months or years in brain, bone, skin, and other organs [see Warnings and Precautions ( 5.5 )]. Metabolism Gadobutrol is not metabolized. Elimination Values for AUC, body weight normalized plasma clearance and half-life are given in Table 4, below.
Gadobutrol is excreted in an unchanged form via the kidneys. In healthy subjects, renal clearance of gadobutrol is 1.1 to 1.7 mL/(min∙kg) and thus comparable to the renal clearance of inulin, confirming that gadobutrol is eliminated by glomerular filtration. Within two hours after intravenous administration more than 50% and within 12 hours more than 90% of the given dose is eliminated via the urine.
Extra-renal elimination is negligible. Specific Populations Gender Gender has no clinically relevant effect on the pharmacokinetics of gadobutrol. Geriatric A single IV dose of 0.1 mmol/kg gadobutrol injection was administered to 15 elderly and 16 non-elderly subjects.
AUC wa…
🧬 Mechanism of Action ▾
12.1Mechanism of Action In MRI, visualization of normal and pathological tissue depends in part on variations in the radiofrequency signal intensity that occurs with: Differences in proton density Differences of the spin-lattice or longitudinal relaxation times (T 1 ) Differences in the spin-spin or transverse relaxation time (T 2 ) When placed in a magnetic field, gadobutrol injection shortens the T 1 and T 2 relaxation times. The extent of decrease of T 1 and T 2 relaxation times, and therefore the amount of signal enhancement obtained from gadobutrol injection, is based upon several factors including the concentration of gadobutrol injection in the tissue, the field strength of the MRI system, and the relative ratio of the longitudinal and transverse relaxation times.
At the recommended dose, the T 1 shortening effect is observed with greatest sensitivity in T 1 -weighted magnetic resonance sequences. In T 2 *-weighted sequences the induction of local magnetic field inhomogeneities by the large magnetic moment of gadolinium and at high concentrations (during bolus injection) leads to a signal decrease.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Gadobutrol injection is a sterile, clear and colorless to pale yellow solution containing 604.72 mg gadobutrol per mL (equivalent to 1 mmol gadobutrol) per mL. Gadobutrol injection is supplied in the following sizes: Single-Dose Containers (Vials) 2 mL single-dose vials, rubber stoppered in cartons of 3 (NDC 70436-218-84) 7.5 mL single-dose vials, rubber stoppered in cartons of 1 (NDC 70436-212-80) 7.5 mL single-dose vials, rubber stoppered in cartons of 20 (NDC 70436-212-54) 10 mL single-dose vials, rubber stoppered in cartons of 10 (NDC 70436-213-82) 15 mL single-dose vials, rubber stoppered in cartons of 1 (NDC 70436-214-80) 15 mL single-dose vials, rubber stoppered in cartons of 20 (NDC 70436-214-54)
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature]. Should freezing occur, gadobutrol injection should be brought to room temperature before use. If allowed to stand at room temperature, gadobutrol injection should return to a clear and colorless to pale yellow solution.
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.
📋 Description ▾
11 DESCRIPTION Gadobutrol injection is a paramagnetic macrocyclic contrast agent administered for magnetic resonance imaging. 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 has a molecular formula of C 18 H 31 GdN 4 O 9 and a molecular weight of 604.72.
Gadobutrol injection is a sterile, clear, colorless to pale yellow solution containing 604.72 mg (1 mmol) of gadobutrol per mL as the active ingredient with 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 (1 mmol/mL solution for injection) are listed below: Density (g/mL at 37°C)
1.3Osmolarity 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 6.6-8 The thermodynamic stability constants for gadobutrol (log K therm and log K cond at pH 7.4) are 21.8 and 15.3, respectively. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Nephrogenic Systemic Fibrosis Instruct patients to inform their physician if they: Have a history of kidney disease and/or liver disease, or Have recently received a GBCA GBCAs increase the risk of NSF among patients with impaired elimination of drugs. To counsel patients at risk of NSF: Describe the clinical manifestation of NSF Describe procedures to screen for the detection of renal impairment 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.
Common Adverse Reactions Inform patients that they may experience: Reactions along the venous injection site, such as mild and transient burning or pain or feeling of warmth or coldness at the injection site Side effects of headache, nausea, abnormal taste and feeling hot Acute Respiratory Distress Syndrome Advise patients that acute respiratory distress syndrome (ARDS) has occurred with GADAVIST. 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 )] .
General Precautions Gadolinium Retention Advise patients that gadolinium is retained for months or years in brain, bone, skin, and other organs 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 )] .
Instruct patients receiving gadobutrol injection to inform their physician if they: Are pregnant or breastfeeding Have a history of allergic reaction to contrast media, bronchial asthma or allergic respiratory disorder Manufactured by: Hainan Poly Pharm. Co., Ltd., Guilinyang Economic Development Zone, Haikou, Hainan, China 571127 Distributed by: Slate Run Pharmaceuticals, LLC, Columbus, Ohio 43215 10000360/06 Revised: 03/2025
💬 Medication Guide ▾
MEDICATION GUIDE GADOBUTROL INJECTION Gadobutrol (gad” oh bue’ trol) Injection for intravenous use What is the most important information I should know about gadobutrol injection? GBCAs like gadobutrol injection may cause serious side effects including death, coma, encephalopathy, and seizures when it is given intrathecally (injection given into the spinal canal). It is not known if gadobutrol injection is safe and effective with intrathecal use.
Gadobutrol injection is not approved for this use. Gadobutrol injection contains a metal called gadolinium. Small amounts of gadolinium can stay in your body including the brain, bones, skin and other parts of your body for a long time (several months to years).
It is not known how gadolinium may affect you, but so far, studies have not found harmful effects in patients with normal kidneys. Rarely, patients have reported pains, tiredness, and skin, muscle or bone ailments for a long time, but these symptoms have not been directly linked to gadolinium. There are different GBCAs that can be used for your MRI exam.
The amount of gadolinium that stays in the body is different for different gadolinium medicines. Gadolinium stays in the body more after Omniscan or Optimark than after Eovist, Magnevist, or MultiHance. Gadolinium stays in the body the least after Dotarem, gadobutrol injection, or ProHance.
People who get many doses of gadolinium medicines, women who are pregnant and young children may be at increased risk from gadolinium staying in the body. Some people with kidney problems who get gadolinium medicines can develop a condition with severe thickening of the skin, muscles and other organs in the body (nephrogenic systemic fibrosis). Your healthcare provider should screen you to see how well your kidneys are working before you receive gadobutrol injection.
What is gadobutrol injection? Gadobutrol injection is a prescription medicine called a gadolinium-based contrast agent (GBCA). Gadobutrol injection, like other GBCAs, is injected into your vein and used with a magnetic resonance imaging (MRI) scanner.
An MRI exam with a GBCA, including gadobutrol injection, helps your doctor to see problems better than an MRI exam without a GBCA. Your doctor has reviewed your medical records and has determined that you would benefit from using a GBCA with your MRI exam. Do not receive gadobutrol injection if you have had a severe allergic reaction to gadobutrol injection.
Before receiving gadobutrol injection, tell your healthcare provider about all your medical conditions, including if you: have had any MRI procedures in the past where you received a GBCA. Your healthcare provider may ask you for more information including the dates of these MRI procedures. are pregnant or plan to become pregnant. It is not known if gadobutrol injection can harm your unborn baby.
Talk to your healthcare provider about the possible risks to an unborn baby if a GBCA such as gadobutrol injection is received during pregnancy. have kidney problems, diabetes, or high blood pressure have had an allergic reaction to dyes (contrast agents) including GBCAs What are the possible side effects of gadobutrol injection? See “What is the most important information I should know about gadobutrol injection?” Allergic reactions. Gadobutrol injection can cause allergic reactions that can sometimes be serious.
Your healthcare provider will monitor you closely for symptoms of an allergic reaction. A serious lung problem called acute respiratory distress syndrome (ARDS). Call your healthcare provider right away if you have shortness of breath with or without a fever, trouble breathing, or a fast rate of breathing after receiving gadobutrol injection.
The most common side effects of gadobutrol injection include: headache, nausea, and dizziness. These are not all the possible side effects of gadobutrol injection. Call your doctor for medical advice about side effects.
You may report side effects to FDA at 1-800-FDA-1088. General infor…