{"id":"gadobenate-dimeglumine","rwe":[{"pmid":"41774304","year":"2026","title":"The value of gadobenate dimeglumine-enhanced MRI quantification in predicting aggressiveness and prognosis of typical intrahepatic mass-forming cholangiocarcinoma: a multicenter retrospective study.","finding":"","journal":"Insights into imaging","studyType":"Clinical Study"},{"pmid":"41730634","year":"2026","title":"Dose Reduction with Gadopiclenol: Implications for DSC Perfusion Imaging.","finding":"","journal":"AJNR. American journal of neuroradiology","studyType":"Clinical Study"},{"pmid":"41711984","year":"2026","title":"Mapping fibrosis in colorectal liver metastases (CRLM) with gadobenate dimeglumine-enhanced MRI: prognostic implications and imaging biomarkers.","finding":"","journal":"International journal of colorectal disease","studyType":"Clinical Study"},{"pmid":"41651668","year":"2026","title":"Prospective MR Evaluation of Endolymphatic Hydrops Using Half-dose Gadopiclenol.","finding":"","journal":"AJNR. American journal of neuroradiology","studyType":"Clinical Study"},{"pmid":"41646297","year":"2026","title":"Pharmacokinetic modeling of hepatospecific MRI contrast agent flux in large animal models by dynamic contrast-enhanced MRI.","finding":"","journal":"Research square","studyType":"Clinical Study"}],"_fda":{"id":"0e7d3da8-78fa-b4ae-4a43-15919e900ebe","set_id":"59077a3e-5f03-4342-ae24-856267545631","openfda":{"unii":["3Q6PPC19PO"],"route":["INTRAVENOUS"],"spl_id":["0e7d3da8-78fa-b4ae-4a43-15919e900ebe"],"brand_name":["MultiHance"],"spl_set_id":["59077a3e-5f03-4342-ae24-856267545631"],"package_ndc":["0270-5164-12","0270-5164-13","0270-5164-14","0270-5164-15"],"product_ndc":["0270-5164"],"generic_name":["GADOBENATE DIMEGLUMINE"],"product_type":["HUMAN PRESCRIPTION DRUG"],"substance_name":["GADOBENATE DIMEGLUMINE"],"manufacturer_name":["BRACCO DIAGNOSTICS INC"],"application_number":["NDA021357"],"is_original_packager":[true]},"version":"20","pregnancy":["8.1 Pregnancy 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, gadobenate dimeglumine has been shown to be teratogenic in rabbits following repeated intravenous administration during organogenesis at doses up to 6 times the recommended human dose. There were no adverse developmental effects observed in rats with intravenous administration of gadobenate dimeglumine during organogenesis at doses up to three times the recommended human dose (see Data ). Because of the potential risks of gadolinium to the fetus, use MultiHance only if imaging is essential and cannot be delayed. The estimated 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 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 Gadobenate dimeglumine has been shown to be teratogenic in rabbits when administered intravenously at 2 mmol/kg/day (6 times the recommended human dose based on body surface area) during organogenesis (day 6 to 18) inducing microphthalmia/small eye and/or focal retinal fold in 3 fetuses from 3 separate litters. In addition, MultiHance administered intravenously at 3 mmol/kg/day (10 times the recommended human dose based on body surface area) has been shown to increase intrauterine deaths in rabbits. There was no evidence that MultiHance induced teratogenic effects in rats at doses up to 2 mmol/kg/day (3 times the recommended human dose based on body surface area), however, rat dams exhibited no systemic toxicity at this dose. There were no adverse effects on the birth, survival, growth, development and fertility of the F1 generation at doses up to 2 mmol/kg in a rat peri- and post-natal (Segment III) study."],"overdosage":["10 OVERDOSAGE Clinical consequences of overdosage with MultiHance have not been reported. Treatment of an overdosage should be directed toward support of vital functions and prompt institution of symptomatic therapy. In a Phase 1 clinical study, doses up to 0.4 mmol/kg were administered to patients. MultiHance has been shown to be dialyzable [ see Clinical Pharmacology (12.3) ]."],"description":["11 DESCRIPTION MultiHance injection is supplied as a sterile, nonpyrogenic, clear, colorless to slightly yellow aqueous solution intended for intravenous use only. Each mL of MultiHance contains 529 mg gadobenate dimeglumine and water for injection. MultiHance contains no preservatives. Gadobenate dimeglumine is chemically designated as (4RS)-[4-carboxy-5,8,11-tris(carboxymethyl)- 1-phenyl-2-oxa-5,8,11-triazatridecan-13-oato(5-)] gadolinate(2-) dihydrogen compound with 1-deoxy-1-(methylamino)-D-glucitol (1:2) with a molecular weight of 1058.2 and an empirical formula of C 22 H 28 GdN 3 O 11 • 2C 7 H 17 NO 5 . The structural formula is as follows: MultiHance has a pH of 6.5-7.5. Pertinent physicochemical parameters are provided below: Osmolality 1.970 osmol/kg @ 37°C Viscosity 5.3 mPas @ 37°C Density 1.220 g/mL @ 20°C MultiHance has an osmolality 6.9 times that of plasma (285 mOsmol/kg water) and is hypertonic under conditions of use. MultiHance Structure"],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied MultiHance (gadobenate dimeglumine) is a clear, colorless to slightly yellow solution containing 529 mg gadobenate dimeglumine per mL. MultiHance is supplied in glass vials; each single dose vial is rubber stoppered with an aluminum seal and the contents are sterile. MultiHance is supplied in boxes of: Five 5 mL single dose 10 mL vials (NDC 0270-5164-12) Five 10 mL single dose 20 mL vials (NDC 0270-5164-13) Five 15 mL single dose 20 mL vials (NDC 0270-5164-14) Five 20 mL single dose 20 mL vials (NDC 0270-5164-15) 16.2 Storage and Handling Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Do not freeze."],"spl_medguide":["This Medication Guide has been approved by the U.S. Food and Drug Administration Revised: 03/2025 MEDICATION GUIDE MULTIHANCE ® (məl-tē-han(t)s) (gadobenate dimeglumine) Injection, for intravenous use What is the most important information I should know about MULTIHANCE? GBCAs like MULTIHANCE may cause serious side effects including death, coma, encephalopathy, and seizures when it is given intrathecally (injection given into the spinal cord). It is not known if MULTIHANCE is safe and effective with intrathecal use. MULTIHANCE is not approved for this use. MULTIHANCE 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, Gadavist, 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 MULTIHANCE. What is MULTIHANCE? MULTIHANCE is a prescription medicine called a gadolinium-based contrast agent (GBCA). MULTIHANCE, like other GBCAs, is injected into your vein and used with a magnetic resonance imaging (MRI) scanner. An MRI exam with a GBCA, including MULTIHANCE, 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 MULTIHANCE if you have had a severe allergic reaction to GBCAs including gadobenate dimeglumine, or any of the ingredients in MULTIHANCE. Before receiving MULTIHANCE, 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 MULTIHANCE can harm your unborn baby. Talk to your healthcare provider about the possible risks to an unborn baby if a GBCA such as MULTIHANCE 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 MULTIHANCE? See “What is the most important information I should know about MULTIHANCE?” Allergic reactions. MULTIHANCE can cause allergic reactions that can sometimes be serious. Your healthcare provider will monitor you closely for symptoms of an allergic reaction. The most common side effects of MULTIHANCE include: nausea, headache, feeling hot, or burning at the injection site. These are not all the possible side effects of MULTIHANCE. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of MULTIHANCE. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your healthcare provider for information about MULTIHANCE that is written for health professionals. What are the ingredients in MULTIHANCE? Active ingredient: gadobenate dimeglumine Inactive ingredients: water Manufactured by: BIPSO GmbH-78224 Singen (Germany) Manufactured for: Bracco Diagnostics Inc., Princeton, NJ 08540 US Patent No. 4,916,246 For more information, go to www.imaging.bracco.com or call 1-800-257-5181."],"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. MultiHance 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 MultiHance 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 systemic 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 (e.g. 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 MultiHance dose and allow a sufficient period of time for elimination of the drug from the body prior to 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. MultiHance 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 MultiHance in these patients unless the diagnostic information is essential and not available with non-contrast 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 (e.g. age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. (5.2)"],"geriatric_use":["8.5 Geriatric Use Of the total number of 4967 adult subjects in clinical studies of MultiHance, 33% were 65 or older. No overall differences in safety or effectiveness were observed between these elderly subjects and the younger subjects. The drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to MultiHance 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."],"pediatric_use":["8.4 Pediatric Use MultiHance is approved for intravenous use for MRI of the CNS to visualize lesions with abnormal blood brain barrier or abnormal vascularity of the brain, spine, and associated tissues in pediatric patients from birth, including term neonates, to less than 17 years of age. Pediatric use is based on evidence of effectiveness in adults and in 202 pediatric patients 2 years of age and older, in addition to experience in 105 pediatric patients birth to less than 2 years of age that supported extrapolation from adult data [see Clinical Studies ( 14 )] . Adverse reactions in pediatric patients were similar to those reported in adults [see Adverse Reactions ( 6.1 )] . No dose adjustment according to age is necessary in pediatric patients two years of age and older. For pediatric patients, less than 2 years of age, the recommended dosage range is 0.1 to 0.2 mL/kg [see Dosage and Administration ( 2.1 ), Pharmacokinetics ( 12.3 )] . The safety of MultiHance has not been established in preterm neonates."],"effective_time":"20250314","nursing_mothers":["8.2 Lactation Risk Summary Limited literature reports that breastfeeding after gadobenate dimeglumine administration to the mother would result in the infant receiving an oral dose of 0.001%-0.04% of the maternal dose. There is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. Additionally, there is limited GBCA gastrointestinal absorption. The developmental and health benefits of breastfeeding should be considered together with the mother’s clinical need for MultiHance and any potential adverse effects on the breastfed infant from MultiHance or from the underlying maternal condition."],"clinical_studies":["14 CLINICAL STUDIES 14.1 MRI of the CNS Adults: MultiHance was evaluated in 426 adult patients in 2 controlled clinical trials of the central nervous system (Study A and Study B), enrolling 217 men and 209 women with a mean age of 52 years (range 18 to 88 years). The racial and ethnic representations were 88% Caucasian, 6% Black, 4% Hispanic, 1% Asian, and 1% other racial or ethnic groups. These trials were designed to compare MultiHance contrast MRI to non-contrast MRI alone. In Study A, patients highly suspected of having a lesion(s) of the CNS based on nuclear medicine imaging, computed tomography (CT), contrast CT, MRI, contrast- MRI, or angiography were randomized to receive two MRI evaluations with 0.05 mmol/kg (n=140) or 0.1 mmol/kg (n=136) of MultiHance. In Study B, patients with known metastatic disease to the CNS were randomized to receive two MRI evaluations with 0.05 mmol/kg (n=74) or 0.1 mmol/kg (n=76) of MultiHance. MRI scans were performed pre-contrast and within 5 minutes after each injection. The studies were designed to evaluate the effect of MultiHance MRI compared to the non-contrast MRI on a lesion level. Pre-contrast, post-contrast, and pre-plus-post contrast images (paired images) were independently evaluated by three blinded readers. The images were evaluated for the following endpoints using a scale from 0 to 4: the degree of lesion border delineation, the degree of visualization of lesion internal morphology, and the degree of lesion contrast enhancement. Lesion counting was also performed for the pre-contrast and paired image sets. The 0.1 mmol/kg dose of MultiHance demonstrated consistently better visualization for all readers for all visualization endpoints. However, the 0.05 mmol/kg dose of MultiHance provided inconsistent visualization results between readers. Comparison of pre-contrast versus post-contrast (0.1 mmol/kg) images showed that the mean score differences were significant and favored contrast for subjects in Study B (all subjects with known metastatic lesions) and for subjects with known tumors in Study A. However, the mean score differences between the pre-contrast and post-contrast images were not significant for non-tumor patients in Study A. These negative results may be attributed to a lack of lesion enhancement in non-tumor CNS disease. Table 4 shows a comparison of paired images (pre-and post-contrast) versus pre-contrast images with respect to the difference in the mean score and with respect to the proportion of lesions read as better, worse, or the same as the pre-contrast MRI images. Table 4 shows that based on a lesion-level analysis 0.1 mmol/kg MultiHance provided a statistically significant improvement for the three structural parameters evaluated. Also, more lesions were seen in the paired images than in the pre-contrast images alone. (a) Difference of means = (paired mean) - (pre mean) (b) Worse = paired score is less than the pre score Same = paired score is the same as the pre score Better = paired score is greater than the pre score * Statistically significant for the mean (paired t test) Table 4: LESION LEVEL RESULTS OF MRI CENTRAL NERVOUS SYSTEM ADULT STUDIES WITH 0.1 mmol/kg MULTIHANCE Study A Study B Reader 1 Reader 2 Reader 3 Reader 1 Reader 2 Reader 3 Endpoints N = 395 N = 384 N = 299 N = 245 N = 275 N = 254 Border Delineation: Difference of Means (a) 0.8* 0.6* 0.8* 1.8* 1.5* 1.9* Worse (b) Same Better 44 (11%) 146 (37%) 205 (52%) 61 (16%) 168 (44%) 155 (40%) 57 (19%) 89 (30%) 153 (51%) 13 (5%) 11 (5%) 221 (90%) 24 (9%) 19 (7%) 232 (84%) 15 (6%) 18 (7%) 221 (87%) Internal Morphology: Difference of Means 0.8* 0.6* 0.7* 1.7* 1.4* 2.1* Worse Same Better 37 (10%) 147 (37%) 211 (53%) 63 (17%) 151 (39%) 170 (44%) 62 (21%) 84 (28%) 153 (51%) 13 (5%) 16 (7%) 216 (88%) 26 (10%) 22 (8%) 227 (82%) 14 (5%) 22 (9%) 218 (86%) Contrast Enhancement: Difference of Means 0.7* 0.5* 0.8* 1.9* 1.3* 1.9* Worse Same Better 75 (19%) 148 (37%) 172 (44%) 74 (19%) 152 (40%) 158 (41%) 50 (17%) 109 (36%) 140 (47%) 13 (5%) 11 (5%) 221 (90%) 32 (12%) 21 (7%) 222 (81%) 17 (7%) 14 (5%) 223 (88%) Pediatric 2 to 17 years The efficacy and safety of MultiHance were evaluated in 92 pediatric patients with known or highly suspected disease of the central nervous system. MRI scans were performed pre-contrast and within 3 to 10 minutes following the administration of MultiHance 0.1 mmol/kg. Pre-contrast, post-contrast, and pre-plus-post contrast images (paired images) were independently evaluated by three blinded readers on a lesion level. The images were evaluated for the same endpoints as in the adult central nervous system trials using a scale from 0 to 4: the degree of lesion border delineation, the degree of visualization of lesion internal morphology, and the degree of lesion contrast enhancement. Lesion counting was also performed for the pre-contrast and paired image sets. The pre-contrast versus the paired image set was the primary comparison. Forty-nine percent of study subjects were male and the overall mean age was 10.6 years (range 2 to 17 years). The racial and ethnic representations were 77% Caucasian, 13% Asian, 5% Black, and 4% other racial or ethnic groups. MultiHance increased lesion border delineation, lesion internal morphology, and lesion contrast enhancement relative to non-contrast and these results were comparable to those seen in adults. Pediatrics below 2 years A study of 90 pediatric patients younger than 2 years of age was performed which supports extrapolation of CNS efficacy findings from adults and older pediatric patients. Three independent, blinded readers evaluated pre-contrast MRI image sets and paired pre-plus-post-contrast MRI image sets using MultiHance and rated the images according to three co-primary endpoints at a lesion level for the primary analysis. Two of the three readers reported improvement in the paired image sets in each of the three co-primary endpoints of lesion border delineation, visualization of lesion internal morphology, and lesion contrast enhancement. 14.2 MRA of Renal and Aorto-ilio-femoral Vessels Safety and efficacy of MultiHance for use in MRA were evaluated in two prospective, multi-center, open-label, clinical trials (one for each arterial vascular territory: renal and aorto-ilio-femoral). Out of 580 patients who received Multihance in these two trials, 62.2% were men and 90.9% were Caucasian; the average age was 63.4 years (range 18 to 93 years). In both trials, patients with known or suspected arterial disease underwent MRA with and without MultiHance as well as catheter-based digital subtraction angiography (DSA). Assessment of diagnostic efficacy for detecting/excluding clinically significant steno-occlusive disease (≥ 51% stenosis measured with electronic calipers) was based on comparisons of sensitivity and specificity between MultiHance MRA and non-contrast MRA, with DSA as a reference standard. In each vascular territory, the primary efficacy analyses were designed to demonstrate superiority in sensitivity and non-inferiority in specificity of MultiHance MRA to non-contrast MRA at the vessel-segment level. The interpretation of MRA images from both trials was conducted by three independent radiologist readers who were blinded to clinical data, including the DSA results. The pre-specified success criteria were to be achieved by at least the same two readers for all primary analyses. Results of both trials showed a statistically significant increase in sensitivity and specificity of MultiHance MRA over non-contrast MRA in detecting clinically significant steno-occlusive disease. Table 5 summarizes the efficacy results by reader. TABLE 5. PERFORMANCE CHARACTERISTICS OF MULTIHANCE-MRA AND NON-CONTRAST MRA * (Based on General Delta Method) READER AORTO-ILIO-FEMORAL ARTERIES SENSITIVITY SPECIFICITY MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)* MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)* 1 77.8% 73.7% 4.5 (1.5, 7.6) 88.1% 78.5% 10.0 (7.3, 12.6) 2 65.2% 52.5% 12.6 (8.5, 16.6) 94.2% 89.4% 4.9 (2.7, 7.1) 3 69.0% 59.1% 10.0 (6.1, 14.0) 90.0% 75.3% 14.9 (12.1, 17.8) READER RENAL ARTERIES SENSITIVITY SPECIFICITY MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)* MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)* 1 67.8% 47.0% 20.8 (12.8, 28.9) 94.0% 86.1% 8.3 (4.2, 12.4) 2 62.4% 46.7% 16.2 (6.8, 25.6) 94.0% 83.5% 10.3 (5.5, 15.0) 3 65.5% 39.6% 25.3 (15.9, 34.6) 94.7% 87.3% 8.0 (3.6, 12.5)","14.1 MRI of the CNS Adults: MultiHance was evaluated in 426 adult patients in 2 controlled clinical trials of the central nervous system (Study A and Study B), enrolling 217 men and 209 women with a mean age of 52 years (range 18 to 88 years). The racial and ethnic representations were 88% Caucasian, 6% Black, 4% Hispanic, 1% Asian, and 1% other racial or ethnic groups. These trials were designed to compare MultiHance contrast MRI to non-contrast MRI alone. In Study A, patients highly suspected of having a lesion(s) of the CNS based on nuclear medicine imaging, computed tomography (CT), contrast CT, MRI, contrast- MRI, or angiography were randomized to receive two MRI evaluations with 0.05 mmol/kg (n=140) or 0.1 mmol/kg (n=136) of MultiHance. In Study B, patients with known metastatic disease to the CNS were randomized to receive two MRI evaluations with 0.05 mmol/kg (n=74) or 0.1 mmol/kg (n=76) of MultiHance. MRI scans were performed pre-contrast and within 5 minutes after each injection. The studies were designed to evaluate the effect of MultiHance MRI compared to the non-contrast MRI on a lesion level. Pre-contrast, post-contrast, and pre-plus-post contrast images (paired images) were independently evaluated by three blinded readers. The images were evaluated for the following endpoints using a scale from 0 to 4: the degree of lesion border delineation, the degree of visualization of lesion internal morphology, and the degree of lesion contrast enhancement. Lesion counting was also performed for the pre-contrast and paired image sets. The 0.1 mmol/kg dose of MultiHance demonstrated consistently better visualization for all readers for all visualization endpoints. However, the 0.05 mmol/kg dose of MultiHance provided inconsistent visualization results between readers. Comparison of pre-contrast versus post-contrast (0.1 mmol/kg) images showed that the mean score differences were significant and favored contrast for subjects in Study B (all subjects with known metastatic lesions) and for subjects with known tumors in Study A. However, the mean score differences between the pre-contrast and post-contrast images were not significant for non-tumor patients in Study A. These negative results may be attributed to a lack of lesion enhancement in non-tumor CNS disease. Table 4 shows a comparison of paired images (pre-and post-contrast) versus pre-contrast images with respect to the difference in the mean score and with respect to the proportion of lesions read as better, worse, or the same as the pre-contrast MRI images. Table 4 shows that based on a lesion-level analysis 0.1 mmol/kg MultiHance provided a statistically significant improvement for the three structural parameters evaluated. Also, more lesions were seen in the paired images than in the pre-contrast images alone. (a) Difference of means = (paired mean) - (pre mean) (b) Worse = paired score is less than the pre score Same = paired score is the same as the pre score Better = paired score is greater than the pre score * Statistically significant for the mean (paired t test) Table 4: LESION LEVEL RESULTS OF MRI CENTRAL NERVOUS SYSTEM ADULT STUDIES WITH 0.1 mmol/kg MULTIHANCE Study A Study B Reader 1 Reader 2 Reader 3 Reader 1 Reader 2 Reader 3 Endpoints N = 395 N = 384 N = 299 N = 245 N = 275 N = 254 Border Delineation: Difference of Means (a) 0.8* 0.6* 0.8* 1.8* 1.5* 1.9* Worse (b) Same Better 44 (11%) 146 (37%) 205 (52%) 61 (16%) 168 (44%) 155 (40%) 57 (19%) 89 (30%) 153 (51%) 13 (5%) 11 (5%) 221 (90%) 24 (9%) 19 (7%) 232 (84%) 15 (6%) 18 (7%) 221 (87%) Internal Morphology: Difference of Means 0.8* 0.6* 0.7* 1.7* 1.4* 2.1* Worse Same Better 37 (10%) 147 (37%) 211 (53%) 63 (17%) 151 (39%) 170 (44%) 62 (21%) 84 (28%) 153 (51%) 13 (5%) 16 (7%) 216 (88%) 26 (10%) 22 (8%) 227 (82%) 14 (5%) 22 (9%) 218 (86%) Contrast Enhancement: Difference of Means 0.7* 0.5* 0.8* 1.9* 1.3* 1.9* Worse Same Better 75 (19%) 148 (37%) 172 (44%) 74 (19%) 152 (40%) 158 (41%) 50 (17%) 109 (36%) 140 (47%) 13 (5%) 11 (5%) 221 (90%) 32 (12%) 21 (7%) 222 (81%) 17 (7%) 14 (5%) 223 (88%) Pediatric 2 to 17 years The efficacy and safety of MultiHance were evaluated in 92 pediatric patients with known or highly suspected disease of the central nervous system. MRI scans were performed pre-contrast and within 3 to 10 minutes following the administration of MultiHance 0.1 mmol/kg. Pre-contrast, post-contrast, and pre-plus-post contrast images (paired images) were independently evaluated by three blinded readers on a lesion level. The images were evaluated for the same endpoints as in the adult central nervous system trials using a scale from 0 to 4: the degree of lesion border delineation, the degree of visualization of lesion internal morphology, and the degree of lesion contrast enhancement. Lesion counting was also performed for the pre-contrast and paired image sets. The pre-contrast versus the paired image set was the primary comparison. Forty-nine percent of study subjects were male and the overall mean age was 10.6 years (range 2 to 17 years). The racial and ethnic representations were 77% Caucasian, 13% Asian, 5% Black, and 4% other racial or ethnic groups. MultiHance increased lesion border delineation, lesion internal morphology, and lesion contrast enhancement relative to non-contrast and these results were comparable to those seen in adults. Pediatrics below 2 years A study of 90 pediatric patients younger than 2 years of age was performed which supports extrapolation of CNS efficacy findings from adults and older pediatric patients. Three independent, blinded readers evaluated pre-contrast MRI image sets and paired pre-plus-post-contrast MRI image sets using MultiHance and rated the images according to three co-primary endpoints at a lesion level for the primary analysis. Two of the three readers reported improvement in the paired image sets in each of the three co-primary endpoints of lesion border delineation, visualization of lesion internal morphology, and lesion contrast enhancement.","14.2 MRA of Renal and Aorto-ilio-femoral Vessels Safety and efficacy of MultiHance for use in MRA were evaluated in two prospective, multi-center, open-label, clinical trials (one for each arterial vascular territory: renal and aorto-ilio-femoral). Out of 580 patients who received Multihance in these two trials, 62.2% were men and 90.9% were Caucasian; the average age was 63.4 years (range 18 to 93 years). In both trials, patients with known or suspected arterial disease underwent MRA with and without MultiHance as well as catheter-based digital subtraction angiography (DSA). Assessment of diagnostic efficacy for detecting/excluding clinically significant steno-occlusive disease (≥ 51% stenosis measured with electronic calipers) was based on comparisons of sensitivity and specificity between MultiHance MRA and non-contrast MRA, with DSA as a reference standard. In each vascular territory, the primary efficacy analyses were designed to demonstrate superiority in sensitivity and non-inferiority in specificity of MultiHance MRA to non-contrast MRA at the vessel-segment level. The interpretation of MRA images from both trials was conducted by three independent radiologist readers who were blinded to clinical data, including the DSA results. The pre-specified success criteria were to be achieved by at least the same two readers for all primary analyses. Results of both trials showed a statistically significant increase in sensitivity and specificity of MultiHance MRA over non-contrast MRA in detecting clinically significant steno-occlusive disease. Table 5 summarizes the efficacy results by reader. TABLE 5. PERFORMANCE CHARACTERISTICS OF MULTIHANCE-MRA AND NON-CONTRAST MRA * (Based on General Delta Method) READER AORTO-ILIO-FEMORAL ARTERIES SENSITIVITY SPECIFICITY MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)* MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)* 1 77.8% 73.7% 4.5 (1.5, 7.6) 88.1% 78.5% 10.0 (7.3, 12.6) 2 65.2% 52.5% 12.6 (8.5, 16.6) 94.2% 89.4% 4.9 (2.7, 7.1) 3 69.0% 59.1% 10.0 (6.1, 14.0) 90.0% 75.3% 14.9 (12.1, 17.8) READER RENAL ARTERIES SENSITIVITY SPECIFICITY MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)* MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)* 1 67.8% 47.0% 20.8 (12.8, 28.9) 94.0% 86.1% 8.3 (4.2, 12.4) 2 62.4% 46.7% 16.2 (6.8, 25.6) 94.0% 83.5% 10.3 (5.5, 15.0) 3 65.5% 39.6% 25.3 (15.9, 34.6) 94.7% 87.3% 8.0 (3.6, 12.5)"],"pharmacodynamics":["12.2 Pharmacodynamics Unlike other tested paramagnetic contrast agents (See Table 3), MultiHance demonstrates weak and transient interactions with serum proteins that causes slowing in the molecular tumbling dynamics, resulting in strong increases in relaxivity in solutions containing serum proteins. The improved relaxation effect can contribute to increased contrast-to-noise ratio and lesion-to-brain ratio, which may improve visualization. TABLE 3: RELAXIVITY (mM –1 s –1 ) OF GADOLINIUM CHELATES r 1 and r 2 relaxivities indicate the efficiency in shortening T1 and T2 relaxation times, respectively. 1 In heparinized human plasma, at 39°C. 2 In citrated human plasma, at 37°C. -- Not available Human plasma r 1 r 2 Gadobenate 9.7 1 12.5 1 Gadopentetate 4.9 1 6.3 1 Gadodiamide 5.4 2 -- Gadoteridol 5.4 2 -- Disruption of the blood-brain barrier or abnormal vascularity allows enhancement by MultiHance of lesions such as neoplasms, abscesses, and infarcts. Uptake of MultiHance into hepatocytes has been demonstrated."],"pharmacokinetics":["12.3 Pharmacokinetics Three single-dose intravenous studies were conducted in 32 healthy male subjects to assess the pharmacokinetics of gadobenate dimeglumine. The doses administered in these studies ranged from 0.005 to 0.4 mmol/kg. Upon injection, the meglumine salt is completely dissociated from the gadobenate dimeglumine complex. Thus, the pharmacokinetics is based on the assay of gadobenate ion, the MRI contrast effective ion in gadobenate dimeglumine. Data for plasma concentration and area under the curve demonstrated linear dependence on the administered dose. The pharmacokinetics of gadobenate ion following intravenous administration can be best described using a two-compartment model. Distribution Gadobenate ion has a rapid distribution half-life (reported as mean ± SD) of 0.084 ± 0.012 to 0.605 ± 0.072 hours. Volume of distribution of the central compartment ranged from 0.074 ± 0.017 to 0.158 ± 0.038 L/kg, and estimates of volume of distribution by area ranged from 0.170 ± 0.016 to 0.282 ± 0.079 L/kg. These latter estimates are approximately equivalent to the average volume of extracellular body water in man. In vitro studies showed no appreciable binding of gadobenate ion to human serum proteins. Following GBCA administration, gadolinium is present for months or years in brain, bone, skin, and other organs [see Warnings and Precautions (5.4) ] . Elimination Gadobenate ion is eliminated predominately via the kidneys, with 78% to 96% of an administered dose recovered in the urine. Total plasma clearance and renal clearance estimates of gadobenate ion were similar, ranging from 0.093 ± 0.010 to 0.133 ± 0.270 L/hr/kg and 0.082 ± 0.007 to 0.104 ± 0.039 L/hr/kg, respectively. The clearance is similar to that of substances that are subject to glomerular filtration. The mean elimination half-life ranged from 1.17 ± 0.26 to 2.02 ± 0.60 hours. A small percentage of the administered dose (0.6% to 4%) is eliminated via the biliary route and recovered in feces. Metabolism There was no detectable biotransformation of gadobenate ion. Dissociation of gadobenate ion in vivo has been shown to be minimal, with less than 1% of the free chelating agent being recovered alone in feces. Pharmacokinetics in Special Populations Renal Impairment: A single intravenous dose of 0.2 mmol/kg of MultiHance was administered to 20 subjects with impaired renal function (6 men and 3 women with moderate renal impairment [urine creatinine clearance >30 to <60 mL/min] and 5 men and 6 women with severe renal impairment [urine creatinine clearance >10 to <30 mL/min]). Mean estimates of the elimination half-life were 6.1 ± 3.0 and 9.5 ± 3.1 hours for the moderate and severe renal impairment groups, respectively as compared with 1.0 to 2.0 hours in healthy volunteers. Hemodialysis: A single intravenous dose of 0.2 mmol/kg of MultiHance was administered to 11 subjects (5 males and 6 females) with end-stage renal disease requiring hemodialysis to determine the pharmacokinetics and dialyzability of gadobenate. Approximately 72% of the dose was recovered by hemodialysis over a 4-hour period. The mean elimination half-life on dialysis was 1.21 ± 0.29 hours as compared with 42.4 ± 24.4 hours when off dialysis. Hepatic Impairment: A single intravenous dose of 0.1 mmol/kg of MultiHance was administered to 11 subjects (8 males and 3 females) with impaired liver function (Class B or C modified Child-Pugh Classification). Hepatic impairment had little effect on the pharmacokinetics of MultiHance with the parameters being similar to those calculated for healthy subjects. Gender, Age, Race: A multiple regression analysis performed using pooled data from several pharmacokinetic studies found no significant effect of sex upon the pharmacokinetics of gadobenate. Clearance appeared to decrease slightly with increasing age. Since variations due to age appeared marginal, dosage adjustment for geriatric population is not recommended. Pharmacokinetic differences due to race have not been systematically studied. Pediatric: A population pharmacokinetic analysis incorporated data from 25 healthy subjects (14 males and 11 females) and 15 subjects undergoing MR imaging of the central nervous system (7 males and 8 females) between ages of 2 and 16 years. The subjects received a single intravenous dose of 0.1 mmol/kg of MultiHance. The geometric mean C max was 62.3 μg/mL (n=16) in children 2 to 5 years of age, and 64.2 μg/mL (n=24) in children older than 5 years. The geometric mean AUC 0-∞ was 77.9 μg⋅h/mL in children 2-5 years of age (n=16) and 82.6 μg⋅h/mL in children older than 5 years (n=24). The geometric mean half-life was 1.2 hours in children 2 to 5 years of age and 0.93 hours in children older than 5 years. There was no significant gender-related difference in the pharmacokinetic parameters in the pediatric patients. Over 80% of the dose was recovered in urine after 24 hours. Pharmacokinetic simulations indicate similar AUC and C max values for MultiHance in pediatric subjects less than 2 years when compared to those reported for adults; no age-based dose adjustment is necessary for this pediatric population."],"adverse_reactions":["6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Nephrogenic systemic fibrosis [see Warnings and Precautions (5.2) ] Hypersensitivity reactions [see Warnings and Precautions (5.3) ] The most commonly reported adverse reactions are nausea (1.3%) and headache (1.2%). (6) To report SUSPECTED ADVERSE REACTIONS, contact Bracco Diagnostics Inc. at 1-800-257-5181 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 practice. Adults In clinical trials with MultiHance, a total of 4967 adult subjects (137 healthy volunteers and 4830 patients) received MultiHance at doses ranging from 0.005 to 0.4 mmol/kg. There were 2838 (57%) men and 2129 (43%) women with a mean age of 56.5 years (range 18 to 93 years). A total of 4403 (89%) subjects were Caucasian, 134 (3%) Black, 275 (6%) Asian, 40 (1%) Hispanic, 70 (1%) in other racial groups, and for 45 (1%) subjects, race was not reported. The most commonly reported adverse reactions in adult subjects who received MultiHance were nausea (1.3%) and headache (1.2%). Most adverse reactions were mild to moderate in intensity. One subject experienced a serious anaphylactoid reaction with laryngeal spasm and dyspnea [ see Warnings and Precautions (5.3) ]. Serious adverse reactions consisting of convulsions, pulmonary edema, acute necrotizing pancreatitis, and anaphylactoid reactions were reported in 0.1% of subjects in clinical trials. Adverse reactions that occurred in at least 0.5% of 4967 adult subjects who received MultiHance are listed below (Table 2), in decreasing order of occurrence within each system. TABLE 2: ADVERSE REACTIONS REPORTED IN ≥ 0.5% OF ADULT SUBJECTS WHO RECEIVED MULTIHANCE IN CLINICAL TRIALS Number of subjects dosed 4967 Number of subjects with any adverse reaction 517 (10.4%) Gastrointestinal Disorders Nausea 67 (1.3%) General Disorders and Administration Site Disorders Injection Site Reaction Feeling Hot 54 (1.1%) 49 (1.0%) Nervous System Disorders Headache Dysgeusia Paresthesia Dizziness 60 (1.2%) 33 (0.7%) 24 (0.5%) 24 (0.5%) The following adverse reactions occurred in less than 0.5% of the 4967 adult subjects who received MultiHance. Serious adverse reactions described above are not repeated below. Blood and Lymphatic System Disorders: Basophilia; Cardiac Disorders: Atrioventricular block first degree; Eye Disorders: Eye pruritus, eye swelling, ocular hyperemia, visual disturbance; Gastrointestinal Disorders: Abdominal pain or discomfort, diarrhea, dry mouth, lip swelling, paresthesia oral, tongue edema, vomiting; General Disorders and Administration Site Conditions: Chest pain or discomfort, chills, malaise; Immune System Disorders: Hypersensitivity; Investigations: Nonspecific changes in laboratory tests (including hematology, blood chemistry, liver enzymes and urinalysis), blood pressure and electrocardiogram parameters (including PR, QRS and QT intervals and ST-T segment changes). Musculoskeletal and Connective Tissue Disorders: Myalgia; Nervous System Disorders: Parosmia, tremor; Respiratory, Thoracic and Mediastinal Disorders: Dyspnea, laryngospasm, nasal congestion, sneezing, wheezing; Skin and Subcutaneous Tissue Disorders: Hyperhidrosis, pruritus, rash, swelling face, urticaria. Pediatric Patients In clinical trials of MultiHance in MRI of the CNS, 307 pediatric subjects received MultiHance at a dose of 0.1 mmol/kg. A total of 160 (52%) subjects were male and the overall mean age was 6.0 years (range, 2 days to 17 years). A total of 211 (69%) subjects were Caucasian, 24 (8%) Black, 15 (5%) Asian, 39 (13%), Hispanic, 2 (<1%) in other racial groups, and for 16 (5%), race was not reported. Adverse reactions were reported for 14 (4.6%) of the subjects. The frequency and the nature of the adverse reactions were similar to those seen in the adult patients. The most commonly reported adverse reactions were vomiting (1.0%), pyrexia (0.7%), and hyperhidrosis (0.7%). No subject died during study participation. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of MultiHance or other GBCAs. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal Disorders: Acute pancreatitis with onset within 48 hours after GBCA administration. Immune System Disorders: Anaphylactic, anaphylactoid and hypersensitivity reactions manifested with various degrees of severity up to anaphylactic shock, loss of consciousness and death. The reactions generally involved signs or symptoms of respiratory, cardiovascular, and/or mucocutaneous abnormalities. General Disorders and Administration Site Conditions: Extravasation of MultiHance may lead to injection site reactions, characterized by local pain or burning sensation, swelling, blistering, and necrosis [see Warnings and Precautions ( 5.5 )] . Adverse events with variable onset and duration have been reported after GBCA administration [see Warnings and Precautions ( 5.4 )] . These include fatigue, asthenia, pain syndromes, and heterogeneous clusters of symptoms in the neurological, cutaneous, and musculoskeletal systems. Respiratory, Thoracic and Mediastinal Disorders: Acute respiratory distress syndrome, pulmonary edema Skin: Gadolinium associated plaques."],"contraindications":["4 CONTRAINDICATIONS MultiHance is contraindicated in patients with known allergic or hypersensitivity reactions to gadolinium-based contrast agents [ see Warnings and Precautions (5.3) ]. MultiHance is contraindicated in patients with known allergic or hypersensitivity reactions to gadolinium-based contrast agents. (4)"],"description_table":["
Osmolality1.970 osmol/kg @ 37°C
Viscosity5.3 mPas @ 37°C
Density1.220 g/mL @ 20°C
"],"drug_interactions":["7 DRUG INTERACTIONS 7.1 Transporter-Based Drug-Drug Interactions MultiHance and other drugs may compete for the canalicular multispecific organic anion transporter (MOAT also referred to as MRP2 or ABCC2). Therefore MultiHance may prolong the systemic exposure of drugs such as cisplatin, anthracyclines (e.g. doxorubicin, daunorubicin), vinca alkaloids (e.g. vincristine), methotrexate, etoposide, tamoxifen, and paclitaxel. In particular, consider the potential for prolonged drug exposure in patients with decreased MOAT activity (e.g. Dubin Johnson syndrome)."],"spl_medguide_table":["
This Medication Guide has been approved by the U.S. Food and Drug AdministrationRevised: 03/2025
MEDICATION GUIDE MULTIHANCE®(məl-tē-han(t)s) (gadobenate dimeglumine) Injection, for intravenous use
What is the most important information I should know about MULTIHANCE?GBCAs like MULTIHANCE may cause serious side effects including death, coma, encephalopathy, and seizures when it is given intrathecally (injection given into the spinal cord). It is not known if MULTIHANCE is safe and effective with intrathecal use. MULTIHANCE is not approved for this use.MULTIHANCE 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, Gadavist, 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 MULTIHANCE.
What is MULTIHANCE?MULTIHANCE is a prescription medicine called a gadolinium-based contrast agent (GBCA). MULTIHANCE, like other GBCAs, is injected into your vein and used with a magnetic resonance imaging (MRI) scanner.An MRI exam with a GBCA, including MULTIHANCE, 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 MULTIHANCE if you have had a severe allergic reaction to GBCAs including gadobenate dimeglumine, or any of the ingredients in MULTIHANCE.
Before receiving MULTIHANCE, 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 MULTIHANCE can harm your unborn baby. Talk to your healthcare provider about the possible risks to an unborn baby if a GBCA such as MULTIHANCE is received during pregnancyhave 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 MULTIHANCE?See “What is the most important information I should know about MULTIHANCE?”Allergic reactions. MULTIHANCE can cause allergic reactions that can sometimes be serious. Your healthcare provider will monitor you closely for symptoms of an allergic reaction.The most common side effects of MULTIHANCE include: nausea, headache, feeling hot, or burning at the injection site. These are not all the possible side effects of MULTIHANCE. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of MULTIHANCE. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your healthcare provider for information about MULTIHANCE that is written for health professionals.
What are the ingredients in MULTIHANCE? Active ingredient: gadobenate dimeglumine Inactive ingredients: water Manufactured by: BIPSO GmbH-78224 Singen (Germany) Manufactured for: Bracco Diagnostics Inc., Princeton, NJ 08540 US Patent No. 4,916,246 For more information, go to www.imaging.bracco.com or call 1-800-257-5181.
"],"mechanism_of_action":["12.1 Mechanism of Action Gadobenate dimeglumine is a paramagnetic agent and, as such, develops a magnetic moment when placed in a magnetic field. The large magnetic moment produced by the paramagnetic agent results in a large local magnetic field, which can enhance the relaxation rates of water protons in its vicinity leading to an increase of signal intensity (brightness) of tissue. In magnetic resonance imaging (MRI), visualization of normal and pathological tissue depends in part on variations in the radiofrequency signal intensity that occur with 1) differences in proton density; 2) differences of the spin-lattice or longitudinal relaxation times (T1); and 3) differences in the spin-spin or transverse relaxation time (T2). When placed in a magnetic field, gadobenate dimeglumine decreases the T1 and T2 relaxation time in target tissues. At recommended doses, the effect is observed with greatest sensitivity in the T1-weighted sequences."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Gadobenate dimeglumine is a paramagnetic agent and, as such, develops a magnetic moment when placed in a magnetic field. The large magnetic moment produced by the paramagnetic agent results in a large local magnetic field, which can enhance the relaxation rates of water protons in its vicinity leading to an increase of signal intensity (brightness) of tissue. In magnetic resonance imaging (MRI), visualization of normal and pathological tissue depends in part on variations in the radiofrequency signal intensity that occur with 1) differences in proton density; 2) differences of the spin-lattice or longitudinal relaxation times (T1); and 3) differences in the spin-spin or transverse relaxation time (T2). When placed in a magnetic field, gadobenate dimeglumine decreases the T1 and T2 relaxation time in target tissues. At recommended doses, the effect is observed with greatest sensitivity in the T1-weighted sequences. 12.2 Pharmacodynamics Unlike other tested paramagnetic contrast agents (See Table 3), MultiHance demonstrates weak and transient interactions with serum proteins that causes slowing in the molecular tumbling dynamics, resulting in strong increases in relaxivity in solutions containing serum proteins. The improved relaxation effect can contribute to increased contrast-to-noise ratio and lesion-to-brain ratio, which may improve visualization. TABLE 3: RELAXIVITY (mM –1 s –1 ) OF GADOLINIUM CHELATES r 1 and r 2 relaxivities indicate the efficiency in shortening T1 and T2 relaxation times, respectively. 1 In heparinized human plasma, at 39°C. 2 In citrated human plasma, at 37°C. -- Not available Human plasma r 1 r 2 Gadobenate 9.7 1 12.5 1 Gadopentetate 4.9 1 6.3 1 Gadodiamide 5.4 2 -- Gadoteridol 5.4 2 -- Disruption of the blood-brain barrier or abnormal vascularity allows enhancement by MultiHance of lesions such as neoplasms, abscesses, and infarcts. Uptake of MultiHance into hepatocytes has been demonstrated. 12.3 Pharmacokinetics Three single-dose intravenous studies were conducted in 32 healthy male subjects to assess the pharmacokinetics of gadobenate dimeglumine. The doses administered in these studies ranged from 0.005 to 0.4 mmol/kg. Upon injection, the meglumine salt is completely dissociated from the gadobenate dimeglumine complex. Thus, the pharmacokinetics is based on the assay of gadobenate ion, the MRI contrast effective ion in gadobenate dimeglumine. Data for plasma concentration and area under the curve demonstrated linear dependence on the administered dose. The pharmacokinetics of gadobenate ion following intravenous administration can be best described using a two-compartment model. Distribution Gadobenate ion has a rapid distribution half-life (reported as mean ± SD) of 0.084 ± 0.012 to 0.605 ± 0.072 hours. Volume of distribution of the central compartment ranged from 0.074 ± 0.017 to 0.158 ± 0.038 L/kg, and estimates of volume of distribution by area ranged from 0.170 ± 0.016 to 0.282 ± 0.079 L/kg. These latter estimates are approximately equivalent to the average volume of extracellular body water in man. In vitro studies showed no appreciable binding of gadobenate ion to human serum proteins. Following GBCA administration, gadolinium is present for months or years in brain, bone, skin, and other organs [see Warnings and Precautions (5.4) ] . Elimination Gadobenate ion is eliminated predominately via the kidneys, with 78% to 96% of an administered dose recovered in the urine. Total plasma clearance and renal clearance estimates of gadobenate ion were similar, ranging from 0.093 ± 0.010 to 0.133 ± 0.270 L/hr/kg and 0.082 ± 0.007 to 0.104 ± 0.039 L/hr/kg, respectively. The clearance is similar to that of substances that are subject to glomerular filtration. The mean elimination half-life ranged from 1.17 ± 0.26 to 2.02 ± 0.60 hours. A small percentage of the administered dose (0.6% to 4%) is eliminated via the biliary route and recovered in feces. Metabolism There was no detectable biotransformation of gadobenate ion. Dissociation of gadobenate ion in vivo has been shown to be minimal, with less than 1% of the free chelating agent being recovered alone in feces. Pharmacokinetics in Special Populations Renal Impairment: A single intravenous dose of 0.2 mmol/kg of MultiHance was administered to 20 subjects with impaired renal function (6 men and 3 women with moderate renal impairment [urine creatinine clearance >30 to <60 mL/min] and 5 men and 6 women with severe renal impairment [urine creatinine clearance >10 to <30 mL/min]). Mean estimates of the elimination half-life were 6.1 ± 3.0 and 9.5 ± 3.1 hours for the moderate and severe renal impairment groups, respectively as compared with 1.0 to 2.0 hours in healthy volunteers. Hemodialysis: A single intravenous dose of 0.2 mmol/kg of MultiHance was administered to 11 subjects (5 males and 6 females) with end-stage renal disease requiring hemodialysis to determine the pharmacokinetics and dialyzability of gadobenate. Approximately 72% of the dose was recovered by hemodialysis over a 4-hour period. The mean elimination half-life on dialysis was 1.21 ± 0.29 hours as compared with 42.4 ± 24.4 hours when off dialysis. Hepatic Impairment: A single intravenous dose of 0.1 mmol/kg of MultiHance was administered to 11 subjects (8 males and 3 females) with impaired liver function (Class B or C modified Child-Pugh Classification). Hepatic impairment had little effect on the pharmacokinetics of MultiHance with the parameters being similar to those calculated for healthy subjects. Gender, Age, Race: A multiple regression analysis performed using pooled data from several pharmacokinetic studies found no significant effect of sex upon the pharmacokinetics of gadobenate. Clearance appeared to decrease slightly with increasing age. Since variations due to age appeared marginal, dosage adjustment for geriatric population is not recommended. Pharmacokinetic differences due to race have not been systematically studied. Pediatric: A population pharmacokinetic analysis incorporated data from 25 healthy subjects (14 males and 11 females) and 15 subjects undergoing MR imaging of the central nervous system (7 males and 8 females) between ages of 2 and 16 years. The subjects received a single intravenous dose of 0.1 mmol/kg of MultiHance. The geometric mean C max was 62.3 μg/mL (n=16) in children 2 to 5 years of age, and 64.2 μg/mL (n=24) in children older than 5 years. The geometric mean AUC 0-∞ was 77.9 μg⋅h/mL in children 2-5 years of age (n=16) and 82.6 μg⋅h/mL in children older than 5 years (n=24). The geometric mean half-life was 1.2 hours in children 2 to 5 years of age and 0.93 hours in children older than 5 years. There was no significant gender-related difference in the pharmacokinetic parameters in the pediatric patients. Over 80% of the dose was recovered in urine after 24 hours. Pharmacokinetic simulations indicate similar AUC and C max values for MultiHance in pediatric subjects less than 2 years when compared to those reported for adults; no age-based dose adjustment is necessary for this pediatric population."],"indications_and_usage":["1 INDICATIONS AND USAGE magnetic resonance imaging (MRI) of the central nervous system (CNS) in adults and pediatric patients (including term neonates), to visualize lesions with abnormal blood-brain barrier or abnormal vascularity of the brain, spine, and associated tissues. (1.1) magnetic resonance angiography (MRA) to evaluate adults with known or suspected renal or aorto-ilio-femoral occlusive vascular disease. (1.2) 1.1 Magnetic Resonance Imaging (MRI) of the Central Nervous System (CNS) MultiHance is indicated for intravenous use in magnetic resonance imaging (MRI) of the central nervous system (CNS) in adults and pediatric patients (including term neonates), to visualize lesions with abnormal blood-brain barrier or abnormal vascularity of the brain, spine, and associated tissues. 1.2 Magnetic Resonance Angiography (MRA) of Renal and Aorto-ilio-femoral Vessels MultiHance is indicated for use in magnetic resonance angiography (MRA) to evaluate adults with known or suspected renal or aorto-ilio-femoral occlusive vascular disease."],"warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS Hypersensitivity: anaphylactic/anaphylactoid reactions with cardiovascular, respiratory and cutaneous manifestations, ranging from mild to severe reactions including shock can occur. Monitor patients closely for need of emergency cardiorespiratory support. (5.3) Gadolinium is retained for months or years in brain, bone, and other organs. (5.4) 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 MultiHance have not been established with intrathecal use. MultiHance is not approved for intrathecal use [see Dosage and Administration (2.1) ] . 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 MultiHance 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/1.73m 2 ) as well as patients with acute kidney injury. The risk appears lower for patients with chronic, moderate kidney disease (GFR 30-59 mL/min/1.73m 2 ) and little, if any, for patients with chronic, mild kidney disease (GFR 60-89 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 MultiHance administration to Bracco Diagnostics (1-800-257-5181) 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 (e.g., 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 the 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 MultiHance 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 Dosage and Administration (2) and Clinical Pharmacology (12) ]. 5.3 Hypersensitivity Reactions Anaphylactic and anaphylactoid reactions have been reported, involving cardiovascular, respiratory, and/or cutaneous manifestations. Some patients experienced circulatory collapse and died. In most cases, initial symptoms occurred within minutes of MultiHance administration and resolved with prompt emergency treatment. Prior to MultiHance administration, ensure the availability of personnel trained and medications to treat hypersensitivity reactions. If such a reaction occurs stop MultiHance and immediately begin appropriate therapy. Additionally, consider the risk for hypersensitivity reactions, especially in patients with a history of hypersensitivity reactions or a history of asthma or other allergic disorders. Observe patients for signs and symptoms of a hypersensitivity reaction during and for up to 2 hours after MultiHance administration. 5.4 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 (e.g. 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 Omniscan (gadodiamide) and Optimark (gadoversetamide) causing greater retention than other linear agents [Eovist (gadoxetate disodium), Magnevist (gadopentetate dimeglumine), MultiHance (gadobenate dimeglumine)]. Retention is lowest and similar among the macrocyclic GBCAs [Dotarem (gadoterate meglumine), Gadavist (gadobutrol), ProHance (gadoteridol)]. Consequences of gadolinium retention in the brain have not been established. Pathologic and clinical consequences of GBCA administration and retention in skin and other organs have been established in patients with impaired renal function [see Warnings and Precautions (5.2) ] . There are rare reports of pathologic skin changes in patients with normal renal function. Adverse events involving multiple organ systems have been reported in patients with normal renal function without an established causal link to gadolinium retention [see Adverse Reactions (6.2) ] . While clinical consequences of gadolinium retention have not been established in patients with normal renal function, certain patients might be at higher risk. These include patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions. Consider the retention characteristics of the agent when choosing a GBCA for these patients. Minimize repetitive GBCA imaging studies, particularly closely spaced studies when possible. 5.5 Acute Renal Failure In patients with renal insufficiency, acute renal failure requiring dialysis or worsening renal function have occurred with the use of gadolinium-based contrast agents. The risk of renal failure may increase with increasing dose of the contrast agent. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. Consider follow-up renal function assessments for patients with a history of renal dysfunction. 5.6 Extravasation and Injection Site Reactions Extravasation of MultiHance may lead to injection site reactions, characterized by local pain or burning sensation, swelling, blistering, and necrosis. In animal experiments, local reactions including eschar and necrosis were noted even on Day 8 post perivenous injection of MultiHance. Exercise caution to avoid local extravasation during intravenous administration of MultiHance. If extravasation occurs, evaluate and treat as necessary if local reactions develop. 5.7 Cardiac Arrhythmias Cardiac arrhythmias have been observed in patients receiving MultiHance in clinical trials [ see Adverse Reactions (6.1) ]. Assess patients for underlying conditions or medications that predispose to arrhythmias. A double-blind, placebo-controlled, 24-hour post dose continuous monitoring, crossover study in 47 subjects evaluated the effect of 0.2 mmol/kg MultiHance on ECG intervals, including QTc. The average changes in QTc values compared with placebo were minimal (<5 msec). QTc prolongation between 30 and 60 msec were noted in 20 subjects who received MultiHance vs. 11 subjects who received placebo. Prolongations ≥61 msec were noted in 6 subjects who received MultiHance and in 3 subjects who received placebo. None of these subjects had associated malignant arrhythmias. The effects on QTc by MultiHance dose, other drugs, and medical conditions were not systematically studied. 5.8 Interference with Visualization of Certain Lesions Certain lesions seen on non-contrast images may not be seen on contrast- images. Exercise caution when interpreting contrast MR images in the absence of companion non-contrast MR images."],"clinical_studies_table":["
(a) Difference of means = (paired mean) - (pre mean) (b) Worse = paired score is less than the pre score Same = paired score is the same as the pre score Better = paired score is greater than the pre score * Statistically significant for the mean (paired t test)
Table 4: LESION LEVEL RESULTS OF MRI CENTRAL NERVOUS SYSTEM ADULT STUDIES WITH 0.1 mmol/kg MULTIHANCE
Study AStudy B
Reader 1Reader 2Reader 3Reader 1Reader 2Reader 3
EndpointsN = 395N = 384N = 299N = 245N = 275N = 254
Border Delineation:
Difference of Means (a)0.8*0.6*0.8*1.8*1.5*1.9*
Worse (b) Same Better44 (11%) 146 (37%) 205 (52%)61 (16%) 168 (44%) 155 (40%)57 (19%) 89 (30%) 153 (51%)13 (5%) 11 (5%) 221 (90%)24 (9%) 19 (7%) 232 (84%)15 (6%) 18 (7%) 221 (87%)
Internal Morphology:
Difference of Means0.8*0.6*0.7*1.7*1.4*2.1*
Worse Same Better37 (10%) 147 (37%) 211 (53%)63 (17%) 151 (39%) 170 (44%)62 (21%) 84 (28%) 153 (51%)13 (5%) 16 (7%) 216 (88%)26 (10%) 22 (8%) 227 (82%)14 (5%) 22 (9%) 218 (86%)
Contrast Enhancement:
Difference of Means0.7*0.5*0.8*1.9*1.3*1.9*
Worse Same Better75 (19%) 148 (37%) 172 (44%)74 (19%) 152 (40%) 158 (41%)50 (17%) 109 (36%) 140 (47%)13 (5%) 11 (5%) 221 (90%)32 (12%) 21 (7%) 222 (81%)17 (7%) 14 (5%) 223 (88%)
","
TABLE 5. PERFORMANCE CHARACTERISTICS OF MULTIHANCE-MRA AND NON-CONTRAST MRA
* (Based on General Delta Method)
READER AORTO-ILIO-FEMORAL ARTERIES
SENSITIVITYSPECIFICITY
MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)*MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)*
177.8%73.7%4.5 (1.5, 7.6)88.1%78.5%10.0 (7.3, 12.6)
265.2% 52.5% 12.6 (8.5, 16.6)94.2% 89.4% 4.9 (2.7, 7.1)
369.0% 59.1% 10.0 (6.1, 14.0)90.0% 75.3% 14.9 (12.1, 17.8)
READER RENAL ARTERIES
SENSITIVITYSPECIFICITY
MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)*MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)*
167.8%47.0%20.8 (12.8, 28.9)94.0% 86.1%8.3 (4.2, 12.4)
262.4%46.7%16.2 (6.8, 25.6) 94.0%83.5%10.3 (5.5, 15.0)
365.5%39.6%25.3 (15.9, 34.6)94.7%87.3%8.0 (3.6, 12.5)
","
(a) Difference of means = (paired mean) - (pre mean) (b) Worse = paired score is less than the pre score Same = paired score is the same as the pre score Better = paired score is greater than the pre score * Statistically significant for the mean (paired t test)
Table 4: LESION LEVEL RESULTS OF MRI CENTRAL NERVOUS SYSTEM ADULT STUDIES WITH 0.1 mmol/kg MULTIHANCE
Study AStudy B
Reader 1Reader 2Reader 3Reader 1Reader 2Reader 3
EndpointsN = 395N = 384N = 299N = 245N = 275N = 254
Border Delineation:
Difference of Means (a)0.8*0.6*0.8*1.8*1.5*1.9*
Worse (b) Same Better44 (11%) 146 (37%) 205 (52%)61 (16%) 168 (44%) 155 (40%)57 (19%) 89 (30%) 153 (51%)13 (5%) 11 (5%) 221 (90%)24 (9%) 19 (7%) 232 (84%)15 (6%) 18 (7%) 221 (87%)
Internal Morphology:
Difference of Means0.8*0.6*0.7*1.7*1.4*2.1*
Worse Same Better37 (10%) 147 (37%) 211 (53%)63 (17%) 151 (39%) 170 (44%)62 (21%) 84 (28%) 153 (51%)13 (5%) 16 (7%) 216 (88%)26 (10%) 22 (8%) 227 (82%)14 (5%) 22 (9%) 218 (86%)
Contrast Enhancement:
Difference of Means0.7*0.5*0.8*1.9*1.3*1.9*
Worse Same Better75 (19%) 148 (37%) 172 (44%)74 (19%) 152 (40%) 158 (41%)50 (17%) 109 (36%) 140 (47%)13 (5%) 11 (5%) 221 (90%)32 (12%) 21 (7%) 222 (81%)17 (7%) 14 (5%) 223 (88%)
","
TABLE 5. PERFORMANCE CHARACTERISTICS OF MULTIHANCE-MRA AND NON-CONTRAST MRA
* (Based on General Delta Method)
READER AORTO-ILIO-FEMORAL ARTERIES
SENSITIVITYSPECIFICITY
MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)*MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)*
177.8%73.7%4.5 (1.5, 7.6)88.1%78.5%10.0 (7.3, 12.6)
265.2% 52.5% 12.6 (8.5, 16.6)94.2% 89.4% 4.9 (2.7, 7.1)
369.0% 59.1% 10.0 (6.1, 14.0)90.0% 75.3% 14.9 (12.1, 17.8)
READER RENAL ARTERIES
SENSITIVITYSPECIFICITY
MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)*MultiHance MRA [A] Non-contrast MRA [B] [A] – [B] (95% CI)*
167.8%47.0%20.8 (12.8, 28.9)94.0% 86.1%8.3 (4.2, 12.4)
262.4%46.7%16.2 (6.8, 25.6) 94.0%83.5%10.3 (5.5, 15.0)
365.5%39.6%25.3 (15.9, 34.6)94.7%87.3%8.0 (3.6, 12.5)
"],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of MultiHance. The results for MultiHance were negative in the following genetic toxicity studies: 1) in vitro bacteria reverse mutation assays, 2) an in vitro gene mutation assay in mammalian cells, 3) an in vitro chromosomal aberration assay, 4) an in vitro unscheduled DNA synthesis assay, and 5) an in vivo micronucleus assay in rats. MultiHance had no effect on fertility and reproductive performance at IV doses of up to 2 mmol/kg/day (3 times the human dose on body surface basis) for 13 weeks in male rats and for 32 days in female rats. However, vacuolation in testes and abnormal spermatogenic cells were observed when MultiHance was intravenously administered to male rats at 3 mmol/kg/day (5 times the human dose on body surface basis) for 28 days. The effects were not reversible following 28-day recovery period. The effects were not reported in dog and monkey studies (at doses up to about 11 and 10 times the human dose on body surface basis for dogs (28 days dosing) and monkeys (14 days dosing), respectively)."],"pharmacodynamics_table":["
TABLE 3: RELAXIVITY (mM–1s–1) OF GADOLINIUM CHELATES
r1 and r2 relaxivities indicate the efficiency in shortening T1 and T2 relaxation times, respectively. 1 In heparinized human plasma, at 39°C. 2 In citrated human plasma, at 37°C. -- Not available
Human plasma
r1r2
Gadobenate9.7112.51
Gadopentetate4.916.31
Gadodiamide5.42--
Gadoteridol5.42--
"],"adverse_reactions_table":["
TABLE 2: ADVERSE REACTIONS REPORTED IN ≥ 0.5% OF ADULT SUBJECTS WHO RECEIVED MULTIHANCE IN CLINICAL TRIALS
Number of subjects dosed4967
Number of subjects with any adverse reaction517 (10.4%)
Gastrointestinal Disorders Nausea 67 (1.3%)
General Disorders and Administration Site Disorders Injection Site Reaction Feeling Hot 54 (1.1%) 49 (1.0%)
Nervous System Disorders Headache Dysgeusia Paresthesia Dizziness 60 (1.2%) 33 (0.7%) 24 (0.5%) 24 (0.5%)
"],"information_for_patients":["17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide) found at www.multihancemedicationguide.com . Nephrogenic Systemic Fibrosis Instruct patients to inform their physician if they: have a history of kidney and/or liver disease, or have recently received a GBCA. GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. To counsel patients at risk for NSF: Describe the clinical manifestations 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 MultiHance 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 feeling hot, nausea, and headache. 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 (5.4) ] . Rx only US Patent No. 4,916,246 Manufactured for Bracco Diagnostics Inc. Princeton, NJ 08540 By BIPSO GmbH 78224 Singen (Germany) March 2025 CL44F-09"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION The recommended dose of MultiHance is 0.2 mL/kg (0.1 mmol/kg) administered as a rapid bolus intravenous injection. For MRI of the CNS in pediatric patients below 2 years of age the recommended dosage range is 0.1 to 0.2 mL/kg. To ensure complete injection of the contrast medium, follow the injection with a saline flush of at least 5 mL in MRI of the CNS and at least 20 mL in MRA. ( 2 ) 2.1 Dosing and Imaging Instructions 2.1.1 MRI of the CNS In adults and in pediatric patients over 2 years of age, the recommended dose of MultiHance for MRI of the CNS is 0.2 mL/kg (0.1 mmol/kg) administered as a rapid bolus intravenous injection. In pediatric patients below 2 years of age, the recommended dosage range is 0.1 to 0.2 mL/kg administered as a rapid bolus intravenous injection. To ensure complete injection of the contrast medium, follow the injection with a saline flush of at least 5 mL. Imaging of the CNS can be performed starting immediately after the bolus injection of MultiHance. 2.1.2 MRA of Renal and Aorto-ilio-femoral Vessels For MRA examination, the recommended dose is 0.2 mL/kg (0.1 mmol/kg) administered as a rapid bolus intravenous injection followed by at least 20 mL saline flush either manually or using an automatic injector system. Start imaging immediately after the administration of MultiHance, with scan delay calculated by test bolus or automatic bolus detection technique. If an automatic contrast detection pulse sequence is not used for bolus timing, then a test bolus injection of 1-2 mL of MultiHance should be used to calculate the appropriate scan delay. 2.2 Dosing Table *For pediatric patients less than 2 years of age, one-half of the per kg dose may be used. TABLE 1: WEIGHT-BASED DOSING VOLUMES FOR: CNS IMAGING (ADULTS AND PEDIATRICS ≥2 YEARS OF AGE*) AND MRA IMAGING (ADULTS ONLY) 0.1mM/kg dose Kilograms (Kg) Pounds (lb) Volume, Milliliters (mL) 2.5 5.5 0.5 5 11 1.0 10 22 2.0 15 33 3.0 20 44 4.0 25 55 5.0 30 66 6.0 35 77 7.0 40 88 8.0 45 99 9.0 50 110 10.0 55 121 11.0 60 132 12.0 65 143 13.0 70 154 14.0 75 165 15.0 80 176 16.0 85 187 17.0 90 198 18.0 95 209 19.0 100 220 20.0 105 231 21.0 110 242 22.0 115 253 23.0 120 264 24.0 125 275 25.0 130 286 26.0 135 297 27.0 140 308 28.0 145 319 29.0 150 330 30.0 2.3 Administration Inspect the MultiHance vial visually for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored or particulate matter is present. Draw MultiHance into a syringe and inject using sterile technique. Do not mix intravenous medications or parenteral nutrition solutions with MultiHance. Do not administer other medications in the same intravenous line with MultiHance. MultiHance vials are intended for single use only. Administer immediately after opening and discard any unused product."],"spl_product_data_elements":["MultiHance gadobenate dimeglumine gadobenate dimeglumine GADOLINIUM CATION (3+)"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS MultiHance is a sterile, nonpyrogenic, clear, colorless to slightly yellow aqueous solution for intravenous use only, containing 529 mg gadobenate dimeglumine per mL. Each mL of MultiHance Injection contains 529 mg gadobenate dimeglumine and is available in single use vials. (3)"],"clinical_pharmacology_table":["
TABLE 3: RELAXIVITY (mM–1s–1) OF GADOLINIUM CHELATES
r1 and r2 relaxivities indicate the efficiency in shortening T1 and T2 relaxation times, respectively. 1 In heparinized human plasma, at 39°C. 2 In citrated human plasma, at 37°C. -- Not available
Human plasma
r1r2
Gadobenate9.7112.51
Gadopentetate4.916.31
Gadodiamide5.42--
Gadoteridol5.42--
"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS Pregnancy: Use only if imaging is essential during pregnancy and cannot be delayed. ( 8.1 ) 8.1 Pregnancy 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, gadobenate dimeglumine has been shown to be teratogenic in rabbits following repeated intravenous administration during organogenesis at doses up to 6 times the recommended human dose. There were no adverse developmental effects observed in rats with intravenous administration of gadobenate dimeglumine during organogenesis at doses up to three times the recommended human dose (see Data ). Because of the potential risks of gadolinium to the fetus, use MultiHance only if imaging is essential and cannot be delayed. The estimated 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 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 Gadobenate dimeglumine has been shown to be teratogenic in rabbits when administered intravenously at 2 mmol/kg/day (6 times the recommended human dose based on body surface area) during organogenesis (day 6 to 18) inducing microphthalmia/small eye and/or focal retinal fold in 3 fetuses from 3 separate litters. In addition, MultiHance administered intravenously at 3 mmol/kg/day (10 times the recommended human dose based on body surface area) has been shown to increase intrauterine deaths in rabbits. There was no evidence that MultiHance induced teratogenic effects in rats at doses up to 2 mmol/kg/day (3 times the recommended human dose based on body surface area), however, rat dams exhibited no systemic toxicity at this dose. There were no adverse effects on the birth, survival, growth, development and fertility of the F1 generation at doses up to 2 mmol/kg in a rat peri- and post-natal (Segment III) study. 8.2 Lactation Risk Summary Limited literature reports that breastfeeding after gadobenate dimeglumine administration to the mother would result in the infant receiving an oral dose of 0.001%-0.04% of the maternal dose. There is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. Additionally, there is limited GBCA gastrointestinal absorption. The developmental and health benefits of breastfeeding should be considered together with the mother’s clinical need for MultiHance and any potential adverse effects on the breastfed infant from MultiHance or from the underlying maternal condition. 8.4 Pediatric Use MultiHance is approved for intravenous use for MRI of the CNS to visualize lesions with abnormal blood brain barrier or abnormal vascularity of the brain, spine, and associated tissues in pediatric patients from birth, including term neonates, to less than 17 years of age. Pediatric use is based on evidence of effectiveness in adults and in 202 pediatric patients 2 years of age and older, in addition to experience in 105 pediatric patients birth to less than 2 years of age that supported extrapolation from adult data [see Clinical Studies ( 14 )] . Adverse reactions in pediatric patients were similar to those reported in adults [see Adverse Reactions ( 6.1 )] . No dose adjustment according to age is necessary in pediatric patients two years of age and older. For pediatric patients, less than 2 years of age, the recommended dosage range is 0.1 to 0.2 mL/kg [see Dosage and Administration ( 2.1 ), Pharmacokinetics ( 12.3 )] . The safety of MultiHance has not been established in preterm neonates. 8.5 Geriatric Use Of the total number of 4967 adult subjects in clinical studies of MultiHance, 33% were 65 or older. No overall differences in safety or effectiveness were observed between these elderly subjects and the younger subjects. The drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to MultiHance 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."],"dosage_and_administration_table":["
*For pediatric patients less than 2 years of age, one-half of the per kg dose may be used.
TABLE 1: WEIGHT-BASED DOSING VOLUMES FOR: CNS IMAGING (ADULTS AND PEDIATRICS ≥2 YEARS OF AGE*) AND MRA IMAGING (ADULTS ONLY)
0.1mM/kg dose
Kilograms (Kg)Pounds (lb)Volume, Milliliters (mL)
2.55.50.5
5111.0
10222.0
15333.0
20444.0
25555.0
30666.0
35777.0
40888.0
45999.0
5011010.0
5512111.0
6013212.0
6514313.0
7015414.0
7516515.0
8017616.0
8518717.0
9019818.0
9520919.0
10022020.0
10523121.0
11024222.0
11525323.0
12026424.0
12527525.0
13028626.0
13529727.0
14030828.0
14531929.0
15033030.0
"],"package_label_principal_display_panel":["MultiHance ® Injection 15 mL NDC 0270–5164–14 multihance-box-15-ml multihance-15-ml-vial-label"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of MultiHance. The results for MultiHance were negative in the following genetic toxicity studies: 1) in vitro bacteria reverse mutation assays, 2) an in vitro gene mutation assay in mammalian cells, 3) an in vitro chromosomal aberration assay, 4) an in vitro unscheduled DNA synthesis assay, and 5) an in vivo micronucleus assay in rats. MultiHance had no effect on fertility and reproductive performance at IV doses of up to 2 mmol/kg/day (3 times the human dose on body surface basis) for 13 weeks in male rats and for 32 days in female rats. However, vacuolation in testes and abnormal spermatogenic cells were observed when MultiHance was intravenously administered to male rats at 3 mmol/kg/day (5 times the human dose on body surface basis) for 28 days. The effects were not reversible following 28-day recovery period. The effects were not reported in dog and monkey studies (at doses up to about 11 and 10 times the human dose on body surface basis for dogs (28 days dosing) and monkeys (14 days dosing), respectively)."]},"tags":[{"label":"gadobenate dimeglumine","category":"class"},{"label":"Small Molecule","category":"modality"},{"label":"Intravenous","category":"route"},{"label":"Injection","category":"form"},{"label":"Off-Patent","category":"patent"},{"label":"Active","category":"status"},{"label":"Bracco","category":"company"},{"label":"Approved 2000s","category":"decade"},{"label":"Contrast Media","category":"pharmacology"},{"label":"Diagnostic Uses of Chemicals","category":"pharmacology"}],"phase":"marketed","safety":{"boxedWarnings":["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. MultiHance 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 MultiHance 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 systemic 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 (e.g. 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 MultiHance dose and allow a sufficient period of time for elimination of the drug from the body prior to 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. MultiHance 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 MultiHance in these patients unless the diagnostic information is essential and not available with non-contrast 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 (e.g. age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. (5.2)"],"safetySignals":[{"llr":989.435,"date":"","count":212,"signal":"Nephrogenic systemic fibrosis","source":"DrugCentral FAERS","actionTaken":"Reported 212 times (LLR=989)"},{"llr":581.171,"date":"","count":377,"signal":"Hypersensitivity","source":"DrugCentral FAERS","actionTaken":"Reported 377 times (LLR=581)"},{"llr":482.006,"date":"","count":282,"signal":"Urticaria","source":"DrugCentral FAERS","actionTaken":"Reported 282 times (LLR=482)"},{"llr":449.809,"date":"","count":88,"signal":"Contrast media reaction","source":"DrugCentral FAERS","actionTaken":"Reported 88 times (LLR=450)"},{"llr":426.031,"date":"","count":198,"signal":"Anaphylactic reaction","source":"DrugCentral FAERS","actionTaken":"Reported 198 times (LLR=426)"},{"llr":422.771,"date":"","count":100,"signal":"Skin hypertrophy","source":"DrugCentral FAERS","actionTaken":"Reported 100 times (LLR=423)"},{"llr":394.652,"date":"","count":92,"signal":"Skin induration","source":"DrugCentral FAERS","actionTaken":"Reported 92 times (LLR=395)"},{"llr":377.593,"date":"","count":408,"signal":"Vomiting","source":"DrugCentral FAERS","actionTaken":"Reported 408 times (LLR=378)"},{"llr":350.368,"date":"","count":87,"signal":"Anaphylactoid reaction","source":"DrugCentral FAERS","actionTaken":"Reported 87 times (LLR=350)"},{"llr":350.017,"date":"","count":87,"signal":"Skin tightness","source":"DrugCentral FAERS","actionTaken":"Reported 87 times (LLR=350)"},{"llr":345.818,"date":"","count":472,"signal":"Nausea","source":"DrugCentral FAERS","actionTaken":"Reported 472 times (LLR=346)"},{"llr":318.838,"date":"","count":108,"signal":"Sneezing","source":"DrugCentral FAERS","actionTaken":"Reported 108 times (LLR=319)"},{"llr":261.113,"date":"","count":39,"signal":"Gadolinium deposition disease","source":"DrugCentral FAERS","actionTaken":"Reported 39 times (LLR=261)"},{"llr":234.179,"date":"","count":50,"signal":"Skin fibrosis","source":"DrugCentral FAERS","actionTaken":"Reported 50 times (LLR=234)"},{"llr":229.825,"date":"","count":253,"signal":"Pruritus","source":"DrugCentral FAERS","actionTaken":"Reported 253 times (LLR=230)"}],"drugInteractions":[{"drug":"cisplatin","severity":"major","mechanism":"competition for canalicular multispecific organic anion transporter (MOAT/MRP2/ABCC2)","management":"consider potential for prolonged drug exposure in patients with decreased MOAT activity","clinicalEffect":"prolonged systemic exposure"},{"drug":"doxorubicin","severity":"major","mechanism":"competition for canalicular multispecific organic anion transporter (MOAT/MRP2/ABCC2)","management":"consider potential for prolonged drug exposure in patients with decreased MOAT activity","clinicalEffect":"prolonged systemic exposure"},{"drug":"daunorubicin","severity":"major","mechanism":"competition for canalicular multispecific organic anion transporter (MOAT/MRP2/ABCC2)","management":"consider potential for prolonged drug exposure in patients with decreased MOAT activity","clinicalEffect":"prolonged systemic exposure"},{"drug":"vincristine","severity":"major","mechanism":"competition for canalicular multispecific organic anion transporter (MOAT/MRP2/ABCC2)","management":"consider potential for prolonged drug exposure in patients with decreased MOAT activity","clinicalEffect":"prolonged systemic exposure"},{"drug":"methotrexate","severity":"major","mechanism":"competition for canalicular multispecific organic anion transporter (MOAT/MRP2/ABCC2)","management":"consider potential for prolonged drug exposure in patients with decreased MOAT activity","clinicalEffect":"prolonged systemic exposure"},{"drug":"etoposide","severity":"major","mechanism":"competition for canalicular multispecific organic anion transporter (MOAT/MRP2/ABCC2)","management":"consider potential for prolonged drug exposure in patients with decreased MOAT activity","clinicalEffect":"prolonged systemic exposure"},{"drug":"tamoxifen","severity":"major","mechanism":"competition for canalicular multispecific organic anion transporter (MOAT/MRP2/ABCC2)","management":"consider potential for prolonged drug exposure in patients with decreased MOAT activity","clinicalEffect":"prolonged systemic exposure"},{"drug":"paclitaxel","severity":"major","mechanism":"competition for canalicular multispecific organic anion transporter (MOAT/MRP2/ABCC2)","management":"consider potential for prolonged drug exposure in patients with decreased MOAT activity","clinicalEffect":"prolonged systemic exposure"}],"commonSideEffects":[{"effect":"Nausea","drugRate":"1.3%","severity":"mild","_validated":true},{"effect":"Headache","drugRate":"1.2%","severity":"mild","_validated":true},{"effect":"Injection Site Reaction","drugRate":"1.1%","severity":"mild","_validated":true},{"effect":"Feeling Hot","drugRate":"1.0%","severity":"mild","_validated":true},{"effect":"Vomiting","drugRate":"1.0%","severity":"mild","_validated":true},{"effect":"Dysgeusia","drugRate":"0.7%","severity":"mild","_validated":true},{"effect":"Hyperhidrosis","drugRate":"0.7%","severity":"mild","_validated":true},{"effect":"Paresthesia","drugRate":"0.5%","severity":"mild","_validated":true},{"effect":"Dizziness","drugRate":"0.5%","severity":"mild","_validated":true},{"effect":"Serious anaphylactoid reaction","drugRate":"0.1%","severity":"serious","_validated":true},{"effect":"Convulsions","drugRate":"0.1%","severity":"serious","_validated":true},{"effect":"Pulmonary edema","drugRate":"0.1%","severity":"serious","_validated":true},{"effect":"Acute necrotizing pancreatitis","drugRate":"0.1%","severity":"serious","_validated":true},{"effect":"Anaphylactoid reactions","drugRate":"0.1%","severity":"serious","_validated":true},{"effect":"Basophilia","drugRate":"reported","severity":"unknown"},{"effect":"Atrioventricular block first degree","drugRate":"reported","severity":"unknown"},{"effect":"Eye pruritus","drugRate":"reported","severity":"unknown"},{"effect":"Eye swelling","drugRate":"reported","severity":"unknown"},{"effect":"Ocular hyperemia","drugRate":"reported","severity":"unknown"},{"effect":"Visual disturbance","drugRate":"reported","severity":"unknown"},{"effect":"Abdominal pain or discomfort","drugRate":"reported","severity":"unknown"},{"effect":"Diarrhea","drugRate":"reported","severity":"unknown"},{"effect":"Dry mouth","drugRate":"reported","severity":"unknown"},{"effect":"Lip swelling","drugRate":"reported","severity":"unknown"},{"effect":"Paraesthesia oral","drugRate":"reported","severity":"unknown"},{"effect":"Tongue edema","drugRate":"reported","severity":"unknown"},{"effect":"Chest pain or discomfort","drugRate":"reported","severity":"unknown"},{"effect":"Chills","drugRate":"reported","severity":"unknown"},{"effect":"Malaise","drugRate":"reported","severity":"unknown"},{"effect":"Hypersensitivity","drugRate":"reported","severity":"unknown"}],"specialPopulations":{"Pregnancy":"Use only if imaging is essential during pregnancy and cannot be delayed. 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. In animal reproduction studies, gadobenate dimeglumine has been shown to be teratogenic in rabbits following repeated intravenous administration during organogenesis at doses up to times the recommended human dose. There were no adverse developmental effects observed in rats with intravenous administration of gadobenate dimeglumine during organogenesis at doses up to three times the recommended human dose. Because of the potential risks of gadolinium to the fetus, use MultiHance only if imaging is essential and cannot be delayed.","Geriatric use":"Of the total number of 4967 adult subjects in clinical studies of MultiHance, 33% were 65 or older. No overall differences in safety or effectiveness were observed between these elderly subjects and the younger subjects. The drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to MultiHance 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 in these patients.","Paediatric use":"MultiHance is approved for intravenous use for MRI of the CNS to visualize lesions with abnormal blood brain barrier or abnormal vascularity of the brain, spine, and associated tissues in pediatric patients from birth, including term neonates, to less than 17 years of age.","Renal impairment":"The risk of toxic reactions to MultiHance may be greater in patients with impaired renal function."}},"trials":[],"aliases":[],"company":"Bracco","patents":[],"pricing":[],"_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=GADOBENATE DIMEGLUMINE","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-20T03:15:02.308924+00:00"},"aiSummary":{"url":"","method":"ai_extraction","source":"AI Strategic Summary","aiModel":"featherless","rawText":"","confidence":0.9,"sourceType":"ai_extraction","retrievedAt":"2026-04-20T03:16:05.876610+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-20T03:15:07.662416+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=GADOBENATE DIMEGLUMINE","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-20T03:15:07.984480+00:00"},"administration.route":{"url":"","method":"deterministic","source":"FDA Label","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:15:01.169385+00:00"},"indications.approved":{"url":"","method":"ai_extraction","source":"FDA Label + AI","aiModel":"featherless","rawText":"","confidence":0.9,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:15:58.577365+00:00"},"safety.boxedWarnings":{"url":"","method":"deterministic","source":"FDA Label (boxed_warning)","rawText":"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. MultiHance 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 o","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:15:01.169403+00:00"},"safety.drugInteractions":{"url":"","method":"ai_extraction","source":"FDA Label + AI","aiModel":"featherless","rawText":"","confidence":0.9,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:15:47.844925+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1200571/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T03:15:08.691502+00:00"},"regulatory.fda_application":{"url":"","method":"deterministic","source":"FDA Label","rawText":"NDA021357","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T03:15:01.169407+00:00"}},"allNames":"multihance","offLabel":[],"synonyms":["multihance","gadobenate dimeglumine"],"timeline":[{"date":"2004-01-01","type":"neutral","source":"FDA Orange Book","milestone":"Rights transferred from BRACCO to Bracco"},{"date":"2004-11-23","type":"positive","source":"DrugCentral","milestone":"FDA approval (Bracco)"}],"aiSummary":"Gadobenate dimeglumine (Multihance), marketed by Bracco, is a contrast agent used primarily for MRI imaging of central nervous system lesions. Its key strength lies in enhancing MRI image contrast through the paramagnetic properties of gadobenate dimeglumine, providing clear visualization of lesions. The primary risk is the key composition patent expiry in 2028, which could lead to increased competition from generic alternatives.","approvals":[{"date":"2004-11-23","orphan":false,"company":"BRACCO","regulator":"FDA"}],"brandName":"Multihance","ecosystem":[],"mechanism":{"modality":"Small Molecule","drugClass":"gadobenate dimeglumine","explanation":"Gadobenate dimeglumine is paramagnetic agent and, as such, developsa magnetic moment when placed in magnetic field. The large magneticmoment produced by the paramagnetic agent results in large localmagnetic field, which can enhance the relaxation rates of water protonsin its vicinity leading to an increase of signal intensity (brightness)of tissue.In magnetic resonanceimaging (MRI), visualization of normal and pathological tissue dependsin part on variations in the radiofrequency signal intensity thatoccur with 1) differences in proton density; 2) differences of thespin-lattice or longitudinal relaxation times (T1); and 3) differencesin the spin-spin or transverse relaxation time (T2). When placed ina magnetic field, gadobenate dimeglumine decreases the T1 and T2 relaxationtime in target tissues. At recommended doses, the effect is observedwith greatest sensitivity in the T1-weighted sequences.","oneSentence":"Multihance works by enhancing the contrast of MRI images through the paramagnetic properties of gadobenate dimeglumine.","technicalDetail":"Gadobenate dimeglumine is a gadolinium-based contrast agent that works by shortening the T1 relaxation time of surrounding tissues, resulting in increased signal intensity on T1-weighted MRI images."},"commercial":{"launchDate":"2004","_launchSource":"DrugCentral (FDA 2004-11-23, BRACCO)"},"references":[{"id":1,"url":"https://drugcentral.org/drugcard/4471","fields":["approvals","synonyms","ATC","PK","indications","contraindications","DDIs","targets","patents","FAERS"],"source":"DrugCentral"},{"id":2,"url":"https://clinicaltrials.gov/search?intr=GADOBENATE%20DIMEGLUMINE","fields":["trials"],"source":"ClinicalTrials.gov"},{"id":3,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=GADOBENATE DIMEGLUMINE","fields":["publications"],"source":"PubMed/NCBI"},{"id":4,"url":"https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files","fields":["patents","exclusivity","genericManufacturers"],"source":"FDA Orange Book"}],"_enrichedAt":"2026-03-30T11:38:23.086623","_validation":{"fieldsValidated":2,"lastValidatedAt":"2026-04-20T03:16:05.877071+00:00","fieldsConflicting":0,"overallConfidence":0.95},"biosimilars":[],"competitors":[],"genericName":"gadobenate dimeglumine","indications":{"approved":[{"id":"gadobenate-dimeglumine-mri-of-cns-lesions","name":"MRI of CNS Lesions","dosing":null,"approvals":[],"diseaseId":"","eligibility":"Adults and pediatric patients (including term neonates)","pivotalTrial":null,"restrictions":[],"patientPopulation":"Adults and pediatric patients (including term neonates)","diagnosticRequired":null,"brandNameForIndication":"Multihance"},{"id":"gadobenate-dimeglumine-mra-of-renal-and-aorto-ilio-fe","name":"MRA of Renal and Aorto-ilio-femoral Vessels","dosing":null,"approvals":[],"diseaseId":"","eligibility":"Adults","pivotalTrial":null,"restrictions":[],"patientPopulation":"Adults","diagnosticRequired":null,"brandNameForIndication":"Multihance"}],"offLabel":[],"pipeline":[]},"currentOwner":"Bracco","drugCategory":"active","labelChanges":[],"patentStatus":"Off-patent — no active Orange Book patents","relatedDrugs":[],"trialDetails":[{"nctId":"NCT02722525","phase":"NA","title":"Cardiac MRI in Measuring the Impact of Anti-androgen Treatment on Cardiac Function in Patients With Prostate Cancer","status":"ACTIVE_NOT_RECRUITING","sponsor":"Ohio State University Comprehensive Cancer Center","startDate":"2014-12","conditions":["Cardiovascular Injury","Prostate Carcinoma"],"enrollment":23,"completionDate":"2026-12-31"},{"nctId":"NCT01237054","phase":"PHASE2","title":"Imaging in MGUS, SMM and MM","status":"COMPLETED","sponsor":"National Cancer Institute (NCI)","startDate":"2010-10-17","conditions":["Multiple Myeloma","Smoldering Multiple Myeloma","Monoclonal Gammopathy of Undetermined Significance"],"enrollment":31,"completionDate":"2011-08-09"},{"nctId":"NCT04373564","phase":"PHASE4","title":"Effect on Body Movement and Mental Skills in Patients Who Received Gadolinium-based Contrast Media for Magnetic Resonance Examination Multiple Times Within 5 Years","status":"RECRUITING","sponsor":"Guerbet","startDate":"2021-03-24","conditions":["Motor Function","Cognitive Function","Contrast Media"],"enrollment":2076,"completionDate":"2028-12-31"},{"nctId":"NCT04910425","phase":"PHASE2","title":"PSMA-Targeted 18F-DCFPyL PET/MRI for the Detection of Prostate Cancer","status":"WITHDRAWN","sponsor":"Northwestern University","startDate":"2023-06-17","conditions":["Prostate Carcinoma"],"enrollment":0,"completionDate":"2028-07"},{"nctId":"NCT05783271","phase":"NA","title":"Validity of Parametric MRI Using VIRADS","status":"RECRUITING","sponsor":"Assiut University","startDate":"2025-12-01","conditions":["Bladder Cancer"],"enrollment":58,"completionDate":"2026-12-31"},{"nctId":"NCT04879628","phase":"PHASE2","title":"Proof-of-concept Study for SAR441344 (Frexalimab) in Relapsing Multiple Sclerosis","status":"ACTIVE_NOT_RECRUITING","sponsor":"Sanofi","startDate":"2021-06-07","conditions":["Multiple Sclerosis"],"enrollment":129,"completionDate":"2027-08-23"},{"nctId":"NCT04973007","phase":"PHASE4","title":"Comparison of Contrast Agents in Liver MR for the Detection of Hepatic Metastases","status":"TERMINATED","sponsor":"University of Colorado, Denver","startDate":"2021-06-22","conditions":["Oligometastatic Disease","Liver Metastases","Colorectal Cancer"],"enrollment":10,"completionDate":"2025-05-08"},{"nctId":"NCT03703492","phase":"PHASE2","title":"Hybrid Molecular Imaging of ER in Breast Cancer Patients With DCIS","status":"COMPLETED","sponsor":"University of Wisconsin, Madison","startDate":"2019-01-03","conditions":["Breast Cancer","Ductal Carcinoma in Situ - Category"],"enrollment":12,"completionDate":"2024-01-02"},{"nctId":"NCT03337594","phase":"","title":"Gadolinium Retention in Human Bone Tissue in Pediatric Patients","status":"COMPLETED","sponsor":"Donna Roberts","startDate":"2017-10-01","conditions":["Gadolinium","MultiHance","Dotarem","Magnetic Resonance Imaging","Gadolinium Retention"],"enrollment":57,"completionDate":"2024-08-31"},{"nctId":"NCT06406517","phase":"PHASE3","title":"Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics","status":"NOT_YET_RECRUITING","sponsor":"University of California, San Diego","startDate":"2024-05","conditions":["Congenital Heart Disease"],"enrollment":160,"completionDate":"2025-06"},{"nctId":"NCT03588286","phase":"NA","title":"Programmed Ventricular Stimulation to Risk Stratify for Early Cardioverter-Defibrillator (ICD) Implantation to Prevent Tachyarrhythmias Following Acute Myocardial Infarction (PROTECT-ICD)","status":"RECRUITING","sponsor":"Western Sydney Local Health District","startDate":"2014-02-27","conditions":["Sudden Cardiac Death"],"enrollment":1058,"completionDate":"2029-12-06"},{"nctId":"NCT02869243","phase":"PHASE1","title":"A Dose Escalation Phase I Study Of Human- Recombinant Bone Morphogenetic Protein 4 Administrated Via CED In GBM Patients","status":"COMPLETED","sponsor":"Stemgen","startDate":"2017-07-18","conditions":["Glioblastoma"],"enrollment":15,"completionDate":"2021-06-30"},{"nctId":"NCT00375830","phase":"PHASE2","title":"Combined 18F-NaF/18F-FDG PET/MRI for Detection of Skeletal Metastases","status":"COMPLETED","sponsor":"Stanford University","startDate":"2006-01","conditions":["Cancer"],"enrollment":114,"completionDate":"2019-03-14"},{"nctId":"NCT02095353","phase":"","title":"Comparison of Contrast Agents for MRI Perfusion Analysis in Brain Tumor Patients","status":"TERMINATED","sponsor":"University of Nebraska","startDate":"2014-09-01","conditions":["Central Nervous System Neoplasms"],"enrollment":6,"completionDate":"2017-03-07"},{"nctId":"NCT00415805","phase":"PHASE3","title":"Renal MRA Crossover Study Comparing Multihance to Another Contrast Agent","status":"COMPLETED","sponsor":"Bracco Diagnostics, Inc","startDate":"2006-12","conditions":["Steno-occlusive Disease"],"enrollment":39,"completionDate":"2009-02"},{"nctId":"NCT03064295","phase":"","title":"Whole-Heart Myocardial Blood Flow Quantification Using MRI","status":"UNKNOWN","sponsor":"Cedars-Sinai Medical Center","startDate":"2018-03-01","conditions":["Coronary Artery Disease","Coronary Microvascular Disease"],"enrollment":160,"completionDate":"2025-01-01"},{"nctId":"NCT04132843","phase":"NA","title":"Novel MRI Techniques for the Characterization and Treatment Assessment of High Grade Brain Lesions","status":"COMPLETED","sponsor":"M.D. Anderson Cancer Center","startDate":"2020-01-10","conditions":["Brain Neoplasm","Lymphoma","Metastatic Malignant Neoplasm in the Brain","Recurrent Malignant Brain Neoplasm"],"enrollment":6,"completionDate":"2022-09-01"},{"nctId":"NCT05292885","phase":"","title":"Mp-MRI in the Diagnosis of Liver Fibrosis After Liver Transplantation","status":"UNKNOWN","sponsor":"The Affiliated Hospital of Qingdao University","startDate":"2022-03-18","conditions":["Liver Fibrosis After Liver Transplantation","Multiparameter Magnetic Resonance Imaging"],"enrollment":40,"completionDate":"2022-12-01"},{"nctId":"NCT02633501","phase":"PHASE2","title":"P03277 Dose Finding Study in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)","status":"COMPLETED","sponsor":"Guerbet","startDate":"2016-06","conditions":["CNS Lesion","Blood Brain Barrier Defect"],"enrollment":312,"completionDate":"2018-01"},{"nctId":"NCT04863911","phase":"","title":"Comparative Study Between CT Arthrography and MRI Arthrography in Detection of Intra-articular Hip Pathology","status":"UNKNOWN","sponsor":"Assiut University","startDate":"2021-10","conditions":["Hip Disease"],"enrollment":50,"completionDate":"2022-12"},{"nctId":"NCT03091803","phase":"","title":"QSM and Regional DCE MRI Permeability Using GOCART Technique","status":"WITHDRAWN","sponsor":"University of Southern California","startDate":"2017-04-04","conditions":["Intracranial Neoplasm"],"enrollment":0,"completionDate":"2021-04-04"},{"nctId":"NCT01986868","phase":"NA","title":"Identification of Adverse Plaque Characteristics by Coronary MR Angiography","status":"COMPLETED","sponsor":"Cedars-Sinai Medical Center","startDate":"2012-04","conditions":["Coronary Artery Disease"],"enrollment":2,"completionDate":"2018-01-24"},{"nctId":"NCT00395863","phase":"PHASE4","title":"Multihance at 3 Tesla (3T) in Brain Tumors","status":"COMPLETED","sponsor":"Bracco Diagnostics, Inc","startDate":"2006-11","conditions":["Brain Tumor"],"enrollment":46,"completionDate":"2008-03"},{"nctId":"NCT01655290","phase":"PHASE2","title":"Comparison of Gadobutrol and Gadobenate Dimeglumin for Delayed Enhancement Cardiac MRI","status":"COMPLETED","sponsor":"Technical University of Munich","startDate":"2012-08","conditions":["Subacute/Chronic Myocardial Infarction"],"enrollment":20,"completionDate":"2014-06"},{"nctId":"NCT03108378","phase":"","title":"Evaluation of Gd Retention in Human Bone and Skin After MultiHance or ProHance Administration Compared With Control","status":"COMPLETED","sponsor":"Bracco Diagnostics, Inc","startDate":"2014-10","conditions":["Gadolinium Retention"],"enrollment":28,"completionDate":"2019-12"},{"nctId":"NCT04346472","phase":"","title":"Longitudinal MRI Assessment in Patients With Diffuse Low-grade Gliomas","status":"COMPLETED","sponsor":"University Hospital, Montpellier","startDate":"2016-03-01","conditions":["Low-grade Glioma"],"enrollment":200,"completionDate":"2020-01-30"},{"nctId":"NCT02599844","phase":"","title":"Impact of Pediatric Acute Renal Injury in Severe Sepsis in Young Adults","status":"WITHDRAWN","sponsor":"University of Florida","startDate":"2015-12","conditions":["Acute Kidney Injury","Chronic Kidney Disease","Hypertension"],"enrollment":0,"completionDate":"2020-02-01"},{"nctId":"NCT02933034","phase":"PHASE1,PHASE2","title":"Clinical Trial of Manganese-Enhanced MRI (MEMRI) to Assess Peri-Infarct Injury","status":"COMPLETED","sponsor":"Stanford University","startDate":"2015-04","conditions":["ISCHEMIC CARDIOMYOPATHY"],"enrollment":33,"completionDate":"2019-02-03"},{"nctId":"NCT00958464","phase":"","title":"The Effect of Perthes' Disease on Hip Cartilage","status":"COMPLETED","sponsor":"University of British Columbia","startDate":"2008-01","conditions":["Perthes' Disease"],"enrollment":20,"completionDate":"2017-06"},{"nctId":"NCT02350829","phase":"NA","title":"T1 Mapping of Diffuse Myocardial Fibrosis in Congenital Heart Disease","status":"COMPLETED","sponsor":"The Hospital for Sick Children","startDate":"2014-02","conditions":["Cardiomyopathy"],"enrollment":65,"completionDate":"2017-08"},{"nctId":"NCT02896946","phase":"NA","title":"Diffusion MRI for Pancreatic Adenocarcinoma","status":"COMPLETED","sponsor":"Hospices Civils de Lyon","startDate":"2011-02","conditions":["Pancreatic Adenocarcinoma"],"enrollment":118,"completionDate":""},{"nctId":"NCT01211873","phase":"PHASE3","title":"Safety and Efficacy Evaluation of DOTAREM® in MRI of Central Nervous System (CNS) Lesions","status":"COMPLETED","sponsor":"Guerbet","startDate":"2010-09","conditions":["Diagnostic Self Evaluation","Central Nervous System Diseases"],"enrollment":416,"completionDate":"2011-11"},{"nctId":"NCT03910114","phase":"","title":"Gadolinium-Based-Contrast-Agents (GBCA) Enhancement During MR Urography","status":"COMPLETED","sponsor":"Vanderbilt University Medical Center","startDate":"1990-07-01","conditions":["Magnetic Resonance Imaging Contrast Agents"],"enrollment":500,"completionDate":"2019-04-01"},{"nctId":"NCT02501759","phase":"NA","title":"Transrectal MRI-Guided Biopsy in Identifying Cancer in Patients With Suspected Prostate Cancer","status":"TERMINATED","sponsor":"OHSU Knight Cancer Institute","startDate":"2015-05","conditions":["Health Status Unknown","Prostate Carcinoma"],"enrollment":2,"completionDate":"2017-02-10"},{"nctId":"NCT03193463","phase":"EARLY_PHASE1","title":"Intratumorally-Administered Topotecan Using CED in High Grade Glioma Undergoing Stereotactic Biopsy","status":"WITHDRAWN","sponsor":"Michael Vogelbaum, MD, PhD","startDate":"2017-11-03","conditions":["Glioma"],"enrollment":0,"completionDate":"2018-11-19"},{"nctId":"NCT03147989","phase":"","title":"Retrospective Study of MRI With MULTIHANCE at 0.10 and 0.05 mmol/Kg Dose in CNS Patients","status":"COMPLETED","sponsor":"Bracco Diagnostics, Inc","startDate":"2017-05-18","conditions":["Central Nervous System Diseases","Central Nervous System Neoplasms"],"enrollment":352,"completionDate":"2018-03-16"},{"nctId":"NCT02057874","phase":"NA","title":"3-Tesla MRI Response to TACE in HCC (Liver Cancer)","status":"TERMINATED","sponsor":"Vanderbilt-Ingram Cancer Center","startDate":"2014-02","conditions":["Adult Primary Hepatocellular Carcinoma","Advanced Adult Primary Liver Cancer","Localized Resectable Adult Primary Liver Cancer","Localized Unresectable Adult Primary Liver Cancer","Stage A Adult Primary Liver Cancer (BCLC)","Stage B Adult Primary Liver Cancer (BCLC)"],"enrollment":2,"completionDate":"2015-12-04"},{"nctId":"NCT01779869","phase":"PHASE4","title":"Development of a PET-MR Myocardial Perfusion Examination Using Regadenoson","status":"COMPLETED","sponsor":"Washington University School of Medicine","startDate":"2013-01","conditions":["Ischemic Heart Disease"],"enrollment":16,"completionDate":"2015-06"},{"nctId":"NCT01988675","phase":"","title":"MRI Study of Radiation-Induced Damage to White Matter and Blood-Brain-Barrier","status":"COMPLETED","sponsor":"University of Michigan Rogel Cancer Center","startDate":"2004-08-26","conditions":["Brain Neoplasms"],"enrollment":91,"completionDate":"2014-06-03"},{"nctId":"NCT01992718","phase":"EARLY_PHASE1","title":"What Are we Missing? Diagnosing Uterine Adenomyosis Using Ultrasound Elastography","status":"COMPLETED","sponsor":"University of Michigan","startDate":"2013-11","conditions":["Uterine Bleeding","Uterine Fibroids","Adenomyosis"],"enrollment":49,"completionDate":"2018-03"},{"nctId":"NCT02092428","phase":"PHASE1","title":"Contrast- Enhanced Whole-Heart Coronary MRA at 3.0T (Tesla)","status":"COMPLETED","sponsor":"Cedars-Sinai Medical Center","startDate":"2011-04","conditions":["Coronary Artery Disease"],"enrollment":333,"completionDate":"2017-03-01"},{"nctId":"NCT01671579","phase":"NA","title":"Comparison of Bowel Ultrasound & MR Enterography in the Follow-up of Previously Diagnosed Pediatric Small Bowel Crohn Disease","status":"TERMINATED","sponsor":"Children's Hospital Medical Center, Cincinnati","startDate":"2012-03","conditions":["Crohn Disease"],"enrollment":33,"completionDate":"2017-08"},{"nctId":"NCT01710254","phase":"PHASE2","title":"Regadenoson Stress-MRI to Identify Coronary Artery Disease in Atrial Fibrillation Patients","status":"COMPLETED","sponsor":"University of Utah","startDate":"2013-01","conditions":["Atrial Fibrillation","Coronary Artery Disease"],"enrollment":30,"completionDate":"2016-10"},{"nctId":"NCT00373152","phase":"PHASE2","title":"MRI in Predicting Tumor Reponse After Radiofrequency Ablation in Women With Invasive Breast Cancer","status":"WITHDRAWN","sponsor":"Masonic Cancer Center, University of Minnesota","startDate":"2005-03","conditions":["Breast Cancer"],"enrollment":0,"completionDate":"2010-06"},{"nctId":"NCT00539253","phase":"NA","title":"Assessment of Liver Cancer Response to TACE Using MultiHance-Enhanced MRI.","status":"COMPLETED","sponsor":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins","startDate":"2007-09","conditions":["Hepatocellular Carcinoma"],"enrollment":45,"completionDate":"2013-12"},{"nctId":"NCT02597543","phase":"PHASE4","title":"Stress Cardiac MRI for Evaluation of Nonspecific Allograft Dysfunction","status":"COMPLETED","sponsor":"Paul Kim","startDate":"2015-11","conditions":["Heart Transplant","Acute Graft Rejection","Chronic Graft Rejection"],"enrollment":14,"completionDate":"2016-06-30"},{"nctId":"NCT00033397","phase":"","title":"Diagnostic Procedures in Women With Locally Advanced Breast Cancer Who Are Receiving Chemotherapy Before Breast Cancer Surgery","status":"COMPLETED","sponsor":"Alliance for Clinical Trials in Oncology","startDate":"2002-02","conditions":["Breast Cancer"],"enrollment":360,"completionDate":"2012-05-01"},{"nctId":"NCT00537056","phase":"NA","title":"Evaluating Sunitinib Therapy in Renal Cell Carcinoma Using F-18 FDG PET/CT and DCE MRI","status":"COMPLETED","sponsor":"Stanford University","startDate":"2007-10","conditions":["Kidney Neoplasms","Carcinoma, Renal Cell","Kidney (Renal Cell) Cancer"],"enrollment":17,"completionDate":"2012-04"},{"nctId":"NCT01996527","phase":"EARLY_PHASE1","title":"3T MRI Biomarkers of Glioma Treatment Response","status":"TERMINATED","sponsor":"Vanderbilt-Ingram Cancer Center","startDate":"2012-05","conditions":["Adult Anaplastic Astrocytoma","Adult Anaplastic Ependymoma","Adult Anaplastic Oligodendroglioma","Adult Giant Cell Glioblastoma","Adult Glioblastoma","Adult Gliosarcoma","Recurrent Adult Brain Tumor"],"enrollment":7,"completionDate":"2016-01-01"},{"nctId":"NCT02278510","phase":"EARLY_PHASE1","title":"Topotecan Using Convection-Enhanced Delivery (CED) in High Grade Glioma","status":"COMPLETED","sponsor":"Michael Vogelbaum, MD, PhD","startDate":"2014-12-09","conditions":["Malignant Glioma","WHO Grade III or IV Recurrent Glioma"],"enrollment":3,"completionDate":"2015-11-10"},{"nctId":"NCT02967380","phase":"NA","title":"Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases","status":"TERMINATED","sponsor":"University of Southern California","startDate":"2011-12-14","conditions":["Adult Anaplastic (Malignant) Meningioma","Adult Anaplastic Astrocytoma","Adult Anaplastic Ependymoma","Adult Anaplastic Oligodendroglioma","Adult Brain Stem Glioma","Adult Choroid Plexus Neoplasm","Adult Diffuse Astrocytoma","Adult Ependymoblastoma","Adult Ependymoma","Adult Giant Cell Glioblastoma","Adult Glioblastoma","Adult Gliosarcoma","Adult Grade II Meningioma","Adult Medulloblastoma","Adult Mixed Glioma","Adult Oligodendroglioma","Adult Papillary Meningioma","Adult Pineal Gland Astrocytoma","Adult Pineoblastoma","Adult Primary Melanocytic Lesion of Meninges","Adult Supratentorial Primitive Neuroectodermal Tumor","Malignant Adult Intracranial Hemangiopericytoma","Metastatic Malignant Neoplasm in the Brain","Multiple Sclerosis","Recurrent Adult Brain Neoplasm"],"enrollment":14,"completionDate":"2015-10-14"},{"nctId":"NCT00019604","phase":"PHASE2","title":"Radiofrequency Ablation in Treating Patients With Unresectable Primary or Metastatic Liver Cancer","status":"TERMINATED","sponsor":"National Institutes of Health Clinical Center (CC)","startDate":"1998-08","conditions":["Liver Cancer","Metastatic Cancer","Unspecified Adult Solid Tumor, Protocol Specific"],"enrollment":44,"completionDate":"2009-01"},{"nctId":"NCT02226666","phase":"","title":"Physiologic Assessment Following Gadoxetic Acid and Gadobenate Dimeglumine Administration","status":"COMPLETED","sponsor":"University of Michigan","startDate":"2013-08","conditions":["Liver Tumor"],"enrollment":107,"completionDate":"2015-12"},{"nctId":"NCT02070380","phase":"PHASE4","title":"Crossover Comparison of MultiHance and Dotarem","status":"COMPLETED","sponsor":"Bracco Diagnostics, Inc","startDate":"2014-02","conditions":["Brain Disease"],"enrollment":179,"completionDate":"2015-03"},{"nctId":"NCT01989195","phase":"PHASE1,PHASE2","title":"Efficacy of EVP 1001-1 (SeeMore) in the Assessment of Myocardial Viability in Patients With Cardiovascular Disease","status":"COMPLETED","sponsor":"Stanford University","startDate":"2013-05","conditions":["ISCHEMIC CARDIOMYOPATHY"],"enrollment":6,"completionDate":"2013-06"},{"nctId":"NCT03000036","phase":"NA","title":"Doxorubicin-associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients","status":"COMPLETED","sponsor":"University of Campinas, Brazil","startDate":"2012-07","conditions":["Breast Cancer Female","Doxorubicin Induced Cardiomyopathy"],"enrollment":27,"completionDate":"2016-07"},{"nctId":"NCT02992847","phase":"","title":"Evaluation of Potential Accumulation of Gadolinium (Dotarem and Multihance) in the French Observatory of Multiple Sclerosis (Www.Ofsep.Org/)","status":"UNKNOWN","sponsor":"Hospices Civils de Lyon","startDate":"2017-01","conditions":["Multiple Sclerosis"],"enrollment":160,"completionDate":"2017-07"},{"nctId":"NCT02371798","phase":"NA","title":"Unilateral Meniere Disease: Can Double Dose Gadolinium and Delayed Imaging Make the Diagnosis?","status":"WITHDRAWN","sponsor":"Emory University","startDate":"2015-02","conditions":["Meniere Disease"],"enrollment":0,"completionDate":"2016-11"},{"nctId":"NCT00577915","phase":"NA","title":"Breast MRI Spectroscopy","status":"COMPLETED","sponsor":"Memorial Sloan Kettering Cancer Center","startDate":"2003-05","conditions":["Suspicion of, or Known Breast Cancer"],"enrollment":150,"completionDate":"2016-06"},{"nctId":"NCT02895633","phase":"NA","title":"Osteoarticular Tumor Characterization by Advanced Imaging","status":"UNKNOWN","sponsor":"Central Hospital, Nancy, France","startDate":"2009-11","conditions":["Bone Tumor","Soft Tissue Tumor"],"enrollment":1090,"completionDate":"2020-11"},{"nctId":"NCT02291822","phase":"","title":"Retrospective Study of MRI in Pediatric Patients","status":"COMPLETED","sponsor":"Bracco Diagnostics, Inc","startDate":"2014-11","conditions":["Central Nervous System Disease","Central Nervous System Neoplasms"],"enrollment":90,"completionDate":"2015-12"},{"nctId":"NCT02400840","phase":"NA","title":"Acute Heart Graft Rejection Screening by Cardiac Magnetic Resonance Imaging","status":"WITHDRAWN","sponsor":"University Hospital, Rouen","startDate":"2015-01","conditions":["Cardiac Graft"],"enrollment":0,"completionDate":"2018-05"},{"nctId":"NCT01047059","phase":"PHASE2","title":"Molecular Imaging With Erlotinib and Bevacizumab","status":"COMPLETED","sponsor":"University of Cologne","startDate":"2010-01","conditions":["Non-Small-Cell Lung Carcinoma"],"enrollment":40,"completionDate":"2016-05"},{"nctId":"NCT02080312","phase":"NA","title":"Magnetic Resonance Imaging Evaluation of Inner Ear Pathology Using Intra-Tympanic Contrast Agent","status":"COMPLETED","sponsor":"University of California, San Diego","startDate":"2012-01","conditions":["Meniere's Disease"],"enrollment":6,"completionDate":"2013-12"},{"nctId":"NCT01956409","phase":"PHASE4","title":"Proton MR Spectroscopy and 18F-Fluorocholine PET for Breast Cancer Diagnosis","status":"UNKNOWN","sponsor":"National Taiwan University Hospital","startDate":"2012-09","conditions":["Breast Cancer Diagnosis","Positron Emission Tomography","Magnetic Resonance Imaging"],"enrollment":80,"completionDate":"2017-03"},{"nctId":"NCT00751920","phase":"PHASE3","title":"Comparative Evaluation of MRI and MDCT for the Detection of Metastic Pulmonary Nodules","status":"TERMINATED","sponsor":"The Hospital for Sick Children","startDate":"2008-08","conditions":["Metastatic Pulmonary Nodules"],"enrollment":1,"completionDate":"2010-12"},{"nctId":"NCT00937391","phase":"PHASE3","title":"Contrast-enhanced MRI in Children 2 Months to <2 Years","status":"COMPLETED","sponsor":"Bayer","startDate":"2010-01","conditions":["Magnetic Resonance Imaging"],"enrollment":54,"completionDate":"2010-09"},{"nctId":"NCT02074150","phase":"PHASE1,PHASE2","title":"ASIS for Botox in Upper Limb Spasticity","status":"UNKNOWN","sponsor":"li nguyen","startDate":"2016-01","conditions":["Upper Limb Spasticity Unilaterally in Adults With History of Stroke","Increased Muscle Tone in Elbow, Wrist, Finger, and Thumb Flexors."],"enrollment":60,"completionDate":"2017-06"},{"nctId":"NCT02074163","phase":"PHASE1,PHASE2","title":"ASIS for Botox in Chronic Migraine","status":"UNKNOWN","sponsor":"ASIS Corporation","startDate":"2016-01","conditions":["Chronic Migraine More than15 Days Per Month, and Lasting 4 Hours a Day or Longer."],"enrollment":60,"completionDate":"2017-06"},{"nctId":"NCT02123615","phase":"PHASE1,PHASE2","title":"ASIS for GAMMAGARD in Primary Immunodeficiency","status":"UNKNOWN","sponsor":"ASIS Corporation","startDate":"2016-01","conditions":["Primary Immunodeficiency"],"enrollment":60,"completionDate":"2016-06"},{"nctId":"NCT02112097","phase":"PHASE1,PHASE2","title":"ASIS for Enbrel in Plaque Psoriasis","status":"UNKNOWN","sponsor":"ASIS Corporation","startDate":"2016-01","conditions":["Plaque Psoriasis."],"enrollment":60,"completionDate":"2017-06"},{"nctId":"NCT02074293","phase":"PHASE1,PHASE2","title":"ASIS for Botox in Cervical Dystonia","status":"UNKNOWN","sponsor":"li nguyen","startDate":"2016-01","conditions":["Cervical Dystonia Adults ,","Abnormal Head Position and Neck Pain for These 7 Muscle Groups: Splenius,Scalene,Sterno-cleido-mastoid,Levator Scapulae,Semispinalis,Trapezius,and Longissimus."],"enrollment":60,"completionDate":"2017-06"},{"nctId":"NCT00395460","phase":"PHASE3","title":"Efficacy and Safety Study to Evaluate Gadavist (Gadobutrol) as Contrast Agent in Magnetic Resonance Imaging (MRI) of Brain or Spine Diseases in Chinese Patients","status":"COMPLETED","sponsor":"Bayer","startDate":"2006-09","conditions":["Central Nervous System Diseases"],"enrollment":147,"completionDate":"2007-04"},{"nctId":"NCT00309075","phase":"PHASE3","title":"Magnevist® Injection Enhanced MRA Compared to Non Contrast MRA for the Detection of Stenosis in the Calf and/or Pedal Arteries","status":"COMPLETED","sponsor":"Bayer","startDate":"2003-12","conditions":["Stenosis"],"enrollment":126,"completionDate":"2004-11"},{"nctId":"NCT01050829","phase":"PHASE3","title":"Gadobutrol Magnevist-controlled Body Study","status":"COMPLETED","sponsor":"Bayer","startDate":"2010-01","conditions":["Magnetic Resonance Imaging"],"enrollment":370,"completionDate":"2011-04"},{"nctId":"NCT00310609","phase":"PHASE3","title":"Magnevist® Injection Enhanced MRA Compared to Non Contrast MRA for the Detection of Structural Abnormalities of the Aortic Arch and Cerebral Branches","status":"COMPLETED","sponsor":"Bayer","startDate":"2003-12","conditions":["Cardiovascular Abnormalities"],"enrollment":123,"completionDate":"2004-10"},{"nctId":"NCT00310596","phase":"PHASE1","title":"Cardiovascular Safety Study of Magnevist® Injection at Two Dose Levels and Two Injection Rates in Normal Subjects","status":"COMPLETED","sponsor":"Bayer","startDate":"2004-01","conditions":["Healthy"],"enrollment":71,"completionDate":"2004-03"},{"nctId":"NCT00310557","phase":"PHASE3","title":"Magnevist® Injection-enhanced MRA Compared to Non Contrast MRA for the Detection of Stenosis of the Renal Arteries","status":"COMPLETED","sponsor":"Bayer","startDate":"2003-12","conditions":["Renal Artery Stenosis"],"enrollment":116,"completionDate":"2004-12"},{"nctId":"NCT00185276","phase":"PHASE3","title":"Magnevist® Injection Enhanced MRA at Two Dose Levels Compared to Non Contrast MRA for the Detection of Structural Abnormalities of the Infrarenal Aorta and Peripheral Arteries","status":"COMPLETED","sponsor":"Bayer","startDate":"2003-03","conditions":["Peripheral Vascular Disease"],"enrollment":365,"completionDate":"2004-08"},{"nctId":"NCT00681551","phase":"PHASE3","title":"Magnevist (SH L 451A) Intra-individual Dose Comparison Study in Patients With Brain Metastasis","status":"COMPLETED","sponsor":"Bayer","startDate":"2003-02","conditions":["Brain Neoplasms"],"enrollment":45,"completionDate":"2004-03"},{"nctId":"NCT00310544","phase":"PHASE2","title":"Depiction of Delayed Enhancement in Patients With Documented Myocardial Infarction","status":"COMPLETED","sponsor":"Bayer","startDate":"2006-03","conditions":["Myocardial Infarction"],"enrollment":73,"completionDate":"2006-09"},{"nctId":"NCT01836055","phase":"","title":"Imaging Multiple Sclerosis Lesions Using Magnevist and Gadavist","status":"TERMINATED","sponsor":"Wayne State University","startDate":"2012-01","conditions":["Multiple Sclerosis"],"enrollment":19,"completionDate":"2014-02"},{"nctId":"NCT00600951","phase":"","title":"Evaluation of the Risk of NSF Following MultiHance Injection in Patients With Chronic Kidney Disease","status":"COMPLETED","sponsor":"Bracco Diagnostics, Inc","startDate":"2008-01","conditions":["Renal Insufficiency"],"enrollment":366,"completionDate":"2013-08"},{"nctId":"NCT01234870","phase":"PHASE2,PHASE3","title":"Comprehensive Evaluation of Ischemic Heart Disease Using MRI","status":"COMPLETED","sponsor":"Northwestern University","startDate":"2010-06","conditions":["Heart Disease, Ischemic","Atherosclerosis, Coronary"],"enrollment":40,"completionDate":"2012-01"},{"nctId":"NCT00744939","phase":"","title":"Risk of Nephrogenic Systemic Fibrosis (NSF) in Patients With Moderate Renal Insufficiency After the Administration of Magnevist","status":"COMPLETED","sponsor":"Bayer","startDate":"2008-11","conditions":["Fibrosis","Kidney Failure","Renal Insufficiency"],"enrollment":168,"completionDate":"2013-11"},{"nctId":"NCT02175069","phase":"PHASE4","title":"Magnetic Resonance Imaging of Interscalene Plexus Block","status":"COMPLETED","sponsor":"Paracelsus Medical University","startDate":"2013-12","conditions":["Disorder of Shoulder"],"enrollment":30,"completionDate":"2014-07"},{"nctId":"NCT00060008","phase":"NA","title":"Fludeoxyglucose F 18 Positron Emission Tomography and Magnetic Resonance Perfusion Imaging in Patients With Neurofibromatosis 1 and Plexiform Neurofibroma","status":"TERMINATED","sponsor":"Children's Hospital of Philadelphia","startDate":"2002-04","conditions":["Neurofibromatosis Type 1","Precancerous Condition"],"enrollment":18,"completionDate":"2011-05"},{"nctId":"NCT01416740","phase":"NA","title":"A Comparison of Indirect and Direct MR Arthrography of the Shoulder Using Arthroscopic Correlation","status":"WITHDRAWN","sponsor":"Milton S. Hershey Medical Center","startDate":"2009-12","conditions":["Shoulder Pain"],"enrollment":0,"completionDate":"2012-09"},{"nctId":"NCT00395733","phase":"PHASE3","title":"Efficacy and Safety Study to Evaluate Gadavist (Gadobutrol) as Contrast Agent in Magnetic Resonance Imaging (MRI) of Vascular Diseases in Chinese Patients","status":"COMPLETED","sponsor":"Bayer","startDate":"2006-10","conditions":["Vascular Diseases"],"enrollment":83,"completionDate":"2007-10"},{"nctId":"NCT00652418","phase":"PHASE2","title":"Magnevist (SH L 451A) Intra-individual Dose Comparison Study in Magnetic Resonance Angiography","status":"COMPLETED","sponsor":"Bayer","startDate":"2004-07","conditions":["Magnetic Resonance Angiography","Peripheral Vascular Diseases","Peripheral Arterial Diseases"],"enrollment":12,"completionDate":"2004-10"},{"nctId":"NCT00043017","phase":"PHASE2","title":"Magnetic Resonance Imaging in Women Receiving Chemotherapy for Stage III Breast Cancer","status":"COMPLETED","sponsor":"American College of Radiology Imaging Network","startDate":"2002-05","conditions":["Breast Cancer"],"enrollment":356,"completionDate":"2011-03"},{"nctId":"NCT00004936","phase":"NA","title":"MRI and CT Scans to Evaluate Invasive Cervical Cancer Before Treating Patients","status":"COMPLETED","sponsor":"American College of Radiology Imaging Network","startDate":"2000-04","conditions":["Cervical Cancer"],"enrollment":0,"completionDate":"2002-10"},{"nctId":"NCT00005790","phase":"NA","title":"Perfusion Magnetic Resonance Imaging in Measuring the Growth of Blood Vessels in Newly Diagnosed Brain Tumors","status":"WITHDRAWN","sponsor":"Northwestern University","startDate":"1996-04","conditions":["Brain and Central Nervous System Tumors"],"enrollment":0,"completionDate":"1999-05"},{"nctId":"NCT01260636","phase":"PHASE3","title":"Crossover Comparison of Two Gadolinium Contrast Agents for Use With MRA of Carotid, Renal and Peripheral Arteries","status":"COMPLETED","sponsor":"Bracco Diagnostics, Inc","startDate":"2009-09","conditions":["Carotid, Aortic, Renal or Peripheral Artery Disease"],"enrollment":120,"completionDate":"2011-12"},{"nctId":"NCT00907530","phase":"PHASE4","title":"Study to Compare MultiHance With Gadovist in Magnetic Resonance Imaging (MRI) of the Brain","status":"COMPLETED","sponsor":"Bracco Diagnostics, Inc","startDate":"2009-09","conditions":["Brain Lesions"],"enrollment":121,"completionDate":"2011-07"},{"nctId":"NCT01376739","phase":"","title":"Magnevist Post-marketing Surveillance in Japan","status":"COMPLETED","sponsor":"Bayer","startDate":"2007-08","conditions":["Diagnostic Imaging"],"enrollment":2051,"completionDate":"2010-06"},{"nctId":"NCT00323310","phase":"PHASE3","title":"Safety and Efficacy of MultiHance in Pediatric Patients","status":"TERMINATED","sponsor":"Bracco Diagnostics, Inc","startDate":"2006-04","conditions":["Central Nervous System Diseases"],"enrollment":92,"completionDate":"2008-09"},{"nctId":"NCT00486473","phase":"PHASE3","title":"Multihance Versus Magnevist in Breast MRI","status":"COMPLETED","sponsor":"Bracco Diagnostics, Inc","startDate":"2007-07","conditions":["Breast Cancer"],"enrollment":130,"completionDate":"2009-12"},{"nctId":"NCT00977093","phase":"PHASE3","title":"A Study of Gadodiamide Injection in Myocardial Perfusion Magnetic Resonance Imaging","status":"COMPLETED","sponsor":"Amersham Buchler, GmbH & Co KG","startDate":"2003-07","conditions":["Coronary Artery Disease"],"enrollment":533,"completionDate":"2004-06"},{"nctId":"NCT00408083","phase":"PHASE3","title":"Crossover Study With MultiHance vs a Comparator for Peripheral MRA","status":"COMPLETED","sponsor":"Bracco Diagnostics, Inc","startDate":"2006-12","conditions":["Peripheral Vascular Disease"],"enrollment":100,"completionDate":"2008-12"}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"administration":{"route":"Intravenous","formulation":"Injection","formulations":[{"form":"INJECTION, SOLUTION","route":"INTRAVENOUS","productName":"MultiHance"}]},"_patentsChecked":true,"crossReferences":{"NUI":"N0000188993","MMSL":"19178","NDDF":"007717","UNII":"3Q6PPC19PO","VUID":"4032768","VANDF":"4032768","RXNORM":"68173","UMLSCUI":"C0209453","chemblId":"CHEMBL1200571","ChEMBL_ID":"CHEMBL1200571","PUBCHEM_CID":"197281","SNOMEDCT_US":"414308003","MESH_SUPPLEMENTAL_RECORD_UI":"C064572"},"formularyStatus":[],"originalProduct":{"form":"INJECTION, SOLUTION","route":"INTRAVENOUS","company":"BRACCO DIAGNOSTICS INC","brandName":"MultiHance","isOriginal":true,"marketingStatus":"NDA"},"_enricherVersion":"v2","developmentCodes":[],"ownershipHistory":[{"period":"2004-","companyName":"Bracco","relationship":"Original Developer"}],"pharmacokinetics":{"source":"FDA label","halfLife":"1.2 hours"},"publicationCount":669,"therapeuticAreas":["Other"],"biosimilarFilings":[],"originalDeveloper":"Bracco","recentPublications":[{"date":"2026 Mar 3","pmid":"41774304","title":"The value of gadobenate dimeglumine-enhanced MRI quantification in predicting aggressiveness and prognosis of typical intrahepatic mass-forming cholangiocarcinoma: a multicenter retrospective study.","journal":"Insights into imaging"},{"date":"2026 Feb 23","pmid":"41730634","title":"Dose Reduction with Gadopiclenol: Implications for DSC Perfusion Imaging.","journal":"AJNR. American journal of neuroradiology"},{"date":"2026 Feb 19","pmid":"41711984","title":"Mapping fibrosis in colorectal liver metastases (CRLM) with gadobenate dimeglumine-enhanced MRI: prognostic implications and imaging biomarkers.","journal":"International journal of colorectal disease"},{"date":"2026 Feb 6","pmid":"41651668","title":"Prospective MR Evaluation of Endolymphatic Hydrops Using Half-dose Gadopiclenol.","journal":"AJNR. American journal of neuroradiology"},{"date":"2026 Jan 14","pmid":"41646297","title":"Pharmacokinetic modeling of hepatospecific MRI contrast agent flux in large animal models by dynamic contrast-enhanced MRI.","journal":"Research square"}],"companionDiagnostics":[],"genericManufacturers":0,"_genericFilersChecked":true,"genericManufacturerList":[],"status":"approved","companyName":"Bracco","companyId":"bracco","modality":"Small molecule","firstApprovalDate":"2004","enrichmentLevel":3,"visitCount":0,"regulatoryByCountry":[{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2004-11-23T00:00:00.000Z","mah":"BRACCO","brand_name_local":null,"application_number":""},{"country_code":"CA","regulator":"Health Canada","status":"approved","approval_date":null,"mah":"","brand_name_local":"","application_number":""},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AU","regulator":"TGA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null}],"trialStats":{"total":1,"withResults":0},"validation":{"fieldsValidated":2,"lastValidatedAt":"2026-04-20T03:16:05.877071+00:00","fieldsConflicting":0,"overallConfidence":0.95},"verificationStatus":"verified","dataCompleteness":{"mechanism":true,"indications":true,"safety":true,"trials":true,"score":4}}