(gadobutrol injection)
(gadobutrol injection) 302 mg/mL (0.5 mmol/mL)
(gadobutrol injection) 604 mg/mL (1.0 mmol/mL) For Intravenous Use Contrast Enhancement Agent for Magnetic Resonance Imaging (MRI) Bayer Inc. Revision Date: 77 Belfield Road October 25, 2007 Toronto, Ontario M9W 1G6 Canada http://www.bayer.ca
(c) 2007, Bayer Inc.
(gadobutrol injection)
(gadobutrol injection) 302 mg/mL (0.5 mmol/mL)
(gadobutrol injection) 604 mg/mL (1.0 mmol/mL) For Intravenous Use Contrast Enhancement Agent for Magnetic Resonance Imaging (MRI)
Contrast Enhancement Agent for Magnetic Resonance Imaging (MRI).
ACTION AND CLINICAL PHARMACOLOGY
GADOVIST (gadobutrol) is a non-ionic paramagnetic contrast agent for magnetic resonance imaging (MRI). The contrast-enhancing effect is mediated by gadobutrol, a neutral complex consisting of gadolinium (Gd3+) and the macrocyclic compound dihydroxy-hydroxymethylpropyl-tetraazacyclododecane-triacetic acid (butrol). Following injection of gadobutrol, improved diagnostic information compared to unenhanced MRI can be obtained in areas with a penetrable or missing blood-brain barrier as a result of altered perfusion or due to an enlarged extracellular space such as in cases of primary and secondary tumors, inflammatory or demyelinating diseases. Gadobutrol produces a distinct shortening of the relaxation times even at low concentrations. At pH 7 and 40EC the relaxivity, as determined from the influence on the spin-lattice relaxation time (T1) of protons in water, is about 3.58 L/mmol *sec and the spin- spin relaxation time (T2) is about 3.99 L/mmol *sec. The relaxivity displays only a slight dependency on the strength of the magnetic field. The macrocyclic ligand forms a firm complex with the paramagnetic gadolinium ion with extremely high in vivo and in vitro stability. Gadobutrol is a highly water-soluble, extremely hydrophilic compound with a partition coefficient between n-butanol and buffer at pH 7.6 of about 0.006. Gadobutrol does not display any significant protein binding or inhibitory action on enzymes. Gadobutrol does not activate the complement system. When a T1 -weighted spin-echo sequence is used in MRI, the shortening of the spin-lattice relaxation time resulting from the administration of gadobutrol leads to an increase in the signal intensity which appears as a positive contrast useful for tissue differentiation. For perfusion studies, a T2 *-weighted gradient echo sequence is recommended. The induction of local magnetic field fluctuations by the large magnetic moment of gadolinium leads to a signal decrease of tissues in such sequences. After intravenous administration, gadobutrol is rapidly distributed in the extracellular space and eliminated in an unchanged form via the kidneys by glomerular filtration. Extra-renal elimination is negligible. In rabbits it has been demonstrated that gadobutrol does not penetrate the intact blood- brain barrier and that placental transfer was insignificant, with 0.01% of the administered dose being detected in the fetuses. In rats an extremely small sequestration of the compound into the milk (0.01% of the dose) was observed. Enterohepatic circulation has not been observed. Absorption after oral administration was found to be very small. The pharmacokinetics of gadobutrol in humans are dose proportional. Up to 0.4 mmol/kg body weight, plasma levels decline after an early distribution phase with a half-life of about 90 minutes, identical to the renal elimination rate. Plasma levels measured at 2 and 60 minutes following injection of 0.1 mmol/kg were 0.59 and 0.3 mmol/L, respectively. Within 2 hours more than 50% of the dose was eliminated in the urine and at 72 hours post- injection approximately 100% of the dose had been excreted. Less than 0.1% of the dose was eliminated in the feces. The average renal clearance of gadobutrol was determined to be approximately 120 mL/min and was, therefore, comparable to that of other aqueous substances, such as inulin. No metabolites were detected in plasma or urine.
QTc Prolongation
In one pharmacokinetic study conducted in healthy volunteers, dose-dependent increases from baseline values in QtcB intervals were noted at 2 min after GADOVIST injection. Increases >60 msec were observed in 1/6 subjects (16.6%) after the 0.5 mmol/kg dose, in 3/6 subjects (50%) after the 1.0 mmol/kg dose, in 2/6 subjects (33.3%) after the 1.25 mmol/kg dose and in 4/6 subjects (66.7%) after the 1.5 mmol/kg dose compared to 1/12 subjects (8%) after placebo injection. However, the increase in the mmol/kg dose group was attributable to a heart rate change which occurred between baseline and the pre-injection time point. In clinical studies with GADOVIST used for CE-MRA in doses of 0.1 to 0.3 mmol/kg, ECG was recorded in 93/415 patients before, immediately after, and 2 - 4 hours and 24 hours after administration of the contrast agent to assess the potential effect of GADOVIST on ventricular repolarization. The incidence of QTc prolongation by 30 - 60 msec was 6% immediately after, 9% at 2 - 4 hours and 11% at 24 hours after GADOVIST injection. Prolongation of QTc by >60 msec was observed only in one of these patients. QTc decreases by the same range were observed in a similar percentage of patients 2 - 4 hours and 24 hours after injection. The clinical relevance of these changes is not known. There were no significant cardiovascular adverse events related to QTc prolongation in patients with known cardiovascular diseases.
INDICATIONS AND CLINICAL USE
GADOVIST (gadobutrol) is indicated for contrast enhancement during cranial and spinal MRI investigations and for contrast-enhanced magnetic resonance angiography (CE-MRA). See DOSAGE AND ADMINISTRATION for specific dosage recommendations. GADOVIST 1.0 is particularly suited for cases where the exclusion or demonstration of additional pathology may influence the choice of therapy or patient management, for detection of very small lesions and for visualization of tumors that do not readily take up contrast media. GADOVIST 1.0 is also suited for perfusion studies for the diagnosis of stroke, detection of focal cerebral ischemia and tumor perfusion. GADOVIST 1.0 is indicated for contrast-enhanced magnetic resonance angiography (CE-MRA).
GADOVIST (gadobutrol) should not be administered to patients who are known or suspected of being hypersensitive to it.
Gadolinium-based contrast agents (GBCAs) increase the risk for Nephrogenic Systemic Fibrosis (NSF) in patients with:
acute or chronic severe renal insufficiency (glomerular filtration rate
<30 mL/min/1.73m2), or acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. In these patients, avoid use of GBCAs unless the diagnostic information is essential and not available with noncontrast-enhanced magnetic resonance imaging (MRI). NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle, and internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a GBCA, do not exceed the recommended dose (see DOSAGE AND ADMINISTRATION section) and allow a sufficient period of time for elimination of the agent from the body prior to any readministration. (See also WARNINGS: General; PRECAUTIONS: Skin; PRECAUTIONS: Renal Impairment; and ADVERSE REACTIONS: Postmarket Adverse Drug Reactions.)
The decision to use GADOVIST (gadobutrol) should be made after careful evaluation of the risk-benefit ratio in patients with a history of allergic disposition or bronchial asthma. Experience with contrast media in general shows that these patients suffer more frequently than others from hypersensitivity reactions. As with other contrast media, delayed reactions occuring hours or days after administration, may occur. As with other contrast media, anaphylactoid reactions including anaphylactic shock may occur. Although these reactions are very rare, it is important to be familiar with the practice of emergency measures so that prompt action may be taken in the event of such incidents. To permit immediate countermeasures to be taken in emergencies, appropriate drugs and instruments, e.g., endotracheal tube and ventilator, should be readily available. Deoxygenated sickle erythrocytes have been shown in in vitro studies to align perpendicularly to a magnetic field which may result in vaso-occlusive complications in vivo. The enhancement of magnetic moment by gadobutrol may possibly potentiate sickle erythrocyte alignment. The use of gadobutrol in patients with sickle cell anemia and other hemoglobinopathies has not been studied. MRI and MRA procedures which involve the use of gadobutrol should be carried out by medical staff who have the prerequisite training and a thorough knowledge of the particular procedure to be performed.
Nephrogenic Systemic Fibrosis (NSF)
Gadolinium-based contrast agents (GBCAs) increase the risk for Nephrogenic Systemic Fibrosis (NSF) in patients with acute or chronic severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73m2), and in patients with acute renal insufficiency of any severity due to the hepato-renal syndrome, or in the perioperative liver transplantation period. In these patients, avoid use of GBCAs unless the diagnostic information is essential and not available with noncontrast-enhanced magnetic resonance imaging (MRI). For patients receiving hemodialysis, healthcare professionals may consider prompt hemodialysis following GBCA administration in order to enhance the contrast agent's elimination. However, it is unknown if hemodialysis prevents NSF. 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 function impairment at the time of exposure. NSF development is considered a potential class-related effect of all GBCAs. Postmarketing reports have identified the development of NSF following single and multiple administrations of GBCAs. These reports have not always identified a specific agent. Where a specific agent was identified, the most commonly reported agent was gadodiamide (Omniscan(r)), followed by gadopentetate dimeglumine (Magnevist(r)) and gadoversetamide (OptiMARK(r)). NSF has also developed following the sequential administration of gadodiamide with gadobenate dimeglumine (MultiHance(r)) or gadoteridol (ProHance(r)). The number of postmarketing reports is subject to change over time and may not reflect the true proportion of cases associated with any specific GBCA. The extent of risk for NSF following exposure to any specific GBCA is unknown and may vary among the agents. Published reports are limited and predominantly estimate NSF risks with gadodiamide. In one retrospective study of 370 patients with 370 patients with severe renal insufficiency who received gadodiamide, the estimated risk for development of NSF was 4%. (1) The risk, if any, for the development of NSF among patients with mild to moderate renal insufficiency or normal renal function is unknown, and the cautious utilization of the lowest possible dose of GBCA is preferable. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a GBCA, do not exceed the recommended dose and allow a sufficient period of time for elimination of the agent from the body prior to any readministration. (See ACTION AND CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.) A skin biopsy is necessary in order to exclude the diagnosis of similarly presenting skin disorders (eg, scleromyxedema). (See WARNINGS: Serious Warnings and Precautions; PRECAUTIONS: Skin; PRECAUTIONS: Renal Impairment; and ADVERSE REACTIONS: Postmarket Adverse Drug Reactions.)
QTc prolongation may lead to an increased risk of ventricular arrhythmias, including torsades de pointes. It has been observed with other drugs that prolong the QT interval that females may be at greater risk compared to males of developing torsades de pointes. GADOVIST may prolong the QT interval of the electrocardiogram in some patients at high doses. Special care is therefore recommended in patients with known prolongation of the QT interval, patients with hypokalemia and patients receiving Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents, due to the lack of clinical experience with the drug in these patient populations and the potential risk. No cardiovascular adverse reactions attributable to QTc prolongation occurred with GADOVIST in clinical trials involving 708 patients. However, certain predisposing conditions may increase the risk of ventricular arrhythmias. In healthy volunteers, after injection of GADOVIST in doses higher than the recommended clinical dose of 0.3 mmol/kg (0.5 to 1.5 mmol/kg), dose-dependent QTc prolongation > 60 msec was observed in a significant proportion of subjects (see ACTION AND CLINICAL PHARMACOLOGY). GADOVIST is not recommended in doses higher than 0.3 mmol/kg (see DOSAGE AND ADMINISTRATION). Pharmacokinetic studies between GADOVIST and other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics and tricyclic antidepressants have not been performed. An interaction between GADOVIST and these drugs cannot be excluded, therefore GADOVIST should be used with caution when given concurrently with these drugs. The effect of GADOVIST on patients with congenital prolongation of the QT interval has not been studied, but it is expected that these individuals may be more susceptible to drug-induced QT prolongation. Because of limited clinical experience, GADOVIST should be used with extreme caution and only after careful risk-benefit assessment in patients with ongoing proarrhythmic conditions such as clinically significant bradycardia, acute myocardial ischemia, clinically relevant heart failure with reduced left ventricular ejection fraction or previous history of symptomatic arrhythmias. Careful risk assessment regarding potential cardiac effects is recommended. Patients with risk factors should remain under observation for at least one hour after the injection of GADOVIST, since possible transient effects would be expected to occur within the first few minutes after administration. To ensure safe and effective use of GADOVIST, patients should be advised of the following information and instructions when appropriate: that GADOVIST may produce changes in the electrocardiogram (QTc interval prolongation) (see ACTION AND CLINICAL PHARMACOLOGY) that GADOVIST should be avoided if they are currently receiving Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic agents that GADOVIST may add to the QTc prolonging effects of other drugs such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants to inform their physician of any personal or family history of QTc prolongation or proarrhythmic conditions such as recent hypokalemia, significant bradycardia, acute myocardial ischemia, clinically relevant heart failure with reduced left ventricular ejection fraction or previous history of symptomatic arrhythmias to contact their physician if they experience palpitations or fainting spells after injection of GADOVIST to inform their physician if they are or may be pregnant or are nursing (see
)
to inform their physician of any medications they take.
GADOVIST (gadobutrol) is intended for intravenous administration only and may cause tissue irritation and pain if administered extravascularly. Pronounced states of excitement, anxiety and pain may increase the risk of adverse reactions or intensify contrast medium-related reactions.
While there is no evidence suggesting that gadobutrol directly precipitates convulsion, the possibility that it may decrease the convulsive threshold in susceptible patients cannot be ruled out. Precautionary measures should be taken with patients predisposed to seizure, e.g., close monitoring and availability of injectable anticonvulsants (see
).
NSF was first identified in 1997 and has, so far, been observed only in patients with renal disease. This is a systemic disorder with the most prominent and visible effects on the skin. Cutaneous lesions associated with this disorder are caused by excessive fibrosis and are usually symmetrically distributed on the limbs and trunk. Involved skin becomes thickened, which may inhibit flexion and extension of joints and result in severe contractures. The fibrosis associated with NSF can extend beyond dermis and involve subcutaneous tissues, striated muscles, diaphragm, pleura, pericardium, and myocardium. NSF may be fatal. (See WARNINGS: Serious Warnings and Precautions; WARNINGS: General; PRECAUTIONS: Renal Impairment, and ADVERSE REACTIONS: Postmarket Adverse Drug Reactions).
Use of products of a similar class to GADOVIST has resulted in cases of acute renal failure. Therefore GADOVIST should be used with caution in patients with renal insufficiency, and in such patients the dose of gadobutrol should be reduced (see DOSAGE AND ADMINISTRATION). In patients with severely impaired renal function, the benefits of gadobutrol must be weighed carefully against the risks, since elimination will be delayed in such patients. In very severe cases, gadobutrol should be removed from the body by hemodialysis. At least 3 dialysis sessions within 5 days of the injection are recommended.
Exposure to GBCAs increase the risk for NSF in patients with:
acute or chronic severe renal insufficiency (glomerular filtration rate
<30 mL/min/1.73m2), or acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. The risk, if any, for the development of NSF among patients with mild to moderate renal insufficiency or normal renal function is unknown, and the cautious utilization of the lowest possible dose of GBCA is preferable. (See WARNINGS: Serious Warnings and Precautions; PRECAUTIONS: Skin, and
Postmarket Adverse Drug Reactions.
)
Pregnancy
The safe use of GADOVIST during pregnancy has not been established. Therefore, it should not be used unless the benefit outweighs the risk.
Nursing mothers
Transfer of GADOVIST into the milk of lactating mothers has not been investigated in humans, but there is evidence from animal studies that small amounts enter breast milk. Breast-feeding should be interrupted for 24 hours following administration of gadobutrol and the milk discarded during this period.
Use in the elderly
No special precautions are required in elderly patients unless renal function is impaired (see WARNINGS: Serious Warnings and Precautions and DOSAGE AND ADMINISTRATION).
Use in children
The safety and effectiveness of gadobutrol in children have not been established.
Use of GADOVIST with concomitant medications known to cause prolonged QT interval should be done with extreme caution. (See WARNINGS: Cardiac effects.)
General
Clinical trials for central nervous system (CNS) indications
The safety of GADOVIST (gadobutrol) was evaluated in 798 patients during clinical trials for CNS indications. Most adverse events reported developed soon after injection; however, the possibility of delayed reactions cannot be ruled out. The most common adverse events reported following administration of GADOVIST were: headache (0.9%), vasodilatation (0.6%), nausea (0.5%), injection site pain (0.4%), dizziness (0.3%), rash (0.3%) and dyspnea (0.3%). These reactions were mild to moderate in severity. The following other adverse events were reported, regardless of causality. Body as a whole: Abdominal pain, allergic reaction, fever and infection Cardiovascular system: Palpitation and postural hypotension Gastrointestinal system: Diarrhea and vomiting Injection site: Pain at the injection site Nervous system: Apathy, aphasia, convulsion, dry mouth, hot flashes, hypesthesia, insomnia, paresthesia, increased sweating and vertigo Special senses: Abnormal vision and parosmia Urogenital system: Urinary urgency and urine abnormality
Clinical trials for CE-MRA indication
The safety of GADOVIST 1.0 was evaluated in a total of 890 patients during clinical trials for CE-MRA. Of these, 708 patients were evaluated for efficacy. A total of 76 patients (8.5%) experienced 93 adverse events; in 31 cases (3.5%), the adverse event was assessed as at least possibly study drug-related. Adverse events most often observed were short-lasting thermal sensations (including paresthesia) (2.5%), headache (1.1%), nausea (0.9%) and vomiting, diarrhea, taste perversion and dizziness in 4 patients each (0.5%). All other events were observed in less than 0.5% of cases. The majority of the adverse events were of mild or moderate intensity. Where GADOVIST was administered in doses in excess of 0.3 mmol/kg in a small number of patients, the rate of adverse events was observed to increase to 25% (4 of 16 patients) compared to 9.5% for doses > 0.2 mmol/kg to 0.3 mmol/kg (29 of 304 patients) and 7.9% for doses 0.1 mmol/kg to 0.2 mmol/kg (35 of 457 patients). Transient sensations of taste or smell perversion may occur during or immediately after injection of GADOVIST. Patients with an allergic disposition suffer more frequently than others from hypersensitivity reactions. As with all contrast media, delayed reactions occuring hours or days after administration, may occur. In very rare instances, anaphylactoid reactions may occur (see WARNINGS). Upon accidental paravascular injection, GADOVIST may cause tissue pain and irritation lasting several minutes. No other local tissue reactions have been observed.
Postmarket Adverse Drug Reactions
Postmarketing reports have identified the development of NSF following single and multiple administrations of GBCAs. These reports have not always identified a specific agent. Where a specific agent was identified, the most commonly reported agent was gadodiamide (Omniscan(r)), followed by gadopentetate dimeglumine (Magnevist(r)) and gadoversetamide (OptiMARK(r)). NSF has also developed following the sequential administration of gadodiamide with gadobenate dimeglumine (MultiHance(r)) or gadoteridol (ProHance(r)). The number of postmarketing reports is subject to change over time and may not reflect the true proportion of cases associated with any specific GBCA. The extent of risk for NSF following exposure to any specific GBCA is unknown and may vary among the agents. Published reports are limited and predominantly estimate NSF risks with gadodiamide. In one retrospective study of 370 patients with 370 patients with severe renal insufficiency who received gadodiamide, the estimated risk for development of NSF was 4%. (1) The risk, if any for the development of NSF among patients with mild to moderate renal insufficiency or normal renal function is unknown, and the cautious utilization of the lowest possible dose of GBCA is preferable. (See also WARNINGS: Serious Warnings and Precautions, General, Skin and Renal).
Single doses of GADOVIST (gadobutrol) as high as 1.5 mmol gadobutrol/kg of body weight have been tested in humans. No signs of intoxication from an overdose have been observed during clinical use. Cardiovascular monitoring and control of renal function are recommended as a measure of precaution. Use of products of a similar class to GADOVIST has resulted in cases of acute renal failure. Therefore GADOVIST should be used with caution in patients with renal insufficiency and in such patients the dose of gadobutrol should be reduced (see DOSAGE AND ADMINISTRATION). In the event of inadvertent overdosage or in the case of severely impaired renal function, GADOVIST can be removed from the body by hemodialysis (see PRECAUTIONS).
The following dosages of GADOVIST (gadobutrol) are recommended for cranial and spinal MRI examinations and in magnetic resonance angiography (CE-MRA).
| TYPE of EXAMINATION | GADOVIST 0.5 | GADOVIST 1.0 |
| CNS Indications | ||
| General -1 st injection -2 nd injection (within 30 min of 1 st injection) in cases where a strong clinical suspicion of a lesion persists despite a normal contrast-enhanced MRI or when more accurate information on the number, size or extent of lesions might influence the choice of therapy or management of the patient. | 0.2 mL/kg 0.2 mL/kg to 0.4 mL/kg (corresponding to 0.2-0.4 mmol/kg of body weight) | 0.1 mL/kg mL/kg to mL/kg (corresponding to 0.1-0.2 mmol/kg of body weight) |
| Exclusion of metastases or recurrent tumors Lesions with poor vascularization and/or small extracellular space or when relatively less heavily T 1 -weighted scanning sequences are used | 0.6 mL/kg (corresponding to 0.6 mmol/kg of body weight) | 0.3 mL/kg (corresponding to 0.3 mmol/kg of body weight) |
| TYPE of EXAMINATION | GADOVIST 0.5 | GADOVIST 1.0 |
| Perfusion studies 1 -T 2 * -weighted gradient echo sequences are recommended for use in combination with cranial and spinal MRI for detection of mass lesions and for detection of focal ischemia without suspected mass lesions. | Not applicable. | 0.3 mL/kg (corresponding to 0.3 mmol/kg of body weight) |
| CE-MRA Indication | ||
| Imaging of 1 field of view (FOV): | Not applicable. | 7.5 mL for body weight below 75 kg, 10 mL for body weight of 75 kg and higher; (corresponding to 0.1-0.15 mmol/kg of body weight). |
| Imaging of > 1 field of view (FOV): | Not applicable. | 15 mL for body weight below 75 kg, 20 mL for body weight of 75 kg and higher (corresponding to 0.2-0.3 mmol/kg of body weight). |
1 For perfusion studies, the use of a non-magnetic, automatic injector is recommended at an infusion rate of 3-5 mL/sec. The required volume of GADOVIST is administered intravenously as a bolus injection. Contrast-enhanced MRI can start shortly after the injection depending on the pulse sequences used and the protocol for the examination. Optimal opacification is generally observed during arterial first pass for CE-MRA and within a period of about 15 minutes after injection of GADOVIST for CNS indications (time depending on type of lesion/tissue). Tissue enhancement is generally sustained up to 45 minutes after injection of GADOVIST. T1-weighted scanning sequences are particularly suitable for contrast-enhanced examinations. The administration of contrast media should, if possible, be done with the patient lying down. The patient should be kept under observation for at least 30 minutes following the administration of contrast media since experience shows that the majority of all severe adverse effects occur within this period.
Use of vials:
GADOVIST should not be drawn into the syringe until immediately before use. Any unused portion must be discarded upon completion of the procedure.
Proper Name: Gadobutrol (INN) Chemical Name: 10-[(1SR,2RS)-2,3-Dihydroxy-1-hydroxymethylpropyl]-1,4,7,10- tetraazacyclododecane-1,4,7-triacetic acid, gadolinium complex (IUPAC) [10-[2,3-dihydroxy-1-(hydroxymethyl)propyl]-1,4,7,10- tetraazacyclododecane-1,4,7-triacetato (3-)-N1, N4, N7, N10, O1, O4, O7]-gadolinium (CAS) Structural Formula: Molecular Formula: C18H31N4O9Gd Molecular Weight: 604.72 Physical Form: white to off-white crystal Solubility: freely soluble in water, very slightly soluble in ethanol, and practically insoluble in hexane, methylene chloride and acetone pKa: < 2.0 Partition coefficient: log Pn-octanol/water = -5.4 +- 0.2 (25degC) Other Properties:
GADOVIST 0.5 GADOVIST 1.0
(approximate values)
Osmolarity at 37degC 470 1117
(mOsm/L solution)
Osmolality at 37degC 557 1603 (mOsm/kg H2O)
Viscosity at 37degC 1.41 4.96
(mPa *s)
GADOVIST is a clear, sterile, aqueous solution. Each mL of GADOVIST 0.5 contains 302.36 mg (0.5 mmol) of gadobutrol, 1.211 mg trometamol, and 0.513 mg calcium sodium butrol in water for injection. Each mL of GADOVIST 1.0 contains 604.72 mg (1.0 mmol) of gadobutrol, 1.211 mg trometamol, and 0.513 mg calcium sodium butrol in water for injection. The pH of GADOVIST 0.5 and GADOVIST 1.0 is adjusted to between 6.6 and with hydrochloric acid.
GADOVIST should be stored between 15EC and 30EC. Protect from freezing.
GADOVIST (gadobutrol) is a clear, sterile, aqueous solution. GADOVIST 0.5 is supplied in single dose vials of 10 mL, 15 mL and 20 mL and in single dose pre-filled syringes of 10 mL and 15 mL. GADOVIST 1.0 is supplied in single dose vials of 7.5 mL, 15 mL and 30 mL and in single dose pre-filled syringes of 7.5 mL and 15 mL.