MAGNEVIST SYRINGE 10ml/Disp Syringe 钆喷葡胺

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 详细处方信息以本药内容附件PDF文件（201061101220823.pdf）的“原文Priscribing Information”为准
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部分中文Magnevist处方资料（仅供参考）

药物名称：马根维显

英文名：Magnevist

别名：钆喷葡胺, 马根维显

外文名：Gadopentetate Dimeglumine, Magnevist

药理作用： Gd3+具有7个不成对电子，为一顺磁性很强的金属离子，能显著缩短T1、T2的驰豫时间，尤以T1更为明显，在浓度0～1mmol／L的范围内驰豫时间呈直线下降，从而影响MRI的信号强度。

药代动力： 本品为葡甲胺的鳌合物，体内过程同葡甲胺有关。静脉给药后很快弥散到体内各组织的细胞外液内，然后经肾小球滤过以原形排出.有少量分泌于胃肠道后随粪便排出。本品可通过受损的血脑屏障进入病变组织。

适应症：用于磁共振成像（MRI）增强，包括：神经系统、心肌、肝脏、乳腺、骨骼、肾脏等器官和组织的增强检查。

用法用量： 静脉注射，0.lmmol／kg。注射后5min行增强成像，其增加效果可维持45min。

不良反应： 本品不良反应显著低于碘造影剂。有轻微的一过性头痛（8.7％），其次为注射部位的冷感（4.8％〕、恶心、呕吐、发麻、头昏（2％）;另有注射部位烧的感、局部水肿、乏力、胸闷、局部淋巴炎、低血压，腹痛、胸痛、流涎、焦虑、惊厥、喉痒、咳嗽、皮疹、口干、味觉异常、出汗、流泪等，其发生率低于1％。

类别：X线造影剂

MAGNEVIST ®
(brand of gadopentetate dimeglumine)
Injection
Rx only

DESCRIPTION
MAGNEVIST® (brand of gadopentetate dimeglumine) Injection is the N-methylglucamine salt of the gadolinium complex of diethylenetriamine pentaacetic acid, and is an injectable contrast medium for magnetic resonance imaging (MRI). MAGNEVIST Injection is provided as a sterile, clear, colorless to slightly yellow aqueous solution for intravenous injection.

MAGNEVIST Injection is a 0.5-mol/L solution of 1-deoxy-1-(methylamino)-D-glucitol dihydrogen [N, N-bis[2-[bis(carboxymethyl)amino]ethyl]-glycinato-(5-)-] gadolinate(2-)(2:1) with a molecular weight of 938, an empirical formula of C28H54GdN5O20.

Each mL of MAGNEVIST Injection contains 469.01 mg gadopentetate dimeglumine, 0.99 mg meglumine, 0.40 mg diethylenetriamine pentaacetic acid and water for injection. MAGNEVIST Injection contains no antimicrobial preservative.

MAGNEVIST Injection has a pH of 6.5 to 8.0. Pertinent physicochemical data are noted below: PARAMETER Osmolality (mOsmol/kg water) at 37°C 1,960 Viscosity (CP) at 20°C 4.9 at 37°C 2.9 Density (g/mL) at 25°C 1.195 Specific gravity at 25°C 1.208 Octanol: H2O at 25°C and pH7 log P w = -5.4

MAGNEVIST Injection has an osmolality 6.9 times that of plasma which has an osmolality of 285 mOsmol/kg water. MAGNEVIST Injection is hypertonic under conditions of use.

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CLINICAL PHARMACOLOGY
Pharmacokinetics
The pharmacokinetics of intravenously administered gadopentetate dimeglumine in normal subjects conforms to a two compartment open-model with mean distribution and elimination half-lives (reported as mean ± SD) of about 0.2 ± 0.13 hours and 1.6 ± 0.13 hours, respectively.

Upon injection, the meglumine salt is completely dissociated from the gadopentetate dimeglumine complex. Gadopentetate is exclusively eliminated in the urine with 83 ± 14% (mean ± SD) of the dose excreted within 6 hours and 91 ± 13% (mean ± SD) by 24 hours, post-injection. There was no detectable biotransformation or decomposition of gadopentetate dimeglumine.

The renal and plasma clearance rates (1.76 ± 0.39 mL/min/kg and 1.94 ± 0.28 mL/min/kg, respectively) of gadopentetate are essentially identical, indicating no alteration in elimination kinetics on passage through the kidneys and that the drug is essentially cleared through the kidney. The volume of distribution (266 ± 43 mL/kg) is equal to that of extracellular water and clearance is similar to that of substances which are subject to glomerular filtration.

In vitro laboratory results indicate that gadopentetate does not bind to human plasma protein. In vivo protein binding studies have not been done.

Pharmacodynamics
Gadopentetate dimeglumine is a paramagnetic agent and, as such, it develops a magnetic moment when placed in a magnetic field. The relatively large magnetic moment produced by the paramagnetic agent results in a relatively large local magnetic field, which can enhance the relaxation rates of water protons in the vicinity of the paramagnetic agent.

In magnetic resonance imaging (MRI), visualization of normal and pathological brain tissue depends in part on variations in the radiofrequency signal intensity that occur with 1) changes in proton density; 2) alteration of the spin-lattice or longitudinal relaxation time (T1); and 3) variation of the spin-spin or transverse relaxation time (T2). When placed in a magnetic field, gadopentetate dimeglumine decreases the T1 and T2 relaxation time in tissues where it accumulates. At usual doses the effect is primarily on the T1 relaxation time.

Gadopentetate dimeglumine does not cross the intact blood-brain barrier and, therefore, does not accumulate in normal brain or in lesions that do not have an abnormal blood-brain barrier, e.g., cysts, mature post-operative scars, etc. However, disruption of the blood-brain barrier or abnormal vascularity allows accumulation of gadopentetate dimeglumine in lesions such as neoplasms, abscesses, and subacute infarcts. The pharmacokinetic parameters of MAGNEVIST in various lesions are not known.

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CLINICAL TRIALS
MAGNEVIST Injection was administered to 1272 patients in open label controlled clinical studies. The mean age of these patients was 46.4 years (range 2 to 93 years). Of these patients, 55% (700) were male and 45% (572) were female. Of the 1271 patients who received MAGNEVIST Injection and for whom race was reported, 82.1% (1043) were Caucasian, 9.7% (123) were Black, 5.3% (67) were Hispanic, 2.1% (27) were Oriental/Asian, and 0.9% (11) were other. Of the 1272 patients, 550 patients were evaluated in blinded reader studies. These evaluated the use of contrast enhancement in magnetic resonance imaging of lesions in the head and neck, brain, spine and associated tissues, and body (excluding the heart). Of the 550 patients, all patients had a reason for an MRI and efficacy assessments were based on pre- and post-MAGNEVIST injection film quality, film contrast, lesion configuration (border, size, and location), and the number of lesions. The protocols did not include systematic verification of specific diseases or histopathologic confirmation of findings.

Of the above 550 patients, 97 patients received 0.1 mmol/kg MAGNEVIST Injection I. V. in two clinical trials of MAGNEVIST MRI contrast enhancement for body imaging. Of these 97, 68 had MRIs of the internal organs/structures of the abdomen or thorax (excluding the heart); 8 had breast images and 22 had images of appendages. The results of MRIs before and after MAGNEVIST use were compared blindly. Overall additional lesions were identified in 22/97 (23%) of the patients after MAGNEVIST Injection. The mean number of lesions identified before (1.49/patient) and after MAGNEVIST (1.75/patient) were similar. Seven (8%) of the patients had lesions seen before MAGNEVIST that were not seen after MAGNEVIST. Overall, after MAGNEVIST Injection, 41% of the images had a higher contrast score than before injection; and 18% of the images had a higher contrast score before MAGNEVIST Injection than after MAGNEVIST Injection. MAGNEVIST MRI of the 8 patients with breast images were not systematically compared to the results to mammography, breast biopsy or other modalities. In the 22 patients with appendage images (e.g., muscle, bone and intraarticular structures), MAGNEVIST MRI was not systematically evaluated to determine the effects of contrast biodistribution in these different areas.

Of the above 550 patients, 66 patients received MAGNEVIST 0.1 mmol/kg I. V. in clinical trials of MAGNEVIST MRl contrast enhancement of lesions in the head and neck. A total of 66 MRI images were evaluated blindly by comparing each pair of MRI images, before and after MAGNEVIST Injection. In these paired images, 56/66 (85%) had greater enhancement after MAGNEVIST and 40/66 (61%) had better lesion configuration or border delineation after MAGNEVIST. Overall, there was better contrast after MAGNEVIST in 55% of the images, comparable enhancement in 44 (36%) before and after MAGNEVIST, and better enhancement in 9% without MAGNEVIST.

In the studies of the brain and spinal cord, MAGNEVIST 0.1 mmol/kg I. V. provided contrast enhancement in lesions with an abnormal blood brain barrier.

In two studies, a total of 108 patients were evaluated to compare the dose response effects of 0.1 mmol/kg and 0.3 mmol/kg of MAGNEVIST in CNS MRI. Both dosing regimens had similar imaging and general safety profiles; however, the 0.3 mmoL/kg dose did not provide additional benefit to the final diagnosis (defined as number of lesions, location and characterization).

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INDICATIONS AND USAGE
Central Nervous System
MAGNEVIST Injection is indicated for use with magnetic resonance imaging (MRI) in adults, and pediatric patients (2 years of age and older) to visualize lesions with abnormal vascularity in the brain (intracranial lesions), spine and associated tissues. MAGNEVIST Injection has been shown to facilitate visualization of intracranial lesions including but not limited to tumors.

Extracranial/Extraspinal Tissues
MAGNEVIST is indicated for use with MRI in adults and pediatric patients (2 years of age and older) to facilitate the visualization of lesions with abnormal vascularity in the head and neck.

Body
MAGNEVIST Injection is indicated for use in MRI in adults and pediatric patients (2 years of age and older) to facilitate the visualization of lesions with abnormal vascularity in the body (excluding the heart).

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CONTRAINDICATIONS
None.

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WARNINGS
As with various other intravenous administrations, caution must be used when administering MAGNEVIST Injection in patients with predisposition to the development of thrombotic syndromes. (See PRECAUTIONS).

Deoxygenated sickle erythrocytes have been shown by in vitro studies to align perpendicular to a magnetic field which may result in vaso-occlusive complications in vivo. The enhancement of magnetic moment by gadopentetate dimeglumine may possibly potentiate sickle erythrocyte alignment. MAGNEVIST Injection in patients with sickle cell anemia and other hemoglobinopathies has not been studied.

Patients with other hemolytic anemias have not been adequately evaluated following administration of MAGNEVIST Injection to exclude the possibility of increased hemolysis.

Hypotension may occur in some patients after injection of MAGNEVIST Injection. In clinical trials two cases were reported and in addition, there was one case of vasovagal reaction and two cases of pallor with dizziness, sweating and nausea in one and substernal pain and flushing in the other. These were reported within 25 to 85 minutes after injection except for the vasovagal reaction which was described as mild by the patient and occurred after 6-1/2 hours. In a study in normal volunteers one subject experienced syncope after arising from a sitting position two hours after administration of the drug. Although the relationship of gadopentetate dimeglumine to these events is uncertain, patients should be observed for several hours after drug administration.

Patients with a history of allergy, drug reactions, or other hypersensitivity-like disorders, should be closely observed during the procedure and for several hours after drug administration. (See PRECAUTIONS - General .)

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PRECAUTIONS
General
As with various other injectable products, cases of phlebitis and thrombophlebitis have been reported also in association with MAGNEVIST Injection. In most cases, symptoms presented during or shortly after injection, and generally within 24 hours of injection and responded to supportive treatment. However, in very rare cases of patients who may have underlying potential to develop thrombotic syndromes, thrombosis with fasciitis and surgical intervention (e.g., compartment release or amputation) of the dosed limb have been reported. The relationship of these events to pre-existing disease, concomitant medications, pre-existing vascular fragility, MAGNEVIST Injection, or the injection procedure was not established. Patency and integrity of the intravenous line should be determined before administration. As with other intravenous injections, appropriate surveillance of the dosing limb for the development of local injection site reactions following administration of MAGNEVIST Injection is recommended.

AS WITH ANY PARAMAGNETIC CONTRAST AGENT, MRI WITH MAGNEVIST CONTRAST ENHANCEMENT MAY IMPAIR THE VISUALIZATION OF EXISTING LESIONS. SOME OF THESE LESIONS MAY BE SEEN ON UNENHANCED, NON-CONTRAST MRI. THEREFORE, CAUTION SHOULD BE EXERCISED WHEN CONTRAST ENHANCED SCAN INTERPRETATION IS MADE IN THE ABSENCE OF A COMPANION UNENHANCED MRI.

Diagnostic procedures that involve the use of contrast agents should be carried out under direction of a physician with the prerequisite training and a thorough knowledge of the procedure to be performed.

In a patient with a history of grand mal seizure, MAGNEVIST Injection was reported to induce such a seizure.

Since gadopentetate dimeglumine is cleared from the body by glomerular filtration, caution should be exercised in patients with impaired renal function. In such patients, increases in serum creatinine and acute renal failure have been reported rarely. MAGNEVIST is not significantly eliminated by the hepatobiliary enteric pathway, but is dialyzable (See Pharmacodynamics Section). Caution should be exercised in patients with either renal or hepatic impairment.

The possibility of a reaction, including serious, life-threatening, or fatal anaphylactoid or cardiovascular reactions or other idiosyncratic reactions (see ADVERSE REACTIONS), should always be considered, especially in those patients with a known clinical hypersensitivity or a history of asthma or other allergic respiratory disorders.

Animal studies suggest that gadopentetate dimeglumine may alter red cell membrane morphology resulting in a slight degree of extravascular (splenic) hemolysis. In clinical trials 15-30% of the patients experienced an asymptomatic transient rise in serum iron. Serum bilirubin levels were slightly elevated in approximately 3.4% of patients. Levels generally returned to baseline within 24 to 48 hours. Hematocrit and red blood cell count were unaffected and liver enzymes were not elevated in these patients. While the effects of gadopentetate dimeglumine on serum iron and bilirubin have not been associated with clinical manifestations, the effect of the drug in patients with hepatic disease is not known and caution is therefore advised.

When MAGNEVIST Injection is to be injected using nondisposable equipment, scrupulous care should be taken to prevent residual contamination with traces of cleansing agents. After MAGNEVIST Injection is drawn into the syringe the solution should be used immediately.

Information for patients
Patients scheduled to receive MAGNEVIST Injection should be instructed to inform their physician if the patient:
•Is pregnant or breast feeding.
•Has any blood disorders; i.e., anemia, hemoglobinopathies, or diseases that affect red blood cells.
•Has a history of renal or hepatic disease, seizure, asthma or allergic respiratory disorders.
Laboratory tests

Transitory changes in serum iron, bilirubin and transaminase levels have been reported in patients with normal and abnormal liver function (See PRECAUTIONS - General ).

MAGNEVIST Injection does not interfere with serum and plasma calcium measurements determined by colorimetric assays

Carcinogenesis, mutagenesis, impairment of fertility
Long term animal studies have not been performed to evaluate the carcinogenic potential of gadopentetate dimeglumine.

A comprehensive battery of in vitro and in vivo studies in bacterial and mammalian systems suggest that gadopentetate dimeglumine is not mutagenic or clastogenic and does not induce unscheduled DNA repair in rat hepatocytes or cause cellular transformation of mouse embryo fibroblasts. However, the drug did show some evidence of mutagenic potential in vivo in the mouse dominant lethal assay at doses of 6 mmol/kg, but did not show any such potential in the mouse and dog micronucleus tests at intravenous doses of 9 mmol/kg and 2.5 mmol/kg, respectively.

When administered intra-peritoneally to male and female rats daily prior to mating, during mating and during embryonic development for up to 74 days (males) or 35 days (females), gadopentetate caused a decrease in number of corpora lutea at the 0.1 mmol/kg dose level. After daily dosing with 2.5 mmol/kg suppression of food consumption and body weight gain (males and females) and a decrease in the weights of testes and epididymis were also observed.

In a separate experiment in rats, daily injections of gadopentetate dimeglumine over 16 days caused spermatogenic cell atrophy at a dose level of 5 mmol/kg but not at a dose level of 2.5 mmol/kg. This atrophy was not reversed within a 16-day observation period following the discontinuation of the drug.

PREGNANCY CATEGORY C
NURSING WOMEN
MAGNEVIST is excreted in human milk. MAGNEVIST Injection was administered intravenously to 18 lactating women with normal renal function at a dose of 0.1 mmol/kg body weight. In these women, less than 0.04% of the administered gadolinium was excreted into the breast milk during the 24-hour period following dosing. Breast milk obtained during the 24 hours following dosing revealed the average cumulative amount of gadolinium excreted in breast milk was 0.57+/- 0.71 micromol. The amount transferred from a 70 kg woman (receiving 0.1 mmol/kg body weight) to an infant by breast feeding over a period of 24 hrs translates into less than 3 micromol of gadolinium.

The overall duration of excretion of gadolinium into breast milk is unknown. The extent of the absorption of MAGNEVIST Injection in infants and its effect on the breast-fed child remains unknown. Caution should be exercised when MAGNEVIST Injection is administered to a nursing woman.

PEDIATRIC USE
The use of MAGNEVIST in imaging the Central Nervous System, Extracranial/Extraspinal tissues, and Body have been established in the pediatric population from the ages of 2 to 16 years on the basis of adequate and well controlled clinical trials in adults and safety studies in this pediatric population. (See CLINICAL TRIALS for details.)

Safety and efficacy in the pediatric population under the age of 2 years have not been established. MAGNEVIST is eliminated primarily by the kidney. The pharmacokinetics of MAGNEVIST in neonates and infants with immature renal function have not been studied. (See INDICATIONS AND USAGE and the DOSAGE AND ADMINISTRATION)

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ADVERSE REACTIONS
The mean age of the 1272 patients who received MAGNEVIST Injection in clinical trials was 46.4 years (range 2 to 93 years). Of these patients, 55% (700) were male and 45% (572) were female. Of the 1271 patients who received MAGNEVIST Injection and for whom race was reported, 82.1% (1043) were Caucasian, 9.7% (123) were Black, 5.3% (67) were Hispanic, 2.1% (27) were Oriental/Asian, and 0.9% (11) were other. The most common noted adverse event is headache with an incidence of 4.8%. The majority of headaches are transient and of mild to moderate severity. Nausea is the second most common adverse experience at 2.7%. Injection site coldness/localized coldness is the third most common adverse experience at 2.3%. Dizziness occurred in 1% of the patients.

The following additional adverse events occurred in fewer than 1% of the patients:

Body as a Whole
Injection site symptoms, namely, pain, localized warmth, and burning sensation; substernal chest pain, back pain, fever, weakness, generalized coldness, generalized warmth, localized edema, tiredness, chest tightness, trembling, shivering, tension in extremities, regional lymphangitis, pelvic pain, and anaphylactoid reactions (characterized by cardiovascular, respiratory and cutaneous symptoms) rarely resulting in death.

Cardiovascular
Hypotension, hypertension, arrhythmia, tachycardia, migraine, syncope, vasodilation, pallor, non-specific ECG changes, angina pectoris, death related to myocardial infarction or other undetermined causes, phlebitis, thrombophlebitis, deep vein thrombophlebitis, compartment syndrome requiring surgical intervention.

Digestive
Gastrointestinal distress, stomach pain, teeth pain, increased salivation, abdominal pain, vomiting, constipation, diarrhea.

Nervous System
Agitation, anxiety, thirst, anorexia, nystagmus, drowsiness, diplopia, stupor, convulsions (including grand mal), paresthesia.

Respiratory System
Throat irritation, rhinorrhea, sneezing, dyspnea, wheezing, laryngismus, cough, respiratory complaints.

Skin
Rash, sweating, pruritus, urticaria (hives), facial edema, erythema multiforme, epidermal necrolysis, pustules.

Special Senses
Tinnitus, conjunctivitis, visual field defect, taste abnormality, dry mouth, lacrimation disorder (tearing), eye irritation, eye pain, ear pain.

OVERDOSAGE
Systemic consequences associated with overdosage of MAGNEVIST Injection have not been reported.

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DOSAGE AND ADMINISTRATION
The recommended dosage of MAGNEVIST Injection is 0.2 mL/kg (0.1 mmol/kg) administered intravenously, at a rate not to exceed 10 mL per 15 seconds. Dosing for patients in excess of 286 lbs have not been studied systematically.

Drug Handling
To ensure complete injection of the contrast medium, the injection should be followed by a 5-mL normal saline flush. The imaging procedure should be completed within 1 hour of injection of MAGNEVIST Injection.

As with other gadolinium contrast agents, MAGNEVIST Injection has not been established for use in magnetic resonance angiography.

Parenteral products should be inspected visually for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored or particulate matter is present.

Any unused portion must be discarded in accordance with regulations dealing with the disposal of such materials.

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HOW SUPPLIED
MAGNEVIST Injection is a clear, colorless to slightly yellow solution containing 469.01 mg/mL of gadopentetate dimeglumine in rubber stoppered vials. MAGNEVIST Injection is supplied in the following sizes:
5 mL single-dose vials, rubber stoppered, in individual cartons, Boxes of 20     NDC 50419-188-05
10 mL single-dose vials, rubber stoppered, in individual cartons, Boxes of 20    NDC 50419-188-01
10 mL pre-filled disposable syringe, Boxes of 5                                  NDC 50419-188-36
15 mL single-dose vials, rubber stoppered, in individual cartons, Boxes of 20    NDC 50419-188-15
15 mL pre-filled disposable syringe, Boxes of 5                                  NDC 50419-188-37
20 mL single-dose vials, rubber stoppered, in individual cartons, Boxes of 20    NDC 50419-188-02
20 mL pre-filled disposable syringe, Boxes of 5                                  NDC 50419-188-38

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STORAGE
MAGNEVIST Injection should be stored at controlled room temperature, between 15-30°C (59-86°F) and protected from light. DO NOT FREEZE. Should freezing occur in the vial MAGNEVIST Injection should be brought to room temperature before use. If allowed to stand at room temperature for a minimum of 90 minutes, MAGNEVIST Injection should return to a clear, colorless to slightly yellow solution. Before use, examine the product to assure that all solids are redissolved and that the container and closure have not been damaged. Should solids persist, discard vial.

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 详细处方信息以本药内容附件PDF文件（201061101220823.pdf）的“原文Priscribing Information”为准
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2010年6月11日更新