马根维显Magnevist

经肾排出的顺磁性造影剂

用于磁共振成像（MRI）

名　称：马根维显Magnevist

成分
1毫升以根维显水溶液中含有469mg钆喷酸葡胺（gadopentetic acid,dimeglumine salt）
特性
马根维显是特别为磁共振成像用经肾排出之造影剂，它具有良好的耐受性，很少发生全身性副反应，一般只是局部轻微的反应。
马根维显几乎在24小时内完全排出体外。注射马根维显后，血脑屏障遭到破坏的区域（如胶质母细胞瘤）以及其它颅内、椎管内的脑外病灶都会有强化，从而比平扫提供更多的诊断信息。

适应证
颅脑及脊信的磁共振成像
特别是用于肿瘤的显示及鉴别：协助诊断可疑的脑（脊）膜瘤、（听）神经鞘瘤，侵入性肿瘤（如神经胶质瘤）及转移瘤；显示较少和/或等信号肿瘤及手术或放疗后复发；鉴别诊断少见肿瘤，如：成血管细胞瘤，室管膜瘤及垂体微小腺瘤；进一步确定非脑原性肿瘤的扩散情况。
全身磁共振成像
包括面颅、颈部、胸部和腹部、女性乳房、骨盆腔、及自主性和被动性运动肢体等部位。
马根维显特别提供了诊断所需的一述资料：
-用于论证或排除肿瘤，炎症和血和损伤；
-用于确定这些损伤部位的扩散及边界；
-用于区分病变的内部结构；
-用于评估正常组织与病理组织的循环情形；
-用于区别治疗后肿瘤组织和疤痕（愈合）组织；
-用于验证手术后复发脱垂之椎产盘；
-用于肾形态学诊断和肾功能半定量评估。

剂量及给药方法
一般资料
患者在检查前2小时必须禁食。
使用马根维显必须遵守MRI检查的安全规范，如禁用于心脏起搏器及铁磁性植入物携带者。
将所需剂量的马根维显从静脉注入，必需时呆行团注，继之立即开始MRI强化扫描，最佳时间为注射马根维显45分钟之内。
在血管内注射造影剂时，患者最好平卧；注射完后至少半小时内，需严密观察患者。
非立即使用时，勿将马根维显抽入注射器，一次检查后剩余的造影剂务必废弃。在强化扫描中彩T1加权扫描的脉冲系列尤为适宜。
马根维显适用于0.14至1.5Tesla的磁场强度。在此范围内，不受场强影响。
剂量
以下剂量原则适用于成人和儿童（包括新生儿和婴儿）：
头部和脊椎的磁共振成像
通常使用0.2ml/kg体重的以根维显，即可获得良好的强化效果并满足临床需要。如MRI强化扫描未见异常而临床仍高度怀疑有病灶时，可于注药后30分钟内再注射与第一次等量的马根维显。成人甚至可用至0.4ml/kg体重并再行扫描，可提高诊断的准确率。
为排除在人肿瘤转移或复发，使用0.6ml/kg体重的马根维显将提高诊断的可信度。
全身的磁共振成像
以下剂量原则适用于成人及儿童，但马根维显在2岁以下儿童“全身磁共振成像”适应症的应用尚无很多经验。
通常使用0.2ml/kg体重的马根维显，即可获得良好的强化效果并满足临床需要。
在特殊情况时，如病变内血管少，或细胞外间隙太小，对比不清，可使用0.4ml/kg体重的马根维显来增强对比是需要的，尤其是在强化扫描中，采用轻度T1加权扫描的脉冲序列检查时。
为排除成人病变或肿瘤复发，使用0.6mlkg体重的马根维显将提高诊断的可信度。

禁忌证
目前的知尚无禁忌证

特别说明
对有过敏倾向的患者，使用本品需特别慎重。因为产生过敏反应的机会较其他患者为高。
对有严重肾功能障碍的患者，决定作用本品前需特别慎重权衡利弊，因为造影剂的排出会受到延迟。除此之外，迄今所知，本品对肾功能不会影响，即使如此，对极严重肾功能障碍的患者，建议用血透方式来排除体内的马根维显。
现在尚未证明怀孕期作用马根维显是否安全，因此，对孕妇作用本品应特别慎重。
动物试验表明少量马根维显（少于注射量的0.2%）进入乳汁。
使用马根维显的部分患者，务清铁和胆红素略有升高。但无症状，可在24小时内很快恢复原值。
在马根维显强化扫描24小内采用络合定量法（如bathophenanthroline）测定血清铁，其结果可能很低，这是由于造影剂溶液中含有二亚乙撑三胺五乙酸（DTPA）的缘故。

耐受性与副作用
在注射马根维显后，偶有恶心、呕吐及皮肤或粘膜的过敏性反应。
有过敏倾向的患者，较他人更易发生地敏反应。在极少情况下，地敏以至休克反应均可能发生。熟知急救措施对抢救造影剂反应至关重要。检查室应配备急救药品及设备（如气管插管、除颤器）。
穿刺静脉或注射造影剂时，极少数患者在注射部位有短暂的轻度温热感与疼痛。极罕见的情况下，在注射马根维显后曾观察到惊劂。偶尔发生一过性头痛，血和扩张，头晕，寒颤及晕厥。但是否与使用此药有关仍未被证实。快速团注可能出现一过性味觉异常。
高渗注射液可能会引起注射血管周围组织疼痛，20分钟左右消失。未发现其他组织的不良反应。
进一步的资料，请医师参与马根维显的科学小册。

包装
10ml瓶装
15ml瓶装
20ml瓶装
请将药品妥为储存，勿使儿童拿到。
生产商：德国先灵公司生产
先灵（广州）药业有限公司分包装

FOR INTRAVENOUS ADMINISTRATION

Pharmacy Bulk Package—Not For Direct Infusion

Rx only

WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF) Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Do not administer MAGNEVIST to patients with: chronic, severe kidney disease (GFR < 30 mL/min/1.73m2), or acute kidney injury (see CONTRAINDICATIONS). Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (for example, age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. Do not exceed the recommended MAGNEVIST dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration (see WARNINGS AND PRECAUTIONS).

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, and has the following structural formula:

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:

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.

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.

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 IV 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 IV 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 IV 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).

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).

CONTRAINDICATIONS

MAGNEVIST is contraindicated in patients with:

• Chronic, severe kidney disease (glomerular filtration rate, GFR < 30 mL/min/1.73m2), or
• Acute kidney injury.

WARNINGS AND PRECAUTIONS

Nephrogenic Systemic Fibrosis (NSF)

Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of GBCAs 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/1.73m2) as well as patients with acute kidney injury. Do not administer MAGNEVIST to these patients. The risk appears lower for patients with chronic, moderate kidney disease (GFR 30- 59 mL/min/1.73m2) and little, if any, for patients with chronic, mild kidney disease (GFR 60- 89 mL/min/1.73m2). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Report any diagnosis of NSF following MAGNEVIST administration to Bayer Healthcare (1-888-842-2937) or FDA (1-800-FDA-1088 or www.fda.gov/medwatch).

Screen patients for acute kidney injury and other conditions that may reduce renal function. Features of acute kidney injury consist of rapid (over hours to days) and usually reversible decrease in kidney function, commonly in the setting of surgery, severe infection, injury or drug-induced kidney toxicity. Serum creatinine levels and estimated GFR may not reliably assess renal function in the setting of acute kidney injury. For patients at risk for chronically reduced renal function (for example, age > 60 years, diabetes mellitus or chronic hypertension), estimate the GFR through laboratory testing.

Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a GBCA and degree of renal impairment at the time of exposure. Record the specific GBCA and the dose administered to a patient. When administering Magnevist, do not exceed the recommended dose and allow a sufficient period of time for elimination of the drug prior to re-administration (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Hypersensitivity Reactions

Anaphylactoid and anaphylactic reactions with cardiovascular, respiratory and/or cutaneous manifestations rarely resulting in death have occurred. If such a reaction occurs, stop MAGNEVIST Injection and immediately begin appropriate therapy, including resuscitation.

Observe closely patients with a history of drug reactions, allergy or other hypersensitivity disorders, during and up to several hours after MAGNEVIST Injection.

Acute Renal Failure

In patients with renal insufficiency, acute renal failure requiring dialysis or worsening renal function have occurred, mostly within 48 hrs of MAGNEVIST Injection. The risk of these events is higher with increasing dose of contrast. Use the lowest possible dose and evaluate renal function in patients with renal insufficiency. (See CLINICAL PHARMACOLOGY, Pharmacokinetics.)

MAGNEVIST is cleared by glomerular filtration and is dialyzable.

Injection Site Reactions

Skin and soft tissue necrosis, thrombosis, fasciitis, and compartment syndrome requiring surgical intervention (e.g. compartment release or amputation) have occurred very rarely at the site of contrast injection or the dosed limb. Total volume and rate of MAGNEVIST Injection, extravasation of contrast agent, and patient susceptibility might contribute to these reactions. Phlebitis and thrombophlebitis may be observed generally within 24 hours after MAGNEVIST Injection and resolve with supportive treatment. Determine the patency and integrity of the intravenous line before administration of MAGNEVIST Injection. Assessment of the dosed limb for the development of injection site reactions is recommended.

Interference with Visualization of Lesions Visible with Non-Contrast MRI

As with any paramagnetic contrast agent, MAGNEVIST Injection might impair the visualization of lesions seen on non-contrast MRI. Therefore, caution should be exercised when MAGNEVIST MRI scans are interpreted without a companion non-contrast MRI scan.

Patient Counseling Information

Patients scheduled to receive MAGNEVIST Injection should be instructed to inform their physician if they are pregnant, breastfeeding, or have a history of renal insufficiency, asthma or allergic respiratory disorders. Additionally 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 of NSF among patients with impaired elimination of drugs. To counsel patients at risk of NSF:

• Describe the clinical manifestation of NSF
• Describe procedures to screen for the detection of renal impairment

Instruct the patients to contact their physician if they develop signs or symptoms of NSF following MAGNEVIST 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.

LABORATORY TEST FINDINGS

Transitory changes in serum iron, bilirubin and transaminase levels were observed in clinical trials.

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

CARCINOGENESIS, MUTAGENESIS AND 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.

Gadopentetate dimeglumine retarded fetal development slightly when given intravenously for 10 consecutive days to pregnant rats at daily doses of 0.25, 0.75, and 1.25 mmol/kg (2.5, 7.5 and 12.5 times the human dose based on body weight) and when given intravenously for 13 consecutive days to pregnant rabbits at daily doses of 0.75 and 1.25 mmol/kg (7.5 and 12.5 times the human dose respectively, based on body weight) but not at daily doses of 0.25 mmol/kg. No congenital anomalies were noted in rats or rabbits.

Adequate and well controlled studies were not conducted in pregnant women. MAGNEVIST Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 breastfeeding 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 DOSAGE AND ADMINISTRATION.)

ADVERSE REACTIONS

Clinical Trial 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.

The mean age of the 1272 patients who received MAGNEVIST Injection in pre-market 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 adverse reaction was headache (4.8%). The majority of headaches were transient and of mild to moderate severity. Other adverse reactions that occurred in ≥ 1% of patients included: nausea (2.7%), injection site coldness/localized coldness (2.3%) and dizziness (1%).

The following additional adverse reactions occurred in less than 1% of the patients:

General Disorders: Injection site symptoms, namely, pain, localized warmth, and burning sensation; substernal chest pain, back pain, pyrexia, asthenia, feeling cold, generalized warmth, localized edema, fatigue, and chest tightness, and anaphylactoid reactions characterized by cardiovascular, respiratory and/or cutaneous symptoms.

Cardiovascular: Hypotension, hypertension, tachycardia, migraine, syncope, vasodilatation, pallor, angina pectoris, phlebitis.

Digestive: Abdominal discomfort, teeth pain, increased salivation, abdominal pain, vomiting, constipation, diarrhea.

Nervous System: Agitation, anxiety, thirst, anorexia, nystagmus, somnolence, diplopia, loss of consciousness, convulsions (including grand mal), paresthesia.

Respiratory System: Throat irritation, rhinitis, sneezing, dyspnea, bronchospasm, cough.

Skin: Rash, sweating (hyperhidrosis), pruritus, urticaria (hives), facial edema, epidermal necrolysis.

Special Senses: Tinnitus, conjunctivitis, visual field defect, taste abnormality, dry mouth, lacrimation, eye irritation, eye pain, ear pain.

Postmarketing Experience

The following additional adverse reactions have been identified during postmarketing use of Magnevist. 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.

The most serious reactions were nephrogenic systemic fibrosis (see Boxed Warning) and acute reactions including cardiac or respiratory arrest, anaphylactic shock, shock, respiratory distress, and laryngeal edema. The most frequently reported adverse reactions in the postmarketing experience were nausea, vomiting, urticaria and rash.

General Disorders and Administration Site Conditions: Nephrogenic systemic fibrosis (see Warnings and Precautions), body temperature decreased, tremor, shivering (chills), regional lymphangitis (lymphangitis), pelvic pain.

Hypersensitivity Reactions: Fatal cardiac or respiratory arrest, respiratory distress, cyanosis, laryngeal edema, laryngospasm, pharyngeal edema, angioedema, and anaphylactoid reactions characterized by cardiovascular, respiratory and/or cutaneous symptoms, rarely resulting in death (see Warnings and Precautions).

Cardiac Disorders: Cardiac arrest, heart rate decreased, arrhythmia, non-specific ECG changes, death related to myocardial infarction or other undetermined causes.

Renal and Urinary Disorders: Acute renal failure, increased serum creatinine in patients with renal insufficiency (see Warnings and Precautions) urinary incontinence, urinary urgency.

Ear and Labyrinth Disorders: Hearing impaired.

Eye Disorders: Visual disturbance.

Musculoskeletal and Connective Tissue Disorder: Arthralgia.

Nervous System Disorders: Coma, parosmia, speech disorder.

Respiratory System: Respiratory arrest, pulmonary edema.

Vascular Disorders: Thrombophlebitis, deep vein thrombophlebitis, compartment syndrome requiring surgical intervention.

Skin Disorders: Erythema multiforme, pustules (rash pustular).

OVERDOSAGE

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

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 has 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.

Pharmacy Bulk Package Preparation:  NOT FOR DIRECT INFUSION 

The Pharmacy Bulk Package is used as a multiple dose container with an appropriate transfer device for filling empty sterile syringes.

a) The transfer of MAGNEVIST Injection from the Pharmacy Bulk Package must be performed in an aseptic work area, such as a laminar flow hood, using aseptic technique.

b) Once the Pharmacy Bulk Package is punctured, it should not be removed from the aseptic work area during the entire 24 hour period of use.

c) The contents of the Pharmacy Bulk Package after initial puncture should be used within 24 hours.

d) Any unused MAGNEVIST Injection must be discarded 24 hours after the initial puncture of the bulk package.

IV tubing and syringes used to administer MAGNEVIST Injection must be discarded at the conclusion of the radiological examination.

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

HOW SUPPLIED

MAGNEVIST Injection is a clear, colorless to slightly yellow solution containing 469.01 mg/mL of gadopentetate dimeglumine. MAGNEVIST Injection is supplied in the following sizes:

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 bottle, 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 bottle.

Manufactured for
Bayer HealthCare Pharmaceuticals Inc.
Wayne, NJ 07470

Manufactured in Germany

© 2010, Bayer HealthCare Pharmaceuticals Inc., All Rights Reserved.

6703104 US December 2010

The following is a representative sample of Magnavist labeling. For a complete list of Magnavist labels, see the How Supplied Section.

Magnavist 50 mL Pharmacy Bulk Package

NDC 50419-188-58 10 x 50 mL

sterile solution

Magnevist ®

(brand of gadopentetate

dimeglumine)

injection

Rx only

Pharmacy Bulk Package

Not for Direct Infusion