Magnevist®
The original extracellular contrast agent for MR imaging.
What is Magnevist®?
Magnevist® is an extracellular, 0.5 molar contrast agent for MRI. In 1988, Magnevist® was the first contrast medium almost simultaneously approved for clinical use by the health authorities in Europe, Japan and the USA.
How does Magnevist® work?
The active ingredient in Magnevist® is gadopentetate dimeglumine. Magnevist® contains gadolinium (Gd3+) which is firmly bound in the complex by the DTPA molecule. Gadolinium is a rare earth element, which causes the contrast enhancement in MRI scans. Magnevist® injection causes in T1 sequences a signal intensity increase in the lesion and in T2*-weighted sequences a short lasting signal intensity decrease in first-pass MRI studies.
Much experience in a broad range of indications
Magnevist® is approved for a broad range of indications and in many countries is indicated for MRI of all body regions. Much experience has been gained in its use. More than 120 million applications have been done with Magnevist® up to now.1
Application
Magnevist® is provided as a ready-to-use solution at a 0.5 molar concentration in a wide range of presentations, e.g.10, 15, 20, 30 mL vials, 100 mL bottles and 5, 10, 15, 20 mL prefilled syringes.
How is Magnevist® administered?
Magnevist® is injected intravenously as a bolus, in some indications preferably via an MRI injector. Magnevist® 2 mmol is injected intra-articularly.
Indications
Magnevist® is used for cranial and spinal magnetic resonance imaging (MRI) MRI of all body regions and MRA, in adults and children.2
Magnevist® is contraindicated in patients with renal insufficiency and a GFR 30 mL/min/1.73 m2.
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Magnevist® 0.5 mmol / mL solution for injection.
Composition: 1 mL solution for injection contains 0.5 mmol (469.01 mg) gadopentetate dimeglumine (Gd-DTPA) as active ingredient. Excipients: meglumine, pentetic acid (DTPA), water for injections.
Indications: For diagnostic use only. Magnevist® is indicated for cranial, spinal and whole body magnetic resonance imaging (MRI).
Contraindications: Hypersensitivity or allergy to the active substance or to any of the excipients.
Special warnings and precautions for use:
Particularly careful risk-benefit assessment is required in patients with known hypersensitivity to Magnevist®. Magnevist® can be associated with anaphylactoid / hypersensitivity or other idiosyncratic reactions (characterised by cardiovascular, respiratory or cutaneous manifestations) ranging to severe reactions including shock.
The risk of hypersensitivity reactions is higher in case of: 1.) previous reaction to contrast media; 2.) history of bronchial asthma and 3.) history of allergic disorders. In patients with an allergic disposition the decision to use Magnevist® must be made after particularly careful evaluation of the risk-benefit ratio. Most of these reactions occur within half an hour of administration. Therefore, post-procedure observation of the patient is recommended. Medication for the treatment of hypersensitivity reactions as well as readiness for institution of emergency measures are necessary. Delayed reactions (after hours or several days) have been rarely observed. Patients who experience hypersensitivity reactions while taking beta blockers may be resistant to treatment effects of beta agonists. Patients with cardiovascular disease are more susceptible to serious or even fatal outcomes of severe hypersensitivity reactions.
Impaired renal function: Prior to administration of Magnevist®, all patients should be screened for renal dysfunction by obtaining laboratory tests. There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of Magnevist® and some other gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR < 30mL / min / 1.73 m2) and / or acute kidney injury. Magnevist® is contraindicated in these patients. Patients undergoing liver transplantation are at particular risk since the incidence of acute renal failure is high in this group. Therefore, Magnevist® must not be used in patients in the perioperative liver transplantation period and in neonates. The risk for development of NSF in patients with moderate renal impairment (GFR 30–59 mL / min / 1.73 m2) is unknown. Therefore, Magnevist® should only be used after careful risk-benefit evaluation in patients with moderate renal impairment. Haemodialysis shortly after Magnevist® administration may be useful at removing Magnevist® from the body. Approximately 70% of the administered dose is removed with each dialysis session, such that after 3 dialysis sessions of 3 hours each, about 97% of the total administered dose is eliminated from the body. There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in patients not already undergoing haemodialysis.
Neonates and infants: Magnevist® is contraindicated in neonates up to 4 weeks of age. Due to immature renal function in infants up to 1 year of age, Magnevist® should only be used in these patients after careful consideration.
Elderly: As the renal clearance of gadopentetate may be impaired in the elderly, it is particularly important to screen patients aged 65 years and older for renal dysfunction.
Seizure disorders: Patients with seizure disorders or intracranial lesions may be at increased risk of seizure activity, as this has been reported rarely in association with Magnevist® administration. For patients predisposed to seizures, precautionary measures should be taken, e.g. close monitoring. All equipment and drugs necessary to counter any convulsions which may occur must be made ready for use beforehand.
Undesirable effects: The overall safety profile of Magnevist® is based on data from post-marketing surveillance and from more than 11,000 patients in clinical trials. The most frequently observed adverse drug reactions (ADRs) (≥ 0.4%) in patients receiving Magnevist® in clinical trials are various injection site reactions, headache and nausea. Most of the ADRs in clinical trials were of mild to moderate intensity. Overall, the most serious ADRs in patients receiving Magnevist® are NSF and anaphylactoid reactions / anaphylactoid shock. Delayed hypersensitivity / anaphylactoid reactions (hours later up to several days) have been rarely observed. ADRs from clinical trials are classified according to their frequencies. Frequency groupings are defined according to the following convention:
Uncommon (≥ 1 / 1,000 to < 1/ 100): dizziness, headache, dysgeusia, vomiting, nausea, pain, feeling hot / cold and rare (≥ 1 / 10,000 to < 1 / 1,000): hypersensitivity / anaphylactoid reaction, disorientation, convulsion, paraesthesia, burning sensation, tremor, tachycardia, arrhythmia, thrombophlebitis, flushing, vasodilatation, throat irritation, pharyngolaryngeal pain / pharynx discomfort, cough, abdominal pain, stomach discomfort, diarrhea, toothache, dry mouth, oral soft tissue pain, paraesthesia, pain in extremity and chest, pyrexia, peripheral edema, malaise, fatigue and asthenia. Cases of NSF have been reported with Magnevist®. In patients with dialysis-dependent renal failure who received Magnevist®, delayed and transient inflammatory-like reactions such as fever, chills and C-reactive protein increase have been commonly observed. These patients had the MRI examination with Magnevist® on the day before aemodialysis.
Overdose: No signs of intoxication secondary to an inadvertent overdose have so far been observed or reported on clinical use. Accidental overdose may cause the following effects due to the hyperosmolality of Magnevist®: increase of pulmonary artery pressure, osmotic diuresis, hypervolaemia and dehydration. In case of inadvertent overdose, renal function should be monitored in patients with renal impairment. Magnevist® can be removed by haemodialysis. However, there is no evidence that haemodialysis is suitable for prevention of NSF.
Reporting of suspected adverse reactions: Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system or to DrugSafety.GPV.US@bayer.com.
Date of revision of text: December 2017.
Please note: For current prescribing information refer to the package insert and / or contact your local Bayer AG.
Disclaimer
Effective November 23, 2017, the European Commission (EC) issued a final decision in the Article 31 referral procedure evaluating the presence of gadolinium (Gd) in the body and gadolinium-based contrast agents (GBCAs) to the EU Member States and countries in the European Economic Area (EEA). In general, the EC has adopted the opinion of the European Medicine’s Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). The EC decision is two-fold:
- Suspension of all multipurpose linear GBCAs, including Bayer’s Magnevist® i.v.
- Updates to the labels / prescribing information of all GBCAs remaining on the market, including Bayer’s Gadovist® 1.0 and its specialty linear GBCAs Primovist® and Magnevist® 2 mmol / L intra-articular formulation.
Importantly, EMA’s CHMP in their final opinion confirms that “there is currently no evidence that gadolinium deposition in the brain has caused any harm to patients; however EMA has recommended restrictions for some intravenous linear agents in order to prevent any risk that could potentially be associated with gadolinium brain deposition.”
Magnevist® is not available in all countries.
Bayer believes that scientific and medical evidence to date demonstrates a favorable benefit-risk profile for all of its GBCAs in the vast majority of patients and will continue to make all of its approved products available in authorized markets.
References
1 Matsumura T et al. Magn Reson Med Sci. 2013 doi:10.2463/mrms.2013-0020
2 Magnevist® SmPC July 2017
