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 (2)].
Anaphylactoid and anaphylactic reactions with cardiovascular, respiratory, and/or cutaneous manifestations rarely resulting in death have occurred. The risk of hypersensitivity reactions is higher in patients with a history of reaction to contrast media, bronchial asthma, or allergic disorders. Hypersensitivity reactions can occur with or without prior exposure to GBCAs.
Have appropriately trained personnel administer Magnevist in a facility that has immediate availability of resuscitative equipment. If a hypersensitivity reaction occurs, stop Magnevist injection and immediately begin appropriate therapy.
Observe closely patients with a history of drug reactions, allergy, or other hypersensitivity disorders, during and up to several hours after Magnevist injection.
In patients with renal impairment, acute renal failure (acute kidney injury) requiring dialysis or worsening renal function has occurred, mostly within 48 hours of Magnevist injection. The risk of acute renal failure is higher with increasing dose of contrast. Use the lowest possible dose, evaluate renal function in patients with renal impairment, and allow sufficient time for contrast elimination before re-administration. Elimination half-life in patients with mild or moderate renal impairment is 3 to 4 hours. Elimination half-life in patients with severe renal impairment is about 11 hours. Magnevist is cleared by glomerular filtration and is dialyzable. After 3 dialysis sessions of 3 hours each, about 97% of the administered dose is eliminated from the body; each dialysis session removes about 70% of the circulating drug [see Clinical Pharmacology ].
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.
USE IN SPECIFIC POPULATIONS
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.
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.
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 micromoles. 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 hours translates into less than 3 micromoles 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.
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 Studies].
Safety and efficacy in the pediatric population under the age of 2 years have not been established. Magnevist is eliminated primarily by the kidney. In a study with pediatric patients aged 2 months to < 2 years the pharmacokinetics (body weight-normalized clearance, body weight-normalized distribution volume, and terminal half-life) of gadopentetate were similar to adults.