|
Important Information about Nephrogenic Systemic Fibrosis (NSF)
Nephrogenic systemic fibrosis (NSF), previously known as nephrogenic fibrosing dermopathy (NFD) is a systemic disease typically characterized by fibrosis of the skin and other connective tissues throughout the body (muscles and internal organs may also be affected.) It was first described in the medical literature in 2000 with the first reported case dating back to 1997(1). To date, NSF has only been reported in patients with severe renal impairment. Symptoms of NSF may include thickening of the skin, swelling of the lower extremities, redness, pruritus, and burning sensations. In approximately 5 percent of patients the course of the disease is rapidly progressive and may potentially lead to a fatal outcome. Definitive diagnosis of NSF requires deep skin biopsy and histopathology.
Based on current information, it appears that males and females are affected in approximately equal numbers, with onset generally during middle age although pediatric cases have also been reported. Currently, there is no known cure for NSF. Improving renal function seems to slow or arrest NSF and may even result in a gradual reversal.
The etiology of NSF is still unknown but is likely to be multifactorial. Specific triggers under scientific evaluation have included surgery and/or the occurrence of thrombosis or other vascular injury(2), proinflammatory state(3), the administration of high doses of erythropoietin(4), and more recently the use of gadolinium-based contrast agents (GBCAs)(5,6,7,8).
The U.S. Food and Drug Administration issued its first Public Health Advisory on NSF in June 2006, and updated that information in December 2006. In May 2007, the agency requested that all GBCAs marketed in the US include a boxed warning and additional warnings about NSF in the product labels. Bayer HealthCare Pharmaceuticals implemented those changes and worked with other GBCA manufactures to issue a Dear Healthcare Provider letter in September 2007 about the potential risk of Nephrogenic Systemic Fibrosis (NSF) in association with the use of GBCAs 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 hepatorenal syndrome or in the perioperative liver transplantation period
The current package insert for Magnevist and the full text of the boxed warning and warnings and precautions section can be found here: vials and pharmacy bulk package.
Since its approval in 1988, Magnevist has established a record as a safe and reliable contrast agent with approximately 95 million applications worldwide, in more than 100 countries, and has been cited in more than 14,000 scientific publications.
Bayer HealthCare Pharmaceuticals urge health care providers and patients to report any adverse event information to either: the FDA via the MedWatch program by phone (1-800-FDA-1088), by fax (1-800-FDA-0178), or by the Internet (www.fda.gov/medwatch); or to Bayer HealthCare Pharmaceuticals by phone (1-888-84BAYER, and choose menu option #4).
Bayer HealthCare Pharmaceuticals receives adverse event reports from various sources. The company has received reports of patients who had reportedly developed NSF following possible Magnevist administration. The company takes all such reports seriously and, in compliance with its regulatory obligations and company policies, provides them, along with any additional information obtained, to the appropriate regulatory authorities.
For more information about these reports, please contact our Medical and Product Information Services at 1-888-BAYER84.
Preclinical studies and interdisciplinary discussions with NSF experts are ongoing to investigate the possible association between GBCAs and NSF, as well as to evaluate in more detail the pathogenesis of this disease entity and potential differences in risk among the various Gd-based MR contrast agents.
Additional resources:
Public Health Advisory on MRI Contrast Agents Containing Gadolinium and Nephrogenic Fibrosing Dermopathy
Questions and Answers on Gadolinium-Containing Contrast Agents
Information for Healthcare Professionals on Gadolinium-Based Contrast Agents for Magnetic Resonance Imaging Scans
Information for Healthcare Professionals Gadolinium-Based Contrast Agents for Magnetic Resonance Imaging (marketed as Magnevist, MultiHance, Omniscan, OptiMARK, ProHance)
October 31, 2008
(1) Cowper SE, Robins HS, Steinberg HM, Su LD, Gupta S, Leboit PE; Scleromyxedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000; 356: 1000-1001
(2) Cowper SE; Nephrogenic fibrosing dermopathy: the first 6 years. Curr Opin Rheumatol 15:785-790, 2003
(3) Sadowski EA, Bennett LK, Chan MR, Wentland AL, Garrett AL, Garrett RW, Djamali A. Nephrogenic Systemic Fibrosis: Risk Factors and Incidence Estimation. Radiology 2007, Published online before print January 31, 2007
(4) Swaminathan S, Ahmed I, Mc Carthy JT, Albright RC, Pittelkow MR, Caplice NM; Nephrogenic fibrosing dermopathy and high-dose erythropoietin therapy. Annals of Internal Medicine Vol. 145 No. 3, August 2004, 234-235
(5) Marckmann P, Skov L, Dupont A, Damholt MB, Heaf JG, Thomsen HS; Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast- enhanced magnetic resonance imaging. J Am Soc Nephrol, August 2, 2006
(6) Thomsen HS. Nephrogenic systemic fibrosis: a serious late adverse reaction to gadodiamide. Eur Radiol. Epub 24 Oct 2006
(7) Broome DR, Girguis MS, Baron PW, Cottrell AC, Kjellin I, Kirk GA. Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. AJR Am J Roentgenol. 2007 Feb;188(2):586-592
(8) Khurana A, Runge VM, Narayanan M, Greene JF Jr, Nickel AE. Nephrogenic Systemic Fibrosis: A Review of 6 Cases Temporally Related to Gadodiamide Injection (Omniscan). Invest Radiol. 2007 Feb; 42(2):139-145
MAGNEVIST FAIR BALANCE STATEMENT:
Important Safety Information
WARNING: NEPHROGENIC SYSTEMIC FIBROSIS
Gadolinium-based contrast agents increase the risk of Nephrogenic Systemic Fibrosis in patients with:
- Acute or chronic severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73 m2), or
- Acute renal insufficiency of any severity due to the hepatorenal syndrome or in the perioperative liver transplantation period
In these patients, avoid the use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast 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 gadolinium-based contrast agent, 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.
MAGNEVIST® (gadopentetate dimeglumine) injection: As with other contrast media, the possibility of serious or life-threatening anaphylactic or anaphylactoid reactions, including cardiovascular, respiratory and/or cutaneous manifestations, should always be considered. As with other paramagnetic contrast agents, caution should be exercised in patients with renal insufficiency, especially at higher doses. As with other injectable products, cases of phlebitis and thrombophlebitis have been reported; assessment of the dosed limb for the development of injection site reactions is recommended.
|
