Gadopentetic Acid/Gadoversetamide 1587 ble for those receiving medium- or low-risk agents, parti­ has paramagnetic properties and is used as a magnetic cularly patients aged 65 years or older. resonance contrast medium (p. 1580.1). It distributes Adverse Effects and Precautions M RA As for Gadopentetic Acid, p. 1586.2 and p. 1586.2, 1. Perazella A Rodby . Gadolinium-induced nephrogenic systemic mainly into extracellular fluid, but does not cross the blood­ fibrosis in patients with kidney disease. Am J Med 2007; 120: 561-2. brain barrier, and is used in imaging of cranial and spinal respectively. 2. Health Canada. Gadolinium-containing contrast agents and nephro­ structures and of the whole body, and in magnetic genic systemic fibrosis: update. Can Adverse React News 2007; 17 (4): 1-2. Reviews. Also available at: http://www.hc-sc.gc.ca/dhp-mps/alt_fonnats/hpfb­ resonance angiography. 1. Runge VM, Parker JR. Worldwide clinical safety assessment of dgpsa/pdf/medeff/carn-bceLvl7n4-eng.pdf (accessed 25/08110) Gadoteric acid is given intravenously as the meglumine gadoteridol injection: an update. Bur Radiol l997; 7 (suppl 5): 243-5. 3. Mareno-Romero JA, et al. Nephrogenic systemic fibrosis: a case series salt. It is available as a solution containing meglumine suggesting gadolinium as a possible aetiological factor. Br J Dermatol gadoterate 376.9mg/mL (0.5 mmol/mL). The usual dose in Hypersensitivity. For a report of an anaphylactoid reaction 2007; 157: 783-7. 4. Penfield JG, Reilly RF. Nephrogenic systemic fibrosis risk: is there a adults and children is 0.2 mL/kg (0.1 mmol/kg) by with gadoteridol, see under Adverse Effects of Gadopente­ difference between gadolinium-based contrast agents? Semin Dial 200B; intravenous injection. A second dose of up to 0.4 mL/kg tic Acid, p. 1586.2. 21: 129-34. (0.2 mmol/kg) may be given within 30 minutes if necessary. 5. FDA. Gadolinium-containing contrast agents for magnetic resonance For angiography, a dose of 0.1 to 0.2 mL/kg (0.05 to imaging (MRI): Omniscan, OptiMARK, Magnevist, ProHance, and Pharmacokinetics MultiHance (issued 8th June 2006, updated 22nd December, 2006 and 0.1 mmol/kg) may be given, repeated if required. 23rd May, 2007). Available at: http://www.fda.gov/Drugs/DrugSafety/ Gadoteridol is distributed into extracellular fluid after PostmarketDrugSafetylnformationforPatientsandProviders/ intravenous injection. About 94% of a dose is excreted Administration in children. For doses of gadoteric add in ucml42884.htm (accessed 24/08/IO) unchanged in the urine within 24 hours. An elimination children, see Uses and Administration, above. 6. MHRA/CHM. Gadolinium-containing MRI contrast agents: nephrogenic half-life of about 1.57 hours has been reported. systemic fibrosis. Drug Safety Update 2007; 1 (I): 2-3. Available at: http:// www.mhra.gov.uk/home/idcplg?IdcService=GET_Fll.E&dDocName=­ CON203180l&RevisionSelectionMethod=LatestReleased (accessed Adverse Effects and Precautions r ti . .. 14/07/08) �r.�J?.?. �. ��� ................................ ............ ................ ............ 7. Health Canada. Association of nephrogenic systemic fibrosis/nephro­ As for Gadopentetic Add, p. 1586.2. Praprietary Preparations (details are given in Volume B) genic fibrosing dermopathy (NSF/NFD) with the use of gadolinium­ containing contrast agents (issued 9th March, 2007). Available at: Single-ingredient Preparations. Austral. : Prohance; Austria: Pro· http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/medeff/ Hypersensitivity. For reports of anaphylactoid reactions hance; Belg.: Prohance; Canad. : ProHance; Cz.: Prohance; gadolinium_nth-aah-eng.pdf (accessed 18/03/09) with gadoterate, see under Adverse Effects of Gadopentetic Denm.: Prohance; Fin.: Prohance; Fr.: Prohance; Ger. : Pro­ 8. Adverse Drug Reactions Advisory Committee (ADRAC). MRI scans with Acid, p. 1586.2. hance; Irl. : Probance; Ita!. : Prohance; Jp n: Prohance; Neth.: gadolinium-containing contrast agents and the risk of nephrogenic systemic fibrosis-caution in patients with renal impairment. Aust Prohance; Norw.: Prohance; Spain: Prohance; Swed.: Prohance; Adverse Drug Read Bull 2008; 17: 2. Also available at: http://www.tga. Switz. : Prohance; UK: Prohance; USA: Prohance. health.gov.au/adr/aadrb/aadr0802.pdf (accessed 18/03/09) Pharmacokinetics 9. MHRA/CHM. Gadolinium-containing contrast agents: new advice to Phannacopaeial Preparations minimise the risk of nephrogenic systemic fibrosis. Drug Safety Update Gadoterate is distributed into the extracellular space after USP 36: Gadoteridol Injection. 2010; 3 (6): 3-5. Available at: http:/lwww.mhra.gov.uk/Publications/ intravenous injection. It is not bound to plasma proteins. A Safetyguidance/DrugSafetyUpdate/CON068297 (accessed 22/03/10) plasma half-life of about 1.5 hours has been reported. It is not metabolised and about 90% of a dose is excreted in the Gadoversetamide (BAN. USAN, r!NNJ Pharmacokinetics urine within 24 hours. Gadopentetate is rapidly distributed into the extracellular space after intravenous injection. An elimination half-life of �.��J?.�.�<J.Ii��� .................................. ........................ ................. 1.6 hours has been reported. It is not metabolised and about Proprietary Preparations (details are given in Volume B) 90% of a dose is excreted in the urine within 24 hours. It does not appear to bind to plasma proteins. A small amount Single-ingredient Preparations. Arg. : Dotarem; Austral. : Dotar· is distributed into breast milk. Gadopentetate is removed by em; Austria: Artirem; Dotarem; Belg.: Artirem; Dotarem; Chile: haemodialysis. Dotarem; Cz. : Dotarem; Denm.: Dotarem; Fin.: Dotarem; Fr. : Artirem; Dotarem; Ger.: Artirem; Dotarem; Gr.: Dotarem; Hung.: Dotarem; Irl. : Dotarem; Israel: Dotarem; Ital. : Dotarem; �.��!?.�.��!����············································································ Neth.: Artirem; Dotarem; Norw. : Dotarem; NZ: Dotarem; Port.: Proprietary Preparations (details are given in Volume B) Dotarem; Rus.: Dotarem (,[{oTapeM); Spain: Dotarem; Swed.: Pharmacopoeias. In us. Dotarem; Switz. : Artirem; Dotarem; Thai. : Dotarem; Turk. : USP 36: Single-ingredient Preparations. Arg. : Magnevist; Opadte; View­ (Gadoversetamide). A white odourless powder. USA: Venez. : gam; Austral. : Magnevist; Austria: Magnegita; Magnevist; Dotarem; Dotarem; Dotarem. Freely soluble in water. Store.in airtight containers. Protect Belg.: Magnegita; Magnevist; Braz. : Magnevistan; Canad. : from light. Magnevist; Chile: Magnevistant; Cz. : Magnegita; Magnetolux; Magnevist; Denm.: Magnegitat; Magnevist; Magnograf; Fin.: Gadoteridol (BAN, USAN, riNNJ Uses and Administration Magnevist; Fr.: Magnegita; Magnevist; Ger.: Magnegita; Mag­ nevist; MR-Lux; Gr.: Magnevist; Hung.: Magnevist; India: Gadoversetamide is a nonionic gadolinium chelate with Magnevist; Irl. : Magnegita; Magnetolux; Magnevist; Israel: actions and uses similar to those of gadopentetic acid Gado-MRI; Magneto!; Ital. : Magnevist; Mex. : Viewgamt; Neth.: (p. 1586.1). It has paramagnetic properties and is used as a Magnegita; Magnevistt; Magnograft; Norw.: Magnevist; NZ: magnetic resonance contrast medium (p. 1580.1). It Magnevist; Philipp. : Gadomin; Port.: Ceacont; Magnegita; distributes mainly into extracellular fluid, but does not Magnevist; Rus.: Magnevist (Marnesucr); S.Afr. : Magnevist; cross the blood-brain barrier, and is used in imaging of Spain: Magnetolux; Magnevist; Magnograft; Swed.: Magnevist; cranial and spinal structures and of the whole body Switz.: Magnevist; Magnograf; MR-Lux; Turk.: Magnevist; UK: (particularly to visualise the liver). Magnevist; Ukr.: Magnilek (MarnUJieK); Tomovist (ToMOBHCT); Gadoversetamide is available as a solution containing USA: Magnevist; Venez. : Magnevistan. 330.9mg/mL (0.5 mmol/mL). The usual dose is 0.2 mL/kg Pharmacopoeial Preparations (0.1 mmol/kg) intravenously. USP 36: Gadopentetate Dimeglumine Injection. USP 36: (Gadoteridol). A white to off-white, odourless, crystalline powder. Freely soluble in water and in methyl Adverse Effects and Precautions alcohol; soluble in isopropyl alcohol. Store in airtight As for Gadopentetic Acid, p. 1586.2. containers. Protect from light. Interference with diagnostic tests. Like gadodiamide (see Uses and Administration p. 1585.3), gadoversetarnide may interfere with colori­ metric methods for measuring serum-calcium concentra­ Gadoteridol is a nonionic gadolinium chelate with actions tions. and uses similar to those of gadopentetic add (p. 1586.1). It Gadoversetamide may also interfere with measurement has paramagnetic properties and is used as a magnetic of serum-copper, iron, and zinc concentrations. resonance contrast medium (p. 1580.1). It distributes mainly into extracellular fluid, but does not cross the blood­ Renal impairment. For the view that gadoversetamide brain barrier, and is used in bnaging of cranial and spinal may carry an increased risk of the development of nephro­ structures and of the whole body. genic systemic fibrosis in patients with renal impainnent, Gadoteridol is available as a solution containing see p. 1586.3. 279.3 mg/mL (0.5 mmol/mL). The usual adult dose is 0.2 mL/kg (0.1 mmol/kg) intravenously; for CNS imaging, an additional dose of up to 0.4mL/kg (0.2 mmol/kg) may be Pharmacokinetics given up to 30 minutes after the first if necessary. A single Gadoversetamide is distributed into the extracellular space dose of 0.2 mL/kg (0.1 mmol/kg) is used in children from 6 after intravenous injection. It is not bound to plasma months of age (see also below).