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?.�.�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). proteins. An elimination half-life of about 1.7 hours has been reported. It is not metabolised and about 95.5% of a Administration in children. In some countries, gadoteridol dose is excreted in the urine within 24 hours. is licensed for use in children from 6 months of age; UK Gadoversetamide is removed by haemodialysis. licensed product information notes that experience is lim­ ited in children between 6 months and 2 years of age, and ti advises particular caution if it is to be used in this age �r.�F.r.�. ���············································································ Proprietary Preparations (details are given in Volume B) group. US licensed product information considers that safety and efficacy have not been demonstrated in this age Single-ingredient Preparations. Arg. : Optimark; Austral. : Opti · Uses and Administration group, and only indicates the product for imaging cranial mark; Austria: Optimark; Belg. : Optimark; Canad.: Optimark; Gadoteric add is an ionic gadolinium chelate with actions and spinal structures in those aged 2 years and over. For Cz.: Optimark; Denm.: Optimarkt; Gr.: Optimark; Hung. : Opti­ and uses similar to those of gadopentetic acid (p. 1586.1). It doses see Uses and Administration, above. mark; Irl.: Optimark; Neth.: Optimark; Norw. : Optimark; Pol. :

The symbol t denotes a preparation no longer actively marketed 1588 Contrast Media

Optimark; Port. : Optimark; Rus.: Optimark (OIITHMapK); Spain: Galactose may be given as a microbubble-microparticle Porphyria. The Drug Database for Acute Porphyria, com­ Optimark; Swed.: Optimark; USA: Optimark. suspension prepared immediately before use by suspending piled by the Norwegian Porphyria Centre (NAPOS) and 3 g of galactose microparticles in 13.5 of a solution the Porphyria Centre Sweden, classifies iobitridol as not Pharmacopoeial Preparations rnL containing 200 mg/mL galactose. When given transcervi­ USP 36: Gadoversetamide Injection. porphyrinogenic; it may be used as a drug of first choice cally to enhance ultrasound imaging of the female genital and no precautions are needed.1 tract, the usual dose is 2 to 5 mL, with additional doses of I 1. The Drug Database for Acute Porphyria. Available at: http:l/www. to 2 mL as required, to a n1axirnum of 30 mL. When given drugs-porphyria.org (accessed 18/10/11) {riNN) Gadoxetic Acid intravenously in echocardiography, the usual dose is 4 to Acide ,Gadoxetiq(!e; ga(loxeticb; 10 mL; infants and children may be given the following P epa a ons ,' Acidum ' Gadoxetrc r r ti...... Gadoxetico; Gd-EO,B-DTPA; , , FiW:iKcetoeilff doses according to age: neonates to 4 weeks, 0.5 mL; 4 ...... wm; I I Proprietary Preparations (details are given in Volume B) Kvtcrror_a. weeks to 12 months, to 2 mL; to 5 years, 2 mL. Adults and children, including infants, may be given the maximum Single�ingredient Preparations. Arg. : Xenetict; Xenetix; Austria: Dihydrogen ,flfc((25)-2-[bis(carbox�mett\yl)�mi') o}-3·(!"t of 5 injections. Xenetix; Belg.: Xenetix; Chile: Xenetix; Cz. : Xenetix; Denm.: "thoxyphenyilpropyi}-N:12-[bis(carboxymethyt}amino}f'thyl} Similar suspensions of galactose, with palmitic acid to Xenetix; Fin.: Xenetix; Fr.: Xenetix; Ger.: Xenetix; Gr.: Xene­ glydnato(5·)l\la ollnate{2-). � stabilise the microbubbles, prepared immediately before use tix; Hung.: Xenetix; Irl. : Xenetix; Israel: Xenetix; Ital.: Xenetix; C11H30GdN,Q.p?6!31.!) by suspending galactose microparticles in water for injection Neth.: Xenetix; Nonv.: Xenetix; Port. : Xenetix; Rus.: Xenetix (KceHeniKc); Spain: Xenetix; Swed. : Xenetix; Switz. : Xenetix; CA� �- 135326, 1 i-3 (gadoXetic acid), to concentrations of 200, 300, and 400 mg/mL are also used. AJC � When given intravenously to enhance ultrasound imaging Thai.: Xenetix; Turk.: Xenetix; Venez. : Xenetix. ATC.\!e :t - of blood vessels and in echocardiography, the dose and UN/1 -- JLUI"I•Ofi'"''J. strength used varies depending on the procedure. When given as a bladder instillation for diagnosis of vesicoureteral locetamic Acid (BAN, USAN, p/NN) reflux in children, the 300 mg/mL suspension is recom­ mended; the volume used in infants is 5 mL and in older children 10% of the measured bladder volume. The clearance of galactose given intravenously has been used as a measure of liver function. Galactose labelled with carbon-13 (p. 2470.3) has also been used.

Administration in children. Galactose is licensed for use in infants and children in echocardiography and for diagnosis of vesicoureteral reflux. For doses, see Uses and Adminis­ tration, above.

Uses and Administration Porphyria. The Drug Database for Acute Porphyria, com­ Gadoxetic acid is an ionic gadolinium chelate with actions piled by the Norwegian Porphyria Centre (NAPOS) and similar to those of gadopentetic acid (p. 1586.1). It has the Porphyria Centre Sweden, classifies galactose as not paramagnetic properties and is used as a magnetic porphyrinogenic; it may be used as a drug of first choice resonance contrast medium (p. 1580.1). It is taken up by and no precautions are needed.1 Iocetamic acid is an ionic monomeric iodinated radiographic the liver and excreted in bile and is used in imaging of the l. The Drug Database for Acute Porphyria. Available at: http://www. contrast medium with similar properties to iopanoic acid liver. drugs-porphyria.org (accessed I 8/10/l I) (p. 1591.1 ). It is absorbed from the gastrointestinal tract and Gadoxetic acid is given intravenously as the sodium salt. excreted in bile and has been given orally for It is available as a solution containing sodium gadoxetate Precautions. Preparations that contain, or are metabolised cholecystography. 181.4mg/mL (0.25 mmol!mL). The usual dose is 0.1 mL/kg to, galactose may interfere with the results from glucose (0.025 mmol!kg). tests (p. 2516.3). Overestimation of glucose results may mask hypoglycaernia, resulting in the inappropriate use of lodamide (BAN, USAN, r!NN) insulin.1•2 Licensed product information warns that galact­ Adverse Effects and Precautions ose should not be used for visualisation in patients with Arnetrioclinic•i\cid; B•41 30; 10<;iamida;·roda midum; Jodarnid;

galactosaemia. J i�>midi;Sll-926; V\o}:laMe�A . . As for Gadopentetic Acid, p. 1586.2...... · Q\J ...... · • · ... . aS·Diacetamido-2,4,ti·tri-lorhm-tof\1i .. 3-Acetm:n ido-5- l. .MHRAMedical device alert: ref MDA/2007 /058 issued I 9th July, 2007. S �cid; • Avail able at: http: llwww .mhra.gov. uk/Printpreview /PublicationSP/ acetal)1iqpmetl)yi·2.4,(Hri-iodr;ybo;nzoic ._!lcid. Pharmacokinetics CON2031807 (accessed 01107/08) . l 2 9 2. FDA. Important safety information on interference with blood glucose (, l'l,,J,N?.0,.=(; 7. Gadoxetate is distributed into the extracellular space after measurement following use of parenteral maltose/parenteral galactose/ C4S __._ 44(}-584 intravenous injection and is also taken up by the liver. It is oral xylose-containing products (issued November 2005). Available at: ATC� VOilA.I\ 03: less than 10% bound to plasma proteins. It is excreted in http: IIwww . fda .gov /BiologicsB loodVaccines/ SafetyA vail a hili ty I ATCVet- OVOSA!\03 about equal amounts in the bile and in the urine. An ucml542l3.htm (accessed 24/08110) elimination half-life of about I hour has been reported. UNII --- 4RII33JQ(}R, .. Description. Iodamide contains about 60.6% of I. Gadoxetate is removed by haemodialysis. Preparat ons ...... i ...... Pharmacopoeias. In Jpn . Proprietary Preparations, (details. are given in Volume B) Single-ingredient Preparations. Austral.: Levovist; Austria: Meglumine lodamide {BANM, riNNM! Proprietary Preparations (details are given in Volume B) Echovist; Fr.: Echovistt; Levovistt; Ger.: Echovist; Levovistt; lodamida . de meg!urnina; .. lodall)ide .Mfglumi e Single�ingredient Preparations. Austral.: Primovist; Austria: Pri­ Gr.: L-Vist; Levovist; Hung.: Echovistt; Israel: Echovist; !tal. : ll (U!i�Nl; movist; Belg.: Primovist; Canad.: Primovist; China: Primovist Levovist; NZ: Levovistt; Spain: Levovistt; Swed.: Echovistt; !od.,mide Meglumine; Megfumint lOd?nlidl!m; iylentyMw>�a Switz.: UK: (tf:��Uffi.); Cz.: Primovist; Fin.: Primovist; Ger.: Primovist; Gr.: Levovistt; Echovistt. li1o,qaoXI.1{!. Primovist; Hung. : Primovist; lrl.: Primovist; Ital. : Primovist; The JV' meth)!!glucaminesalt Multi�ingredient Preparations.India: Osmowin; Ital. : Reumilase. Neth.: Primovist; Nonv.: Primovist; Port. : Primovist; Rus.: Pri­ C 12H, , t,N204,C7H1 ,NOs=8232 movist (flpnMOBHCT); Spain: Primovist; Swed.: Primovist; Switz. : 18656-2 1-8 Primovist; Turk.: Primovist; UK: Primovist; USA: Eovist. (:.!'p i-- .. lobitridol (BAN, r/NN) A"f,C ,.:.,_ V08AA03, Yet __._ QV08AAOJ. · A7'C i<:l b!gi.d i m; Jol;litriclol; Jobitrld.oli; o6MTP>1il[)11. UN11 .�- 6X283535A3.. Galactose (USAN! q y !1 NN-.Bis(2J;diMygroxypropylJ-5-[2-(hydrol!ymeth)l)hyclracry­ Description. Meglumine iodamide contains about 46.3% lami(lo}2,4,6:trifodq,N:t-f·iodine). The dose and strength used varies depending on the been used for computed tomography. Galactose is a naturally occurring monosaccharide used as procedure and route. It has been given as a 24 to 65% solution of the meglumine sa It, or as a mixture of the sodium and an ultrasound contrast medium (p. 1580.2); dissolution of References. galactose microparticles releases microbubbles of air that l. Petersein J, et al. Results of the safety and efficacy of iobitridol in more meglumine salts; solutions of the sodium salt have also been provide echo-enhancement. than 61,000 patients. Bur Radiol 2003; 13: 2006-1 1. used. The dose varies according to the procedure and route.

All cross-references refer to entries in Volume A