[03 April 2013]
Products Affected - Description
Ethiodol solution for injection, 99%, Savage Laboratories (a division of Nycomed US)
10 mL (NDC 00281-7062-37) - discontinued
Reason for the Shortage
- Savage / Nycomed Laboratories is no longer manufacturing Ethiodol solution for injection due to a marketing decision.1
- Guerbet recently acquired the Ethiodol New Drug Application from Savage / Nycomed. The company is working with FDA to resume manufacturing of this product.2,3 In cooperation with FDA, Guerbet is providing Lipiodol Ultra-Fluide to the US market. Lipiodol Ultra-Fluide and Ethiodol are similar products. However, Lipiodol Ultra-Fluide is different from Ethiodol in that iodine content is expressed differently. Ethiodol iodine content is 37% weight/weight (475 mg/mL) and Lipiodol is 48% weight/volume (480 mg/mL).4-6
No presentations are fully available.
Estimated Resupply Dates
- Savage / Nycomed discontinued Ethiodol in March, 2010 for marketing reasons.1
- Guerbet recently acquired the Ethiodol New Drug Application from Savage / Nycomed. The company is working with FDA to resume manufacturing of this product. There is currently no estimated release date.2,3
- Guerbet in conjunction with FDA is allocating Lipiodol Ultra-Fluide.2,3
Implications for Patient Care
- Ethiodized oil is a lipophilic non-ionic iodinated contrast medium, derived from poppyseed oil7,8 There are no other lipophilic non-ionic contrast media available in the US.7-9
- Ethiodized oil is labeled for use in patients undergoing hysterosalpingography or lymphography.7,10 It has been used off-label for computed tomography of the liver and spleen, and to detect hepatic metastases.10 Ethiodized oil is also commonly used in chemoembolization procedures for the treatment of primary and secondary hepatic malignancies.10-13
- The Society of Interventional Radiology considers this a critical drug shortage and has been working with FDA to find another source for ethiodized oil for practitioners in the US.1,14
Use caution when switching between modalities used for embolization procedures. Preparation and administration methods, required safety precautions, and adverse event profile may differ between the various modalities.11-13
Alternative Agents & Management
- Alternatives to ethiodized oil may not be available for all clinical uses.
- Alternatives to ethiodized oil for chemotherapy embolization procedures may include embolization using chemotherapy in combination with drug eluting beads (eg, DC Beads, LC Beads, starch microspheres) or radioembolization using radioactive Yttrium Y90 in microspheres.11-13
- The available treatment guidelines for embolization of hepatic malignancy do not make any recommendations for specific procedures to use or specify any preference between chemoembolization, embolization with drug eluting beads, and radioembolization.11-13
- Table 1 summarizes the available literature for each strategy.
- Savage Laboratories. Personal communication. March 4, 2010.
- FDA. FDA Drug Shortages. Accessed August 25, 2010.
- Guerbet. Personal communication. November 11, 2010; January 12, March 30, June 7, August 26, and November 16, 2011; February 8, April 30, June 29, August 13, and November 7, 2012; January 28, and April 3, 2013.
- Lipiodol Ultra-Fluide (ethiodized oil) product information. Cedex, France: Guerbet, 2005
- Ethiodol (ethiodized oil) product information. Melville, NY: Savage Laboratories, 2008.
- FDA. Healthcare Professional Letter: Accessed August 25, 2010.
- Wickersham RM, Novak KK, managing eds., Drug Facts and Comparisons (eFacts). St. Louis, MO: Wolters Kluwer Health, Inc.; 2010.
- Swanson D, Maywood C. Miscellaneous radiopaque contrast media. II. Hysterosalpingographic contrast media. In: Swanson D, Chilton H, Thrall J, eds. Pharmaceuticals in Medical Imaging. Radiopaque Contrast Media, Radiopharmaceuticals, Enhancement Agents for Magnetic Resonance Imaging and Ultrasound. New York, NY: MacMillan Publishing Co; 1990:227-236.
- Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc.; 2010.
- Anon. Drug Evaluation: Ethiodized oil. In: Hutchison TA, Shahan DR, Anderson ML, eds. Drugdex System [internet database]. Greenwood Village, CO: Thomson Healthcare; 2010.
- Brown DB, Geschwind JF, Soulen MC, Millward SF, Sacks D. Society of Interventional Radiology position statement on chemoembolization of hepatic malignancies. J Vasc Interv Radiol. Feb 2006;17(2 Pt 1):217-223.
- Reidy DL, Schwartz JD. Therapy for unresectable hepatocellular carcinoma: review of the randomized clinical trials-I: hepatic arterial embolization and embolization-based therapies in unresectable hepatocellular carcinoma. Anticancer Drugs. Jun 2004;15(5):427-437.
- American College of Radiology. ACR Appropriateness Criteria. Hepatic Malignancy: Accessed March 12, 2010; 2007.
- Society of Interventional Radiology. Message From SIR President: Report on Ethiodol Shortage. Accessed March 15, 2010; Updated March 14,; 2010.
- Poon RT, Tso WK, Pang RW, et al. A phase I/II trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol. Sep 2007;5(9):1100-1108.
- Furuse J, Ishii H, Satake M, et al. Pilot study of transcatheter arterial chemoembolization with degradable starch microspheres in patients with hepatocellular carcinoma. Am J Clin Oncol. Apr 2003;26(2):159-164.
- Sikander A, Sadashiv S, Ronald S, Milind J. Transarterial chemoembolization in a patient with recurrent hepatocellular carcinoma and portal vein thrombosis: a case report and review of the literature. Am J Clin Oncol. Dec 2005;28(6):638-639.
- Varela M, Real MI, Burrel M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol. Mar 2007;46(3):474-481.
- Del Poggio P, Maddeo A, Zabbialini G, Piti A. Chemoembolization of hepatocellular carcinoma with drug eluting beads. J Hepatol. Jul 2007;47(1):157-158; author reply 159.
- Kirchhoff TD, Rudolph KL, Layer G, et al. Chemoocclusion vs chemoperfusion for treatment of advanced hepatocellular carcinoma: a randomised trial. Eur J Surg Oncol. Mar 2006;32(2):201-207.
- Grosso M, Vignali C, Quaretti P, et al. Transarterial chemoembolization for hepatocellular carcinoma with drug-eluting microspheres: preliminary results from an Italian multicentre study. Cardiovasc Intervent Radiol. Nov-Dec 2008;31(6):1141-1149.
- Marelli L, Stigliano R, Triantos C, et al. Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol. Jan-Feb 2007;30(1):6-25.
- Aliberti C, Tilli M, Benea G, Fiorentini G. Trans-arterial chemoembolization (TACE) of liver metastases from colorectal cancer using irinotecan-eluting beads: preliminary results. Anticancer Res. Sep-Oct 2006;26(5B):3793-3795.
- Martin RC, Robbins K, Tomalty D, et al. Transarterial chemoembolisation (TACE) using irinotecan-loaded beads for the treatment of unresectable metastases to the liver in patients with colorectal cancer: an interim report. World J Surg Oncol. 2009;7:80.
- Fiorentini G, Aliberti C, Turrisi G, et al. Intraarterial hepatic chemoembolization of liver metastases from colorectal cancer adopting irinotecan-eluting beads: results of a phase II clinical study. In Vivo. Nov-Dec 2007;21(6):1085-1091.
- Fiorentini G, Aliberti C, Del Conte A, et al. Intra-arterial hepatic chemoembolization (TACE) of liver metastases from ocular melanoma with slow-release irinotecan-eluting beads. Early results of a phase II clinical study. In Vivo. Jan-Feb 2009;23(1):131-137.
- Burger I, Hong K, Schulick R, et al. Transcatheter arterial chemoembolization in unresectable cholangiocarcinoma: initial experience in a single institution. J Vasc Interv Radiol. Mar 2005;16(3):353-361.
- King J, Quinn R, Glenn DM, et al. Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer. Sep 1 2008;113(5):921-929.
- Andrews JC, Walker SC, Ackermann RJ, Cotton LA, Ensminger WD, Shapiro B. Hepatic radioembolization with yttrium-90 containing glass microspheres: preliminary results and clinical follow-up. J Nucl Med. Oct 1994;35(10):1637-1644.
- Goin JE, Salem R, Carr BI, et al. Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. J Vasc Interv Radiol. Feb 2005;16(2 Pt 1):205-213.
- Goin JE, Salem R, Carr BI, et al. Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: a risk-stratification analysis. J Vasc Interv Radiol. Feb 2005;16(2 Pt 1):195-203.
- Keng GH, Sundram FX, Yu SW, et al. Preliminary experience in radionuclide therapy of hepatocellular carcinoma using hepatic intra-arterial radio-conjugates. Ann Acad Med Singapore. May 2002;31(3):382-386.
- Kulik LM, Carr BI, Mulcahy MF, et al. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology. Jan 2008;47(1):71-81.
- Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol. Dec 2005;16(12):1627-1639.
- Shepherd FA, Rotstein LE, Houle S, Yip TC, Paul K, Sniderman KW. A phase I dose escalation trial of yttrium-90 microspheres in the treatment of primary hepatocellular carcinoma. Cancer. Nov 1 1992;70(9):2250-2254.
- Young JY, Rhee TK, Atassi B, et al. Radiation dose limits and liver toxicities resulting from multiple yttrium-90 radioembolization treatments for hepatocellular carcinoma. J Vasc Interv Radiol. Nov 2007;18(11):1375-1382.
- Lau WY, Leung WT, Ho S, et al. Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study. Br J Cancer. Nov 1994;70(5):994-999.
- Rhee TK, Naik NK, Deng J, et al. Tumor response after yttrium-90 radioembolization for hepatocellular carcinoma: comparison of diffusion-weighted functional MR imaging with anatomic MR imaging. J Vasc Interv Radiol. Aug 2008;19(8):1180-1186.
- Rosler H, Triller J, Baer HU, et al. Superselective radioembolization of hepatocellular carcinoma: 5-year results of a prospective study. Nuklearmedizin. Oct 1994;33(5):206-214.
- Kennedy AS, Coldwell D, Nutting C, et al. Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys. Jun 1 2006;65(2):412-425.
- Mulcahy MF, Lewandowski RJ, Ibrahim SM, et al. Radioembolization of colorectal hepatic metastases using yttrium-90 microspheres. Cancer. May 1 2009;115(9):1849-1858.
- Sharma RA, Van Hazel GA, Morgan B, et al. Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol. Mar 20 2007;25(9):1099-1106.
- Ibrahim SM, Mulcahy MF, Lewandowski RJ, et al. Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study. Cancer. Oct 15 2008;113(8):2119-2128.
- Kennedy AS, Nutting C, Jakobs T, et al. A first report of radioembolization for hepatic metastases from ocular melanoma. Cancer Invest. Jul 2009;27(6):682-690.
- Kennedy AS, McNeillie P, Dezarn WA, et al. Treatment parameters and outcome in 680 treatments of internal radiation with resin 90Y-microspheres for unresectable hepatic tumors. Int J Radiat Oncol Biol Phys. Aug 1 2009;74(5):1494-1500.
Updated: April 3, 2013 by Leslie Jensen, PharmD, Drug Information Specialist; January 28, 2013 by Jane Chandramouli, PharmD, Drug Information Specialist. Created March 15, 2010, by M. Christina Beckwith, PharmD, Drug Information Specialist, and Michelle M. Wheeler, PharmD, Drug Information Specialist. Copyright 2013, Drug Information Service, University of Utah, Salt Lake City, UT.
This information is provided through the support of Novation to ASHP solely as a service to its members, which shall not use this information for their further commercial use. The content was prepared by the Drug Information Center of University of Utah. Novation, ASHP, and the University of Utah make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, which respect to such information, and specifically disclaim all such warranties. Users of this information are advised that decisions regarding the use of drugs and drug therapies are complex medical decisions and that in using this information, each user must exercise his or her own independent professional judgment. Neither Novation, ASHP nor the University of Utah assumes any liability for persons administering or receiving drugs or other medical care in reliance upon this information, or otherwise in connection with this bulletin. Neither Novation, ASHP nor University of Utah endorses or recommends the use of any drug.
« Back to Drug Shortage Product Bulletins