Abbas, Z

Abid, Shahab

Azam, Zahid

Hilal, Imran

Islam, Muhammad

Jafri, Wasim

Yakoob, javed

English

eCommons@AKU

eCommons@AKUSection of Gastroenterology Department of MedicineOctober 2009Is Furazolidone Therapy for Helicobacter pyloriEffective and Safe? ReplyZ AbbasAga Khan University, zaigham.abbas@aku.edujaved YakoobAga Khan University, javed.yakoob@aku.eduShahab AbidAga Khan University, shahab.abid@aku.eduWasim JafriAga Khan University, wasim.jafri@aku.eduMuhammad IslamAga Khan University, muhammad.islam@aku.eduSee next page for additional authorsFollow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_med_gastroenterolPart of the Gastroenterology CommonsRecommended CitationAbbas, Z., Yakoob, j., Abid, S., Jafri, W., Islam, M., Azam, Z., Hilal, I. (2009). Is Furazolidone Therapy for Helicobacter pylori Effectiveand Safe? Reply. DIGESTIVE DISEASES AND SCIENCES ., 54(10), 2299-2299.Available at: http://ecommons.aku.edu/pakistan_fhs_mc_med_gastroenterol/119AuthorsZ Abbas, javed Yakoob, Shahab Abid, Wasim Jafri, Muhammad Islam, Zahid Azam, and Imran HilalThis letter to the editor is available at eCommons@AKU: http://ecommons.aku.edu/pakistan_fhs_mc_med_gastroenterol/119CORRESPONDENCEIs Furazolidone Therapy for Helicobacter pylori Effectiveand Safe?Vincenzo De Francesco Æ Enzo Ierardi ÆCesare Hassan Æ Angelo ZulloPublished online: 20 February 2009 Springer Science+Business Media, LLC 2009We have read with great interest the study performed inPakistan by Abbas et al. [1] on the efficacy and safety of a‘‘rescue’’ therapy to cure Helicobacter pylori infection.Briefly, following a quadruple therapy including high-doseesomeprazole, bismuth salts, amoxicillin-clavulanic acid,and furazolidone, an 81% eradication rate was achieved atITT analysis, with a side-effects incidence as high as 50%.The authors concluded that ‘‘it is reasonably well toleratedand is an effective second-line regimen’’ and even sug-gested it could be used as a first-line therapy. We havesome concerns about these conclusions. First, following thefirst-line therapy, H. pylori eradication was achieved in119 (67.6%) out of 176 enrolled patients. Consequently, 57eradication failure patients were available instead of 52, aswas reported. If all these patients received a second-linetherapy, then both ITT and PP analysis should be accord-ingly calculated. Second, the reported side-effectsincidence (up to 50%) would appear much higher than thatobserved following a simpler, 10-day levofloxacin-basedsecond-line triple therapy, which is 18% in near 1,000patients, with an 81% eradication rate [2]. Third, it hasbeen claimed that drug cost is a cause for concern indeveloping countries [1]. However, esomeprazole is themost expensive proton pump inhibitor, and the dose used(40 mg b.i.d.) in this study was twice that widely suggestedin the literature [3]. This markedly increased the overalltherapeutic cost of eradication therapy, contrasting one ofthe aims of the study. In addition, when bismuth salts areadministered with a high-dose of the proton pump inhibi-tor, bismuth toxicity may also be a cause for concern, sincevery high blood bismuth concentrations within the Hille-mand alarm levels have been found in 9% of patientsreceiving a quadruple therapy, suggesting there should bemore caution in prescribing bismuth salt with proton pumpinhibitors [4]. Finally, some relevant ethical concerns arisewith the use of furazolidone. This is an antibiotic that wasused in the 1980s for parasitic infections, and some studiesdescribed its use in human subjects to treat H. pyloriinfection. In the 1990s, studies were published that raisedseveral concerns about this agent and its potential forcausing tumors. At the same time, the company that madethe agent in the United States (Roberts Pharmaceuticals)was sold to Shire Pharmaceuticals, and the FDA withdrewits approval for furazolidone in March 2005. The drug wasordered removed even from animals as an antibiotic by theFDA in 2002. The FDA has subsequently sued companiesthat illegally imported the drug from Mexico for use inanimals. Simultaneously, the European Medicinal Agency(EMEA; the equivalent of the FDA in the European Union)banned the drug in Europe. Although the drug continues tobe available in some developing countries such as Iran,Pakistan, India, Mexico, and Brazil, a number of public andpress campaigns from concerned individuals have urgedgovernments to ban the drug in some of those countries.Therefore, can we consider a therapy including furazoli-done as the authors declared as ‘‘safe’’? Although it hasbeen stated that the study was approved by the EthicalCommittee, were patients informed of the possible geno-toxic and carcinogenetic effects [5, 6] for whichfurazolidone is not currently approved by the FDA andEMEA?V. De Francesco  E. IerardiGastroenterology Unit, ‘‘Riuniti’’ Hospital, Foggia, ItalyC. Hassan  A. Zullo (&)Gastroenterology and Digestive Endoscopy, Nuovo ReginaMargherita Hospital, Rome, Italye-mail: zullo66@yahoo.it123Dig Dis Sci (2009) 54:2298–2299DOI 10.1007/s10620-009-0748-xReplyTo the Editor,We would like to thank Dr. Francesco, et al. for criti-cally reading our article and take this opportunity toaddress their concerns. We felt that we should not includethose patients in the analysis who could not be enrolled forthe new regimen and did not receive even a single dose.Side-effects reported were mild and no one discontinuedthe treatment. The cost of esomeprazole is at par with otherproton pump inhibitors in our country. We are aware of theconcerns about the safety of furazolidone and bismuthcompounds. The metabolites of nitrofuran drugs may havesome carcinogenic effect in rodents, however, furazolidonehas been extensively used and is still being used in humans[7–9] and we find no reports of such side-effects. We find asimilar dilemma against nitroimidazoles in literature. Inspite of the mutagenic, genotoxic, and carcinogenic activityof metronidazole in animal models [10, 11], the drug is stillbeing used all over the world, not only as an anti-H. pyloriagent but also for many other indications. There are morethan 100 papers related to the use of nitrofuran drugs forH. pylori treatment [9]. In fact, the furan compounds arealso being researched as anticancer agents [12]. Similarly,bismuth compounds are still a part of the alternate therapiesfor patients who fail to respond to classical triple therapyand are considered safe and well-tolerated agents [13].However, we agree that in such trials there is a need tostudy the long-term safety of the compounds used.Zaigham AbbasJaved YakoobShahab AbidWasim JafriMuhammad IslamZahid AzamImran HilalDepartment of Medicine, The Aga Khan UniversityHospital, Karachi, PakistanReferences1. Abbas Z, Yakoob J, Abid S, et al. Furazolidone, co-amoxiclav,colloidal bismuth subcitrate, and esomeprazole for patients whofailed to eradicate Helicobacter pylori with triple therapy. DigDis Sci. 2008 Dec 5 (Epub ahead of print).2. Gisbert JP, De La Morena F. Systematic review and meta-anal-ysis: levofloxacin-based rescue regimens after Helicobacterpylori treatment failure. Aliment Pharmacol Ther. 2006;23:35–44. doi:10.1111/j.1365-2036.2006.02737.x.3. Gisbert JP, Pajares JM. Esomeprazole-based therapy in Helico-bacter pylori eradication: a meta-analysis. Dig Liver Dis.2004;36:253–259. doi:10.1016/j.dld.2003.12.010.4. Phillips RH, Whitehead MW, Doig LA, et al. Is eradication ofHelicobacter pylori with colloidal bismuth subcitrate quadrupletherapy safe? Helicobacter. 2001;6:151–156. doi:10.1046/j.1523-5378.2001.00022.x.5. Tatsuta M, Iishi H, Baba M, Taniguchi H. Attenuating effect ofthe monoamine oxidase inhibitor furazolidone on the anti-carci-nogenetic effect of cysteamine on gastric carcinogenesis inducedby N-methyl-N0-nitro-N-nitrosoguanidine in Wistar rats. Int JCancer. 1991;48:605–608. doi:10.1002/ijc.2910480420.6. Ahmed HH, El-Aziem SH, Abdel-Wahhab MA. Potential role ofcysteine and methionine in the protection against hormonalimbalance and mutagenicity induced by furazolidone in femalerats. Toxicology. 2008;243:31–42. doi:10.1016/j.tox.2007.09.018.7. Felga GE, Silva FM, Barbuti RC, Navarro-Rodriguez T, ZaterkaS, Eisig JN. Quadruple therapy with furazolidone for retreatmentin patients with peptic ulcer disease. World J Gastroenterol.2008;14:6224–6227.8. Taghavi SA, Jafari A, Eshraghian A. Efficacy of a new thera-peutic regimen versus two routinely prescribed treatments foreradication of Helicobacter pylori: a randomized, double-blindstudy of doxycycline, co-Amoxiclav, and omeprazole in IranianPatients. Dig Dis Sci. 2009;54(3):599–603 Jul 2 (Epub ahead ofprint).9. Buza´s GM, Jo´zan J. Nitrofuran-based regimens for the eradica-tion of Helicobacter pylori infection. J Gastroenterol Hepatol.2007;22:1571–1581.10. Dobia´s L, Cerna´ M, Ro¨ssner P, Sra´m R. Genotoxicity and car-cinogenicity of metronidazole. Mutat Res. 1994;317:177–194.11. Park BC, Park SY, Lee JS, Mousa SA, Kim JT, Kwak MK, KangKW, Lee ES, Choi HG, Yong CS, Kim JA. The anti-angiogeniceffects of 1-furan-2-yl-3-pyridin-2-yl-propenone are mediatedthrough the suppression of both VEGF production and VEGF-induced signaling. Vascul Pharmacol 2009;50(3-4):123–131 Nov28 (Epub ahead of print).12. Lee KI, Park Y, Park SJ, et al. Naphthofuroquinone derivatives:inhibition of receptor tyrosine kinases. Bioorg Med Chem Lett.2006;16:737–742.13. Ford AC, Malfertheiner P, Giguere M, Santana J, Khan M,Moayyedi P. Adverse events with bismuth salts for Helicobacterpylori eradication: systematic review and meta-analysis. World JGastroenterol. 2008;14:7361–7370.Dig Dis Sci (2009) 54:2298–2299 2299123

Is Furazolidone Therapy for Helicobacter pylori Effective and Safe? Reply

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Is Furazolidone Therapy for Helicobacter pylori Effective and Safe? Reply

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