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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/12 22:07:34」(JST)

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Rifaximin(Rifagut) is a semisynthetic antibiotic based on rifamycin. It has poor oral bioavailability, meaning that very little of the drug will be absorbed into the blood stream when it is taken orally. Rifaximin is used in the treatment of traveler's diarrhea and hepatic encephalopathy, for which it received orphan drug status from the U.S. Food and Drug Administration in 1998.

Uses

Rifaximin is licensed by the U.S. Food and Drug Administration to treat traveler's diarrhea caused by E. coli.^[1] Clinical trials have shown that rifaximin is highly effective at preventing and treating traveler's diarrhea among travelers to Mexico, with few side effects and low risk of developing antibiotic resistance.^[2]^[3]^[4] It is not effective against Campylobacter jejuni, and there is no evidence of efficacy against Shigella or Salmonella species.

It may be efficacious in relieving chronic functional symptoms of bloating and flatulence that are common in irritable bowel syndrome (IBS).^[5]^[6]

There was recently a pilot-study done on the efficacy of rifaximin as a means of treatment for rosacea, according to the study, induced by the co-presence of small intestinal bacterial overgrowth.^[7]

In the United States, rifaximin has orphan drug status for the treatment of hepatic encephalopathy.^[8] Although high-quality evidence is still lacking, rifaximin appears to be as effective as or more effective than other available treatments for hepatic encephalopathy (such as lactulose), is better tolerated, and may work faster.^[9] The drawbacks to rifaximin are increased cost and lack of robust clinical trials for HE without combination lactulose therapy.

Mechanism of action

Rifaximin interferes with transcription by binding to the β-subunit of bacterial RNA polymerase. This results in the blockage of the translocation step that normally follows the formation of the first phosphodiester bond, which occurs in the transcription process.^[10]

Efficacy

A 2011 study in patients with IBS (sans constipation) indicated 11% showed benefits over a placebo.^[11] The study was supported by Salix Pharmaceuticals, the patent holder.^[11] A 2010 study in patients treated for Hepatic Cirrhosis with hospitalization involving Hepatic encephalopathy resulted in 22% of the Rifaxmin treated group experiencing a breakthrough episode of Hepatic encephalopathy as compared to 46% of the placebo group. The majority patients were also receiving Lactulose therapy for prevention of hepatic encephalopathy in addition to Rifaximin.^[12]

Availability

In the United States, Salix Pharmaceuticals holds a US Patent for rifaximin and markets the drug under the name Xifaxan, available in tablets of 200 mg and 550 mg.^[13]^[14] While FDA approved for traveler’s diarrhea and (marketing approved for)^[14] hepatic encephalopathy, Xifaxan has not yet received FDA approval for IBS. Medical insurance may not cover drug costs when prescribed for “off-label” uses, such as Xifaxan prescribed for IBS. No generic formulation is available in the US and none will appear while the FDA approval process is ongoing. If Xifaxan receives full FDA approval for hepatic encephalopathy it is likely that Salix will maintain marketing exclusivity and be protected from generic formulations until March 24, 2017.^[14] Price quotes received on February 21, 2013 for Xifaxan 550 mg in the Denver Metro area were between $23.57 and $26.72 per tablet.

Rifaximin is approved in 33 countries for GI disorders,.^[15]^[16] On August 13, 2013, Health Canada issued a Notice of Compliance to Salix Pharmaceuticals Inc. for the drug product Zaxine.^[17] Though lower cost, generic formulations of rifaximin may be offered via Canadian web domains, these products have not been evaluated or authorized for sale in Canada and may not be in compliance with Canadian law. The Canadian government, via Health Canada, has warned of the dangers of purchasing drugs over the internet.^[18] The US government, through the FDA,^[19]^[20]^[21]^[22]^[23] and the National Association of Boards of Pharmacy^[24] are among other organizations that have issued similar warnings about “Canadian” and other drugs available online and offer resources for consumers to help ensure the safety of internet drugs.^[19]^[25]^[26] In India it is available under the brand name of CIBOZ, XIFAPILL 200/400 (ORDAIN EXELTIS).^{[citation needed]}

References

^ Xifaxan label information PDF Retrieved November 15, 2008.
^ DuPont, H (2007). "Therapy for and Prevention of Traveler's Diarrhea". Clinical Infectious Diseases 45 (45 (Suppl 1)): S78–S84. doi:10.1086/518155. PMID 17582576.
^ Ruiz J, Mensa L, Pons MJ, Vila J, Gascon J (May 2008). "Development of Escherichia coli rifaximin-resistant mutants: frequency of selection and stability". Journal of antimicrobial chemotherapy 61 (5): 1016–9. doi:10.1093/jac/dkn078. PMID 18325895.
^ Martinez-Sandoval F, Ericsson CD, Jiang ZD, Okhuysen PC, Romero JH, Hernandez N, Forbes WP, Shaw A, Bortey E, DuPont HL. (Mar–Apr 2010). "Prevention of travelers' diarrhea with rifaximin in US travelers to Mexico.". J Travel Med. 17 (2): 111–7. doi:10.1111/j.1708-8305.2009.00385.x. PMID 20412178.
^ Sharara A, Aoun E, Abdul-Baki H, Mounzer R, Sidani S, ElHajj I. (2006). "A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence". Am J Gastroenterol 101 (2): 326–33. doi:10.1111/j.1572-0241.2006.00458.x. PMID 16454838.
^ Antibiotic May Help Ease Irritable Bowel, Businessweek, January 05, 2011
^ Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Parodi A, Paolino S, Greco A, Drago F, Mansi C, Rebora A, Parodi A, Savarino V.
^ Wolf, David C. (2007-01-09). "Hepatic Encephalopathy". eMedicine. WebMD. Retrieved 2007-02-15.
^ Lawrence KR, Klee JA (2008). "Rifaximin for the treatment of hepatic encephalopathy". Pharmacotherapy 28 (8): 1019–32. doi:10.1592/phco.28.8.1019. PMID 18657018. Free full text with registration at Medscape.
^ http://www.drugbank.ca/drugs/DB01220
^ ^a ^b http://www.nejm.org/doi/full/10.1056/NEJMoa1004409#t=article
^ Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081. PMID 20335583
^ http://www.salix.com/products/xifaxan550.aspx
^ ^a ^b ^c http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=022554&TABLE1=OB_Rx
^ http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/GastrointestinalDrugsAdvisoryCommittee/UCM203248.pdf
^ http://www.salix.com/news-media/news/previous-years-news/fda-approves-xifaxan%C2%AE-550-mg-tablets-for-reduction-in-risk-of-overt-hepatic-encephalopathy-he-recurrence.aspx
^ http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/sbd_smd_2013_zaxine_161256-eng.php
^ http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/internet-eng.php
^ ^a ^b http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/BuyingMedicinesOvertheInternet/BeSafeRxKnowYourOnlinePharmacy/default.htm
^ http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm321068.htm
^ http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSecurity/default.htm
^ http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/ucm289143.htm#ODSIR
^ http://www.fda.gov/forconsumers/consumerupdates/ucm048164.htm
^ http://www.nabp.net/programs/consumer-protection/buying-medicine-online
^ http://www.nabp.net/programs/accreditation/vipps/
^ http://www.nabp.net/programs/accreditation/vet-vipps/

External links

FDA label approved for Xifaxan (PDF warning)
Xifaxan (manufacturer's website)

UpToDate Contents

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1. 成人における過敏性腸症候群の治療 treatment of irritable bowel syndrome in adults
2. 成人における肝性脳症：治療 hepatic encephalopathy in adults treatment
3. 炎症性腸疾患治療のための抗菌薬 antibiotics for treatment of inflammatory bowel diseases
4. 成人におけるクロストリジウム・ディフィシル：治療 clostridium difficile in adults treatment
5. 旅行者下痢症：臨床症状、診断、および治療 travelers diarrhea clinical manifestations diagnosis and treatment

English Journal

Is irritable bowel syndrome an infectious disease?

Thompson JR1.
World journal of gastroenterology.World J Gastroenterol.2016 Jan 28;22(4):1331-4. doi: 10.3748/wjg.v22.i4.1331.
Irritable bowel syndrome (IBS) is the most common of all gastroenterological diseases. While many mechanisms have been postulated to explain its etiology, no single mechanism entirely explains the heterogeneity of symptoms seen with the various phenotypes of the disease. Recent data from both basic
PMID 26819502

Novel Prevention Strategies for Bacterial Infections in Cirrhosis.

Yan K1,2, Garcia-Tsao G1,2.
Expert opinion on pharmacotherapy.Expert Opin Pharmacother.2016 Jan 22. [Epub ahead of print]
Introduction Bacterial infections are a serious complication of cirrhosis, as they can lead to decompensation, multiple organ failure, and/or death. Preventing infections is therefore very relevant. Because gut bacterial translocation is their main pathogenic mechanism, prevention of infections is m
PMID 26799197

Role of antibiotics for treatment of inflammatory bowel disease.

Nitzan O1, Elias M1, Peretz A1, Saliba W1.
World journal of gastroenterology.World J Gastroenterol.2016 Jan 21;22(3):1078-87. doi: 10.3748/wjg.v22.i3.1078.
Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease (CD) and ulcerative colit
PMID 26811648

Japanese Journal

経口抗菌薬 (新薬展望2011) -- (治療における最近の新薬の位置付け〈薬効別〉--新薬の広場)

佐藤雄己,伊東弘樹,武山正治
医薬ジャ-ナル 47(S1), 137-145, 2011
NAID 40018712237

Sensitive quantification of rifaximin in human plasma by liquid chromatography-tandem mass spectrometry

ZHANG Xianhua,DUAN Jingli,LI Ke,ZHOU Liya,ZHAI Suodi
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 850(1), 348-355, 2007-05-01
NAID 10025798304

A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence

SHARARA AI
Am J Gastroenterol 101, 326-333, 2006
NAID 30010262978

「リファキシミン」

Rifaximin
Systematic (IUPAC) name
	(2S,16Z,18E,20S,21S,22R,23R,24R,25S,26S,27S,28E)-5,6,21,23,25-pentahydroxy-27-methoxy-2,4,11,16,20,22,24,26-octamethyl-2,7-(epoxypentadeca-[1,11,13]trienimino)benzofuro; [4,5-e]pyrido[1,2-a]-benzimida-zole-1,15(2H)-dione,25-acetate
Clinical data
Trade names	Xifaxan, Xifaxanta, Normix
AHFS/Drugs.com	monograph
MedlinePlus	a604027
Pregnancy cat.	C (US)
Legal status	℞ Prescription only
Routes	Oral
Pharmacokinetic data
Bioavailability	< 0.4%
Metabolism	Hepatic
Half-life	6 hours
Excretion	Fecal (97%)
Identifiers
CAS number	80621-81-4
ATC code	A07AA11 D06AX11 QG51AA06 QJ51XX01
PubChem	CID 6436173
DrugBank	DB01220
ChemSpider	10482302
UNII	L36O5T016N
KEGG	D02554
ChEBI	CHEBI:75246
ChEMBL	CHEMBL1617
Chemical data
Formula	C43H51N3O11
Mol. mass	785.879 g/mol
	SMILES CC(=O)O[C@H]3[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(\C)C(=O)Nc6c2c(nc1cc(C)ccn12)c5c4C(=O)[C@@](C)(O/C=C/[C@H](OC)[C@H]3C)Oc4c(C)c(O)c5c6O;
	InChI InChI=1S/C43H51N3O11/c1-19-14-16-46-28(18-19)44-32-29-30-37(50)25(7)40-31(29)41(52)43(9,57-40)55-17-15-27(54-10)22(4)39(56-26(8)47)24(6)36(49)23(5)35(48)20(2)12-11-13-21(3)42(53)45-33(34(32)46)38(30)51/h11-18,20,22-24,27,35-36,39,48-51H,1-10H3,(H,45,53)/b12-11+,17-15+,21-13-/t20-,22+,23+,24+,27-,35-,36+,39+,43-/m0/s1 ; Key:NZCRJKRKKOLAOJ-XRCRFVBUSA-N ;
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　　[★]

英: rifaximin

非吸収性抗生物質;過敏性腸症候群治療
Rifaximin is a semisynthetic, rifamycin-based non-systemic antibiotic, meaning that very little of the drug will pass the gastrointestinal wall into the circulation as is common for other types of orally administered antibiotics. It is used in the treatment of traveler's diarrhea and hepatic encephalopathy, for which it received orphan drug status from the U.S. Food and Drug Administration in 1998.(wikipedia en)

参考

http://en.wikipedia.org/wiki/Rifaximin#cite_ref-0

http://www.drugs.com/mtm/rifaximin.html

https://members.kaiserpermanente.org/kpweb/drugency/drugdetails.do?drugID=561118

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/GastrointestinalDrugsAdvisoryCommittee/UCM201081.pdf

[1] Xifaxan label information PDF Retrieved November 15, 2008.

[2] DuPont, H (2007). "Therapy for and Prevention of Traveler's Diarrhea". Clinical Infectious Diseases 45 (45 (Suppl 1)): S78–S84. doi:10.1086/518155. PMID 17582576.

[pmid18325895-3] Ruiz J, Mensa L, Pons MJ, Vila J, Gascon J (May 2008). "Development of Escherichia coli rifaximin-resistant mutants: frequency of selection and stability". Journal of antimicrobial chemotherapy 61 (5): 1016–9. doi:10.1093/jac/dkn078. PMID 18325895.

[4] Martinez-Sandoval F, Ericsson CD, Jiang ZD, Okhuysen PC, Romero JH, Hernandez N, Forbes WP, Shaw A, Bortey E, DuPont HL. (Mar–Apr 2010). "Prevention of travelers' diarrhea with rifaximin in US travelers to Mexico.". J Travel Med. 17 (2): 111–7. doi:10.1111/j.1708-8305.2009.00385.x. PMID 20412178.

[5] Sharara A, Aoun E, Abdul-Baki H, Mounzer R, Sidani S, ElHajj I. (2006). "A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence". Am J Gastroenterol 101 (2): 326–33. doi:10.1111/j.1572-0241.2006.00458.x. PMID 16454838.

[6] Antibiotic May Help Ease Irritable Bowel, Businessweek, January 05, 2011

[7] Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Parodi A, Paolino S, Greco A, Drago F, Mansi C, Rebora A, Parodi A, Savarino V.

[8] Wolf, David C. (2007-01-09). "Hepatic Encephalopathy". eMedicine. WebMD. Retrieved 2007-02-15.

[9] Lawrence KR, Klee JA (2008). "Rifaximin for the treatment of hepatic encephalopathy". Pharmacotherapy 28 (8): 1019–32. doi:10.1592/phco.28.8.1019. PMID 18657018. Free full text with registration at Medscape.

[10] ttp://www.drugbank.ca/drugs/DB01220

[nejm.org-11] ttp://www.nejm.org/doi/full/10.1056/NEJMoa1004409#t=article

[12] Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081. PMID 20335583

[13] ttp://www.salix.com/products/xifaxan550.aspx

[accessdata.fda.gov-14] ttp://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=022554&TABLE1=OB_Rx

[15] ttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/GastrointestinalDrugsAdvisoryCommittee/UCM203248.pdf

[16] ttp://www.salix.com/news-media/news/previous-years-news/fda-approves-xifaxan%C2%AE-550-mg-tablets-for-reduction-in-risk-of-overt-hepatic-encephalopathy-he-recurrence.aspx

[17] ttp://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/sbd_smd_2013_zaxine_161256-eng.php

[18] ttp://www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/internet-eng.php

[fda.gov-19] ttp://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/BuyingMedicinesOvertheInternet/BeSafeRxKnowYourOnlinePharmacy/default.htm

[20] ttp://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm321068.htm

[21] ttp://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSecurity/default.htm

[22] ttp://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/ucm289143.htm#ODSIR

[23] ttp://www.fda.gov/forconsumers/consumerupdates/ucm048164.htm

[24] ttp://www.nabp.net/programs/consumer-protection/buying-medicine-online

[25] ttp://www.nabp.net/programs/accreditation/vipps/

[26] ttp://www.nabp.net/programs/accreditation/vet-vipps/

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rifaximin