Rifaximin is used to treattravelers' diarrhea caused byE. coli bacteria in people aged twelve years of age and older. It treats travelers' diarrhea by stopping the growth of the bacteria that cause diarrhea. Rifaximin will not work to treat travelers' diarrhea that is bloody or occurs with fever.[7]
Rifaximin is used for the treatment ofirritable bowel syndrome (IBS). It possesses anti-inflammatory and antibacterial properties, and is a non-absorbable antibiotic that acts locally in the gut. These properties make it efficacious in relieving chronic functional symptoms of non-constipation type irritable bowel syndrome.[8] It appears to retain its therapeutic properties for this indication, even after repeated courses.[9][10] It is particularly indicated wheresmall intestine bacterial overgrowth is suspected of involvement in irritable bowel syndrome. Symptom relief or improvement can be obtained for global irritable bowel syndrome symptoms, including: abdominal pain,flatulence,bloating, andstool consistency. A drawback is that repeated courses may be necessary for remission of symptoms.[10][11]
Rifaximin may also be a useful addition tovancomycin when treating people with relapsingC. difficile infection.[12][13] However, the quality of evidence of these studies was judged to be low.[14] Because exposure to rifamycins in the past may increase risk for resistance, rifaximin should be avoided in such cases.[15]
Rifaximin is used to prevent episodes ofhepatic encephalopathy (changes in thinking, behavior, and personality caused by a build-up of toxins in the brain in adults who have liver disease). It treats hepatic encephalopathy by stopping the growth of bacteria that produce toxins and that may worsen the liver disease. Although high-quality evidence is lacking, it appears to be as effective as, or more effective than, other available treatments for hepatic encephalopathy (such aslactulose), is better tolerated, and may work faster.[11][16] It prevents reoccurring encephalopathy and is associated with high patient satisfaction. People are more compliant and satisfied to take this medication than any other due to minimal side effects, prolonged remission, and overall cost.[17] The drawbacks are increased cost, and lack of robust clinical trials for hepatic encephalopathy without combination lactulose therapy.[18]
People should avoid rifaximin if they are allergic eitherrifabutin,rifampin, orrifapentine. It may causeattenuated vaccines (such as typhoid vaccine) not to work well. Health-care professionals should be informed about its usage before givingimmunizations.[26] Pregnant or breastfeeding women should avoid rifaximin: it can harm thefetus.[27] Caution is required in people withcirrhosis who have aChild–Pugh score of C.[11]
Rifaximin has an excellent safety profile due to its lack of systemic absorption. Clinical trials did not show any serious adverse events while using rifaximin. There were no deaths while using it in the clinical trials.[9][10][28]
As rifaximin is not significantly absorbed from the gut, the great majority of this drug's interactions are negligible in people with healthy liver function, so healthcare providers usually do not worry about drug interactions unless liver impairment is present.[9] It may decrease the effectiveness ofwarfarin, a commonly prescribed anticoagulant, in people with liver problems.[30]
Rifaximin is asemisynthetic broad spectrum antibacterial drug, derived through chemical modification of the natural antibioticrifamycin.[31] It has very lowbioavailability due to its poor absorption after oral administration. Because of this local action within the gut and the lack of horizontal transfer of resistance genes, the development ofbacterial resistance is rare, and most of the drug taken orally stays in thegastrointestinal tract where the infection takes place.[32]
Rifaximin interferes withtranscription by binding to the β-subunit of bacterialRNA polymerase.[11] This results in the blockage of the translocation step that normally follows the formation of the firstphosphodiester bond, which occurs in the transcription process.[33] This in turn results in a reduction of bacteria populations, including gas-producing bacteria, which may reducemucosal inflammation,epithelial dysfunction, andvisceral hypersensitivity. Rifaximin has broad spectrum antibacterial properties against bothgram positive andgram negativeanaerobic andaerobic bacteria. As a result ofbile acid solubility, its antibacterial action is limited mostly to thesmall intestine and less so thecolon.[11] A resetting of the bacterial composition has also been suggested as a possible mechanism of action for relief of irritable bowel syndrome symptoms.[34] Additionally, rifaximin may have a direct anti-inflammatory effect on gut mucosa via modulation of thepregnane X receptor.[34] Other mechanisms for its therapeutic properties include inhibition of bacterial translocation across theepithelial lining of theintestine, inhibition of adherence of bacteria to theepithelial cells, and a reduction in the expression ofproinflammatory cytokines.[35]
In the United States, Salix Pharmaceuticals holds a US Patent for rifaximin and markets it under the brand name Xifaxan.[3] In addition to receiving FDA approval for travelers' diarrhea and (marketing approved for)[36] hepatic encephalopathy, rifaximin received FDA approval for irritable bowel syndrome in May 2015.[37] No generic formulation is available in the US and none has appeared due to the fact that the FDA approval process was ongoing. If rifaximin receives full FDA approval for hepatic encephalopathy it is likely that Salix will maintain marketing exclusivity and be protected from generic formulations until 24 March 2017.[36] In 2018, a patent dispute withTeva was settled which delayed a generic in the United States, with the patent set to expire in 2029.[38]
Rifaximin is approved in many countries for the treatment of certain gastrointestinal disorders.[39] In August 2013,Health Canada issued a Notice of Compliance to Salix Pharmaceuticals for the drug product Zaxine.[40] In India, it is available under the brand names Ciboz and Xifapill.[41][42] In Russia and Ukraine the drug is sold under the name Alfa Normix (Альфа Нормикс), and under the name Flonorm in Mexico, produced by Alfa Wassermann S.p.A. (Italy).[43] In 2018, the FDA approved a similar drug byCosmos Pharmaceuticals called Aemcolo for traveler's diarrhea.[44]
Comparison of molecular packings of four different crystalline forms of rifaximin. The index value shows the stoichiometric ratio of hydration.[45][46]
Rifaximin can exist in differentcrystalline forms depending on the degree ofhydration. They drastically differ in water solubility, which has to be taken into account during the manufacturing process.[45][46] Wet rifaximin exists in the β-form, which can be dehydrated to obtain forms α and δ. ε-Form can be only obtained by dehydrating δ-form. Amongst them, γ-form is the most stable and is resistant to high humidity levels.[47]
Based upon animal-model studies,bioavailability (Cmax,tmax,AUC0-24, AUC∞) increases in the following order: β, α, ε, δ, γ.[47] Thus, structures with lower bioavailability exert their antimicrobial activity more locally in the gastrointestinal tract, whereas δ- and γ-forms are more suitable for systemic treatment[47] (however the problem with cross-resistance with rifampicin inMycobacterium tuberculosis might lead to multidrug-resistant strain selection[50]).
^abcPonziani FR, Pecere S, Lopetuso L, Scaldaferri F, Cammarota G, Gasbarrini A (July 2016). "Rifaximin for the treatment of irritable bowel syndrome - a drug safety evaluation".Expert Opinion on Drug Safety.15 (7):983–991.doi:10.1080/14740338.2016.1186639.PMID27149541.S2CID25426888.
^Triantafyllou K, Sioulas AD, Giamarellos-Bourboulis EJ (2015). "Rifaximin: The Revolutionary Antibiotic Approach for Irritable Bowel Syndrome".Mini Reviews in Medicinal Chemistry.16 (3):186–192.doi:10.2174/1389557515666150722105340.PMID26202193.
^Weinstock LB, Steinhoff M (May 2013). "Rosacea and small intestinal bacterial overgrowth: prevalence and response to rifaximin".Journal of the American Academy of Dermatology.68 (5):875–876.doi:10.1016/j.jaad.2012.11.038.PMID23602178.
^Hoffman JT, Hartig C, Sonbol E, Lang M (May 2011). "Probable interaction between warfarin and rifaximin in a patient treated for small intestine bacterial overgrowth".The Annals of Pharmacotherapy.45 (5): e25.doi:10.1345/aph.1P578.PMID21505109.S2CID12214785.
^Noeske J, Nguenko PN (July 2002). "Impact of resistance to anti-tuberculosis drugs on treatment outcome using World Health Organization standard regimens".Transactions of the Royal Society of Tropical Medicine and Hygiene.96 (4):429–433.doi:10.1016/S0035-9203(02)90383-4.PMID12497982.
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