Rifaximin
Rifaximin, sold under the brand name Xifaxan (USA) and Zaxine (Canada) among others, is an antibiotic medication used to treat travelers' diarrhea, irritable bowel syndrome, and hepatic encephalopathy. It has poor absorption when taken by mouth. It is based on rifamycin. Rifaximin was approved for medical use in the United States in May 2004. Medical uses. Rifaximin is indicated in the United States for the treatment of irritable bowel syndrome in adults, travelers' diarrhea in those age 12 and older, and reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults. Irritable bowel syndrome. Rifaximin is approved in  the United States for the treatment of irritable bowel syndrome. It possesses anti-inflammatory and antibacterial properties, and is a nonabsorbable antibiotic that acts locally in the gut. These properties make it efficacious in relieving chronic functional symptoms of non-constipation type irritable bowel syndrome (IBS). It appears to retain its therapeutic properties for this indication, even after repeated courses. Rifaximin is particularly indicated where small intestine bacterial overgrowth is suspected of involvement in a person's IBS. Symptom relief or improvement can be obtained for global IBS symptoms, including: abdominal pain, flatulence, bloating, and stool consistency. A drawback is  that repeated courses may be necessary for relapse of symptoms. There is evidence that rifaximin can be curative in some people with IBS. Section::::"C. difficile" infection. Rifaximin may also be a useful addition to vancomycin when treating patients with relapsing "C. difficile" infection. However, the quality of evidence of these studies was judged to be low. Because exposure to rifamycins in the past may increase risk for resistance, rifaximin should be avoided in such cases. Hepatic encephalopathy. In the United States, rifaximin has orphan drug status for the treatment of hepatic encephalopathy. 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. Rifaximin is taken by mouth. It has minimal side effects, 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. It reduces the levels of intestinal ammonia-producing bacteria, thus alleviating the symptoms of hepatic encephalopathy and reducing mortality. The drawbacks to rifaximin are increased cost, and lack of robust clinical  trials for HE without combination lactulose therapy. Other uses. Other uses include treatment of: infectious diarrhea, small intestinal bacterial overgrowth, inflammatory bowel disease, and diverticular disease. Rifaximin is effective in treating small intestinal bacterial overgrowth regardless of whether it is associated with irritable bowel syndrome or not. Rifaximin has also shown efficacy with rosacea, ocular rosacea which also presents as dry eyes for patients with co-occurrence with small intestinal bacterial overgrowth (SIBO). Special caution. Cautious use is required in individuals with cirrhosis of the liver who have a Child-Pugh score of class C severity. Side effects. Rifaximin has  few side effects. Side effects are generally mild and uncommon; this is largely because very little of the drug is absorbed from the gut, meaning systemic side effects are absent. "Clostridium difficile" infection does not typically result from rifaximin therapy, unless risk factors such as immunosuppression and hospitalisation are present. Rifaximin is active against "C. difficile". Side effects may include the following and doctor should be contacted if they become severe or don't "go away": nausea, stomach pain, dizziness, excessive tiredness, headache, muscle tightening, joint pain. Doctor should be contacted immediately in case of occurrence of serious side effects : Interactions. Rifaximin is not significantly absorbed from the gut, and therefore does not have much significant interactions with other drugs in people with normal liver function. Pharmacology. Rifaximin is a semisynthetic broad spectrum antibacterial drug, derived through chemical modification of the natural antibiotic rifamycin by the Italian company Alfa Farmaceutici. It has very low bioavailability due to its poor absorption after oral administration. Because of this local action within the gut and the lack of horizontal transfer of resistant genes, the development of bacterial resistance is rare. Because of this poor absorption, most of the drug taken orally stays in  the gastrointestinal tract where the infection takes place. However, due to drug polymorphisms and differences between crystalline and amorphous forms of the compounds, certain generic drug versions are more readily absorbable than the original brand name version. 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. This in turn results in a reduction of bacteria populations, including gas-producing bacteria, which may reduce mucosal inflammation, epithelial dysfunction , and visceral hypersensitivity. Rifaximin has broad spectrum antibacterial properties against both gram positive and gram negative anaerobic and aerobic bacteria. As a result of bile acid solubility, its antibacterial action is limited mostly to the small intestine and less so the colon. A resetting of the bacteria composition has also been suggested as a possible mechanism of action for relief of IBS symptoms. Additionally, rifaximin may have a direct anti-inflammatory effect on gut mucosa via modulation of the pregnane X receptor. Other mechanisms for its therapeutic properties include inhibition of bacterial translocation across the epithelial lining of the intestine , inhibition of adherence of bacteria to the epithelial cells, and a reduction in the expression of proinflammatory cytokines. Availability. In the United States, Salix Pharmaceuticals holds a US Patent for rifaximin and markets the drug under the name Xifaxan. In addition to receiving FDA approval for travelers' diarrhea and (marketing approved for) hepatic encephalopathy, rifaximin received FDA approval for IBS in May 2015. 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 March 24, 2017. In 2018, a patent dispute with Teva was settled which delayed a generic in the United States, with the patent set to expire in 2029. Rifaximin is approved in 33 countries for GI disorders. On August 13, 2013, Health Canada issued a Notice of Compliance to Salix Pharmaceuticals Inc. for the drug product Zaxine. In India it is available under the brand names Ciboz and Xifapill. In Russia and Ukraine the drug is sold under the name Alfa Normix (Альфа Нормикс), produced by Alfa Wassermann S.p .A. (Italy). In 2018, the FDA approved a similar drug by Cosmos Pharmaceuticals called Aemcolo for traveler's diarrhea.