|Trade names||Xifaxan, Xifaxanta, Normix, others|
|Main uses||Hepatic encephalopathy, irritable bowel syndrome, traveler's diarrhea|
|Side effects||Nausea, headache, abdominal discomfort|
|Elimination half-life||6 hours|
|Chemical and physical data|
|Molar mass||785.891 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Rifaximin, sold under the trade name Xifaxan among others, is an antibiotic used to treat hepatic encephalopathy, irritable bowel syndrome, and traveler's diarrhea. Specifically it can be used to decrease the number of episodes of hepatic encephalopathy. It is not effective for a number of types of diarrhea including Salmonella. It is taken by mouth.
Common side effects include nausea, headache, and abdominal discomfort. Other side effects may include joint pain, mood changes, swelling, skin rash, and Clostridium difficile colitis. Use in pregnancy is not recommended while use during breastfeeding is believed to be safe for the baby. It is in the rifamycin family of medications.
Rifaximin was approved for medical use in the United States in 2004. In United States the dose for hepatic encephalopathy costs $1,864 per month as of January 2017. In the UK, 56 tablets of the 550mg dose costs the NHS around 260 pounds as of 2020. As of 2020 no generic version is available in the United States.
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.
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 additionally, it 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.
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. Although exposure to rifamycins in the past may increase risk for resistance, so rifaximin should be avoided in such cases.
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.
The recommended dose in hepatic encephalopathy is 550 mg two times per day while for traveler's diarrhea 200 mg three times per day for three days is used.
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 Clostridium difficile.
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.
Rifaximin is a semisynthetic broad spectrum antibacterial drug, that 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.
Society and culture
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 traveler's 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 United States the dose for hepatic encephalopathy costs $1,864 per month as of January 2017. This amount in the United Kingdom costs the NHS about 260 pounds as of 2020. In Russia, as of 2016, a daily dose costs 231.25 RUB (approximately US$4), Colombia as 2019, it is 6286 COP (approximately US $2). A course of treatment for travelers diarrhea in the UK costs about 15 pounds.
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