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Rifaximin

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Information about Rifaximin

Rifaximin is a nonabsorbable antibiotic that is used as treatment and prevention of travelers’ diarrhea and, in higher doses, for prevention of hepatic encephalopathy in patients with advanced liver disease and to treat diarrhea in patients with irritable bowel syndrome.

Rifaximin
Rifaximin

Liver safety of Rifaximin

Rifaximin has minimal oral absorption and has not been implicated in causing liver test abnormalities or clinically apparent liver injury.

FDA approval information for Rifaximin

Rifaximin (rif ax' i min) is a synthetic antibiotic and derivative of rifamycin specifically designed to have minimal gastrointestinal absorption (<0.4%). It is a broad spectrum antibiotic with activity against both aerobic and anaerobic organisms, both gram negative and gram positive. The antibiotic activity of rifaximin is attributed to its binding to bacterial RNA polymerases, preventing RNA and subsequent protein synthesis.

Clinical use of Rifaximin

Rifaximin was approved for use as treatment and means of preventing travelers’ diarrhea in 2004. In 2009, the indications were expanded to include prevention of hepatic encephalopathy in patients with cirrhosis and in 2015 to treat diarrhea in patients with irritable bowel syndrome.

Dosage and administration for Rifaximin

Rifaximin is available as tablets of 200 mg under the brand name of Xifaxan for traveler’s diarrhea (recommended dose being 200 mg thrice daily for 3 days) and as tablets of 550 mg under the brand name Xifaxan 550 for hepatic encephalopathy (recommended dose being 550 mg twice daily usually in combination with lactulose) and diarrhea-predominant irritable bowel syndrome (recommended dose being 550 mg 3 times daily for 14 days).

Side effects of Rifaximin

Side effects include peripheral edema, nausea, dizziness, fatigue, muscle spasms and gastrointestinal upset. Long term use has been associated with fungal or bacterial super-infections including C. difficile associated diarrhea.

Antidiarrheal agents

Antidiarrheal agents include bulk forming agents, hydroscopic agents, bile acid resins, bismuth, inhibitors of intestinal motility, non-absorbed antibiotics and hormones. Bulk forming agents include methylcellulose; hydroscopic agents include pectin and kaolin; bile acid resins are cholestyramine, colestipol and colesevalam; inhibitors of intestinal motility include opioids such as diphenoxylate and loperamide. Antibiotics include rifamycin and rifaximin which are non-absorbed and are used for travelers' diarrhea. Hormones with antidiarrheal activity include octretide and somatostatin. Most antidiarrheal agents are active locally in the small intestine and colon and are largely not absorbed. Some, however, have been implicated in rare causes of liver injury (senna, cascara, cholestyramine). Telotristat is a relatively new agent that inhibits the synthesis of serotonin and is used specifically for the diarrhea of carcinoid syndrome.

Antiemetics are a diverse group of medications that act at different points in the pathways that regulate nausea and vomiting. These include antihistamines, anticholinergic agents, phenothiazines, serotonin type 3 receptor blockers, centrally acting benzamides, cannabinoid receptor agonists, substance P antagonists and miscellaneous.

Anticholinergic Agents

Antihistamines

Cannabinoid Receptor Agonists

Serotonin 5-HT3 Receptor Antagonists

Substance P/Neurokinin 1 Receptor Antagonists

Miscellaneous

Acid peptic disease/antiulcer agents that include antacids, the histamine type 2 receptor blockers (H2 blockers), and the proton pump inhibitors (PPIs). These agents are some of the most commonly taken medications and are very well tolerated, most being available both by prescription and over-the-counter. While many of these drugs are approved for use in duodenal and gastric ulcer disease, their major use is for acid reflux and indigestion.

Histamine H2 Receptor Antagonists (H2 Blockers) Cimetidine, Famotidine, Nizatidine, Ranitidine

Proton Pump Inhibitors

Cathartics, laxatives or agents for constipation include bulk forming agents, osmotic agents, stool wetting agents, nonspecific stimulants, prokinetic agents and agents that increase fluid secretion. Many of these therapies are not systemically absorbed and none are considered particularly hepatotoxic. Naldemedine and naloxegol are opioid antagonists and are used to treat the constipation associated with opioid use.

Inflammatory bowel disease encompasses several disorders, most commonly ulcerative colitis and Crohn colitis. Agents can be classified as 5-aminosalicyclic acid (5-ASA) based agents, immunosuppressive drugs, antitumor necrosis factor agents, corticosteroids, antibiotics and miscellaneous.

5-Aminosalicyclic Acid (5-ASA) Derivatives

Immunosuppressive Agents

Tumor Necrosis Factor Antagonists

Miscellaneous

Irritable Bowel Syndrome Agents Antimuscarinics/Antispasmodics [See Anticholinergic agents

Prokinetic Agents - See Serotonin 5-ht4 receptor agonists Alosetron, Cisapride, Domperidone, Linaclotide, Lubiprostone, Metoclopramide, Plecanatide, Prucalopride, Tegaserod

Other

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