Rifaximin, is a non-absorbable, broad spectrum antibiotic mainly used to treat travelers' diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in over more than 30 countries for the treatment of a variety of gastrointestinal diseases like irritable bowel syndrome, and hepatic encephalopathy. It acts by inhibiting RNA synthesis in susceptible bacteria by binding to the RNA polymerase enzyme. This binding blocks translocation, which stops transcription.[4] It is marketed under the brand name Xifaxan by Salix Pharmaceuticals.[5]
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Clinical data | |
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Trade names | Xifaxan, Zaxine, Xifaxanta, Normix, others[1] |
AHFS/Drugs.com | Monograph |
MedlinePlus | a604027 |
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Routes of administration | By mouth |
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Pharmacokinetic data | |
Bioavailability | < 0.4% |
Metabolism | Liver |
Elimination half-life | 6 hours |
Excretion | Fecal (97%) |
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ECHA InfoCard | 100.111.624 |
Chemical and physical data | |
Formula | C43H51N3O11 |
Molar mass | 785.891 g·mol−1 |
3D model (JSmol) | |
Melting point | 200 to 205 °C (392 to 401 °F) (dec.) |
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Medical uses
editTravelers' diarrhea
editRifaximin is used to treat travelers' diarrhea (TD) caused by E. coli bacteria in adults and children at least 12 years of age. 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.[6]
Irritable bowel syndrome
editRifaximin is used for the treatment of irritable bowel syndrome (IBS). 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 IBS.[7] It appears to retain its therapeutic properties for this indication, even after repeated courses.[8][9] It 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.[9][10]
Clostridioides difficile infection
editRifaximin may also be a useful addition to vancomycin when treating patients with relapsing C. difficile infection (CDI).[11][12] However, the quality of evidence of these studies was judged to be low.[13] Because exposure to rifamycins in the past may increase risk for resistance, rifaximin should be avoided in such cases.[14]
Hepatic encephalopathy
editRifaximin is used to prevent episodes of hepatic encephalopathy (changes in thinking, behavior, and personality caused by a build-up of toxins in the brain in people who have liver disease) in adults who have liver disease. It treats hepatic encephalopathy (HE) by stopping the growth of bacteria that produce toxins and that may worsen the liver disease. Although high-quality evidence is still lacking, it 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.[10][15] 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.[16] The drawbacks are increased cost, and lack of robust clinical trials for HE without combination lactulose therapy.[17]
Other uses
editOther uses include treatment of: infectious diarrhea, small intestinal bacterial overgrowth, inflammatory bowel disease, and diverticular disease.[18][10][19][20] It is effective in treating small intestinal bacterial overgrowth regardless of whether it is associated with irritable bowel syndrome or not.[21] It 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).[22]
Special caution
editPatients should avoid rifaximin if they are allergic to any of rifabutin, rifampin, and rifapentine. It may cause attenuated vaccines (such as typhoid vaccine) not to work well. Health-care professionals should be informed about its usage before receiving immunization.[23] Pregnant or breastfeeding women should avoid rifaximin: it is a pregnancy category C drug and can harm the fetus.[24] Caution is required in persons with cirrhosis who have a Child–Pugh score of C.[10]
Side effects
editRifaximin has an excellent safety profile due to its lack of systemic absorption. Clinical trials did not show any serious adverse events while using the drug. There were no deaths while using it in the clinical trials.[8][9][25]
The most common side effects includes nausea, stomach pain, dizziness, fatigue, headaches, muscle tightening and joint pain. It may also cause reddish discoloration of urine.[26]
The most serious side effects of rifaximin are:
- Clostridioides difficile-associated diarrhea (CDAD)
- Drug-resistant bacterial superinfection
- Severe allergic reactions including hives, rashes and itching
Interactions
editAs rifaximin is not significantly absorbed from the gut, the great majority of these drug interactions are negligible in people with healthy liver function, so healthcare providers usually do not worry about drug interactions unless liver impairment is present.[8] It may decrease the effectiveness of warfarin, a commonly prescribed anticoagulant, in people with liver problems.[27]
Pharmacology
editRifaximin is a semisynthetic broad spectrum antibacterial drug, derived through chemical modification of the natural antibiotic rifamycin.[28] 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, and most of the drug taken orally stays in the gastrointestinal tract where the infection takes place.[29]
Mechanism of action
editRifaximin interferes with transcription by binding to the
Availability
editIn the United States, Salix Pharmaceuticals holds a US Patent for rifaximin and markets the drug under the name Xifaxan.[33] In addition to receiving FDA approval for travelers' diarrhea and (marketing approved for)[34] hepatic encephalopathy, rifaximin received FDA approval for IBS in May 2015.[35] 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.[34] 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.[36]
Rifaximin is approved in 33 countries for GI disorders.[37] On 13 August 2013, Health Canada issued a Notice of Compliance to Salix Pharmaceuticals Inc. for the drug product Zaxine.[38] In India, it is available under the brand names Ciboz and Xifapill.[39][40] 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).[41] In 2018, the FDA approved a similar drug by Cosmos Pharmaceuticals called Aemcolo for traveler's diarrhea.[42]
References
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- ^ "Rifaximin". go.drugbank.com. Retrieved 26 June 2022.
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- ^ Kane JS, Ford AC (2016). "Rifaximin for the treatment of diarrhea-predominant irritable bowel syndrome". Expert Review of Gastroenterology & Hepatology. 10 (4): 431–442. doi:10.1586/17474124.2016.1140571. PMID 26753693. S2CID 13607138.
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- ^ Johnson S, Schriever C, Galang M, Kelly CP, Gerding DN (March 2007). "Interruption of recurrent Clostridium difficile-associated diarrhea episodes by serial therapy with vancomycin and rifaximin". Clinical Infectious Diseases. 44 (6): 846–848. doi:10.1086/511870. PMID 17304459.
- ^ Garey KW, Ghantoji SS, Shah DN, Habib M, Arora V, Jiang ZD, et al. (December 2011). "A randomized, double-blind, placebo-controlled pilot study to assess the ability of rifaximin to prevent recurrent diarrhoea in patients with Clostridium difficile infection". The Journal of Antimicrobial Chemotherapy. 66 (12): 2850–2855. doi:10.1093/jac/dkr377. PMID 21948965.
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- ^ Lawrence KR, Klee JA (August 2008). "Rifaximin for the treatment of hepatic encephalopathy". Pharmacotherapy. 28 (8): 1019–1032. doi:10.1592/phco.28.8.1019. PMID 18657018. S2CID 25662917. Free full text with registration at Medscape.
- ^ Kimer N, Krag A, Gluud LL (March 2014). "Safety, efficacy, and patient acceptability of rifaximin for hepatic encephalopathy". Patient Preference and Adherence. 8: 331–338. doi:10.2147/PPA.S41565. PMC 3964161. PMID 24672227.
- ^ Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, et al. (August 2014). "Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver". Hepatology. 60 (2): 715–735. doi:10.1002/hep.27210. PMID 25042402. S2CID 3155213.
- ^ Piccin A, Gulotta M, di Bella S, Martingano P, Crocè LS, Giuffrè M (February 2023). "Diverticular Disease and Rifaximin: An Evidence-Based Review". Antibiotics. 12 (3): 443. doi:10.3390/antibiotics12030443. PMC 10044695. PMID 36978310.
- ^ Bianchi M, Festa V, Moretti A, Ciaco A, Mangone M, Tornatore V, et al. (April 2011). "Meta-analysis: long-term therapy with rifaximin in the management of uncomplicated diverticular disease". Alimentary Pharmacology & Therapeutics. 33 (8): 902–910. doi:10.1111/j.1365-2036.2011.04606.x. PMID 21366632.
- ^ Kruse E, Leifeld L (April 2015). "Prevention and Conservative Therapy of Diverticular Disease". Viszeralmedizin. 31 (2): 103–106. doi:10.1159/000377651 (inactive 1 July 2024). PMC 4789966. PMID 26989379.
{{cite journal}}
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