Rifaximin – Uses, Dosage, Side Effects, Interactions

Rifaximin is an orally administered, semi-synthetic, nonsystemic antibiotic derived from rifamycin SV with antibacterial activity. Rifaximin binds to the beta-subunit of bacterial DNA-dependent RNA polymerase, inhibiting bacterial RNA synthesis and bacterial cell growth. As rifaximin is not well absorbed, its antibacterial activity is largely localized to the gastrointestinal tract.

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

Mechanism of Action of Rifaximin

Rifaximin acts by inhibiting RNA synthesis in susceptible bacteria by binding to the beta-subunit of bacterial deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase enzyme.  Rifaximin binds to the beta-subunit of bacterial DNA-dependent RNA polymerase, inhibiting bacterial RNA synthesis and bacterial cell growth. As rifaximin is not well absorbed, its antibacterial activity is largely localized to the gastrointestinal tract. This binding blocks translocation, which stops transcription.

Rifaximin interferes with transcription by binding to the β-subunit of bacterial RNA polymerase.[9] 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 bacterial 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.[9] A resetting of the bacteria composition has also been suggested as a possible mechanism of action for the relief of IBS symptoms.[10] 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.[rx]

Indications of Rifaximin

  • Rifaximin has multiple indications by the FDA: for the treatment of patients (≥12 years of age) with traveler’s diarrhea caused by noninvasive strains of Escherichia coli; for the reduction of overt hepatic encephalopathy recurrence in patients ≥18 years of age; and in May 2015 it was approved for irritable bowel syndrome with diarrhea (IBS-D) treatment in adult men and women.
  • Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion
  • Bacterial Infections
  • Clostridium difficile infection recurrence
  • Hepatic Encephalopathy
  • Irritable Bowel Syndrome (IBS)
  • Travelers’ Diarrhea
  • 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.

Contraindications of Rifaximin

  • Are allergic to rifaximin or any ingredients of the medication
  • Are allergic to any other rifamycin antibacterial medications
  • Rifamycin hypersensitivity.
  • Colitis, diarrhea, dysentery, fever, GI bleeding, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis.
  • Pregnancy.
  • Breast-feeding.
  • Children, infants, neonates.
  • Geriatric.
  • Hepatic disease.

Dosage of Rifaximin

Strengths: 550 mg; 200 mg

Traveler’s Diarrhea

  • 200 mg orally 3 times a day for 3 days

Hepatic Encephalopathy

  • 550 mg orally twice a day

Irritable Bowel Syndrome

  • 550 mg orally 3 times a day for 14 days

Pediatric Dose for Traveler’s Diarrhea

  • 12 years or older: 200 mg orally 3 times a day for 3 days

Side Effects of Rifaximin

More common

  • abdominal pain
  • muscle spasms
  • signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
  • signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
  • signs of a severe allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
  • skin rash
  • Black, tarry stools
  • dizziness or lightheadedness
  • muscle spasm
  • rapid breathing
  • shortness of breath
  • trouble sleeping
  • lower back or side pain
  • muscle pain or stiffness
  • pain in the joints
  • stomach pain
  • straining while passing stool
  • swelling of the hands, ankles, feet, or lower legs

Common

  • Blood in the urine
  • bloody nose
  • chest pain
  • bloating
  • diarrhea (mild)
  • dizziness
  • headache
  • itchiness
  • nausea
  • reddish color to sweat, urine or tears
  • continuing ringing or buzzing or other unexplained noise in the ears
  • fainting
  • the feeling of constant movement of self or surroundings
  • increased heart rate
  • sensation of spinning
  • sunken eyes
  • ulcers, sores, or white spots in the mouth
  • unusual bleeding or bruising
  • unusual tiredness or weakness

Rare

  • signs of bowel inflammation (e.g., fever that appears after starting the medication, watery and severe diarrhea [may also be bloody])
  • Cracks in the skin
  • hives or welts, itching skin, or rash
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of heat from the body
  • red, swollen skin
  • redness of the skin
  • scaly skin


Drug Interactions of Rifaximin

Rifaximin may interact with following drugs, supplements, & may change the efficacy of drugs

  • BCG vaccine
  • cyclosporine
  • sodium picosulfate
  • warfarin
  • spironolactone
  • amoxicillin
  • amoxicillin/clavulanate
  • diphenhydramine
  • Fish Oil (omega-3 polyunsaturated fatty acids)
  • metronidazole
  • ibuprofen
  • loperamide
  • lactulose
  • furosemide
  • neomycin
  • esomeprazole
  • acetaminophen
  • pantoprazole
  • rifampin
  • levothyroxine
  • Vitamin B12 (cyanocobalamin)
  • Vitamin C (ascorbic acid)
  • Vitamin D3 (cholecalciferol)
  • Voltaren Gel (diclofenac topical)
  • alprazolam
  • ondansetron
  • sertraline
  • cetirizine

Pregnancy Category of Rifaximin

FDA Pregnancy Category – C

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding

It is not known if rifaximin passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding. The safety and effectiveness of using this medication have not been established for children.

References

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