Rifaximin

BRAND NAMES

• Rifaximin is an antibiotic sold globally under various brand names.

• In the United States, its most commonly known brand name is Xifaxan.

• In other countries, especially India, it is marketed under several additional names, including:

• Alfa Normix

• Ciboz

• Flonorm

• Rafle

• Rcifax

• Rifacare

MECHANISM OF ACTION

Rifaximin works by blocking RNA synthesis in susceptible bacteria. It does this by attaching to the beta subunit of the DNA-dependent RNA polymerase enzyme, preventing translocation and thereby halting the transcription process.

PHARMACOKINETICS:

Absorption

Rifaximin is an oral antibiotic that is absorbed only minimally, with under 0.4% of the dose reaching the systemic circulation. This extremely low absorption is an important pharmacological characteristic, enabling the drug to work primarily and effectively within the gastrointestinal (GI) tract.

Distribution

Rifaximin's distribution is unique because it is a poorly-absorbed, non-systemic antibiotic that acts locally within the gastrointestinal (GI) tract. Very little of the drug enters the bloodstream, and most is excreted unchanged in the feces. 

Metabolism

The small amount of absorbed rifaximin is primarily metabolized by the liver enzyme CYP3A4.

Excretion

Nearly all (around 97%) of the administered dose is excreted in the feces, predominantly as the unchanged drug. Urinary recovery is minimal, typically less than 0.4%.

PHARMACODYNAMICS

Rifaximin is a structural analog of rifampin and functions as a non-systemic, gut-targeted antibiotic. Its lack of systemic absorption results from the addition of a pyridoimidazole ring, which makes the compound non-absorbable. Rifaximin works by inhibiting bacterial RNA synthesis and helps correct imbalances in the intestinal microbiota. Research has also shown that rifaximin activates the pregnane X receptor (PXR). Because PXR suppresses the pro-inflammatory transcription factor NF-κB—whose activity is reduced in inflammatory bowel disease (IBD)—rifaximin has been found to be effective in treating IBS-D.

ADMINISTRATION

Rifaximin is an antibiotic administered orally, with or without food, in tablet form. The specific dosage and duration of treatment vary depending on the condition being treated, as it is designed to act locally within the gastrointestinal tract

DOSAGE AND STRENGTH

Rifaximin (brand name Xifaxan) is an antibiotic available in 200 mg and 550 mg oral tablets. The dosage and strength used depend on the specific medical condition being treated, as prescribed by a healthcare provider. 

Rifaximin Dosages and Strengths

Typical adult dosage regimens for rifaximin vary based on the condition being treated. 

• For Traveler's Diarrhea caused by noninvasive E. coli, the recommended dosage is one 200 mg tablet taken three times a day for 3 days. This is not for diarrhea with fever or blood in the stool.

• To reduce the risk of Hepatic Encephalopathy recurrence, the usual dose is one 550 mg tablet taken twice daily, often as a long-term treatment

DRUG INTERACTIONS

Rifaximin generally has a low risk of drug interactions because very little of it enters systemic circulation. Nonetheless, important interactions may still occur with specific medications, especially those that influence the P-glycoprotein (P-gp) efflux transporter or drugs that require careful monitoring, such as warfarin and cyclosporine.

FOOD INTERACTIONS

Rifaximin has no known significant interactions with food in most individuals and can be taken with or without meals. However, there is a potential interaction with grapefruit or its juice. 

CONTRAINDICATIONS

• Patients who are hypersensitive to rifaximin, other rifamycins, or any of the drug’s excipients should avoid using this medication, as serious allergic reactions—including exfoliative dermatitis, angioedema, and anaphylaxis—have been reported.

• Coadministration with P-glycoprotein (P-gp) inhibitors such as cyclosporine can markedly increase systemic exposure to rifaximin, which may result in toxicity.

• Severe hepatic impairment: Patients with significant liver dysfunction may experience elevated systemic levels of rifaximin. Because clinical studies included only those with MELD scores below 25, caution is advised when prescribing rifaximin to individuals with severe hepatic impairment (Child-Pugh Class C).

SIDE EFFECTS

• Gastrointestinal symptoms: Includes gas (flatulence), stomach or abdominal pain, nausea, vomiting, constipation, and a sudden urge to have a bowel movement.

• Neurological symptoms: May present as headache, dizziness, or fatigue (extreme tiredness).

• Musculoskeletal symptoms: Can include muscle spasms, cramps, and joint pain.

• Other symptoms: May involve swelling of the hands, feet, or ankles (edema), fever, and skin reactions such as rash or itching.

OVER DOSE

In case of a rifaximin overdose, you should immediately seek emergency medical attention or call a poison control center. Rifaximin is poorly absorbed into the bloodstream, and symptoms from high doses are generally similar to its usual side effects, but medical guidance is essential.

TOXICITY

Rifaximin is associated with a very low risk of systemic toxicity due to its minimal absorption after oral administration, with typically less than 0.4% entering the bloodstream. This limited systemic exposure reduces the likelihood of systemic side effects and drug interactions in most patients.