RIFAXIM

Indications

• Irritable bowel syndrome with diarrhea (IBS-D)
• Hepatic encephalopathy
• Traveler's diarrhea
• Non-tuberculous mycobacterial disease (in combination with other drugs)

Dosage

Children: Refer to the BNF for Children for specific pediatric dosing information, as this may vary based on the condition being treated.

Adults: For hepatic encephalopathy, the adult dose is 550 mg orally 3 times daily. For IBS-D, the recommended dose is 200 mg orally 3 times daily for 14 days. For traveler's diarrhea, the usual dose is 200 mg orally 3 times a day for 3 days.

Mechanism of action

Rifaximin inhibits RNA synthesis in susceptible bacteria by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase. This binding prevents transcription by blocking translocation, thereby halting bacterial growth.

Pharmacodynamics

As a structural analog of rifampin, rifaximin is a gastrointestinal site-specific antibiotic, which is a result of its non-absorbable nature due to the pyridoimidazole ring addition. It not only inhibits bacterial RNA synthesis but also aids in restoring intestinal microflora balance. Furthermore, rifaximin has been shown to activate the pregnane X receptor (PXR), which can inhibit the pro-inflammatory transcription factor NF-kappa B, suggesting a role in managing inflammatory bowel disease.

Pharmacokinetics

Rifaximin is minimally absorbed from the gastrointestinal tract, leading to high local concentrations in the gut while systemic absorption is negligible. This pharmacokinetic profile allows for effective treatment of localized infections without significant systemic exposure. The drug is primarily excreted in the feces, with minimal renal excretion.

Contra-indications

• Hypersensitivity to rifaximin or any of its components
• Severe hepatic impairment
• Intestinal obstruction

Adverse effects

• Nausea
• Vomiting
• Malaise
• Jaundice
• Abdominal pain
• Constipation
• Flatulence
• Headache
• Dizziness
• Fatigue
• Skin reactions
• Urine discolouration
• Uveitis
• Neutropenia
• Thrombocytopenia
• Respiratory disorders
• Muscle weakness

Interactions

• Ciclosporin (may increase exposure to rifaximin)
• Drugs that increase plasma concentration of rifaximin

Precautions

• Caution in patients with hepatic impairment
• Monitor for signs of liver disorder
• Caution in patients with renal impairment
• Use with caution in patients with a history of acute porphyrias

Pregnancy

Manufacturer advises caution; safety has not been established in pregnant women.

Breast-feeding

Manufacturer advises avoiding use during breastfeeding due to insufficient information.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension

Mechanism of action

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. This binding blocks translocation, which stops transcription.

Pharmacodynamics

Rifaximin is a structural analog of rifampin and a non-systemic, gastrointestinal site-specific antibiotic. This non-systemic property of the drug is due to the addition of a pyridoimidazole ring, which renders it non-absorbable. Rifaximin acts by inhibiting bacterial ribonucleic acid (RNA) synthesis and contributes to restore intestinal microflora imbalance. Other studies have also shown rifaximin to be an pregnane X receptor (PXR) activator. As PXR is responsible for inhibiting the proinflammatory transcription factor NF-kappa B (NF-κB) and is inhibited in inflammatory bowel disease (IBD), rifaximin was proven to be effective for the treatment of IBS-D.