Rifaximin binds to bacterial DNA-dependent RNA polymerase resulting in the inhibition of bacterial RNA synthesis. It is a gut-antiseptic that clears the intestines of bacterial overgrowth especially in patients with liver disease, malabsorption, IBS, and diabetes.

Rifaximin (Xifaxan) Uses (Indications):

• Hepatic encephalopathy:

  • It is used in the reduction in the risk of overt hepatic encephalopathy recurrence in adults

• Irritable bowel syndrome with diarrhea:

  • It is used for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults

• Traveler's diarrhea:

  • It is used for the treatment of traveler's diarrhea caused by noninvasive strains of E. coli in adults and pediatric patients ≥12 years of age
  •  Rifaximin should not be used in patients having diarrhea complicated by fever or blood in the stool or diarrhea caused by pathogens other than E. coli.

• Off Label Usage of Rifaximin in Adults:

  • Recurrence of Clostridioides difficile infection.
  • Treatment of Overt hepatic encephalopathy episodes

Read: Linaclotide (Linzess) for IBS

Rifaximin (Xifaxan) Dose in Adults

Off label Dosage in the treatment of Clostridioides (formerly Clostridium) difficile infection (second or subsequent recurrence):

• Orally 400 mg 3 times daily is given for 20 days
• Give after a standard course of oral vancomycin

Rifaximin (Xifaxan) Dose in the treatment of Hepatic encephalopathy:

• Reduction of overt hepatic encephalopathy recurrence:
  • 550 mg 2 times daily is given.

Rifaximin (Xifaxan) Off label dosage in the treatment of hepatic encephalopathy:

• 400 mg is given every 8 hours for 5 to 10 days

Rifaximin (Xifaxan) Dose in the treatment of Irritable bowel syndrome with diarrhea (IBS-D):

• Orally 550 mg 3 times daily is given for 14 days
• It may be retreated up to 2 times with the same dosing regimen if symptoms recur.

Rifaximin (Xifaxan) Dose in the treatment of Traveler's diarrhea:

• Orally 200 mg 3 times is given daily for 3 days

Rifaximin (Xifaxan) Dose in Children:

Rifaximin (Xifaxan) Dose in the treatment of Travelers' Diarrhea:

• Consider alternative medication if symptoms persist or worsen after 24 to 48 hours of treatment.

• Children 3 to 11 years:

  • 100 mg 4 times daily is given for up to 5 days has been used in 38 children (age range: 3 to 8 years) to treat infectious diarrhea

• Children ≥12 years and Adolescents:

  • 200 mg 3 times is given daily for 3 days

Rifaximin dose in the treatment of Hepatic encephalopathy:

• Adolescents ≥18 years:
  • For reduction of overt hepatic encephalopathy recurrence, the dose is  550 mg 2 times daily

Rifaximin (Xifaxan) Dosage in the treatment of Inflammatory bowel disease (IBD) (Crohn disease and ulcerative colitis):

• Children ≥8 years and Adolescents:
  • 10 to 30 mg/kg/day is given in divided doses
  • The maximum daily dose is 1200 mg/day

Rifaximin (Xifaxan) Dose in the treatment of small intestinal bacterial overgrowth (SIBO) (eg, irritable bowel syndrome [IBS] and chronic abdominal pain):

• Children ≥3 years and Adolescents:
  • 200 mg 3 times daily is given,

Pregnancy Risk Factor: C

• Some animal reproduction studies have shown adverse events.
• The fetus' exposure to rifaximin is likely to be low due to its limited oral absorption in patients with normal liver function.

Rifaximin use during breastfeeding:

• It is unknown if the drug is found in human milk.
• According to the manufacturer breast-feeding during therapy is a decision that should be made after considering the risks to the infant as well as the benefits to the mother.
• Due to the low oral absorption of rifaximin by patients with normal hepatic function it is unlikely that the infant will be exposed to it.

Rifaximin dose in Kidney disease:

• There are no dosage adjustments given in the manufacturer’s labeling (has not been studied).

Rifaximin dose in Liver disease:

• No dosage adjustment required.
• Use cautiously in severe impairment (Child-Pugh class C).
• However, systemic absorption is limited and pharmacokinetic parameters are highly variable.

• The frequency of side effects is generally higher after the treatment for hepatic encephalopathy (HE).

Common Side Effects of Rifaximin:

• Cardiovascular:

  • Peripheral Edema

• Central Nervous System:

  • Dizziness
  • Fatigue

• Hepatic:

  • Ascites

• Gastrointestinal:

  • Nausea

Less Common Side Effects of Rifaximin (Xifaxan):

• Central Nervous System:

  • Headache
  • Depression

• Dermatological:

  • Pruritus
  • Skin Rash

• Gastrointestinal:

  • Abdominal Pain
  • Pseudomembranous Colitis

• Hematologic & Oncologic:

  • Anemia

• Hepatic:

  • Increased Serum ALT

• Neuromuscular & Skeletal:

  • Muscle Spasm
  • Arthralgia
  • Increased Creatine Phosphokinase

• Respiratory:

  • Nasopharyngitis
  • Dyspnea
  • Epistaxis

• Miscellaneous:

  • Fever

Contraindications to Rifaximin (Xifaxan):

• Hypersensitivity to rifaximin or other rifamycin anti-biotics or any part thereof

Warnings and precautions

• Hypersensitivity

  • Exfoliative dermatitis, angioneurotic swelling, pruritus and urticaria have all been reported.
  • As little as 15 minutes after drug administration, allergic reactions can occur.

• Superinfection

  • Long-term use can lead to fungal and bacterial superinfections, such as C. difficile-associated diarrhea(CDAD) or pseudomembranous collitis.
  • CDAD was seen after more than two months of post-antibiotic treatment.

• Diarrhea:

  • Avoid use in the treatment or prevention of diarrhea with fever and/or bloody stool.
  • If symptoms persist or worsen, consider alternate treatment.

• Hepatic impairment

  • Patients with End-Stage Liver Diseases (MELD) scores >25 have not shown any evidence of efficacy in preventing encephalopathy.
  • Use caution in patients with severe liver impairment (Child-Pugh Class C).

Rifaximin: Drug Interaction

Monitor:

• Hypersensitivity reactions
• temperature
• blood in stool
• change in symptoms
• monitor changes in mental status in hepatic encephalopathy

How to administer Rifaximin (Xifaxan)?

• Administer orally with or without food.

Mechanism of action of Rifaximin (Xifaxan):

• Rifaximin usually inhibits bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase.

Absorption: Oral: Traveler's diarrhea: Low Hepatic encephalopathy: Increased absorption in Child-Pugh class C patients compared with patients with Child-Pugh class A

Protein binding:

• In Healthy subjects: 67.5%
• In patients with Hepatic impairment: 62%

Metabolism:

• Extensive, mainly by CYP3A

Half-life elimination:

• Healthy subjects: 5.6 hours
• IBS-D patients: 6 hours

Time to peak:

• In Healthy subjects and ISB-D patients: ~1 hour

Excretion:  

• Via Feces (96.6%; primarily as unchanged drug) & urine (0.32%)

International Brands of Rifaximin:

• Xifaxan
• Zaxine
• Alfa Normix
• Arfla
• Aximin
• Bang Yi
• Colidimin
• Coloximina
• Fatroxim
• Faxinorm
• Flonorm
• Henlix
• Idibact
• Ifaxim
• Lormyx
• Normix
• Qian Er Fen
• Refero
• Rifadom
• Rifatime
• Rifax
• Rifaxin
• Rifxima
• Spiraxin
• Targaxan
• Tixtar
• Tixteller
• Tixtetller
• Trencedia
• Xifamin
• Xifaxan
• Xifaxanta

Rifaximin Brand Names in Pakistan: