Rifaximin

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

•  Reduction in recurrence of episodes of overt hepatic encephalopathy

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to rifamycin-derivatives
• Bowel obstruction

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Severe hepatic impairment
  - Child-Pugh class C
  - MELD score >25
• Porphyria
• Coadministration with other rifamycins
• Coadministration with P-glycoprotein inhibitor (e.g ciclosporin)
• May impair ability to drive and operate machinery 

Forms avail. in SA and covered in this monograph: fct

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

Infections caused by: Escherichia coli spp, Clostridium spp, Enterobacteriaceae, Bacteroides spp

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African manufacturer recommendations

Reduction in recurrence of episodes of overt hepatic encephalopathy (Additional agent required)

• Oral (fct): 550mg, 12hrly; Treatment duration: 6 months

---

Rifaximin is used in addition to lactulose and should be used with appropriate lactulose dosages

---

Rifaximin should be taken orally with a glass of water, and can be administered with or without food

---

International manufacturer recommendations

Reduction in recurrence of episodes of overt hepatic encephalopathy

• Oral (fct): 550mg, 12hrly as long term treatment

---

Consideration should be given to official guidance on the appropriate use of antibacterial agents

---

In the pivotal study, 91% of the patients were using concomitant lactulose

---

Rifaximin can be administered with or without food

Not established for use in children below 18 years

Pregnancy

• Caution; positive evidence of risk in animal studies
• There is no or limited data from the use of rifaximin in pregnant women
• Animal studies showed transient effects on ossification and skeletal variations in the foetus
• As a precautionary measure, use of rifaximin during pregnancy is not recommended

Breastfeeding

South African manufacturer recommendations

• Caution; not recommended 
• It is unknown whether rifaximin or its metabolites are excreted in human milk. A risk to the breastfed child cannot be excluded
• Rifaximin should not be used by women breastfeeding their infants

International manufacturer recommendations

• Caution; not recommended 
• It is unknown whether rifaximin or its metabolites are excreted in human milk. A risk to the breastfed child cannot be excluded
• A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from rifaximin therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Fertility

• Animal studies do not indicate direct or indirect harmful effects with respect to male and female fertility

Renal Impairment

• Caution; no dose adjustment recommended 
  No clinical data are available on the use of rifaximin in patients with impaired renal function
  Although dosing change is not anticipated, caution should be used in patients with impaired renal function

Hepatic Impairment

• Mild to moderate (Child-Pugh class A and B): No dose adjustment recommended 
  No dosage adjustment is necessary for patients with hepatic insufficiency
• Severe (Child-Pugh class C): Caution; no dose adjustment recommended 
  Use with caution in patients with severe (Child-Pugh C) hepatic impairment and in patients with MELD (Model for End-Stage Liver Disease) score >25
  See additional prescribing points

Elderly

• No dose adjustment recommended 
  The safety and efficacy data of rifaximin showed no differences between the elderly and the younger patients

Porphyria Information

• Not yet classified (NC) 

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Headache
• Depression
• Confusional state
• Anxiety
• Hypersomnia
• Insomnia
• Balance disorders
• Amnesia
• Seizures
• Attention disorders
• Memory impairment
• Hypoesthesia
• Asthenia

Cardiovascular Disorders

• Hot flushes
• Hypertension
• Hypotension
• Presyncope
• Syncope

Respiratory Disorders

• Dyspnoea
• Pleural effusion
• Pneumonia
• Upper respiratory tract infection
• Rhinitis
• Chronic obstructive pulmonary disease

Gastrointestinal Disorders

• Ascites
• Nausea and vomiting
• Upper abdominal pain
• Abdominal distension
• Diarrhoea
• Abdominal pain
• Haemorrhage of oesophageal varices
• Dry mouth
• Stomach discomfort
• Clostridial infection
• Constipation
• Clostridium difficile-associated diarrhoea
• Pseudomembranous colitis

Hepatobiliary Disorders

• Abnormal hepatic function tests

Genitourinary Disorders

• Dysuria
• Pollakiuria
• Urinary tract infection
• Proteinuria

Endocrine and Metabolic Disorders

• Anorexia
• Hyperkalaemia
• Dehydration

Musculoskeletal Disorders

• Muscle spasms
• Arthralgia
• Myalgia
• Back pain

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Rash
• Cellulitis
• Contusion
• Dermatitis
• Eczema

Immune, Blood and Lymphatic System Disorders

• Peripheral oedema
• Oedema
• Anaemia
• Pyrexia
• Candidiasis
• Thrombocytopenia
• Anaphylactic reaction
• Angioedema
• Hypersensitivity
• Abnormalities in INR
  - See additional prescribing points

Others

• Fall
• Procedural pain
• Reddish discolouration of the urine

• CYP3A4 substrates
• Oral anticoagulants
• Warfarin
• Antiepileptics
• Antiarrhythmics
• Oral contraceptives

Other interactions

• International normalised ratio (INR)

None routine. Specific cases may require

• Temperature
• Serum ammonia
• International normalized ratio (INR) 
  - See additional prescribing points
• Hepatic function tests

Additional observations

• Hypersensitivity reactions
• Blood in stool
• Change in symptoms

Hepatic impairment

• Use with caution in patients with severe (Child-Pugh C) hepatic impairment and in patients with MELD (Model for End-Stage Liver Disease) score >25
• Clinical data available for patients with hepatic impairment showed a systemic exposure higher than that observed in healthy subjects
• The systemic exposure of rifaximin was about 10-, 13-, and 20-fold higher in those patients with mild (Child-Pugh A), moderate (Child-Pugh B), and severe (Child-Pugh C) hepatic impairment, respectively, compared to that in healthy volunteers
• The increase in systemic exposure to rifaximin in subjects with hepatic impairment should be interpreted in light of rifaximin gastrointestinal local action and its low systemic bioavailability, as well as the available rifaximin safety data in subjects with cirrhosis
• Therefore, no dosage adjustment is recommended because rifaximin is acting locally

Abnormalities in INR

• Both decreases and increases in international normalized ratio have been reported in patients maintained on warfarin and prescribed rifaximin
• If coadministration is necessary, the international normalized ratio should be carefully monitored with the addition or withdrawal of treatment of rifaximin
• Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation

Rifaximin is an antibacterial agent of the rifamycin class that irreversibly binds the beta subunit of the bacterial enzyme DNA-dependent RNA polymerase and consequently inhibits bacterial RNA synthesis. Rifaximin has a broad antimicrobial spectrum against most of the Gram-positive and negative, aerobic and anaerobic bacteria, including ammonia producing species. Rifaximin may inhibit the division of urea-deaminating bacteria, thereby reducing the production of ammonia and other compounds that are believed to be important to the pathogenesis of hepatic encephalopathy. Rifaximin is a non-absorbed antibacterial agent. In vitro susceptibility testing cannot be used to reliably establish susceptibility or resistance of bacteria to rifaximin. There are currently insufficient data available to support the setting of a clinical breakpoint for susceptibility testing. Due to the very low absorption from the gastrointestinal tract rifaximin is not clinically effective against invasive pathogens, even though these bacteria are susceptible in vitro.

The development of resistance to rifaximin is primarily a reversible chromosomal one step alteration in the rpoB gene encoding the bacterial RNA polymerase. Experimental and clinical data suggest that the treatment with rifaximin of patients harbouring strains of Mycobacterium tuberculosis or Neisseria meningitidis will not select for rifampicin resistance.

Spectrum of activity: Escherichia coli spp, Clostridium spp, Enterobacteriaceae, Bacteroides spp.

Film-coated tablet 550mg

• Xifaxan (Equity Pharmaceuticals)