Non-Absorbable Antibiotic (Hepatic Encephalopathy / IBS-D) Pregnancy: Avoid — limited data. Rifaximin has minimal systemic absorption but category C status. Hepatic encephalopathy treatment in pregnancy requires specialist hepatology input.

Rifaximin

Brand names: Targaxan, Xifaxanta

Adult dose

Dose: HE prevention: 550 mg twice daily. Traveller's diarrhoea: 200 mg three times daily for 3 days. IBS-D: 550 mg three times daily for 14 days (US licence; off-label UK for IBS-D)

Route: Oral

Frequency: Twice daily (HE) or three times daily (traveller's diarrhoea, IBS-D)

Max: 1650 mg/day (IBS-D short course); 1100 mg/day (HE maintenance)

Hepatic encephalopathy (HE) secondary prophylaxis: 550 mg twice daily continuously (licensed in UK — Targaxan). Traveller's diarrhoea: only for non-invasive strains (no blood/fever — use if Shigella/Salmonella suspected). Source: BNF 90; NICE TA337.

Paediatric dose

Dose: Not licensed under 18 years for HE in UK N/A/kg

Route: Oral

Frequency: N/A

Max: N/A

Rifaximin not licensed for paediatric HE in UK. Specialist use only in children.

Dose adjustments

Renal

No dose adjustment required — <1% systemic absorption; renal excretion negligible.

Hepatic

No dose adjustment — non-absorbable antibiotic. Used in severe hepatic impairment (its primary indication). Monitor for accumulation if systemic absorption increases in severe portal hypertension (rare).

Paediatric weight-based calculator

Patient weight (kg)

Rifaximin not licensed for paediatric HE in UK. Specialist use only in children.

Clinical pearls

NICE TA337: rifaximin-α (Targaxan) is recommended for prevention of hepatic encephalopathy (HE) recurrence in adults who have had ≥2 episodes of overt HE in the past 6 months while on optimal lactulose therapy. Reduces HE episodes by 57% vs placebo (NEJM 2010 Bass et al.).
Combination with lactulose: rifaximin is used in addition to — not instead of — lactulose for HE secondary prophylaxis. Bass trial 2010 allowed concurrent lactulose. Adding rifaximin to lactulose reduces hospitalisation by 50% over 6 months.
Non-absorbable mechanism: rifaximin acts intraluminally by reducing ammonia-producing gut bacteria (Bacteroides, Escherichia coli) without systemic antibiotic effects. This explains the excellent tolerability and low C. diff risk. Course can be continued indefinitely in cirrhotics with recurrent HE.
C. difficile safety advantage: as a non-absorbable antibiotic, rifaximin has dramatically lower C. diff risk compared to systemic antibiotics. Relevant in cirrhotics who are at higher risk of C. diff due to frequent hospitalisation and lactulose-induced diarrhoea.
Minimal resistance emergence: despite continuous use for HE prophylaxis, gut bacteria do not develop clinically significant rifaximin resistance — likely because systemic concentrations are negligible, preventing the selection pressure that drives systemic antibiotic resistance. Source: BNF 90; NICE TA337; Bass et al. NEJM 2010.

Contraindications

Intestinal obstruction
Hypersensitivity to rifaximin or rifamycin antibiotics (cross-reactivity with rifampicin — check rifampicin allergy)
Invasive bacterial diarrhoea (bloody diarrhoea, fever, Salmonella/Shigella/Campylobacter) — not effective for invasive pathogens

Side effects

Nausea, flatulence, abdominal pain (mild — generally well tolerated)
Peripheral oedema (reported in HE trials — may be disease-related)
Clostridium difficile: rare — significantly lower risk than systemic antibiotics (poor GI absorption = less microbiome disruption)
Urine discolouration (orange-red — minimal systemic rifaximin absorbed; reassure patient)

Interactions

Systemic rifamycins (rifampicin): potential cross-resistance development — avoid prolonged concomitant use
P-glycoprotein substrates: rifaximin is a weak P-gp inducer — minor clinical significance given low systemic absorption
Warfarin: theoretical CYP3A4 induction (minor) — monitor INR if starting or stopping rifaximin in anticoagulated patients
Ciclosporin: rare case reports of reduced ciclosporin levels — monitor

Monitoring

Clinical assessment of hepatic encephalopathy episodes (frequency, severity — Number Connection Test or Conn score)
LFTs and liver function status (underlying disease progression monitoring)
No specific drug level monitoring required

Reference: BNFc; BNF 90; NICE TA337 (rifaximin for HE); Bass et al. NEJM 2010 (RFHE trial); MHRA SPC Targaxan. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways