Pouchitis: rifaximin

Targaxan 550 mg film-coated tablets for the reduction in recurrence of episodes of overt hepatic encephalopathy.

Xifaxanta 200 mg film-coated tablets for the treatment of travellers' diarrhoea.

There is limited published research examining rifaximin for the treatment of pouchitis, including only 1 small randomised controlled trial (RCT).

Isaacs et al. (2007) (n=18) reported a double-blind placebo-controlled RCT examining 4 weeks' treatment with rifaximin (400 mg 3 times daily) for active pouchitis (acute or chronic). Among the 17 people who had at least 1 post-baseline efficacy evaluation, all of those in the rifaximin group (8/8) and nearly all of those in the placebo group (8/9) had received previous antibiotic treatment. Of these 17 people, 2 of the 8 people in the rifaximin group and no one in the placebo group obtained clinical remission at 4 weeks (Pouchitis Disease Activity Index [PDAI] score of less than 7 points and a decrease from baseline PDAI score of 3 points). This was not statistically significant (p=0.211) but the study was underpowered. No one in the study obtained complete remission (PDAI score of 0).

Two small, non-comparative observational studies reported rates of remission (PDAI score of 0) or improvement (PDAI score reduction of at least 3 points) after treatment with rifaximin 1 g twice daily in combination with ciprofloxacin 500 mg twice daily for 2 weeks for chronic pouchitis that was not responsive to at least 4 weeks' treatment with other antibiotics (usually metronidazole or ciprofloxacin monotherapy). The study by Gionchetti et al. (1999) included 18 adults, of whom 6 obtained remission with treatment and 10 had an improvement in their condition. The study by Abdelrazeq et al. (2005) included 8 adults: after treatment, 5 of them remained in remission for at least 6 months and a further 2 had an improvement in their condition.

Shen et al. (2008) reported experience with rifaximin for maintenance treatment after antibiotic-induced remission in 51 people with antibiotic-dependent pouchitis, at a daily dose of 200 mg up to a maximum 1800 mg for up to 24 months. At 3 months, 33 were still in remission. Four of these people later relapsed at between 3 and 12 months. Antibiotic induction regimen, symptom score after induction and rifaximin dose were not predictive of maintaining remission.

In the RCT by Isaacs et al. (2007), adverse events were experienced by 6 of the 8 people in the rifaximin group and 5 of the 10 people in the placebo group (statistical significance not reported). One case of each of the following adverse events was experienced by people in the rifaximin group: flatulence, frequent bowel movements, proctalgia, rectal haemorrhage, thirst, candida, upper respiratory tract infection, cluster headache and headache. In the study by Shen et al. (2008), 1 person discontinued rifaximin because of a transient facial rash. No adverse events were reported in the 2 other non-comparative observational studies.

Rifaximin is contraindicated in people with intestinal obstruction. The summaries of product characteristics for Targaxan and Xifaxanta state that Clostridium difficile-associated diarrhoea has been reported with the use of rifaximin. The potential association of rifaximin treatment with Clostridium difficile-associated diarrhoea and pseudomembranous colitis cannot be ruled out. The effects on gut flora may also lead to reduced effectiveness of oral contraceptives, and additional contraceptive precautions are recommended. Despite limited systemic absorption, there may also be reddish discolouration of the urine.

Common adverse events associated with rifaximin (occurring in more than 1 in 100 people) include dizziness and headaches, pruritus and rashes, and abdominal symptoms of pain, distension, nausea and vomiting, diarrhoea or constipation. Other adverse events affecting most systems of the body have been observed less frequently.

The 4 published studies provide limited evidence about rifaximin in the care of people with pouchitis. Large, double-blind RCTs are needed to better assess the safety and efficacy of rifaximin for the treatment of acute or chronic pouchitis and pouchitis refractory to other antibiotics, or for maintenance of antibiotic-induced remission.