Evidence review: safety

Summary of product characteristics

Rifaximin is contraindicated in people with intestinal obstruction. The summaries of product characteristics for both Targaxan and Xifaxanta state that, as with nearly all antibacterial agents, Clostridium difficile-associated diarrhoea has been reported with 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, and abdominal symptoms of pain, distension, nausea and vomiting, diarrhoea or constipation. Studies of Targaxan (for its licensed indication: reduction in recurrence of episodes of overt hepatic encephalopathy) have also commonly reported depression, dyspnoea, pruritus and rashes, and arthralgia. Studies of Xifaxanta (for its licensed indication: treatment of travellers' diarrhoea) have commonly reported pyrexia. Other adverse events affecting most systems of the body have been observed but were uncommon (fewer than 1 in 100), rare (fewer than 1 in 1000) or an unknown frequency.

Adverse events observed in studies

In the RCT by Isaacs et al. (2007), all 18 randomised participants were included in the safety analyses. A similar proportion of people in both study groups experienced adverse events: 6 of the 8 people in the rifaximin group and 5 of the10 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. There were no withdrawals because of adverse events in either group, and no serious adverse events in either group.

In the study by Gionchetti et al. (1999), there were no adverse events and no changes in laboratory measures (including full blood count and blood chemistry) in the 18 people who took rifaximin plus ciprofloxacin.

In the study by Abdelrazeq et al. (2005), no side effects and no significant changes from baseline values in any of the laboratory tests examined were observed in the 8 people who took rifaximin plus ciprofloxacin.

In the study by Shen et al. (2008), rifaximin was well tolerated when used for maintenance for up to 24 months. One person discontinued rifaximin 2 weeks after starting treatment because of a transient facial rash. No other adverse effects were reported.