Xifaxanta

Xifaxanta contains rifaximin, a member of the rifamycin family that stops bacteria from making RNA and so from multiplying. Less than 1% of a dose is absorbed into the bloodstream, which keeps the action concentrated in the intestine and explains why rifaximin is used for bowel problems and not for chest or urinary infections. Some of the effects of rifampicin-type drugs, such as a reddish tint to the urine, can still appear even though so little reaches the blood.

Two rifaximin products are licensed in Britain, both from Norgine. The 200 mg tablet, called Xifaxanta, treats travellers’ diarrhoea in adults when it is not accompanied by fever, bloody diarrhoea, eight or more unformed stools in 24 hours, or blood or white cells in the stool, and it may shorten diarrhoea linked with non-invasive strains of E. coli. The 550 mg tablet, sold as Targaxan, is licensed to reduce the recurrence of episodes of overt hepatic encephalopathy in patients aged 18 and over, the confusion and drowsiness that follow when the liver cannot clear toxins produced by gut bacteria, and in the main trial nine in ten patients were also taking lactulose.

The listing has 200 mg, 400 mg and 550 mg tablets, and each strength comes in 10, 20, 30, 60, 90, 120, 180 or 270. For travellers’ diarrhoea the SmPC dose is one 200 mg tablet every 8 hours for three days, nine doses in all, and rifaximin must not be taken for more than three days even if symptoms continue, nor a second course given. For hepatic encephalopathy the licensed dose is 550 mg twice daily as long-term treatment. Tablets may be taken with or without food and are swallowed with a glass of water. The UK Xifaxanta 200 mg pack holds 9 tablets and UK rifaximin 550 mg packs hold 14 to 98; the stock listed here is imported, and 400 mg is not a UK-licensed strength.

Allergy to rifaximin, to other rifamycins such as rifampicin and rifabutin, or to an ingredient rules it out, as does intestinal obstruction. Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported, mostly in people with liver disease, and anyone who has had such a reaction with rifaximin must never receive rifaximin again. Care is advised in severe liver impairment (Child-Pugh C) and with a MELD score above 25. Rifaximin is not effective in travellers’ diarrhoea caused by invasive germs such as Campylobacter, Salmonella and Shigella, so fever, blood in the stool or a worsening illness means seeing a doctor, and a second course for diarrhoea that has not cleared is not given. Use during pregnancy is not recommended, whether to continue breastfeeding has to be weighed up, and safety and efficacy in under-18s have not been established.

Both rises and falls in INR have been reported in people on warfarin who start rifaximin, so the INR is checked closely when it is added or withdrawn. Ciclosporin, a potent P-glycoprotein inhibitor, raised rifaximin levels many times over in healthy volunteers, though the significance is unknown, and in people with liver impairment rifaximin may reduce exposure to other CYP3A4 substrates such as antiepileptics, antiarrhythmics and oral contraceptives. Rifaximin should be taken at least two hours after activated charcoal. Taking another rifamycin to treat a systemic infection alongside it is not recommended.

Dizziness, headache, nausea, abdominal pain, wind, bloating, constipation and an urgent need to open the bowels are among the reactions listed for the 200 mg tablet, and in the hepatic encephalopathy trial peripheral swelling, ascites, nausea, dizziness, anaemia, depression, itching, rash, muscle spasms, joint pain and breathlessness were reported more often than on placebo. Persistent watery diarrhoea during or after a course may be a sign of Clostridioides difficile infection, and a rash that blisters or peels needs urgent attention. Anyone with liver disease whose confusion or sleepiness gets worse should be seen quickly. Rifaximin has a negligible influence on driving. Whether Xifaxanta is suitable, which strength is appropriate and for how long is for the prescriber to decide.