Evidence review: safety

Colesevelam compared with placebo for diarrhoea-predominant irritable bowel syndrome

In Odunsi-Shiyanbade et al. (2010), the most common adverse effects seen with colesevelam were headache (colesevelam 40% compared with placebo 33%), flatulence (colesevelam 24% compared with placebo 8%), nausea (colesevelam 17% compared with placebo 24%), lower abdominal cramps (colesevelam 17% compared with placebo 0%) and green-coloured stools (17% in both groups). The statistical significance of any differences between the groups was not reported. There were no serious adverse events and no participants had to stop the study because of an adverse event.

Colesevelam for treating bile acid malabsorption (case series)

Wedlake et al. (2009) reported bloating (n=3, 7%), constipation (n=2, 4%), heartburn (n=2, 4%), abdominal pain (n=1, 2%), flatulence (n=1, 2%), perianal soreness (n=1, 2%), weight gain (n=1, 2%), and leg and facial oedema (n=1, 2%) in people taking colesevelam. After at least 1 year of treatment, 9 people (20%) developed vitamin D deficiency.

Adverse effects led to 5 people stopping colesevelam (11%). Other reasons for stopping treatment were lack of efficacy (n=5); having to take too many tablets or finding them difficult to swallow (n=3); resolution of symptoms (n=2); and switching to another medicine (n=1). One person was lost to follow-up.

No adverse effects were reported by Puleston et al. (2005) in the 5 people with bile acid malabsorption, who had not previously tolerated colestyramine.

Other sources of safety information

The summary of product characteristics for colesevelam states that the most frequent adverse effects are flatulence and constipation. These affected at least 1 in 10 people in controlled clinical studies and during post-approval use for hypercholesterolaemia. Headache, vomiting, diarrhoea, dyspepsia, abdominal pain, abnormal stools, nausea, abdominal distension and increased levels of serum triglycerides were seen in between 1 in 100 and 1 in 10 people. Dysphagia, myalgia and increased levels of serum transaminases affected between 1 in 1000 and 1 in 100 people. Pancreatitis was a very rare adverse effect, affecting less than 1 in 10,000 people.

The summary of product characteristics notes that colesevelam may affect the bioavailability of other medicines. Therefore, when a clinically important drug interaction cannot be excluded, colesevelam should be taken at least 4 hours before or 4 hours after the other medicine to minimise the risk of reduced absorption. The tablets can be taken once a day if needed. However, it is not known whether a once-daily dose is effective in bile acid malabsorption. In Odunsi-Shiyanbade et al. (2010), 1.875 g colesevelam was taken twice daily and, in Wedlake et al. (2009), 1.25 g was taken 3 times daily. Colesevelam was taken at doses between 1.25 g and 3.75 g per day in Puleston et al. (2005). However, the exact dosage regimens were not reported.