Colesevelam

Colesevelam is a bile acid sequestrant, a non absorbed resin that binds bile acids in the gut. It lowers LDL cholesterol by 15% to 20%, lowers blood glucose modestly in type 2 diabetes, and treats bile acid diarrhoea. It is better tolerated than cholestyramine because it binds fewer other drugs and causes less constipation, bloating and bad taste. It raises triglycerides. It is rarely available in East Africa.

Classification. Bile acid sequestrant; non absorbed polymer.

Mechanism. Binds bile acids in the intestine and prevents their return to the liver; the liver makes new bile acids from cholesterol, raises LDL receptors and takes more LDL from blood. The glucose lowering mechanism is not fully known.

Pharmacodynamics. LDL cholesterol falls within 2 weeks. Triglycerides rise by about 10% to 20%. HbA1c falls by about 0.5% in type 2 diabetes.

Pharmacokinetics. Not absorbed; less than 0.05% appears in urine. Excreted in faeces. No metabolism.

Primary hypercholesterolaemia, adult.

• 3.75 g once daily (six 625 mg tablets once daily) or 1.875 g twice daily (three tablets twice daily) with a meal and a liquid.

• Maximum 4.375 g daily (seven tablets).

Type 2 diabetes (add-on to other glucose lowering drugs), adult. 3.75 g once daily (six 625 mg tablets once daily, or three tablets twice daily).

Bile acid diarrhoea, adult (off label). 1.875 g once or twice daily, increased to 3.75 g daily.

Heterozygous familial hypercholesterolaemia in children aged 10 to 17 years, specialist. 1.875 g once daily, or 3.75 g once daily in older children, with a meal.

Kidney impairment. No adjustment.

Liver impairment. No adjustment.

Contraindications. Bowel obstruction; history of hypertriglyceridaemia induced pancreatitis; serum triglycerides above 5.7 mmol/L (500 mg/dL); hypersensitivity.

Warnings. Raised triglycerides (check at baseline and at 4 to 6 weeks); constipation; dysphagia and swallowing disorders (tablets are large); fat soluble vitamin deficiency (A, D, E, K) with long use; gastroparesis, severe gastrointestinal motility disorders or major bowel surgery (higher risk of obstruction); hypothyroidism may worsen through reduced levothyroxine absorption.

Adverse effects. Constipation, dyspepsia, nausea, flatulence, bloating, abdominal pain, raised triglycerides, headache.

Interactions. Give these at least 4 hours before colesevelam: ciclosporin, levothyroxine, combined oral contraceptives (ethinylestradiol and norethisterone), glibenclamide, phenytoin, warfarin (check the INR), verapamil, olmesartan, vitamins A, D, E and K. Metformin extended release: take together with caution. Statins and ezetimibe: no clinically important interaction, and the combination is effective.

Special groups.

• Pregnancy: acceptable if essential (not absorbed); give vitamin supplements and monitor vitamin K.

• Breastfeeding: acceptable (not absorbed).

• Patients of African ancestry: no dose change.

• Older adults: no dose change; watch for constipation.

• Kidney impairment: no adjustment.

• Liver impairment: no adjustment.

Formulations. Tablets 625 mg; oral suspension sachets 1.875 g and 3.75 g.

Administration. Oral with a meal and a full glass of water or other liquid. For the suspension, mix the sachet in 120 to 240 mL of water, fruit juice or a diet soft drink and drink it all. Swallow tablets whole.

Baseline. Lipid profile including triglycerides, alanine aminotransferase, HbA1c if diabetic, INR if on warfarin, swallowing and bowel history, pregnancy status, a full list of other medicines.

Monitoring. Lipid profile and triglycerides at 4 to 6 weeks, then every 6 to 12 months. HbA1c if diabetic. Bowel habit. INR after starting if on warfarin. Vitamin levels if treatment is long.

Stopping. Stop if triglycerides rise above 5.7 mmol/L, for pancreatitis, for bowel obstruction, or if the tablets cannot be swallowed.

Common prescribing errors. Giving it at the same time as levothyroxine or contraceptives; using it with high triglycerides; taking tablets without a meal; prescribing in dysphagia; omitting the INR check with warfarin.