Cholestyramine

Cholestyramine is a bile acid sequestrant, a non absorbed resin that binds bile acids in the gut. It lowers LDL cholesterol by 15% to 25%. It treats itching in partial biliary obstruction and primary biliary cholangitis, bile acid diarrhoea after ileal resection or cholecystectomy, and as a washout for some drugs such as leflunomide and teriflunomide. It is unpleasant to take, binds many other drugs, and raises triglycerides. It is available in East Africa at modest cost, though supply varies.

Classification. Bile acid sequestrant; anion exchange resin.

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. In cholestasis, it binds the bile acids that cause itching.

Pharmacodynamics. LDL cholesterol falls within 1 to 2 weeks. Itching improves in 1 to 3 weeks. Triglycerides rise by 10% to 20% in some patients.

Pharmacokinetics. Not absorbed. Excreted in faeces with the bound bile acids. No metabolism.

Primary hypercholesterolaemia, adult.

• Start 4 g once or twice daily.

• Increase gradually at intervals of 1 month or longer to 8 to 16 g daily in 2 divided doses (up to 24 g daily; labels allow up to 36 g daily).

• Take before meals.

Pruritus in partial biliary obstruction or primary biliary cholangitis, adult. 4 to 8 g daily, in 1 to 2 doses, before meals (breakfast); up to 16 g daily.

Bile acid diarrhoea, adult. 4 g once to four times daily, with the lowest effective dose.

Drug washout (leflunomide, teriflunomide), adult. 8 g three times daily for 11 days (or 4 g three times daily if 8 g is not tolerated).

Children (specialist). 240 mg/kg daily of anhydrous resin in 2 to 3 divided doses; start low and titrate to a usual maximum of 8 g daily.

Kidney impairment. No adjustment; watch for hyperchloraemic acidosis.

Liver impairment. No adjustment; vitamin K deficiency is a risk in cholestasis.

Contraindications. Complete biliary obstruction (the resin cannot work); bowel obstruction; serum triglycerides above 5.7 mmol/L (500 mg/dL); hypersensitivity.

Warnings.

• Constipation (can cause impaction, haemorrhoids and obstruction)
• Raised triglycerides
• Hyperchloraemic acidosis in children and kidney impairment
• Deficiency of fat soluble vitamins A, D, E and K (vitamin K deficiency may cause bleeding), and folate
• Phenylketonuria (some products contain phenylalanine)
• Never take the dry powder (aspiration and oesophageal obstruction)
• Dysphagia
• Worsened hypothyroidism through reduced levothyroxine absorption

Adverse effects. Constipation, bloating, flatulence, nausea, abdominal pain, unpleasant taste, rash, raised triglycerides, steatorrhoea at high doses.

Interactions. Give other drugs at least 1 hour before or 4 to 6 hours after cholestyramine. Affected drugs include warfarin (check the INR), levothyroxine, digoxin, thiazides, loop diuretics, propranolol, tetracyclines, penicillin, phenobarbital, fat soluble vitamins, mycophenolate, ciclosporin, oral contraceptives, ursodeoxycholic acid, and statins. Leflunomide and teriflunomide: reduced levels, used purposely for washout.

Special groups.

• Pregnancy: acceptable if essential; give vitamin A, D, K and folate supplements.

• Breastfeeding: acceptable (not absorbed); watch for vitamin deficiency.

• Patients of African ancestry: no dose change.

• Older adults: start 4 g once daily; watch for constipation.

• Kidney impairment: no adjustment; monitor chloride and bicarbonate.

• Liver impairment: no adjustment; give vitamin K in cholestasis.

Formulations. Powder in sachets of 4 g (some products with sugar, aspartame or sucralose) and cans.

Administration. Mix each 4 g sachet with at least 120 to 180 mL of water, juice, soup, milk or thin cereal; let it stand 1 to 2 minutes and stir until well mixed; drink it all. Give before meals. Never take dry powder. Keep other drugs apart: take them 1 hour before or 4 to 6 hours after.

Baseline. Lipid profile including triglycerides, alanine aminotransferase, bowel habit, INR and vitamin K status in cholestasis, a full list of other medicines, pregnancy status.

Monitoring. Lipid profile and triglycerides at 4 to 6 weeks, then every 6 to 12 months. Bowel habit. INR on warfarin, after starting or changing the dose. Fat soluble vitamin levels, folate and bicarbonate in long treatment, children and cholestasis.

Stopping. Stop if triglycerides rise above 5.7 mmol/L, for impaction or obstruction, or for severe vitamin deficiency; no taper is needed, but recheck the INR and the doses of drugs it was binding, as their effect may rise.

Common prescribing errors. Giving other drugs at the same time; taking the powder dry; starting at a high dose; missing a rising INR on warfarin; using it with high triglycerides; omitting vitamin supplements in long courses.