| Cholestyramine, colestipol, clofibrate, gemfibrozil, nicotinic acid
(niacin), probucol, neomycin, and dextrothyroxine are the most
commonly used drugs in the treatment of hyperlipoproteinaemic
disorders. While adverse reaction data are available for all of them,
definitive data regarding the frequency and severity of potential
adverse effects from well-controlled trials using large numbers of
patients (greater than 1000) are available only for cholestyramine,
clofibrate, nicotinic acid and dextrothyroxine. In adult patients
treated with cholestyramine, gastrointestinal complaints, especially
constipation, abdominal pain and unpalatability are most frequently
observed. Continued administration along with dietary manipulation
(e.g. addition of dietary fibre) and/or stool softeners results in
diminished complaints during long term therapy. Large doses of
cholestyramine (greater than 32 g/day) may be associated with
malabsorption of fat-soluble vitamins. Most significantly,
osteomalacia and, on rare occasions, haemorrhagic diathesis are
reported with cholestyramine impairment of vitamin D and vitamin K
absorption, respectively. Paediatric patients have been reported to
experience hyperchloraemic metabolic acidosis or gastrointestinal
obstruction. Concurrent administration of acidic drugs may result in
their reduced bioavailability. Serious adverse reactions to
clofibrate will probably limit its role in the future. Of particular
concern are ventricular arrhythmias, induction of cholelithiasis and
cholecystitis, and the potential for promoting gastrointestinal
malignancy which far outweigh the reported benefits in preventing new
or recurrent myocardial infarction, cardiovascular death and overall
death. Patients with renal disease are particularly prone to
myositis, secondary to alterations in protein binding and impaired
renal excretion of clofibrate. Drug interactions with coumarin
anticoagulants and sulphonylurea compounds may produce bleeding
episodes and hypoglycaemia, respectively. Nicotinic acid produces
frequent adverse effects, but they are usually not serious, tend to
decrease with time, and can be managed easily. Dermal and
gastrointestinal reactions are most common. Truncal and facial
flushing are reported in 90 to 100% of treated patients in large
clinical trials. Significant elevations of liver enzymes, serum
glucose, and serum uric acid are occasionally seen with nicotinic
acid therapy. Liver enzyme elevations are more common in patients
given large dosage increases over short periods of time, and in
patients treated with sustained release formulations.(ABSTRACT
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